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Ozempic gains expanded approval; MS treatment gets Boxed Warning added to label; Monotherapy approval granted for treatment resistant depression Tx Spravato; Leqembi gains maintenance regimen; Enhertu gains new Breast CA indication.
Good morning from Pharma and Biotech Daily, the podcast that gives you only what's important to hear in the Pharma and Biotech world.AbbVie has entered into a collaboration with Neomorph worth up to $1.64 billion for molecular glue. Neomorph, a protein degradation-focused company, has secured its third big pharma deal in less than a year. In other news, Vigil Neuroscience's Alzheimer's treatment has shown early promise in reducing Trem2 levels. Vanda lost a confidentiality complaint against the FDA. Biogen is trimming its research workforce while their higher-dose SMA drug is under regulatory review. Samsung Biologics has secured a $1.4 billion European contract. Teva's Copaxone receives a boxed warning from the FDA. Tris Pharma has recorded a late-stage win for a non-opioid painkiller. J&J predicts that deals are likely to shrink after their $14.6 billion acquisition of Intra-Cellular. In the biopharma industry, there are questions surrounding policies under the new administration. Gilead executives have started over with a new spinoff after almost 5 years into a $5 billion partnership with Galapagos.
*) Israel kills 26 Palestinians in air strikes across Gaza Israel continues with its deadly strikes on besieged Gaza. At least 26 Palestinians were killed and 47 wounded in Israeli air strikes on besieged Gaza. At least 16 Palestinians were killed and 30 wounded, including children, in strikes that targeted two houses north of the Nuseirat refugee camp in central Gaza. Horrific and heart-wrenching experiences continue to haunt Palestinians in Gaza. In one such incident, a Palestinian ambulance worker made a horrific discovery when the corpse on the stretcher that he was carrying turned out to be his mother, killed by an Israeli air strike in central besieged Gaza. *) Arab League calls for UN resolution against Israel's UNRWA ban Meanwhile, the Arab League called for the passage of a UN resolution opposing Israel's move to ban the UN Agency for Palestinian Refugees (UNRWA) from operating in the country. The meeting demanded that the representatives of Arab countries in New York coordinate with the ambassadors and representatives of friendly countries and the UN Secretariat to request a special session of the UN General Assembly, as it is the body that issued the decision to establish UNRWA, to discuss the repercussions of this serious Israeli law and to issue a UN resolution rejecting this illegal Israeli measure. However, Israel continued with its defiance and demolished the office of the UN Agency for Palestinian Refugees (UNRWA) in the Nur Shams refugee camp in the occupied West Bank. *) North Korea launches a new ballistic missile North Korea has launched a new intercontinental ballistic missile in its first test in almost a year of a weapon designed to threaten the US mainland and occurring days ahead of the US election. North Korean leader Kim Jong Un ordered the missile test and was at the launch site calling the launch “an appropriate military action” to show North Korea's ''resolve to respond to its enemies' moves'' that have threatened the North's safety. In response to this, South Korea announced new export controls on materials needed to produce solid-fuel missiles to restrict North Korea's ballistic missile development. *) Canada labels India as a cyber threat According to a report, a cyber defence agency charged with keeping foreign actors from infiltrating Canada's computer networks identified India as a cyber threat for the first time. According to its National Cyber Threat Assessment report the Indian state-sponsored cyber threat actors are likely to conduct cyber threat activity against Government of Canada networks for espionage. The report also said that as a breakdown in Canada-India relations continues, India will step up its cyber threats after Prime Minister Justin Trudeau linked New Delhi to serious crimes against Sikh Canadians. *) EU slaps $502M fine on the world's largest generic drugmaker Teva The EU has slapped the world's largest generic drugmaker Teva with a $502 million fine for "abusing its dominant position" to impede competition for its blockbuster multiple sclerosis medicine. The Israeli company said it would appeal against the EU's fine. The European Commission said that it found Teva artificially extended the patent protection of its drug Copaxone and "systematically spread misleading information about a competing product to hinder its market entry and uptake.
Los servicios y los alimentos vuelven a tirar al alza de la inflación de la eurozona. En octubre, el IPC repuntó tres décimas hasta el 2%. La subyacente, por s uparte, sigue aún en el 2,7% cuando se esperaba aunque fuera un mínimo retroceso. La presidenta del BCE, Christine Lagarde, pide calma.. "el objetivo está a la vista pero no voy a decirles que la inflación está bajo control". En clave empresarial, los ingresos de Stellantis retroceden en el tercer trimestre un 27% y, dentro del sector bancario, bien para SG que sube un 8% y mal para BNP Paribas, que se deja casi un 6%. La petrolera Shell logra unas ganancias de 6.000 millones de dólares en el tercer trimestre, 700 millones más de lo que esperaba el mercado mientras que los de Airbus celebra sus cuentas con subidas en bolsa de casi el 3%. Bruselas multa con 462 millones a la farmacéutica Teva por abusar de su posición dominante para retrasar la entrada en el mercado de medicamentos rivales a su producto estrella contra la esclerosis múltiple, el Copaxone, en contra de las reglas de competencia justa de la UE. Entrevistaremos a Esther Pérez, Jefa de EStudios Ingeniería Civil/Caminos y Directora del Máster en Sistemas Integrales de Gestión de la Escuela Politécnica Superior de UAX. Los temas de la actualidad los debatiremos en la Tertulia de Cierre de Mercados con Ignacio Ruiz Jarabo, exdirector de la Agencia Tributaria, y Pedro Fernández, abogado y profesor.
MS-Perspektive - der Multiple Sklerose Podcast mit Nele Handwerker
Glatirameracetat, bekannt als Copaxone und Clift, wird für milde und moderate Verläufe der schubförmigen Multiplen Sklerose empfohlen. Den vollständigen Beitrag zum Nachlesen gibt es auf meinem Blog: https://ms-perspektive.de/258-glatirameracetat Diesmal stelle ich Glatirameracetat vor, das als Copaxone oder Clift bekannt ist und zu den zugelassenen verlaufsmodifizierenden Medikamenten für schubförmige MS gehört. Es war eines der ersten Medikamente, das als präventive Therapie für MS-Patienten zugelassen wurde, und war eine zufällige Entdeckung. Ursprünglich sollte es zu Forschungszwecken MS bei Mäusen auslösen, doch plötzlich entdeckte man, dass es eine schützende Wirkung hat. Wie die bereits vorgestellten Fumarate hat es einen breiter angelegten Wirkmechanismus. Ich werde im Folgenden versuchen, einen guten Überblick zu geben, ohne in die absolute Tiefe zu gehen. Und wie immer gilt: Lass dich bitte von MS-Spezialisten beraten, die deine individuelle Situation, deine Wünsche, deine Ängste und deinen allgemeinen Gesundheitszustand kennen. Inhaltsverzeichnis General Information Wie wird Glatirameracetat (Copaxone, Clift) bei den Immuntherapien eingestuft? Wofür ist Glatirameracetat (Copaxone, Clift) zugelassen? Wie sieht die Situation für spezielle Patientengruppen aus? Wer sollte Glatirameracetat meiden? Wie wird Glatirameracetat (Copaxone, Clift) angewendet? Wie wird es eingenommen? Wie wirksam ist Glatirameracetat? Risiken und Nebenwirkungen von Glatirameracetat (Copaxone, Clift) Impfungen Quellen Schlussbemerkung Quellen Für die Erstellung des Inhalts habe ich die folgenden Quellen verwendet: Vorlesung über Glatirameracetat (Copaxone und Generika) von Prof. Tjalf Ziemssen im Rahmen des Masterstudiengangs Multiple Sklerose Management Qualitätshandbuch der KKNMS zu Glatirameracetat MS-Selfie Cards von Prof. Dr. Gavin Giovannoni Deutsches Multiple Sklerose- und Kinderwunschregister (DMSKW) Informationen aus dem Interview mit Prof. Dr. Barbara Kornek zur pädiatrischen MS Schlussbemerkung Bitte denke daran, dass es nicht das eine gute Medikament gibt, das allen hilft, sondern dass immer abgewogen werden muss, was für die jeweilige Person am besten geeignet ist. Auch andere Krankheiten, persönliche Ziele und Vorlieben müssen berücksichtigt werden. Dein Neurologe und die MS-Schwester sind die richtigen Ansprechpartner und können individuelle Empfehlungen aussprechen. Dieser Artikel dient nur zu Informationszwecken und stellt keine Empfehlung dar. Was dem einen hilft, ist für den anderen vielleicht wirkungslos. Ich hoffe, dass du zusammen mit deinem Neurologen und deiner MS-Schwester schnell die richtige Immuntherapie für dich finden wirst. Und dass du ein erfülltes, glückliches und selbstbestimmtes Leben mit MS führen kannst, unterstützt durch einen gesunden Lebensstil und eine Portion Glück. --- Bis bald und mach das Beste aus Deinem Leben, Nele Mehr Informationen und positive Gedanken erhältst Du in meinem kostenlosen Newsletter. Hier findest Du eine Übersicht zu allen bisherigen Podcastfolgen.
In this week's comprehensive MS news digest, we begin with the uplifting journey of Dr. Antonio Barbera, who discovered therapeutic benefits in table tennis after his MS diagnosis. The spotlight then shifts to Genentech's pioneering strides in MS treatment, offering hope to many. Octave Bioscience's significant funding and its implications for precision MS care is another highlight. From South Africa, we unravel potential underestimations of MS cases, providing a fresh perspective on global MS data. The safety of the drug Copaxone during breastfeeding takes center stage in a vital segment, followed by an exploration of the societal challenges faced by Kristin Kliphuis, an MS patient wrongly accused of DUI. We conclude with a thought-provoking piece on the potential benefits of oral tobacco for MS progression. This round-up offers a blend of hope, innovation, and awareness for the MS community.Show Notes: Weekly MS News Round-Up, Week of July 31st - Aug 6thPing Pong Therapy: Dr. Antonio Barbera transforms his MS journey by leveraging the therapeutic benefits of table tennis. His initiative, the "Neuropong Program", has now expanded across four states. https://www.denver7.com/news/positive-news/former-doctor-with-multiple-sclerosis-goes-from-prescribing-medications-to-playing-ping-pong Promising MS Treatment: Genentech's new subcutaneous form of ocrelizumab offers a shorter, more convenient treatment process for both relapsing and primary progressive multiple sclerosis patients. - https://www.clinicaltrialsarena.com/comment/phase-iii-trial-ocrevus/Precision Care Revolution: Octave Bioscience secures significant funding to advance their precision care for MS and other neurodegenerative diseases, focusing on personalizing patient care and improving treatment outcomes. - https://www.healio.com/news/neurology/20230731/octave-bioscience-gets-30m-to-advance-ms-neurodegenerative-treatment-platformSpotlight on South Africa: Experts discuss potential underestimations of MS diagnoses in South Africa, emphasizing the importance of awareness and early professional treatment. - https://www.news24.com/citypress/news/a-study-for-multiple-sclerosis-might-be-an-underestimate-for-sa-cases-experts-20230801Safety First: A recent study provides reassuring evidence on the safety of the drug Copaxone for mothers with MS who are breastfeeding. - https://www.managedhealthcareexecutive.com/view/new-study-finds-copaxone-safe-to-use-while-breastfeedingSocietal Misconceptions: The story of Kristin Kliphuis, an MS and Lupus patient, offers a glimpse into the misunderstandings and challenges that those with MS can face in everyday situations. - https://bocanewsnow.com/2023/08/01/why-did-pbso-charge-woman-suffering-from-multiple-sclerosis-lupus-with-dui/Oral Tobacco Findings: Research from the Karolinska Institutet in Stockholm reveals a potential link between oral tobacco use and slower MS progression, introducing new discussions on nicotine replacement therapy for those diagnosed with MS. - https://www.medscape.com/viewarticle/995075?form=fpfThe Just MS (Multiple Sclerosis) Show, w host Justin Loizos, is a podcast that connects, educates and tries to uplift others living with multiple sclerosis. It provides real-life stories, interviews, and information about DMTs (disease modification therapies) and updates on research developments.www.justmultiplesclerosis.com
This week is my 7 year anniversary, in terms of the last time I took conventional medicine to manage my MS. On 16th April 2016, against the wishes of my medical team and almost everyone else, I stopped taking the disease modifying therapy, "COPAXONE" and all other medication I may have been taking intermittently. I had made the decision to transition to lifestyle medicine, with the view to trying to facilitate the healing process in my body. Thankfully, 7 years later, my health is tremendous, physically and mentally, and determination is robust, in terms of attacking each day and sticking to my plan. There are alot of people keeping an eye on my health, and all I really want to do by continuing to share my own life experiences, is to prove that there could be another way, and that it is possible for all of us to heal, but with one condition- we must help and facilitate this process, by taking the appropriate action. I hope some of you guys get some value from this, and that some of my own experiences, resonates with you. If you want to reach me, send a mail to conor@conordevine.com Untill next time, Look after yourself, Keep the faith
Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, reads a news article reporting on how symptoms that are evident before MS begins could help predict disease type and likely course. He also reads “MS News Notes: DMT Costs, Copaxone, EBV, Rituximab” by Ed Tobias, from his column “The MS Wire.” =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/
Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, reads a news article about a machine learning algorithm that uses genetic, clinical, and demographic information to more accurately predict disease severity. He also reads “MS News Notes: DMT Costs, Copaxone, EBV, Rituximab” by Ed Tobias, from his column “The MS Wire.” =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/
Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, reads the news article about a patent that has been filed in Australia for EmtinB in combination with Copaxone as a potential MS treatment. He also reads about a new CAR T-cell therapy that eliminates the self-reactive immune cells that drive MS without destroying healthy immune cells. =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/
Stock2Me's latest podcast features Amir Reichman, CEO of BiondVax Pharmaceuticals Ltd. (NASDAQ: BVXV), a biotechnology company focused on developing, manufacturing and commercializing innovative immunotherapeutic products primarily for the treatment of infectious diseases and autoimmune diseases. In this podcast episode, Reichman introduced the history of BiondVax leading up to his appointment as CEO before discussing the company's recent development efforts focused on innovative nanosized antibody (NanoAb) therapies addressing diseases underserved by current treatments and with large and growing markets. “BiondVax is a biotechnology company focused on research and development. It is located in Jerusalem, Israel. It was founded about 17 years ago by an entrepreneur who took a spinoff from the Weizmann Institute of Science in Israel with a mission to develop a universal influenza vaccine,” Reichman said. “The vaccine was developed in the laboratory of Professor Ruth Arnon, a world-renowned professor and researcher mostly known for co-developing Copaxone, the multiple sclerosis drug marketed by Teva Pharmaceuticals. The universal influenza vaccine was then developed by BiondVax throughout the next 15 years, covering Preclinical, Phase I and multiple Phase II trials before ending up with a Phase III – the biggest Phase III ever conducted by an Israeli pharma company, with 12,400 participants spanning seven countries. The latest installment of The Stock2Me Podcast continues to reinforce IBN's commitment to the expansion of its robust network of brands, client partners, followers and the growing IBN Podcast Series. For more than 15 years, IBN has leveraged this commitment to provide unparalleled distribution and corporate messaging solutions to 500+ public and private companies. To learn more about IBN's achievements and milestones via a visual timeline, visit: https://IBN.fm/TimeLine
Stock2Me's latest podcast features Amir Reichman, CEO of BiondVax Pharmaceuticals Ltd. (NASDAQ: BVXV), a biotechnology company focused on developing, manufacturing and commercializing innovative immunotherapeutic products primarily for the treatment of infectious diseases and autoimmune diseases. In this podcast episode, Reichman introduced the history of BiondVax leading up to his appointment as CEO before discussing the company's recent development efforts focused on innovative nanosized antibody (NanoAb) therapies addressing diseases underserved by current treatments and with large and growing markets. “BiondVax is a biotechnology company focused on research and development. It is located in Jerusalem, Israel. It was founded about 17 years ago by an entrepreneur who took a spinoff from the Weizmann Institute of Science in Israel with a mission to develop a universal influenza vaccine,” Reichman said. “The vaccine was developed in the laboratory of Professor Ruth Arnon, a world-renowned professor and researcher mostly known for co-developing Copaxone, the multiple sclerosis drug marketed by Teva Pharmaceuticals. The universal influenza vaccine was then developed by BiondVax throughout the next 15 years, covering Preclinical, Phase I and multiple Phase II trials before ending up with a Phase III – the biggest Phase III ever conducted by an Israeli pharma company, with 12,400 participants spanning seven countries. The latest installment of The Stock2Me Podcast continues to reinforce IBN's commitment to the expansion of its robust network of brands, client partners, followers and the growing IBN Podcast Series. For more than 15 years, IBN has leveraged this commitment to provide unparalleled distribution and corporate messaging solutions to 500+ public and private companies. To learn more about IBN's achievements and milestones via a visual timeline, visit: https://IBN.fm/TimeLine
Trisha Bordelon is a patient advocate and active participant with the PatientsLikeMe organization. Trisha talks about her journey from when the doctors first diagnosed multiple sclerosis through her attempts to find an effective medication. Along the way, she discovered some genetic and environmental factors in developing this disease. She also found a community of patients and advocates on PatientsLikeMe, where she found guidance and where she shares resources and advocacy support. Trisha explains, "I found PatientsLikeMe just by surfing the internet, and I didn't want somebody else to go through what I went through when I was first diagnosed. My doctor, when I was diagnosed with MS, handed me two brochures. One was for Copaxone, and the other one was for, I believe, Avonex. And he said, "Take these home, take a look at them, come back next week, and we'll decide which medicine you're going to start on." I didn't know anything about MS, in my mind's eye, since I had a relative that had it, I'm thinking, "Oh my gosh, I'm going to end up in a wheelchair within six months. I won't be to work anymore. My life as I know it is over." I want to spare somebody else going through that agony." "I stayed off work from 2017 to 2021 and then went back to work full-time for one of the hospitals. They were so short-staffed and could not get enough people that they were reaching out to people that might have a disability or might have a problem. I did not try to hide my MS from them, but I also didn't volunteer it. I put down that I had been formally on disability, and I told my boss that I did have some limitations, but no one ever asked, so I did not disclose them." @PatientsLikeMe #MultipleSclerosis #MS #ChronicKidneyDisease #PatientAdvocacy #ChronicIllness PatientsLikeMe.com Listen to the podcast here
Trisha Bordelon is a patient advocate and active participant with the PatientsLikeMe organization. Trisha talks about her journey from when the doctors first diagnosed multiple sclerosis through her attempts to find an effective medication. Along the way, she discovered some genetic and environmental factors in developing this disease. She also found a community of patients and advocates on PatientsLikeMe, where she found guidance and where she shares resources and advocacy support. Trisha explains, "I found PatientsLikeMe just by surfing the internet, and I didn't want somebody else to go through what I went through when I was first diagnosed. My doctor, when I was diagnosed with MS, handed me two brochures. One was for Copaxone, and the other one was for, I believe, Avonex. And he said, "Take these home, take a look at them, come back next week, and we'll decide which medicine you're going to start on." I didn't know anything about MS, in my mind's eye, since I had a relative that had it, I'm thinking, "Oh my gosh, I'm going to end up in a wheelchair within six months. I won't be to work anymore. My life as I know it is over." I want to spare somebody else going through that agony." "I stayed off work from 2017 to 2021 and then went back to work full-time for one of the hospitals. They were so short-staffed and could not get enough people that they were reaching out to people that might have a disability or might have a problem. I did not try to hide my MS from them, but I also didn't volunteer it. I put down that I had been formally on disability, and I told my boss that I did have some limitations, but no one ever asked, so I did not disclose them." @PatientsLikeMe #MultipleSclerosis #MS #ChronicKidneyDisease #PatientAdvocacy #ChronicIllness PatientsLikeMe.com Download the transcript here
Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, reads a news article about how the use of pregnancy hormone estriol with Copaxone significantly reduced levels of neurofilament light chain, a marker of nerve damage. He also reads “Fatigue Was One of the First ‘Tells' of My Primary Progressive MS”, from Stephen De Marco's column “Goldilochs.” =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/
Whether we adults admit it or not, kids see everything. That includes seeing a parent or other family member who's living with MS. And because kids don't have an understanding of neurological conditions, they use their imaginations to fill in the blanks. That can very quickly take them down a rabbit-hole that's far scarier than the reality of living with MS. So, when do you talk to your kids about MS? And what do you say? Licensed social worker and behavioral specialist Erin Martin joins me to talk about talking to kids about your MS. If you're living with MS and you still smoke, we're sharing results of a study that you may want to carefully consider. We'll also share the results of two different studies that might help inform your COVID-19 strategy if you're on a b-cell depleting disease-modifying therapy. We'll let you know how you can catch the video replay of an excellent webinar presented by the International Progressive MS Alliance. We'll share the details about how a group of international experts discovered a method for measuring remyelinated MS lesions (And we'll tell you why that's become important right now) We'll also share some encouraging results of a study that looked at the impact of estriol and Copaxone on women living with MS. We have a lot to talk about! Are you ready for RealTalk MS??! Talking to kids about MS :22 Smoking is shown to affect MS progression 1:29 COVID-19 vaccines, breakthrough infections, and Evusheld 3:44 Catch the video replay of the International Progressive MS Alliance Webinar 8:31 A team of international experts discover a way to measure myelin repair 9:08 Combination of Estriol plus Copaxone is shown to reduce neurofilament light chain levels 11:57 Behavioral specialist Erin Martin discusses talking about MS with your kids 14:27 Share this episode 29:03 Download the RealTalk MS app for your iOS or Android device 29:24 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/254 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.com Phone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com National MS Society COVID-19 Vaccine Guidance for People Living with MS https://www.nationalmssociety.org/coronavirus-covid-19-information/multiple-sclerosis-and-coronavirus/covid-19-vaccine-guidance STUDY: The Effect of Smoking on Long-Term Grey Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis https://nn.neurology.org/content/9/5/e200008 STUDY: Tixagevimab and Cligavimab (Evusheld) Boost Antibody Levels to SARS-COV2 in Patients with Multiple Sclerosis on B-Cell Depleters https://sciencedirect.com/science/article/pii/S2211034822004163 VIDEO: Solving the Mystery of Progression: The Key to New Treatments for Progressive MS https://youtube.com/watch?v=U5sm54HSBpY STUDY: A New Advanced MRI Biomarker for Remyelinated Lesions in Multiple Sclerosis https://onlinelibrary.wiley.com/doi/10.1002/ana.26441 STUDY: Decreased Neurofilament Light Chain Levels in Estriol-Treated Multiple Sclerosis https://onlinelibrary.wiley.com/doi/10.1002/acn3.51622 Join the RealTalk MS Facebook Group https://facebook.com/groups/realtalkms Download the RealTalk MS App for iOS Devices https://itunes.apple.com/us/app/realtalk-ms/id1436917200 Download the RealTalk MS App for Android Deviceshttps://play.google.com/store/apps/details?id=tv.wizzard.android.realtalk Give RealTalk MS a rating and review http://www.realtalkms.com/review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 254 Guest: Erin Martin Tags: MS, MultipleSclerosis, MSResearch, MSSociety, RealTalkMS Privacy Policy
MS-Perspektive - der Multiple Sklerose Podcast mit Nele Handwerker
Today I'm talking to Dr. Aaron Boster about the 10 red flags when you should talk to your neurologist or maybe even look for a new one. This episode exists in two language versions. The original one is this English inteview. But there is a transcripted and translated German version, where I speak both parts. We go a bit more into details, how a good relationship and care should look like in order to keep multiple sclerosis under control as best as possible. Summary of the ten red flags: Before we go into detail, please list once the ten red flags patients should be aware of when going to their neurologist [05:53] Dr. Aaron Boster: Yeah, sure. So, these are in the order that I presented them. And the context is if your neurologist does one of these things, you should be concerned and consider whether you stay with them. All right. Quote, unquote, number one is being seen only once a year. It's my opinion that that's not frequent enough. We'll come back to all of these. [06:15] Nele: Agreed. [06:15] Dr. Aaron Boster: Number two is not getting at least an annual MRI of your brain. So, if you're not getting an annual MRI, I'm concerned about that. Number three is not showing you your scans. So, just telling you, oh, it's okay. Or, oh, there's a new spot is inadequate. Number four is not checking laboratories because every drug except Copaxone requires monitoring. And so, if they're never ordering labs, then that's a red flag to me. Number five is not screening you for common, invisible symptoms. Invisible symptoms that plague MS such as the up there's thinking of memory, energy mood, you know, the down, there's bowel, bladder, bedroom, other things like pain, like those are invisible, but they're really important. And so, if your doctor's not asking you about them, I'm bothered by that. Number six is not discussing medication adherence because taking medicine is hard and adults aren't always good at it. And that's not a bad thing. That's just something that we must be discussing. So, if they're not asking you about that, that bothers me. Number seven is not watching you walk. So, if they're not going to do a full-blown exam, there's an argument to be made, not to do a full-blown exam, but they at least need to do some physical assessment. And that bare minimum watching you walk informs them significantly. So, if they're not, even if they're only seeing you seated in a chair with no testing, that's a red flag. [07:46] Number eight is offering a first-line injection new here in 2022. And I will put some caveats around that. There are some patients that I have that are super responders to first-line therapies, and I'm not going to take them off them. I'm talking about your newly diagnosed, and they say, okay, we're going to start you off in 2022 with the first line injection. Or if you have a breakthrough disease on a drug and the doctor's offering the first-line injection as a switch, I'm not okay with that. Number nine is if the doctor says, well, go home and pick up your medicine. Here are five pamphlets let me know what you think. And the last one, number 10 is the doctor not taking any efforts to learn about you as a human being. So, it's my contention that if those things are present, you should take pause and explore that relationship. You can find the full transcripted version of the interview at: https://ms-perspektive.de/interview-with-dr-boster-10-red-flags-when-to-change-your-neurologist ++++++++++++++++++++ Many thanks to Dr. Aaron Boster for providing a guideline, what are some main cornerstones in the relationship of neurologist and MS-patient. And please speak up, if you feel something is wrong, and just realized that there are to less checks or insights provided. You always have to bare in mind, that its your life and you deserve to live it in the best possible way and health! So stay informed and make conscious choices. Good luck and all the best, Nele For more information about MS, check out my free German MS-Letter. Here you can find an overview of all previous German podcast episodes.
Episode 298 Comic Book talk about Charlie's Angels vs the Bionic Woman #1, Count Draco Knuckleduster #1, Flash Gordon #1 to 8, Rocket Girl #6. Multiple Sclerosis Health Talk about Copaxone side effects and MS. Send comments, questions and tips to kevintheduckpool@gmail.com please help us out by rating and reviewing us and telling a friend. Also check out audio and video versions of Crimson Cowl Comic Club & Under the Cowl podcasts. A fun variety of great people talk comic books, entertainment or whatever and you can see or hear me on many episodes of those podcasts as well with many more great episodes to come out in the future. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/kevin-kleinhans/message Support this podcast: https://anchor.fm/kevin-kleinhans/support
Its Time to get serious - BOOO!!!! --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/rex-penland/support
In the first segment, Dr. Jason Crowell talks with Eric Pachman about his report on copaxone and drug pricing. Next, Dr. Jeffrey Ratliff talks with Dr. Yi Li about her Neurology: Clinical Practice paper discussing ultrasound-guided lumbar puncture. Disclosures can be found at Neurology.org. No CME this week: Interviews based on articles from Neurology: Clinical Practice®, Neurology® Genetics, and Neurology® Neuroimmunology & Neuroinflammation are excluded from the CME program.
Eric Pachman, Founder and President of 46brooklyn, discusses his study, "The Flawed Design of Medicare Part D: A Copaxone Case Study". Show references: https://www.46brooklyn.com/research/2020/8/12/copaxone
Disease-modifying therapies are the cornerstone of any effective MS treatment plan. But with more than 20 approved prescription medications available today, the choices can seem overwhelming. People living with MS have questions -- Do you start out with a safe but less effective medication, or do you hit MS hard with a high-efficacy drug that may carry more risks? When is the right time to consider switching medications, and how do you have that conversation with your neurologist? Do things like other health conditions affect which disease-modifying therapy you're on? And what about aging? My guest is Dr. Scott Newsome, an Associate Professor of Neurology, and Director of Neurosciences Consultation and Infusion Center at Johns Hopkins Medicine. Dr. Newsome also serves as the Co-Director of the Multiple Sclerosis Experimental Therapeutics Program at Johns Hopkins. And I'm devoting this entire episode of RealTalk MS to taking a deep-dive into disease-modifying therapies with Dr. Newsome. We'll also give you the details about two major events taking place this week -- the MSVirtual2020 conference and the Keep Moving Forward benefit celebrating the MS Movement. We have a lot to talk about! Are you ready for RealTalk MS??! ECTRIMS + ACTRIMS = MSVirtual2020 :24 Don't miss Keep Moving Forward 1:08 My Interview with Dr. Scott Newsome 1:38 Share this episode 33:06 Leave a rating & review 33:26 Please Support the National MS Society COVID-19 Response Fund 34:45 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: realtalkms.com/158 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.comPhone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com Give RealTalk MS a Rating and Review National MS Society's Ask An MS Expert Video Replay National MS Society COVID-19 Response Fund Join the RealTalk MS Facebook Group Download the RealTalk MS App for iOS Download the RealTalk MS App for Android Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 158 Hosted By: Jon Strum Guests: Dr. Scott Newsome Tags: MS, MultipleSclerosis, MSResearch, MSSociety, Tecfidera, Ocrevus, Kesimpta, Copaxone, Gilenya, RealTalkMS Privacy Policy
Multiple Sclerosis News Today's columnist, Jenn Powell, discusses how paramagnetic rim lesions are showing promise as a diagnostic marker of MS. Plus, Multiple Sclerosis News Today's columnist and forums moderator, Ed Tobias, reports on a lawsuit against the maker of Copaxone and says there are two sides to the coin. ===================================== Treatment for Relapsing MS Progression | MAYZENT® (siponimod) Read about MAYZENT, a once daily pill that can significantly slow down disability progression in people with relapsing MS. See full prescribing & safety info. http://ChangesInRMS.com ===================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/
Whether you call it brain fog, cog-fog, or you don't happen to have a name for it, cognitive dysfunction affects more than half of all the people with MS. Joining me once again is Dr. Meghan Beier, a Rehabilitation Neuropsychologist and Assistant Professor of Physical Medicine at the Johns Hopkins University School of Medicine. Dr. Beier specializes in cognitive rehabilitation and neuropsychological assessment and intervention and she's back to answer more of our questions about managing the cognitive issues typically associated with MS. We're also talking about Kesimpta (ofatumumab), the high-efficacy b-cell disease-modifying therapy that just received FDA approval. We'll tell you about the case study of a patient who lost their vaccination immunity to the Varicella-Zoster virus (causes chickenpox & shingles) after receiving their first Ocrevus infusion. We'll give you the details about the generic for Tecfidera that's going to be available in just a few weeks. And we'll tell you why the U.S. Department of Justice is suing Teva, the manufacturer of Copaxone. We'll share all the details and let you know where to register for the National MS Society's Black MS Experience Summit. And we'll tell you how a research team from Facebook (yup -- you read that right!) and New York University is hoping to speed up MRI exams. We have a lot to talk about! Are you ready for RealTalk MS??! We're trending! :22 FDA approves ofatumumab (Kesimpta) for treating relapsing-remitting MS and active secondary-progressive MS 3:53 Patient loses vaccination immunity for Varicella-Zoster virus after Ocrevus infusion 5:44 Generic for Tecfidera will be available in September 8:25 U.S. Department of Justice sues Coaxone manufacturer, Teva 9:18 National MS Society to convene the Black MS Experience Summit 12:24 Facebook & New York University research team develop artificial intelligence technology that will speed up MRI exams 13:26 My Interview with Dr. Meghan Beier 15:48 Share this episode 29:38 Leave a rating & review 29:58 Please Support the National MS Society COVID-19 Response Fund 30:22 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/156 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.comPhone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com Give RealTalk MS a Rating and Review National MS Society's Ask An MS Expert Video Replay What You Need to Know About Coronavirus (COVID-19) Varicella-Zoster Immunity Loss in Multiple Sclerosis Patient Treated with Ocrelizumab National MS Society Black MS Experience Summit National MS Society COVID-19 Response Fund Join the RealTalk MS Facebook Group Download the RealTalk MS App for iOS Download the RealTalk MS App for Android Give RealTalk MS a Rating and Review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 156 Hosted By: Jon Strum Guests: Dr. Meghan Beier Tags: MS, MultipleSclerosis, MSResearch, MSSociety, Tecfidera, Ocrevus, Kesimpta, Ofatumumab, RealTalkMS Privacy Policy
Welcome to our fourth installment of Living Well with MS Coffee Break, where we welcome Natalie Cooper as our guest! As you now know, we decided to do something a little different in expanding the range of content we produce here at Living Well with MS. To honor the community that forms the beating heart of Overcoming MS, this special series called Coffee Break features short interviews with members of the OMS community talking about their personal journeys adopting and staying on the OMS 7 Step Recovery Program, the challenges they encountered and how they overcame them, and their tips and tricks for sticking to the path that leads to better health. We hope you enjoy and learn from these intermezzos between our regular episodes, and as always, your comments and suggestions are always welcome by emailing podcast@overcomingms.org. Bio: Natalie currently lives in Los Gallardos, Spain with her parents, which at 41 is a little embarrassing (by her own admission). If the world had not been locked down, she would be enjoying the scenery somewhere else in Spain or Portugal or one of the Balearic Islands, in her campervan with her dog. A few months before her diagnosis, Natalie had decided to sell her house and move to Spain and work online selling travel holidays. A few months after that she woke up one morning with blurred vision and was eventually diagnosed with MS. She was told by many to wait and start medication, so she put everything on hold and did so. That was a really depressing time for her, with everything seeming to go wrong, all her plans cancelled. How could she travel if she needed medications, blood tests, etc., so it seemed like it would never happen. Then she came across the OMS book and started the program, and after a few months, she was feeling really good and much more positive. So, she stopped her Copaxone treatment and put her travel plans back on track. Fast forward to last year: Natalie started a 6-month hiatus from her career to hit the road in her motorhome with her dog Mylo. She saw amazing places and met lovely people. That's when she started her Facebook page, which was a diary of her travels. It started as something quite personal and grew into a project she began sharing with friends and the wider MS community. In July 2019, while back in the UK, she caught the travel bug again and took the leap of leaving her job of nearly 9 years to come back to Spain in December. She didn't have any specific plans but was excited about the idea of setting up OMS-friendly holidays. Then COVID-19 arrived and the entire world shut down. But Natalie is not deterred. She will try to relaunch her vision in 2021 and strike a balance between working half the year and hitting the road with Mylo for the other half. If Natalie has learned anything on her journey, it’s to remain flexible, positive and open to all the possibilities in life. Questions: Can you tell us a little about yourself, your family, your life, where you live and anything about yourself you’d like to share? When were you diagnosed with MS and how long have you been following the Overcoming MS 7 Step Recovery Program? What is your favorite thing about the program, namely what do you feel has made the biggest positive impact? What was your greatest challenge in adopting the OMS program, and how did you overcome it? How have you had to adapt your daily healthy habits to the new realities imposed by COVID-19? Do you have any other tips or tricks you can share with our audience that might help them on their journeys? Links: Me, My Dog, a Motorhome and a Midlife Crisis If you post something concerning OMS and COVID-19, especially if it’s a bit of good news during this rough patch, don’t forget to use the hashtag #positivelyOMS. Coming up on our next episode: On the next full-length episode of Living Well with MS, launching June 17, 2020, join Geoff Allix as he explores Building Community through OMS Circles with Vickie Hadge, Ambassador of the OMS Circle (aka community support group) in Connecticut. Vickie is deeply committed to helping others – her family, community, clients and her OMS Circle members – and her enthusiasm is contagious! Don’t miss out: Subscribe to this podcast and never miss an episode. You can catch any episode of Living Well with MS here or on your favorite podcast listening app. Don’t be shy – if you like the program, leave a review on Apple Podcasts or wherever you tune into the show.
MS-Perspektive - der Multiple Sklerose Podcast mit Nele Handwerker
Name & Vorstellung Ich bin Anne, besser bekannt als »Annie« vom Instagram-Konto »positive_ms_power_annie«. Obwohl ich auf dem Papier schon 42 Jahre alt bin, fühle ich mich eher wie 25, manchmal auch wie 85. Ich bin mit meinem »persönlichen Apotheker« verheiratet und habe einen 15-jährigen Sohn. Diagnose Multiple Sklerose Seit Oktober 2005, vorangegangen waren zwei Schübe. Erst nach dem Wechsel des Neurologen wurde die richtige Diagnose auf MS gestellt. Vorher hieß es nur »Sehnerventzündung, Trigeminusneuralgie«. Erfahrungen mit Basistherapien Ich habe mich 13 Jahre mit Copaxone gespritzt, davon zwölf Jahre täglich und das letzte Jahr dreimal wöchentlich. Wobei in dem letzten Jahr fünf Schübe auftraten und dann im September 2017 der Wechsel zu Tecfidera erfolgte. Anfangs hatte ich heftige Nebenwirkungen: Übelkeit, sowie Magen- und Darmkrämpfe, dreimonatige Erkältung, Gürtelrose im Gesicht und am Kopf, die eine Woche lang im Krankenhaus mit Infusionen behandelt werden musste. Danach entwickelten sich Miniwarzen. Die Therapie möchte ich jedoch nicht beenden, da die Schübe unter dem Medikament weniger intensiv waren und ich davon überzeugt bin, dass die Therapie gut wirkt. Mein Lebensmotto »Das wird schon alles irgendwie gut werden.« Mein schlimmster Tiefpunkt Als ich fünf Schübe innerhalb von 18 Monaten hatte und absolut keine Kontrolle mehr unterhalb des Bauchnabels. Damals war ich auf einen Rollstuhl angewiesen, komplett inkontinent, musste einen Katheter nutzen und mein damaliger Ehemann verkündete mir während der Kortisonstoßtherapie im Krankenhaus, dass er sich scheiden lassen will. Mein 1,5 Jahre alter Sohn war meine größte Motivation, schnell meine Selbstständigkeit zurückzuerlangen, damit ich um das Sorgerecht für ihn kämpfen konnte. Mit ganz viel Physio- und Ergotherapie sowie weiteren Maßnahmen ging es recht schnell bergauf. Mehrere Neurologen haben mir versichert, dass wenn mein Körper nicht schon immer an viel Sport und ständiges Lernen sowie Sich-Umstellen-Müssen gewöhnt wäre, ich mich nicht so gut und schnell von diesem Schub erholt hätte. Dennoch wurde ich in der Folge berentet und brauchte zehn Jahre, um diese Tatsache zu akzeptieren und anzunehmen. Da ich nie wieder auf Hilfe angewiesen sein möchte, ist es mir sehr wichtig, alles dafür zu tun, dass mein Gehirn viele verschiedene Reize bekommt, um aktiv gegen das Fortschreiten der MS anzugehen. Deshalb treibe ich täglich Sport (als ehemalige Aerobic-, Step Aerobic und Thai Bo Instructor eine Selbstverständlichkeit) um meinen Körper zu kräftigen, mache Step Aerobic, dehne mich und fahre Rennrad. Außerdem lese ich viele Bücher und Zeitschriften in Deutsch, Englisch und Polnisch, schaue mir Youtube Videos an, und höre Podcasts sowie Talks auf Spotify. Das Ganze ergänze ich mit einer gesunden Ernährung. Ich koche sehr gerne frisch, saisonal und regional, und backe mein Dinkelschrot- und Müslibrot selbst. Meine Symptome habe ich recht gut im Griff. Gegen die Blasen- und Darmentleerungsstörungen nehme ich zwei verschiedene Medikamente. Regelmäßig merke ich die Fatigue, kognitive Störungen (temporär schlechte Konzentration und Wortfindungsstörungen), neuropathische Schmerzen, Missempfindungen, Sensibilitätsstörungen, das Lhermitte-Zeichen, das Uhthoff-Phänomen, und habe Probleme meine Temperatur zu regulieren. Da ich schon immer sehr aktiver Mensch bin, versuche ich auf meinen Körper zu hören, mich nicht zu überfordern und mir genügend Pausen zu gönnen. Mein größter Traum Einmal intensiv Australien zu bereisen. Davon träume ich bereits seit der Mittelstufe. Wichtigste Internetquellen - MS-Perspektive - der Multiple Sklerose Podcast - @doctor.gretchen - auf Instagram - F.U.MS Germany - auf Facebook Buchempfehlungen »Drei Irre unterm Flachdach« von Bastienne Voss »Erstgeborene. Über eine besondere Geschwisterposition«, Jirina Prekop »Hardwiring Happiness. How to reshape your brain and your life«, Rick Hanson »Die Pest«, Albert Camus (Hier geht es zu meiner Besprechung vom Buch auf meiner zweiten Webseite www.nelehandwerker.de) Meine Tipps für MS-Patienten Macht euch nicht verrückt. Lasst euch selbst und eurer Familie Zeit, das »Neue Ich" zu akzeptieren. Erklärt eueren Kindern die MS kindgerecht und zeigt ihnen, wie ihr euch spritzt, um ihnen die Angst vor Spritzen wegzunehmen. Lebt und genießt euer Leben. Riskiert auch mal was. Keiner weiß, was in den nächsten fünf Minuten passiert. So kannst du Annie erreichen Instagram: https://www.instagram.com/positive_ms_power_annie/ Viel Spaß mit der Folge und beste Gesundheit wünscht dir, Nele Mehr Informationen und positive Gedanken erhältst du in meinem kostenlosen Newsletter auf www-ms-perspektive.de. ---------- Im MS Perspektive Podcast stelle ich dir meine Sichtweise auf die Multiple Sklerose vor und wie du das beste aus der Diagnose machen kannst. Denn ein schönes und erfülltes Leben ist auch mit einer chronischen Autoimmunerkrankung wie Multipler Sklerose möglich. Hier findest du Informationen und Strategien, wie du aktiv Einfluss nehmen kannst. Ich will dir Mut machen und zeigen, was du alles selbst in der Hand hast. Dazu veröffentliche ich Solobeiträge mit meinen Erfahrungen zur Basistherapie, zur Ernährung, zum Reisen, Arbeiten und der Familienplanung. Außerdem interviewe ich Experten zu verschiedensten Themen rund um ein Leben mit MS. Und einige Folgen dienen der puren Entspannung, die in jedem Leben einen wichtigen Platz einnehmen sollte.
Aujourd'hui on reçoit une nouvelle guerrière, j'ai nommé Sabine. Sabine est atteinte de la sclérose en plaques. Si tu connais ne connais pas cette maladie, ne t'inquiète pas on te donne toutes les explications nécessaires dès le début du podcast. Dans cet épisode on parle, du diagnostic de Sabine, de sa façon de vivre avec sa maladie et de sa passion pour le sport. Tu es une source d'inspiration et de courage Sabine, merci beaucoup pour la confiance et l'énergie que tu m'as donnée. A la semaine prochaine, Muxu !! Instagram de Sabine : https://www.instagram.com/oxy__more/ Instagram de Pas Toute La Vie : https://www.instagram.com/pastoutelavie/ Instagram de Petit musclor : https://www.instagram.com/petitmusclor/ Site de l'association SepAvenir : https://www.sepavenir.com Association APF France Handicap pour la Sep : http://www.sclerose-en-plaques.apf.asso.fr/ mireille.fouqueau@apf.asso.fr (mail de la fondactrice de l'asso. Elle réponds à toutes les questions. Elle fait également sur le pays basque des activités pour les sépiens, que ça soit pour le bien-être du corps et de l'esprit.) La théorie des cuillères a été inventé par Christine Miserandino. Groupe Facebook sur le traitement Copaxone®: https://www.facebook.com/groups/223304355359/ Groupe Facebook où Sabine a trouvé son parrain de Sep : https://www.facebook.com/groups/838978699584236/
Important Listening Nothing in this, or any other episode, constitutes medical advice, Also, a quick summary of the latest Covid advice for people with MS Copyright: Bron Webster 2020
Pink Sheet editor and reports discuss pharma’s wins in the latest coronavirus stimulus bill, explain Gilead’s decision to pull the remdesivir orphan designation, and consider Teva’s suit to force Copaxone’s transition to regulation as a biologic.
The DISabled to ENabled podcast for people with chronic illnesses
Part 1 - Diagnosis (includes mild language) Diagnosed at 22. He started having pain in his shoulder, doctors thought it was a trapped nerve. Dismissed with ibuprofenAbout a month after, whilst at work, George could barely see. His balance was not right. Started continuously vomiting.Feared meningitis which was quickly ruled out by a lumbar puncture.Feared brain tumor, ruled out after scans. Quickly deteriorated. The hospital he was in at the time didn't have an MRI scanner so another appointment was scheduledFound out he had MS which he hadn't heard of. Automatically associated older people and wheelchairs. Diagnosis of MS is most common in their 20s-30s It's a lifelong condition and there are far more treatments available now. George was put onto Rebif to start with then mitoxantrone, then Copaxone. Listen out for the daily checks George used to do (I used to do this too!) How to know the difference between a relapse and just a bad day. How George recovered from relapses. The false hope George was given by his neurologist.There's no benefit in saying that things are going to be ok by a doctor. MS can be a cruel condition. It needs to be made clear that each individual has a level of responsibility for how their condition might turn out. There's a huge support for changes in lifestyle and the role it plays in a long term health condition. That word ‘lifelong' is scary but the thing I find most challenging to accept is the uncertainty. It can change at any time. ______________________________________This episode is sponsored by iHerb. Quality supplements at an affordable price for every need and condition, including pet healthcare. iHerb believes in providing an education to impoverished children worldwide will be the most meaningful, long-term return on investment. Go to: http://mmini.me/iherb this is an affiliate link, meaning for every purchase made iHerb supports the running of the disabled to enabled podcast. Please go get your supplements :)
Mylan launches a generic "at-risk" and Flexion's big drug opportunity becomes clearer. Editor's note: Mylan's drug was mistakenly referred to in the episode as a biosimilar. Copaxone, however, was approved under an NDA, not a BLA, so Mylan's copycat is a generic, not a biosimilar.
This week's episode focuses on some of the cutting edge research being done in the Progressive MS arena. Jon's guest, Dr. Tim Coetzee, Chief Advocacy, Services & Research Officer at the National Multiple Sclerosis Society, takes us through the work of the International Progressive MS Alliance. Jon and Tim also talk about Ocrevus -- the very first drug to receive FDA approval for the treatment of Progressive MS, and what that means for future Progressive MS drug therapy. We'll also be talking about a new research study at Duke University that will be taking full advantage of your iPhone to capture your individualized data, and we'll be letting you know how you can register for that study. And last week, the FDA approved a higher dosage generic version of Copaxone. Generic Copaxone isn't really new...but the higher dosage is, and we'll be talking about why that might be good news for the thousands of people currently using Copaxone. We've got news, views, interviews & breakthroughs in the MS world. Are you ready for RealTalk MS?
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
[intro music] Host – Dan Keller Hello, and welcome to Episode Ninety of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller. Welcome to the weird world of the U.S. pharmaceutical market. A few outrageous cases of drug price gouging have made the headlines, but in multiple sclerosis, a more serious concern is the steady annual rise in cost of all disease-modifying therapies, or DMTs. So says Dr. Daniel Hartung, a researcher at the Oregon State University/Oregon Health and Science University College of Pharmacy. In a recent study, he found that MS drug prices over time outpaced both inflation and similar biologics. It’s not just the new drugs. As each more expensive DMT comes to market, the prices of older drugs also race to catch up. It’s affecting the drugs available to patients and causing other concerns. Interviewer – Carol Morton Can you tell me what questions you were asking and why? Interviewee – Daniel Hartung Sure. So the study that we did had its origin after having some conversations with some neurologists at OHSU about increasing frequency of seeing their patients facing larger and larger, not only cost sharing and copays from the insurance companies for drugs for MS, but also increasing restrictions, typically from insurance companies in kind of what medications they were supposed to take first prior to perhaps failing one, then going to another medication for MS. And so this is all kind of happening in the context of what they were seeing as just higher prices for some of these medications. And so what we decided to do is…no one's really done this…is look at in a systematic way the trajectory of pricing for MS drugs, essentially since their approval until we went through the end of 2013. And to look at what the just general trend was, try to figure out if there were certain specific factors that were associated with higher prices over time, like the approval of newer agents, things like that. That was kind of the general objective of the study. MSDF And then how did you go about conducting this study? Is it hard to find that data? Dr. Hartung It can be. So I'm fortunate to have access to some data set that has longitudinal pricing data for pharmaceuticals for the past 30 years or so. And so from my perspective, it wasn't difficult. But essentially we used this data set that collected average wholesale price, as well as wholesale acquisition cost, so kind of the two usual, most common (I'll call them) sticker prices for drugs. And so this data set for all medications, it kind of tracked pricing of medications over time. And so that was the core data set for our analysis. MSDF And so you pulled the multiple sclerosis disease-modifying therapies out of that. How many did you look at? Dr. Hartung So in our study we looked at 11 medications for MS. They included the three what are typically called platform therapies that have been on the market for about 20 years now. Those include Avonex, Copaxone, and Betaseron, and just followed them through time, through the approval of several other new agents, like Tysabri. And then there's in the last five to six or seven years, the FDA has approved several agents that can be taken orally, Gilenya, Aubagio, and Tecfidera now. And there was a couple other kind of miscellaneous agents that were kind of variants of the interferons and things like that. MSDF And then what did you find? Dr. Hartung Well, there are several interesting things, but I think one of the most striking things is that the prices for the platform therapies, Avonex, Betaseron, and Copaxone, were pretty stable for at least 10 years from their approval in early to mid-90s. And then, essentially what we observed is that new agents that came on the market, starting with Rebif in about 2001, came out, and they were usually priced about 20% to 30% higher than the existing therapies. And what we observed is that when these new agents came out or approved, that these higher prices, the cost or the price of kind of the platform therapies quickly escalated to almost match the price of the newer agents that were approved. And this pattern kind of repeated itself and actually became more intense when the newer oral agents came on the market in the last five or six years. So the cumulative effect of that is in the early 2000s, Copaxone, Betaseron, and Avonex were priced about $10,000 to $15,000 a year. And at the end of our study, all of the agents that are currently approved were priced between $50,000 and $60,000 per year. And so we tried to quantify kind of the rate of increase and compare that with other kind of benchmarks: inflation, prescription drug inflation. What we found is that the price increase for those agents was well above what you'd expect for not only just general inflation, but also prescription drug inflation. MSDF MS drugs, the cost of all of them, not just the new ones, are increasing at a rate higher than any other drug category? Dr. Hartung In addition to looking at kind of standard metrics of inflation, we compared the price increases for the platform therapies to what we considered kind of comparable biologics. So we looked at a class of medications called tumor necrosis factor inhibitors, which are used for immunologic conditions like rheumatoid arthritis. And what we found is that the price increases for the platform therapies for MS increased substantially and significantly above price increases for those medications for the tumor necrosis factor inhibitor. So from our study, from our perspective, prices increased higher than they did for these TNF inhibitors. We haven't really compared them across other classes of drugs, but there are some new publications that have looked at price increases for other agents, such as in other classes like insulin, drugs for diabetes, and cancer agents as well. The numbers are slightly different, but the trajectories look pretty similar. So in the last, you know, 10 years, there's been almost it seems like a logarithmic increase in the price of many of these agents and classes. MSDF So is this a case of a system that has incentives that maybe aren't as well matched to patient needs as they should? What's going on here? Dr. Hartung I mean, that's a good question. Definitely there's a system. The market-based system for pharmaceuticals in the United States is incredibly dysfunctional in that it's very dissimilar from any other kind of consumer market for technology, phones, cars, things like that, where you typically see prices go down after a while. And you don't see that in health care or in drugs. You see just prices increase. And so there's a dysfunction that just kind of is core to the economics of health care. And then I think there is an element of pharmaceutical industries pricing these agents essentially what the market will bear. Now my opinion is that a lot of the aggressive increases in price were initially seen with some of the cancer agents. And so I think that in that field there is a kind of pushing of the envelope for many anti-cancer drugs that's now has proliferated to other classes of drugs, including MS agents. The other element that's kind of unclear and adds to the murkiness to this is that, you know, our study and other studies that have looked at what I'm calling pricing of the agents use average wholesale or WAC and with some sort of adjustments for rebates or discounts. So typically third party payers or pharmaceutical benefits managers will negotiate with pharmaceutical industry to lower the cost of the agent for the payer. But all that information is typically proprietary, and so it's really difficult to know what the actual cost of the medication is, unless you're paying cash. If you're paying cash, then the cost is going to be pretty close to the price that's set. So people who don't have insurance are paying the most, and the people with insurance, Medicaid, any sort of governmental insurance, they're paying typically AWP minus a certain proportion or WAC plus a proportion percentage essentially based on the rebate that they get. So that adds a little bit of kind of uncertainty. Pharmaceutical industry may come back to say that, you know, we're giving pretty good discounts on certain medications in certain payers, but from the data we have and the pricing data, there's just been this aggressive increasing in prices. And we don't know if it's being mitigated by increasing rebates and discounts over time. So it's complicated. MSDF What do you hope people will do with this information? It does sound like a complicated system that's almost unapproachable for the individual patient or individual doctor. What can people start doing now? Where does the responsibility or responsibilities lie? Dr. Hartung You know, I think that the data we generated in our study has been useful for some of the advocacy groups in the multiple sclerosis community. So the National Multiple Sclerosis Society has been using it to try to, you know, advocate or perhaps political reforms or some other meaningful reforms in kind of how these things are reimbursed, things like that. Drug prices has been in the news quite a bit over the last several years, and now even more with the election season in full tilt. And so I think a lot of the candidates are talking about potential solutions to the issue. From the patient's perspective, they're in a real quandary in a sense that even a sharp move with the Affordable Care Act to a lot of high deductible, high cost sharing plans where if your monthly cost of a MS agent is $5,000, you pay 20% of it until you hit your deductible. You know, that's $1,000 at the pharmacy, and that's a pretty big out-of-pocket cost that you face. So I think that there's some, you know, movement in the advocacy groups to try to…especially working with insurance companies to make sure that access is open because these medications are incredibly individualized. And there's not really good predictors of who will respond to each type of medication, and they're all different. Some of them are administered subcutaneously, intramuscularly, orals, and so there's some patient preferences that fall into play here as well as the price. And so I think there's been some movement and some discussion making sure that access to all the agents is relatively easy for patients. But from a solutions to the pricing situation, you know, I think we're still kind of in discussion phases about what we can do as a country to kind of deal with this issue because it's not exclusive to the MS drugs. MSDF So what's next with you? Are you following up on this? Dr. Hartung So from our perspective, the group that I worked with, the two neurologists' project, we just submitted a grant, well, it was in January, that we hope to be competitive and hope to get that's looking at how these high drug prices actually affect patients in terms of their medication taking and potentially adverse outcomes because they're not taking their medication. Either they're hitting access restrictions from insurance companies or they just can't afford or have problems with the cost sharing or something like that, and so trying to quantify how this is affecting patients. And so from a research perspective, I think that's kind of our next move. My colleagues, my two neurologist colleagues, they're really active in kind of speaking with representatives at the state about the issue, bringing it to increased visibility from our elected officials as well as making sure that the MS Society is aware of kind of the current status of the pricing trajectory. So we've been updating our graph that we published as new agents come online and things like that. MSDF Can you give us a couple of the updates you've made since the study? Dr. Hartung They haven't been dramatic, but there's been a couple new agents that have been approved. And I guess most notably is that the first generic drug for MS was approved, I believe, last April. So a generic for Copaxone came online. I think there's two manufacturers of it. When it came online, there was one. And so I think it was priced just modestly lower than the brand name Copaxone. But something interesting also just dealing with Copaxone, which is the number one MS drug in terms of sales, so when Copaxone lost its patents and lost its kind of patent disputes, in preparation for that, Teva released a different formulation of Copaxone. So Copaxone is traditionally a daily injection. And so they released a three-times-a-week higher strength injection and basically switched everyone from the once-a-day to the three-times-a week 40-mg injection. And so I think a large proportion of patients who were originally on the once-daily Copaxone were switched to the 40-mg three-times-a-week Copaxone. So that really to some extent mitigated if there's any sort of savings due to this new generics in the field, kind of really mitigated any kind of savings due to the new generic as most people are now on the 40-mg three-times-a-week product. And the generic is not substitutable for the 40-mg three-times-a-week product. So that's a very common tactic in pharmaceutical industry approach to try to like sustain their franchise with a particular drug that's going off patent. But the big questions are the ones that don't have a good answer. Essentially, what do patients do about this? What do we do as a society to deal with this issue? And you know, there's been proposals that have been put out by different elected officials and other folks about, you know, we should allow Medicare to aggressively and directly negotiate with pharmaceutical industry on price. We should allow importation of medications from other countries, similar industrialized countries like Canada. So the United States pays by far and away the highest prices than any other country in the world. And so many people think that we should be able to import these drugs that are the same drugs that are going to Canada into the United States. You know, some people suggest that there should be some sort of forms of price control. You know, maybe medications shouldn't be allowed to increase 10% a year or something like that. And so all of these are being kind of discussed and played out and the pros and cons are weighed. And whenever you talk about limiting price increases, the usual response you get from industry is that any constraint on the amount of money that they're able to make and the profits that they're able to make for their shareholders is going to have some sort of effect on kind of future innovation potentially. Whether that comes to bear or not is unclear, but that's usually the number one response you get is that we need to have these high profits in place because it's an incredibly risky endeavor that we're doing. Only a very small proportion of drugs that are under development actually make it through the developmental process and are approved and make it to market. So any constraint on profits is going to have an effect in terms of future innovations and future breakthrough medications and things like that. Incentives are a big…they are real. And so that is something that needs to be weighed carefully in kind of any solution, essentially. I don't think it's the best solution, but just people are talking about a wide variety of things, I think. MSDF I appreciate your raising all these issues and going through the study. Is there anything else that I haven't asked that you wanted to add or emphasize as take-home lessons? Something to mitigate the rage, I don't know… [laughter]? Dr. Hartung Yeah, well I mean there's been a lot with all this, you know, the Valeant Pharmaceutical issue and the other company, Martin Shkreli guy who's castigated for increasing the price of this drug for toxoplasmosis by like 5,000% and buying the company and jacking up the price. That's a separate phenomenon of what is happening. But I think the outrage over that type of exploitation of the dysfunctional pharmaceutical market kind of masks and kind of hides the other issues that are happening on a consistent and aggressive basis in terms of just regular 6% to 10% increases in price on a year-to-year basis for drugs that a lot of people use, like drugs for diabetes or MS products, cancer agents, things like that. And so, you know, you have these really highly visible cases of really dramatic increases that are kind of morally outrageous. They draw your attention from the real and kind of moderate but aggressive and year in, year out, increases that are seen across the board in a lot of different agents. And that's where our focus should be essentially. MSDF That's helpful. Well, thank you so much. Dr. Hartung Yeah. My pleasure. [transition music] MSDF Thank you for listening to Episode Ninety of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. [outro music] We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller.
Dr Jacqueline Palace is interviewed about her 10 year analysis of the UK Multiple Sclerosis risk sharing scheme study, presented at this year's Association of British Neurologists (ABN)conference, in Brighton, UK. Jackie Palace, who is interviewed in this podcast by Ralph Gregory, is a clinical lead for the UK MS risk sharing scheme study assessing the long term effects of beta-interferon and Copaxone. The ABN conference 2016, which theme was "The Seven Ages of Man", was held in May, in Brighton, UK.
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
Full Transcript: [intro music] Host – Dan Keller Hello, and welcome to Episode Eighty-five of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller. Many MS patients will require a change of drug therapy over the course of their disease, possibly because of relapse or tolerability. At last fall's ECTRIMS conference in Barcelona, I spoke with Eva Havrdová MD PhD, professor of neurology and head of the MS Center at Charles University in Prague, Czech Republic, about when and how to change therapy. I first asked her how she detects a need to change therapy because of a suboptimal response. Interviewee – Eva Havrdová It's very difficult to find the right solution for each patient, but as to our opinion, the best thing is to really start early treatment and monitor closely the patient. It means that you look not only at relapses or progression. It's too late. We also look at MRI after six months after starting treatment. And I think it is now quite proven that, if the patient has either relapse or new MRI activity, the response in the first year is suboptimal and the treatment should be already changed. Interviewer – Dan Keller So you have a very high suspicion? Dr. Havrdová Yes, definitely very high suspicion. And you can add some quality of life measures. You can add cognitive measures. You can ask the patient, what’s the level of fatigue. And of course, all this together brings you to the solution to change the treatment. MSDF Do you generally find that you will pick something sooner on MRI then by patient report? Dr. Havrdová Yes, of course, because the events on MRI occur 10 times more frequently. But on the other hand, as to regulations for reimbursement, I cannot change the treatment just based on MRI in our country. So definitely in the future, this will be an option. But we need more data to prove to the sick fund that it's really worth doing it because if you do these changes and find optimal treatment for patients early, then the patient stays at work, and of course, the cost effectiveness of the drugs increases. MSDF I suppose that depends on having a unified system, which is not built into silos. You know, when you get one payer here and one payer there; they don't care what's coming out of the other guy's pocket. Dr. Havrdová Yeah, yeah, of course. It's very difficult; and therefore, I think we need guidelines. And one of the ECTRIMS activities is to start working on some guidelines, and I hope next year we will have it. MSDF So what do you do when you find something that would raise your suspicion or prompt you to do something different? Dr. Havrdová We monitor the patient even more closely, in three-month intervals. And very often we see that the patient develops a relapse after some MRI activity occurs. So we can change the treatment. MSDF Do you often escalate the present drug? Or switch drugs immediately? Dr. Havrdová We have to start with injectables in our country, not with oral drugs, which is the mainstream now in other countries. And we hope we will also push our authorities to this strand because patients, of course, want orals. On the other hand, the safety of injectables is well-proven for more than 20 years. So for those especially who want to get pregnant, the safety is number one. And we try to switch as early as possible, because if another relapse comes, the relapse may be disabling, and we are just losing time in the brain of the patient. And as you know, here at ECTRIMS, the one day before, the health of brain was promoted in MS. And we would like to stick to this idea. MSDF So it sounds like you change drugs, not escalate the present drug? Dr. Havrdová The escalation means the change as well. So we try not to switch within the first line, but we want to see more effect. Just because of intolerability or some known adherence of patient on injectables, we can switch within the line if there is no activity of the disease itself. Or if there are neutralizing antibodies on interferon, we can switch to Copaxone. But on the other hand, it was now published, based on data in MS base, which is a big registry of real world data, that it's really worth escalating to the higher efficacy drugs because you can reach much better effect. MSDF Over the years, do most patients require some change? Dr. Havrdová Most of them do, though there are patients who are completely stable and not developing higher EDSS steps on injectables, but it's less than 25% of them. MSDF Is there any way to generalize and say what the time course is? Or is it so variable? Dr. Havrdová No, it's very variable. And we do not know if it is based just on genes or on environment or lifestyle changes the patient is willing to undertake. We do not know yet. MSDF So I don't know if you can generalize because each country is different, but do you have some scheme or algorithm in mind about how you would escalate therapy? Dr. Havrdová The problem is if the patient is not responding to the second line or higher efficacy therapy, because we then have to switch within that line. And we do not know if he doesn't respond to anything we have. We do not know what to do. So we cannot switch or jump from one treatment to the other after six months of treatment, because you have to allow the treatment to have an effect. So at least six or nine months is okay. If the patient is not responding, then you can jump to other treatment. But hopefully the patient will respond to the third or fourth treatment, because it's not without limitations. MSDF Is combination therapy every indicated? Dr. Havrdová Not yet. I have thought many years ago that neurologists are just reluctant to use combination therapies, but now there were some trials, and it's not showing that effect. So it's not like in oncology. Though the principle is so clear, that you can combine drugs with various mechanisms of action decrease, some side effects, and increase the efficacy. Oncologists do that. We don't have drugs in the multiple sclerosis with this potential yet. MSDF Right. In hypertension they've just assumed they're always going to have two or three drugs, and same thing now with diabetes and things like that. But I guess this would be a big conceptual breakthrough for neurologists? Dr. Havrdová Yeah, and doesn't seem to be today's issue. MSDF What has been tried in combination? Dr. Havrdová The first combination which was tried was natalizumab and interferon. And it seems that it didn't work. And then, of course, it was also a small trial, natalizumab plus glatiramer acetate, and nothing just to safety was, of course, seen that. And some others, but nothing really. MSDF When there's an acute exacerbation, do you overlap steroids with the ongoing drug? Dr. Havrdová Yes, of course. Yes. It was proven that it's safe, and it's okay. MSDF So there is a combination, but short-term? Dr. Havrdová Yeah, it's a short-term combination. And definitely it helps because all the underlying immunomodulating drugs do not work against the acute relapse. MSDF What have we missed or is important to add on the topic? Dr. Havrdová I think that neurologists have to be aware, and of course, pharmacovigilent. You have to know the mechanism of action of the drug; you have to know the adverse events possible and how to prevent them—how to monitor the patient to be safe. [transition music] MSDF Thank you for listening to Episode Eighty-five of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. [outro music] We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller.
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
[intro music] Host – Dan Keller Hello, and welcome to Episode Eight-two of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller. Depression affects as many as 50 percent of people with MS during their lifetimes. But according to Dr. Adam Kaplin, a psychiatrist in the Johns Hopkins MS Center in Baltimore, it is treatable to a large extent, and with good results. Dr. Kaplin studies the immune basis of depression and cognitive impairment, specifically in MS and central nervous system-related autoimmune diseases. We met in Baltimore. Interviewer – Dan Keller Let’s talk about depression in multiple sclerosis. Is it a reaction to someone having a chronic disease, or is there something more going on because of the disease? Interviewee – Adam Kaplin It’s a great question, and what I will tell you is one of my patients says to me that you’re either stressed, or you’re dead. We all have stress going on, and it’s always possible to look at something in our life and say, ah, that’s what caused the trouble. But we know now, in multiple sclerosis, the depression is due primarily and dramatically significantly to the inflammation going on in the brain that causes all of the symptoms that you see in MS, such as cognitive impairment, or weakness/numbness/tingling, autonomic nervous system dysfunction; all of those are effects of the MS on the CNS. And in the case of depression, it is similar. It’s not a character flaw. It’s not a personal weakness. And just to, you know, clarify, one of the best pieces of evidence we have for that is, number 1, that people who are depressed with MS, it does not correlate with their EDSS scores. It doesn’t correlate with their level of disabilities. So if it was you know, gee, it’s just a matter of stress, then those people who are in wheel chairs or on ventilators should be depressed, and those people who are upright and walking around shouldn’t. But in fact, I think the key element is that this is one of the, as they often say, silent symptoms of MS. It occurs to 50% of patients across their lifetime. And it is important you know for people to understand that this is not something that people aren’t rising to the occasion, or those kinds of things. MSDF Is depression accompanying MS more prevalent than in the general population, and how serious is it? Dr. Kaplin You know people often ask why, as a neuropsychiatrist, why study MS? And I say, you know, why did Willie Sutton rob banks? That’s where the money is. MS has the highest rate of clinical depression of any medical neurological or surgical disease. Again, 50% of people, following the diagnosis of MS, will have a clinical depression. We can talk about what that is. And it turns out that that’s in any clinic you go into – neurology clinic – that’s one in four patients. If you go out to the waiting room, one in four patients will be suffering from a clinical depression. MSDF How serious a problem is it? What aspects of life does it affect? Does it affect everything, and how serious is it? Dr. Kaplin I think what is often misunderstood about the depression in MS is, I would argue, that it has the highest morbidity and mortality of any of the symptoms of MS, in the sense that it is the third leading cause of death in the largest study that looked at, across the lifespan, what causes death in people with MS, [found] a study out of Canada, where it’s more prevalent because of the higher elevation and the lower vitamin D levels, probably. And it is absolutely the case that seven-and-a-half times the rate – the suicide rate in MS – to the general population. And in fact, in the studies that were done, 30% of people with multiple sclerosis will have thoughts of suicide at some point during their life. Ten percent – fully 10% will attempt suicide. And that lethality is profound. But if it doesn’t kill you, it is important to understand that it has significant, significant morbidity associated with it. Just to begin with, the number one correlate of quality of life of patients—more important than their pain, or more important than their cognitive impairment, or weakness, or other symptoms—the number one correlate of the quality of life of the patient is their depression or whether they are depressed or not. And it’s similarly the number one quality of life of the care givers—not whether they have to push them around in a wheelchair, it is whether their loved one is suffering from a clinical depression. So it has significant morbidity and mortality associated with it. MSDF Are there aspects of serious depression in MS that are very characteristic? Any different from other severe depression? Or can it be recognized in the same way with the same diagnostic criteria? Dr. Kaplin There actually are some specifics to MS, although that hasn’t been well-published. I can be clear about things that are well-supported by the literature, and then those that are my clinical experiences. What I can tell you is that the way we diagnose depression in MS is the same way we diagnose depression in people without MS, which is you have to have 5 of 9 symptoms greater than two weeks, one of which must be either decreased mood or decreased interest. And we remember it by SIG-EM-CAPS, the nine symptoms. Trouble with sleep, where people are often having early morning awakenings or hypersomnia where they just sleep all day. Loss of interest, people’s get up and go has gotten up and gone. Feelings of guilt or worthlessness – and that’s a big problem, because patients who are depressed as a result of that often won’t seek help. You have to ask about it. They won’t volunteer it. And loss of energy or fatigue; low mood – that’s the sadness part; concentration problem; appetite changes, either increased or decreased weight; and psychomotor retardation, they’re not their normal bubbly self; and thoughts of death or suicide. With MS, what I will tell you, I find that patients with MS often, rather than sadness, have very frequently irritability. That tends to be more common. And sleep is usually decreased, not increased, so I see very frequently increased early morning awakening and those kinds of things. One pearl, though, to keep in mind is – or two pearls – if you’re trying to make the diagnosis of depression in somebody with MS, the first thing to do, because there are overlapped symptoms like fatigue, like concentration problems between depression and MS, so there is frequently, in up to 80% of people, will have diurnal variations in their moods; so usually worst in the morning and better at night. Sometimes it’s reversed, but you know that person has the same life circumstance, the same disease circumstance in the evening that they did in the morning, but their mood has changed dramatically, often, with MS with these cyclical changes. And that’s a good indication that it’s not demoralization; it’s depression. The other thing is ask the loved one. Get an outside informant, because nobody gets the brunt of it quite like the family. And they know that person, and if the family member says the one thing I hear so often, this is not the person I married, then you’re pretty much on the right track if you’re thinking about depression. MSDF How amenable to treatment is depression in MS? Dr. Kaplin I think that that is probably one of the key aspects is to understand that it is very treatable. So my expectation when patients come to me and I diagnose them with depression is that I will get them a hundred percent well with respect to those SIG-EM-CAPS symptoms, back to their baseline. And it’s very hard to get patients a hundred percent well from their gait problems; a hundred percent well from their cognitive problems. And, again, what I tell people is, look, I can’t tell you whether your cognitive impairment is due to the depression or due to the MS, or maybe it’s 10% depression/90% MS or 90% depression/10% MS. But I can promise you this: treating the depression, the depression is much more amenable to treatment. We don’t have good treatments for cognitive impairment in MS to reverse the cognitive impairment, but boy, we can reverse it if it’s a symptom of depression. What’s really exciting now is that we are now understanding more and more that many of the treatments you use for depression end up being good nerve tonics. So, there was a double-blind placebo-controlled study of fluoxetine demonstrating that, in patients who weren’t depressed with MS, they had fewer gadolinium-enhancing lesions over 24 weeks. And then there was the FLAME study in a related kind of way looking at fluoxetine as a way of significantly enhancing the recovery of hemiplegic stroke patients. So it turns out that I wasn’t so misguided in thinking that studying the immune basis of depression would be important, because as it turns out, our treatments actually do have an effect on the nervous system and the immune system for general types of depression as well. MSDF That sort of covers the SSRI class. What about tricyclic antidepressants? What about SNRIs? Do those fit in? Dr. Kaplin Yes, so absolutely. So the topic of how to choose and select the right treatment for patients with MS is … we could spend an hour and just sort of get only the highlights done there. But generally there’re sort of two strategies. One is to use a medication that has the fewest side effects, so that you won’t have drug-drug interactions with the patient if they’re on a numerous medicines for other concerns—their other symptoms and syndromes—that the antidepressant won’t interfere with it. And so along those lines, escitalopram and sertraline have the fewest drug-drug interactions. You essentially don’t need to look up drug-drug interactions if your patient is on one of those two medicines. The other approach is to say let’s choose a medicine that will have favorability with respect to the side effects, will be beneficial for the problems that the patient has. So a classic example is duloxetine is FDA-approved, not just for depression, not just for anxiety, but also for neuropathic and musculoskeletal pain. So here you’re talking about one treatment that will help you with the fact that your patient, their depression will get better; their neuropathic pain will get better if they have migraines—which are often a comorbidity—that will also benefit the neuropathic pain from that as well. And you know you will get two birds with one stone, as it were. And then the tricyclics, as you had asked about, we’ve had a lot of experience with them. They also will benefit in terms of the urinary incontinence problem. They are strongly anticholinergic, and so you can also benefit in terms of preventing the urinary/bowel problems. So really Cymbalta as just sort of son-of-tricyclics, has some fewer side effects, but doesn’t, therefore, cover some of the things that the tricyclics will. MSDF As you alluded to earlier, the depression in MS may largely be a result of immune processes going on—inflammation, cytokines, things like that. So how well do the disease-modifying therapies of MS attack the depression? Dr. Kaplin You know you mentioned cytokines. So that is another way that we know that this is due to the inflammation—the depression in MS—and not just other things, because for instance, interferon-alpha used to treat patients with hepatitis C will cause depression in upwards of 20 to 25% of people who take it, not when they first start it, but within you know a week to two weeks after starting it, you know, then up to eight weeks. So that’s just one cytokine, and in MS, all of the cytokines get activated. And similarly, interferon-beta that’s used, or Copaxone, you know, the ABCR drugs that we’ve used to try to—you know, with great effect since 1993—to slow the exacerbations down in MS; they don’t stop the inflammation, they just alter it. And so not surprisingly, they do not have antidepressant properties. But when you look at something like Tysabri, we actually have not published this yet. We did present it at a MS conference but working in collaboration with Biogen. We are going to publish shortly data that shows that, in a double-blind placebo-controlled study of adding natalizumab to Avonex, or adding placebo to Avonex, those patients who were depressed to begin with show a dramatic and statistically significantly decrease in their depression as a result of the natalizumab. So natalizumab is actually quite a good antidepressant—we have data for it—because that really does shut the inflammation down in the brain, and since that’s causing the depression in MS, that’s what benefits them. MSDF Just to clarify, natalizumab is a good antidepressant in MS. Dr. Kaplin Exactly right. That’s exactly right. Although, you know, it’s good that you clarified that. What’s interesting is that now that people are beginning to appreciate the role of the immune system in idiopathic depression, people are beginning to say, hmm, maybe we should be looking at these anti-inflammatories and seeing if the anti-inflammatories benefit patients with depression. Now, nobody has tried natalizumab, but TNF-alpha inhibitors have actually been tried. There was a study out of Emory looking at using TNF-alpha inhibitors for refractory depression. And I think coming down the road there will be more and more studies that begin to show the role of anti-inflammatories for not all, but some people with refractory depression. MSDF Yes, I’ve seen some studies on anti-inflammatories—traditional ones, NSAIDS sort of things—presented a German study at a neurology conference. Didn’t do too much. Dr. Kaplin Yes. What I can tell you is that not all NSAIDs are created equal. Celecoxib actually now has five studies that are placebo-controlled that have shown its benefit for depression or bipolar disorder. And so when added to antidepressant by itself: No. But when added to fluoxetine or—I can’t remember what other; it might have been sertraline—it clearly had a statistically significant improvement in the depression response, celecoxib. But not all NSAIDs are created the same. MSDF What about non-drug therapies, cognitive behavioral therapy, even just physical activity? And, if someone’s depressed, isn’t it hard to get them up and do physical activity? Dr. Kaplin Well, I’m so glad brought that up, because I’d be remiss to forget that. So all of the data says, look, therapies like cognitive behavioral therapy are effective for mild and moderate depression. Antidepressants are effective as well. The data shows that the antidepressants work quicker, but that the combination of antidepressants and psychotherapy is much better than either one alone. So that’s a crucial issue. And to make sense of what has happened—and often when people are depressed, they’ve been depressed, and that’s caused damage to their professional life and personal life, and having someone help them sort of, depending how long the depression’s been going on, sort of talk them through, coach them through, how to get back up and going. However, in severe depression, you can talk till the cows come home. If your patient is so depressed that basically they have this tunnel vision, and all of the options that are in front of them, the kind of mental flexibility that you need for CBT to work, for instance, it will not work if you patient is really severely depressed. You have to get them started with the antidepressant, which really then serves as a catalyst for the psychotherapy to kick in. And then the aspect of exercise, you can’t really pick a topic related to MS where the answer isn’t exercise. Cognitive impairment, absolutely exercise is beneficial. Depression, exercise is beneficial. It stimulates growth hormones that have positive neurological effects on the CNS, as well as on the peripheral nervous system and body. What I tell people, again, is that if your patient is severely depressed, they’re not going just go back out and start running. So you’ve got to begin to have a plan where you say, look, we’re going to begin this medicine. As you start to be able to have the ability to you know maybe push yourself more than you might usually and just sort of walk down the block, and then you know walk for a mile and then start jogging for a mile and sort of build up to it, that’s very beneficial. MSDF Are there barriers to recognizing and/or treating depression both on the patient’s side and on the physician’s side? Dr. Kaplin The big barrier on the physician’s side is, you know, don’t ask, don’t tell. So if you don’t think of depression, or worse, if the neurologist says, well, I went into neurology not psychiatry, you know, this whole depression thing, that’s not my bailiwick, that’s not my responsibility, you’re missing the fact that this is —first of all, this is very rewarding. There’s nothing else that you could treat that gets a patient from being non-functional, sitting at home, not taking care of the family, not working, in a bed to fully functional, taking care of the family, back at work, like treating the depression can. But also it is. It affects all aspects. It affects the patient’s compliance with all your other medicines. It affects their ability to exercise, etc., etc. So, you know, you’ve got to think of it. And then you have to know something about treating it. One of the big problems with neurologists when they treat depression is that they don’t appreciate the fact that the goal is to get that patient a hundred percent well, because you sort of have this sigma curve where, if you get them 50% well, they’re still in that sort of steep portion of the curve where something comes along—an MS attack or you even a viral infection—and they will slip right down that curve. Whereas, if you can push them way out into the hundred percent well, that’s great. Now you can’t always do it with one medicine. You take the dose as high as the patient can tolerate, where the side effects don’t become worse than the depression you’re trying to treat. But then you might need to add another medicine, an augmenting agent or something, so you’ve got to make sure you recognize it and treat it. And then, what I always tell my colleagues—and my colleagues at Hopkins are wonderful; they do appreciate you know you’re treating the whole patient, not just you know their reflex arcs and that kind of stuff—and what they are very good at is, if the patient is depressed and suicidal, that is the psychiatric equivalent of a heart attack. So then they will get in touch with me and we’ll work together. So if you’ve got someone who’s suicidal, you really want to get in touch. Unless you have the utmost experience and confidence in treating the worst cases of depression, you probably want to get a psychiatrist involved, or mental health professional involved, to help coordinate the care for someone like them. MSDF Very good! I appreciate it. [transition music] MSDF Thank you for listening to Episode Eighty-two of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. [outro music] We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller.
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
Full transcript: [intro music] Host – Dan Keller Hello, and welcome to Episode Eighty of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller. Interferon beta is a well-known and long used treatment for relapsing-remitting MS, but it's not without potential problems for some patients. While at the ECTRIMS conference in Barcelona last fall, I spoke with Kaarina Kowalec, a post-doctoral fellow in the Division of Neurology at the University of British Columbia in Vancouver, Canada. We discussed interferon beta and other drugs and their potential for liver toxicity. Interviewer – Dan Keller In terms of liver toxicity of interferon beta, what's the problem? Interviewee – Kaarina Kowalec I would say that about 1 in 50 patients that are exposed to this drug will experience a side effect known as drug-induced liver injury, or liver toxicity, essentially; it's an abnormality in their blood work. Most times it'll just go back down to normal and everything is fine, but in the rare occurrence sometimes it can lead to more severe outcomes such as needing a liver transplant, sometimes even liver failure, and sometimes even death. That's definitely a very rare scenario, but it certainly is an issue, and it's definitely a worry for some patients and definitely for clinicians, as well. MSDF Also, it's not only interferon, a lot of drugs have liver effects. Is that right, new drugs especially? Dr. Kowalec It's the number one reason that drugs are taken off the market, and it's usually one of the top concerns for any new drug that's entering into the market. Obviously, the liver has many different functions, but one being that it detoxify foreign components like drugs like interferon, like alcohol, food, many different things. So it definitely plays a major role, that's why it's usually effected so much. MSDF What are some of the factors that affect both efficacy and toxicity of drugs in general? Dr. Kowalec You know, if you see it kind of a pie chart, the genetic component can be pretty variable. So from person to person, it could be anywhere from a few percent to up to 50 to 60%. But the rest of that pie, I guess, is made up of variation in how much of an enzyme we make that needs to detoxify the drug, as well as our age, our BMI—how much we weigh—how tall we are, whether or not we're male or female. There's a variety of different demographic-type factors that come into play, as well. It's definitely very difficult to predict who will have a safe and effective response to a drug. MSDF Does polypharmacy play a role, especially you had mentioned enzymes; things that induce or suppress enzymes? Dr. Kowalec Yeah, definitely. So in the case of an interferon, there's some evidence to suggest that interferon might suppress some of the cytochrome, or drug-metabolizing enzymes. And in that case if they were taking any additional medications, such as like Tylenol (acetaminophen) or ibuprofen, that could create an issue because interferon is inhibiting the enzymes that are necessary to detoxify the acetaminophen, then obviously the body might have trouble with just acetaminophen on its own. MSDF All interferon betas, do they vary in their effects? Dr. Kowalec Yes. The versions that people with MS get as a drug therapy, there is a few different variations. So I guess half of them are made in a Chinese hamster ovary cell line, and then the other half are made in an E. coli cell line. So there are differences in the immunogenicity of those two forms, so the ones that are made in the animal cell lines are more similar to the version that we would all make endogenously, whereas the versions that are made in the E. coli cell lines are different, they're slightly more immunogenic. They're just more foreign than what we would normally make. MSDF Is it a difference in amino acid sequence, or glycosylation, or both? Dr. Kowalec Yeah, exactly. So the amino acid sequence is slightly different for the E. coli cell line versions, as well as the E. coli version is not glycosylated. So, again, that's why it's a little bit different than the human version. MSDF Do you know some of the mechanisms by which interferon betas cause liver injury? Dr. Kowalec So how it causes liver injury exactly is certainly unknown, and that's definitely an area of which I'm trying to figure out. There's two sort of competing theories, I guess. One is that interferon, because we make it endogenously, but this version is obviously still different than the version we make, it might be that obviously in MS they have an aberrant immune system; they could be recognizing the interferon as being a foreign agent and its attacking it, and then some of the cytokines that are released might be targeting the liver. So that's one theory. The other theory is that once interferon is incorporated into the cell, it might have some sort of direct effect on the mitochondria, and so it might be that it's reducing the energy metabolism of the cell and causing harm into the liver. But which of those two, we're not sure yet. MSDF Do you know risk factors for liver injury, and as they are picked up by aminotransferase elevations? Dr. Kowalec Yes. And some of the risk factors that we know for interferon-induced liver injury are related to gender, age. Sometimes it's polypharmacy, so whether or not they're taking acetaminophen or ibuprofen. One study will come out that'll say that there is an effect, one study comes out there's no effect, so it's still a little bit unclear. With gender, we know that for males they are more likely to have some of the more minor transient elevations in the aminotransferases, whereas females are more likely to be at risk for the more severe symptomatic hepatitis, or liver injury, I guess. MSDF And is it equally prevalent, or there's different gender prevalences? Dr. Kowalec I would say that overall when we looked at all the genders together, it was about the same, about 1 in 50, or 2% or so. I would say that if you're looking at just severe injury, the effect that's more symptomatic, something that a patient would actually notice, it's likely that females are more susceptible. MSDF What about duration of treatment, does that have an effect; early, late, how long? Dr. Kowalec Yeah, typically it's quite quick that they would experience this. So the median time is about the first 3 months is the greatest risk period—I guess probably 3 to 6 months – but it certainly can still occur later on, say even 2 to 5 years, or even 7 years later on, so that's why it's still really necessary to remain diligent on testing their liver aminotransferase levels even later on, even like I said, 5 to 7 years after being on treatment. The effect doesn't seem to go away, for some people anyways. MSDF I suppose while you're taking it you're getting older, and also you probably have different medications coming in and out. Dr. Kowalec Yeah, and it's not even just the other pharmaceutical therapies that you're taking, it could also be your diet, how much you exercise. There's a lot of things that can affect the liver aminotransferases, unfortunately, so sometimes it can be difficult to determine whether or not it's actually interferon beta that's the causative agent. MSDF What should patients be looking for? Dr. Kowalec You know, I think just staying up with a healthy lifestyle; not drinking excessively, eating the right foods, making sure that whatever therapies that you are taking are compatible with interferon. Your neurologist or your clinician will advise you on those areas anyways, and also keeping an open dialog with your neurologist in that you know exactly what the risks are with taking any medication. And most times your clinician will be able to tell you everything that'll be possible side effects, so just keeping an open dialog with the clinicians, I think, is great. MSDF Are there symptoms which might raise concern? Dr. Kowalec You know, I mean sort of the typical things that we think of with liver issues, like jaundice, abdominal pain—they're really like, I mean, abdominal pain that can be a symptom from many different things, right? Malaise, same thing. Really I would say jaundice is probably one of the things that would stick out in my mind to most people as having an issue with your liver, right? By the time you notice symptoms, it certainly is in the more severe end, so usually you have something else that would precede that, like the abnormal blood work. So most people don't get to that stage, which is good. MSDF Is there something physicians should be doing or looking out for? Dr. Kowalec No, I would say they're doing a really great job with just monitoring the blood work. They know that once typically patients get to 5 times the upper limit of normal for ALT, or the liver aminotransferase, that's when it's recommended that they stop the drug. So normally because they are tested quite often for the blood work abnormalities, the clinicians are really going to go about monitoring by lowering the dose of the drug or just stopping them, and then slowly titrating them back on again. They still have many options if they experience the side effects, so they're doing a great job with monitoring. MSDF Is this becoming less of a problem with new drugs, vis-à-vis, interferon beta itself? Dr. Kowalec I believe almost all of the new oral medications have all had some case reports of having liver injury associated with them, which is unfortunate. But, again, like I said, most drugs will use the liver in order to be detoxified, it's not, I guess, surprising that this is happening. So I think that we definitely need to study the theory. And that's sort of why we're studying interferon beta, because there's so many people that have taken it, there's enough people that we can study, whereas the new medications, they haven't reached sort of that level yet; they don't have 20 years of data yet. So that's why interferon beta really represents a really great way to study this type of side effect, because now hopefully maybe some of these findings we can apply to the new medications that are going to be more relevant in the future. MSDF Have you been able to see whether a history of interferon beta affects susceptibility to liver injury with any of the newer drugs? Dr. Kowalec I've seen a few patients that have had liver toxicity from interferon, and then gone on to take, say, glatiramer, and they have had that same reaction, or Copaxone. Individual clinic, they've seen it, but they just haven't had many publications on that, so it's sort of unclear, I guess, right now. I guess I should still say in the wider literature in other liver toxicity from, say, like antibiotics, there are some common mechanisms. It seems like that some people, that if they have it to one drug, they have it to multiple drugs. So there could be some underlying, I guess, common mechanisms between all of them. MSDF It would be hard to separate out whether it's a function of the patient being susceptible liver to liver injury from almost anything, versus having a history specifically of beta-interferon. Dr. Kowalec Yeah, we don't know the long-term effects of interferon beta, we don't know really what happens to them in the long run. We can only really follow the ones that have had the really severe outcomes, like liver transplant, for example. But people that experience the more minor elevations, or even the level that we study, most often we see that the liver enzymes go back down to normal. But, you know, we're only looking at this for maybe 5 to 7 years, and then after that we don't know what happens. And then, of course, then once they get older, you would expect that things might go downhill and they might have more issues. MSDF Have we missed anything important? Dr. Kowalec This is an area that with respect to toxicity with the MS medications, it's definitely an area that is not as well studied, because, of course, the overall goal is to have an effective treatment. If we have an effective and safe treatment, that's the end goal, but that's not always what happens, because we can't sort of have everything that we really need. And so I think studying these areas is definitely really important, because although patients want their disability to be prevented, they're willing to take a lot of risk. And they shouldn't have to, they should be able to have an effective treatment that is safe, as well. So I think by studying these adverse drug reactions more often, I think we'll hopefully get to that end goal eventually. MSDF Very good, thank you. [transition music] Thank you for listening to Episode Eighty of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. [outro music] We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller.
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
Full transcript: [intro music] Host — Dan Keller Hello, and welcome to Episode Seventy-seven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller. Pregnancy and the postpartum period present special concerns to women with MS. Dr. Annette Langer-Gould, a neurologist and epidemiologist at Kaiser Permanente in Los Angeles, investigates ways to lessen the risk of relapses in these women. We discussed the effects of breastfeeding, among other topics, when we met at the ECTRIMS meeting last fall in Barcelona. Interviewer – Dan Keller In terms of pregnancy and breastfeeding in MS, what are you looking at? Interviewee – Annette Langer-Gould We're studying modifiable risk factors for postpartum relapses in women with multiple sclerosis. And specifically, we are looking at starting therapy shortly after delivery, whether that can reduce the risk of postpartum relapses, whether breastfeeding, particularly breastfeeding exclusively, could reduce the risk of postpartum relapses, and whether vitamin D levels play any role in increasing or decreasing the risk of postpartum relapses. MSDF And are these women who are on disease-modifying therapy throughout pregnancy or not? Dr. Langer-Gould No. In our population, a little over 60% were treated prior to pregnancy. But we do have a decent number of women who had decided to never go on disease-modifying therapies before, and almost all of them stopped disease-modifying therapies either shortly before or when they find out that they're pregnant. MSDF In terms of each of those outcomes, what are you finding? Dr. Langer-Gould We haven't analyzed the data for the vitamin D yet, but in the German pregnancy registry, we just published the data in exclusive breastfeeding, and once again showed that exclusive breastfeeding does protect against postpartum relapses. In that population, actually 96% of the women had been on some sort of DMT prior to pregnancy, and none of them were treated throughout pregnancy. We also found that resuming DMTs does not seem to have a big effect on reducing the risk of relapses, particularly in the first six months postpartum. MSDF Is that in women who are exclusively breastfeeding or not? Dr. Langer-Gould Ah, so that's a good question. So there is no good safety data on taking the medications during breastfeeding. And therefore, many clinicians and most patients are concerned about potential theoretical risks. So behaviors are actually mutually exclusive. Women typically will either breastfeed or resume medications early in the postpartum course. The other thing we find in the Kaiser population is that there are still a fair number of women who neither breastfeed exclusively or resume their medications, which presents sort of an interesting opportunity. If we could show that one or the other behaviors is protective, perhaps we could encourage either exclusive breastfeeding or resuming DMT. MSDF If women are not breastfeeding, do you have an idea of the time course of resumption of risk for relapse? Dr. Langer-Gould Yes, so the concern about postpartum relapses really is about having a relapse in the first three to four months postpartum. If we look over at the whole pregnancy year, and that's about 30% to 40% of women. So this is actually still the best defined risk period for having a relapse and actually the only clear trigger—with perhaps the exception of upper respiratory tract infections—of relapses. So we know that having just had a baby or having an upper respiratory tract infection is a pretty strong predictor of having a relapse. So it presents sort of a unique opportunity to also look at other biological factors, like vitamin D, which is why we're interested in it, to see if any of these things have a strong role in relapses as well. MSDF If women are breastfeeding postpartum, what is the hormonal profile like? Is this almost like an extension of pregnancy? Dr. Langer-Gould For women who breastfeed exclusively, meaning that they breastfeed to the point of suppressing their ovaries and not resuming menstruation—so that essentially there's no regular meal that's being replaced by formula or by table food in the baby—they have very high prolactin levels. So it's actually a little bit different than being postmenopausal, in the sense that they have very high prolactin levels. And they have incredibly low nonpulsatile FSH and LH levels. In the postmenopausal period, there occurs a very high FSH and LH levels. The similarity, though, is that they both have bottomed-out estradiol and progesterone levels, in both women who are breastfeeding to the point of suppressing menses and also postmenopausal women. And of course the other similarity is that there's no ovulation occurring, either during pregnancy, during exclusive breastfeeding, or after menopause. MSDF So it sounds like breastfeeding is really a hypothalamic pituitary suppressant as opposed to in menopause, where you still have those cranking away, but just no response from the ovaries. Dr. Langer-Gould Correct. MSDF Can this be used in any clinical sense? Do you see an application? Dr. Langer-Gould The most obvious direct way to translate these findings is that that, if you have a woman with MS in front of you and she is pregnant and she tells you she'd like to breastfeed, we certainly have no good reason to discourage her. And that if anything, I would suggest that the data we've already published would point to the fact that we may want to encourage exclusive breastfeeding, provide them with lactation counseling, and also sort out exactly what the optimal duration of exclusive breastfeeding may be for these women. Is it really only eight weeks, which we had defined arbitrarily? Or does longer duration of exclusive breastfeeding have additional suppressive properties? And that would, of course, have implications in the United States for things like maternity leave and work accommodations to allow that to continue, if it has a strong therapeutic effect for the mother. MSDF What's the relapse rate among postmenopausal women compared to postpartum women? Dr. Langer-Gould So relapse rate declines with age. And so it typically in postmenopausal women, although there's not great data, we would expect them to have relapse rates of less than 0.3 per year, Annualized relapse rates of less than 0.3 per year. And in postpartum women, that first three to four months, the annualized relapse rate exceeds one. MSDF But men also have a decline in relapse rate as they age, too. So you can't attribute it to lower estradiol. Dr. Langer-Gould Exactly. Yeah, I think it's far more complicated than just a simple sex hormone effect. You know, that was sort of our first instinct from pregnancy or the reason pregnancy must be protective. It has to have something to do with estradiol or the very high progesterone levels. And that's what prompted the postpartum study and also the estradiol randomized control trial. And both of those, of course, disappointingly have been negative. In isolation, the sex hormones associated with the protective effect of pregnancy don't really have a protective effect on inflammation. It's probably more of a combination of factors that play into modulating the immune response. MSDF Where do you go from here? Dr. Langer-Gould I think that if we are able to reproduce the findings, looking at this population-based source, that early resumption of DMTs is not particularly helpful, but perhaps it may be later in the postpartum year, and that exclusive breastfeeding is, again, protective, then I think the next step really is to establish the safety of some of these medications during lactation. For several of them, there's really no biologically plausible reason to think that they would have an effect on the baby, as they're not likely to be absorbed through the gut or enter into the baby's bloodstream. Examples of that would be the large molecules like Copaxone, the interferons, and also the infusion medications, Tysabri (natalizumab), and rituximab as well. Although you may be able to detect them in breast milk, they are such large molecules that they would not diffuse across the baby's stomach and into the bloodstream. Think about it. If the mom has to take it as a pill, it is very likely to be transmitted to the baby. If the mom has to take it as an infusion or injection, very unlikely that oral route through the baby would have any effect. MSDF How sensitive is this effect to, as you said, exclusive breastfeeding? Can you start introducing formula, or it's all or none? Dr. Langer-Gould That's a really good question. So we did look at that also in the German pregnancy registry. So first of all, women tend to have very defined behavior. They tend to decide to supplemental feed with formula very, very early, before they've even established their full milk supply. So to back up even further, a healthy woman gives birth to her child. Usually menstruation will resume two months after delivery, not one month. So it does take the HPA gonadal axis a little chance to recover from those high-circulating hormones of pregnancy. And in women who introduce supplemental feedings, particularly early, we also see the very same thing; that they will resume their period at two months postpartum. Actually, most of the work done in this field has been done by nutritionists who are in developing countries who are interested in knowing what you should do if you see a starving mother and a starving baby. Who should you feed? It turns out that if you feed the baby, the mother's ovarian function will resume. So any regular supplemental feedings and very quickly their prolactin levels will drop. The pulsatility of the FSH and LH secretion will return. Ovulation returns, and so does menses. It's essentially sending the mother's body a signal that the baby no longer needs nutrition from the mom to survive, so she's ready to have another child. So the right thing to do in that situation would be feed the mom, and let her nurse the child. Biologically, it's very interesting. Even though some breastfeeding is better than none for the baby, in terms of the effect on the mother's HP [hypothalamic-pituitary] ovarian axis, some supplemental feeding is just like all supplemental feeding. MSDF Have we missed anything or anything interesting to add? Dr. Langer-Gould So I guess I would say just in general, women's, and now even men's, desire to have naturally-born children has taken on a new significance with a lot of the small molecule agents, because we need to consider family planning and discuss it much earlier, as small molecules are likely to have an effect even if they get pregnant accidentally on the developing fetus. This is a challenge we haven't had before, because large molecules won't cross the placenta in the first trimester. And the first trimester is the critical period for organ development. So it's sort of new era for MS neurologists, where we really, really have to think carefully about which medication we put them on if they're planning on having children soon. So I’d strongly encourage that you have that conversation very early and have it with every followup visit. I typically will ask them, are you planning on having children within the next two years? And if they say, no, I ask what kind of birth control they're on, or in some cases they're in same-sex couples. That's obviously an exception. And if they are not on a reliable form of birth control, I think you need to think twice about giving the small-molecule agents—so the pills, basically. MSDF Should MS neurologists work with high-risk OB/GYNs? Dr. Langer-Gould I think for the most part it's not necessary, because women with MS, they don't have abnormal complications at pregnancy. I think there are certainly situations that we're running into now. If they get pregnant accidentally on fingolimod, teriflunomide, or Tysabri, we do need to work with them, mostly for the baby. So you may want to do more intense early screening if the mother is culturally open to the idea of having an abortion. You may want to do more fetal ultrasounds, perhaps even a fetal MRI, if there's suspicion of major malformations early on in pregnancy. And also for the Tysabri, really, it's not so much about organogenesis, but if they've had later exposure to Tysabri during pregnancy, which unfortunately on occasion has been necessary to control rebound disease activity during pregnancy, that, you know, we have seen hematological abnormalities in some of these children, so far none with clinical complications. Only one child had a subclinical intraventricular hemorrhage that resolved. It's still concerning. Our experience is very small, and we would certainly highly recommend that those women give birth in a hospital that has a neonatal intensive care unit available and a pediatrician on call to examine the child and also make sure that the child doesn't have a severe thrombocytopenia or anemia at birth. MSDF Do the different drugs have different risks for fetal malformations or other dysfunctions? Dr. Langer-Gould Yes. So teriflunomide, or Aubagio, is the most concerning medication because if a woman gets pregnant on that accidentally, it is, you know, a category X drug because it can interfere with neural tube development. And although you can chelate to get the medication out very quickly, the safety data from other indications, you know, the rheumatoid arthritis and lupus literature, is not particularly reassuring in terms of fetal outcomes. So I think that's sort of the number one to stay away from if a woman is planning on getting pregnant. And it's also one where, you know, there is some concern, although not strong evidence, that it may also affect the offspring of men with MS who are on the medication. In terms of the other ones, of course, again, small molecules in fingolimod has about a 15% to 16% major fetal malformation risk with early pregnancy exposure. It has a very long half-life. So even if they stop the medicine the minute they find out they're pregnant, it takes over two months for it to be cleared, which means that the baby has seen it now through the entire first trimester. That can have significant effects, both on cardiac and brain development. And then with dimethyl fumarate, we haven't seen—now of course, this is a very new drug, so we don't have nearly as much experience—we have not seen any major malformations, but there was concern in the animal models that it could interfere with cognitive development. In particular, the rats had maze-finding difficulty. MSDF Is alemtuzumab indicated at all? It seems to have a long tail. Dr. Langer-Gould I'm not sure what the half-life of alemtuzumab, but it's probably similar to other monoclonal antibodies, which is usually around 15 to 20 days. So monoclonal antibodies don't cross the placenta in the first trimester, because it's a very large molecule. So large molecules only get across if there's an active transport system. For antibodies, there is an active transport system, because it's very important that the child be born with a high dose of antibodies received from the mother to help protect them during the early part of their infancy while their own immune system is still developing. So we see maternal antibodies being transported, and of course, monoclonal antibody medications would be dragged along with that during second trimester. And it goes up in elliptical fashion, with very, very high amounts being pumped across the placenta in third trimester. And they also, of course, have a very delayed clearance mechanism, both the fetus really has no clearance mechanism, and then even the neonate has a very slow clearance mechanism. So in TNF alpha studies, if the drug is given during third trimester, it's typically not cleared until about six to nine months postpartum. So you also have to be concerned that a baby exposed would have some of that medication hanging around during the early neonatal period and give some thought to whether or not their immunization scheme would need to be adjusted, as the cautionary tale there would be TNF alpha exposure during pregnancy. There was a case reported of a woman who had very severe rheumatological disease, had discussed with her rheumatologist the potential risks and benefits of taking it throughout pregnancy, opted to take it throughout pregnancy. And then living in an endemic area for tuberculosis, the baby got the BCG vaccine and got disseminated mycobacterium and died. And that, you know, was probably directly related to impaired immunity from the TNF alpha antagonist. And sure enough, the baby was born with fairly high cord levels and also had very high levels still remaining in the blood in the neonatal period. So it's not just once the baby's born, it's like the drug is out. So drugs like alemtuzumab and rituximab, the way in which they work, even though the drug could be long gone, but the effect of the medication works very long time. So those are actually good choices for women with highly active disease who are planning on getting pregnant. And you have concerns about rebound. I mean, we typically use rituximab because it's obviously much safer than alemtuzumab and seems to do a fairly good job. But you know, these aren't medications we should be giving while they're pregnant, but probably not a big effect in crossing the placenta and on the baby if they're used prior to pregnancy. MSDF If they can plan that well and get a pulse of that early, and then get pregnant a few months later. Dr. Langer-Gould Yes. Yeah, that's always the trick, right? And they do get pregnant accidentally on just about everything we put them on. So the infrequent infusion medications is the easiest because you can ask about last menstrual period. And you can ask about birth control use, and you can do a pregnancy test the day of, a quick urine dipstick and find out so that you don't accidentally infuse a pregnant woman. Of course with Tysabri, when you're giving them an infusion every month, it gets a little tricky. Usually people just kind of get tired of it. The nurses forget. The doctor forgets to order it, although it's not necessarily bad practice if you know you have a patient who is not on a reliable form of birth control. MSDF Very good. I appreciate it. Thank you. Dr. Langer-Gould You're welcome. [transition music] MSDF Thank you for listening to Episode Seventy-seven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. [outro music] We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller.
March is Multiple Sclerosis awareness month. MS is an autoimmune disease in which the immune system eats away at the protective covering (Myelin Sheath) of the nerves throughout the Central Nervous System. Since the specific regions where the Myelin is damaged is random, symptoms experienced vary vastly. In this episode I speak with my fiancée Zoila, about her first hand experience of having MS. We cover her symptoms early on before she knew what was wrong, which ranged from extreme fatigue to limb numbness to losses of balance and bladder control issues. We spoke about the medications she has used; Glatiramer by injection (Copaxone) and Fingolimod (Gilenya). Millions of people around the world have been diagnosed with MS. Studies have shown anecdotal genetic links as well as environmental ones, but nothing concrete, hence it being dubbed the “mystery disease”. There is no known cause or cure. According to the Mayo Clinic, there are fewer than 200,000 U.S. cases per year. This is our attempt at spreading awareness. Thanks for checking it out. Links referenced in this episode: What is Multiple Sclerosis video from ASAP Science: https://www.youtube.com/watch?v=Naecv3h868c To donate for MS research or partake in activities like Bike MS, Walk MS, or just to learn more, check out the National MS Society: http://www.nationalmssociety.org/ Fill out my 5-question survey if you’re passionate about your craft. I’ll share your insight and motivation on the Podcast: http://www.spuntoday.com/questionnaire/ Order prints of my Photography (Posters, Canvas, Framed):www.crated.com/spuntoday Shop on Amazon using this link, to support the Podcast: www.amazon.com Shop on iTunes using this link, to support the Podcast: https://itunes.apple.com/WebObjects/MZStore.woa/wa/viewTop?genreId=38&id=27820&popId=42&uo=10 Check out my Book: Make Way for You – Tips for getting out of your own way http://www.spuntoday.com/books/ (e-Book & Paperback are now available). Sound effects are credited to: http://www.freesfx.co.uk Listen on: iTunes, Stitcher, Pocket Casts and YouTube
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
[intro music] Host – Dan Keller Hello, and welcome to Episode Fifty-Seven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller. This week’s podcast comes to you from last week’s big MS meeting in Barcelona, Spain, with an interview with Dr. Timothy Vollmer, who gives his take on the early results of a large Phase 3 study of ocrelizumab for primary progressive MS. The experimental drug blocks circulating B cells. We will have several extra meeting-related podcasts for you in the next two weeks. In the next one, Dr. Gavin Giovannoni talks about a new push to use long term brain health as a goal in MS treatment. And Dr. Vollmer will return in the coming weeks to discuss the Denver treatment experience with another B cell blocking drug, rituximab. But first, here are some new items in the MS Discovery Forum. Every week MSDF lists the latest scientific papers related to MS with links to the abstracts on PubMed. Of nearly 100 new studies published last week, we selected three as editor’s picks. Two of our editor’s picks come from a larger collection on MS in JAMA Neurology. One study reports on an equivalence clinical trial comparing a generic glatiramer acetate, Synthon, with Copaxone, the branded glatiramer acetate, for relapsing remitting MS. A global team of investigators found equivalent efficacy, safety, and tolerability in the randomized, controlled trial. The findings provide reassurance about well-made generics for patients and neurologists, say other researchers in an editorial. But the whole idea of generics is to make a dent in the skyrocketing costs of MS drugs, and the generic is priced at $63,000 a year instead of $65,000 and $74,000 for the two versions of the branded drug. Another paper in the same JAMA Neurology checked to see what the vitamin D levels of nearly 1500 people treated with interferon beta-1B might say about the course of their disease. Higher vitamin D levels were associated with fewer new active lesions in the mostly white, mostly female patients with relapsing remitting MS, but there was no correlation with clinical disability or brain atrophy. Our third editor’s pick is a paper investigating the cancer risk from cladribine compared to other MS disease modifying treatments. A large Phase 3 study showed the experimental drug to be highly effective in relapsing remitting MS, with nearly half of patients showing no evidence of disease activity after two years and two courses of the treatment. But it was refused a license by the European Medicines Agency in 2013. Now, based on their new meta-analysis of eleven studies, the authors say they cannot confirm nor deny a cancer risk, and that cladribine should be investigated further as an MS therapy. Our drug development pipeline contains 44 investigational and approved agents for MS. Last week, we added results from two new trials, we updated information from 16 other trials, and we added 20 other pieces of information. Trial updates include findings about ocrelizumab’s ability to reduce relapses and minocycline’s capacity to reduce the risk of conversion to MS after an initial demyelinating event. [transition music] And now to our interview with Dr. Timothy Vollmer, Professor of Neurology and Medical Director of the Rocky Mountain MS Center at the University of Colorado in Denver. When we met at the European Committee for Treatment and Research in MS, or ECTRIMS, meeting in Barcelona, Dr. Vollmer laid out how results of the ORATORIO trial of ocrelizumab shed light on two hypotheses of what goes wrong in primary progressive MS, and which one is most likely. Interviewee – Timothy Vollmer There currently are two hypotheses for what drives primary progressive disease. One is that it’s like relapsing disease, and it’s driven by inflammation. And the other one is that it’s a noninflammatory disease that’s being driven by neurodegeneration and has a separate biology. Now that we have positive results from the ORATORIO study, which is a study of ocrelizumab which is an anti-CD20 monoclonal antibody that deletes B lymphocytes from circulation, given that this is the very first time we’ve ever succeeded, it’s telling us very important thing, and that is: inflammation does drive primary progressive MS. And the other important message from here is that this study studied a significantly younger patient population with primary progressive MS than all the other studies. The mean age was around 44. The reason that’s important is because, epidemiologically, we see a decrease in inflammatory activity as a function of age, and older patients often don’t express any evidence of that. And so far, in all the primary progressive studies, especially the OLYMPUS trial, those patient populations don’t respond to anything. So it’s telling us that we can treat primary progressive MS, but you’ve got to start early. Interviewer – Dan Keller That seems to be the message overall in MS, in general, though. Dr. Vollmer Yes it is. And the reason is, is because MS results in an accelerated brain volume loss, and brain volume loss is going to translate into disability, at some point, for almost everybody. Maintaining brain volume so that you can age normally late in life is a critical goal, not just in MS, but in other neurological diseases. MSDF Does that brain volume loss or other changes in the brain relate to really the onset of the progressive phase? Dr. Vollmer The answer is yes and no. From a statistical standpoint, it’s very hard to sort of identify a specific point in the process of brain volume loss that you can say, okay, they’re going to transition into progressive disease. That’s probably due to the fact that the mechanisms that underlie reserve capacity in brains may vary a little bit from patient to patient, and that they have different capacity to compensate for this injury. The other complication is that MS, as a multifocal disease, is not necessarily distributed evenly throughout the nervous system, though. In some patients, they have a relatively small amount of disease, but it’s in the neck, and they’re still highly disabled. And because of that very complicated pattern for it, it is hard just to use one global measure to predict how patients are going to be from a disability standpoint. MSDF Do the results of the ORATORIO study give us more confidence in pursuing the B cell as an important effector in MS? Dr. Vollmer Absolutely. The converging data, now, both in progressive forms and in relapsing forms, says the B cell is playing a critical role. There are CD20-positive T cells, and so there’s still some discussion whether the drug may be having an effect on those, but in the most recent reports, it does decrease those with first administration, but then they recover very quickly. And at subsequent administrations of the anti-CD20, they’re not deleted. So that pattern suggests to me it’s not an effect on T cells, it’s an effect on B cells which remain suppressed for months after a single injection. MSDF CD20 is on B cells but, as I understand, not on plasmablasts or plasma cells. So what is the relative contribution of B cell biology versus just antibody? Dr. Vollmer A major difference is that plasmablasts and plasma cells are not very good antigen presenting cells. Whereas, B cells, if they can engage the antigen that their B cell receptor is targeted for, become extremely effective antigen presenting cells: the most effective antigen presenting cells in the body. And they can be about ten thousand times more effective that dendritic cells or macrophages. So that’s why I think that, given the fact that the most effective therapies we’ve currently studied right now are all B cell based therapies, I think it’s telling us is that the B cell is playing that critical role, and most likely, that is in both cytokine release and in antigen presentation in the brain. MSDF From the ORATORIO study, what more do you want to see? The data is just coming out, and they’re going to do a bunch of analyses. What sort of things should they be looking at? Dr. Vollmer Well, they have a number of other clinical measures, and I believe they also have some patient reported outcomes, so I’d be very interested to see if the patients actually perceive a benefit as measured by those PROs. They have the timed twenty-five foot walk out, which they reached and was statistically significant. They had sustained disability progression at both three and six months which was statistically significant. And they reported brain volume loss was decreased in the ocrelizumab treated patients and was statistically significant. We would like to know more about the inflammatory markers in the patients and the correlation between having baseline evidence of disease activity, such as a gadolinium enhancing lesion, and the probability of response to therapy. MSDF What about the time course of response to the therapy? It seems like it’s more rapid than you would expect if an insult sometime in the past led to what you see today. But the ocrelizumab results seem to be on a faster track than that. Dr. Vollmer Well, the reason I believe that is, is because, as I said before, they really pushed down the median age in their population to much younger patients. And again, in long term studies that have looked at gadolinium enhancing disease activity, we do see it in primary progressive disease. So it’s not true, in my view, that primary progressive MS patients have a different MRI pattern. In studies that actually controlled for observer bias, where the neurologist didn’t have a chance to look with an MRI scan, but made the decision whether it was progressive or not progressive disease based on clinical history, which is the only way that we really can do it, then the previously reported biases of having nonspecific noninflammatory MRIs disappears. And that paper was published about six years ago. So, I think that we have a lot of built in biases, as a field, when you think about MS, and, unfortunately, those biases are often not supported by objective data. And yet, they do make their way into the literature, mainly because they don’t control for age. And when comparing progressive patients, relapsing patients, or primary progressive patients to relapsing patients the fundamental difference is progressive patients tend to be 10 to 15 years older on average than the relapsing patients they’re comparing them to. And it’s that age difference that explains most of the differences that people talk about. It’s not the fact they have a different form of the disease. MSDF Anything else to add on this that we’ve missed? Dr. Vollmer As I said, we need to get subset analysis out of the ORATORIO study to see just which age group and demographic the patients really got the most benefit. My suspicion is we’re going to again find it’s the younger patients that show the biggest effect, again emphasizing that starting early in the disease with therapy is a key issue. And, again, I think it’s going to argue that you need to use highly effective therapies as early as possible, in order to get the best effect. MSDF Very good, thank you. Dr. Vollmer Thank you. [transition music] MSDF Thank you for listening to Episode Fifty-Seven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Heather McDonald curated the MSDF drug database updates. Msdicovery.org is part of the nonprofit Accelerated Cure Project for multiple sclerosis. Robert McBurney is our President and CEO, and Holly Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. We’re interested in your opinions. Please join the discussion on one of our online forums or send a comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I’m Dan Keller. [outro music]
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
Transcript [intro music] Host – Dan Keller Hello, and welcome to Episode Fifty-Six of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller. This week’s podcast features an interview with Dr. Gavin Giovannoni who discusses the first experimental drug to show some benefit in a progressive form of multiple sclerosis in a major trial. The drug is ocrelizumab, and the trial is called ORATORIO. But first, here are some new items in the MS Discovery Forum. The ocrelizumab findings were the big news at last week’s large international MS meeting in Barcelona, Spain. Our Research Roundup highlights other breaking stories from the meeting. Stay tuned for more in the days to come. We’ll be rolling out in-depth stories on some research themes we followed at the meeting. And we will have some extra meeting-related podcasts for you in the next two weeks. Every week, MSDF lists the latest scientific papers related to MS, with links to the abstracts on PubMed. Of 138 new studies published last week, we selected three as editor’s picks. In one study, a British team found a new reason why remyelination fails in disease. When damaged axons lose their myelin sheath, as in multiple sclerosis, they strike up a conversation with immature myelin-making cells. The axons reach out with new synapses to order the cells to grow up and make new myelin. If axons can’t call for help, as also may happen in MS, the myelin-making cells cannot respond. The team made their discovery in rat brains. They also found new synapses and telltale signaling molecules in postmortem brain lesion samples from people with MS. In another paper, a Spanish group looked at other factors that may block the brain’s ability to repair itself after inflammatory damage. A pair of molecules, known as semaphorins, may block myelin-making cells from coming to the rescue of damaged axons. The findings come from human tissue samples and may hold promise as targets for future treatment. Our third editor’s pick paper looks at factors influencing the intention to exercise and the execution of exercise among people with multiple sclerosis. A Danish team did an extensive review of rehabilitation and sports medicine literature. They found that health professionals can help on both fronts. Our Drug-Development Pipeline contains 44 investigational and approved agents for MS. Last week, we added two new findings from clinical trials, we updated information from another trial, and we added 10 other pieces of information to the database. The drugs with important additions are alemtuzumab, dalfampridine, fingolimod, glatiramer acetate, idebenone, natalizumab, and teriflunomide. One update summarizes the finding that fingolimod induces the expression of neuroprotective factors by human astrocytes. [transition music] And now to our interview with Dr. Gavin Giovannoni, head of neurology at Barts and The London School of Medicine and Dentistry in the U.K. We spoke with him at the recent European Committee for Treatment and Research in MS, or ECTRIMS, meeting in Barcelona about the Brain Health report that was launched at the meeting and about the ORATORIO trial of ocrelizumab in primary progressive MS. We'll cover the Brain Health report in future podcasts with him and other authors of the report. But today, Dr. Giovannoni lays out the methodology of ORATORIO, which may explain some of the very good reduction in disease progression, observed in this trial for the first time in primary progressive MS. Interviewer – Dan Keller In the ORATORIO trial, what was the aim, and I guess what's the big outcome? Interviewee – Gavin Giovannoni Well, the ORATORIO trial is essentially a phase III trial of depleting anti-CD20 monoclonal antibody called ocrelizumab in primary-progressive MS. As you're aware, almost every trial done in primary-progressive MS has been negative. And then the motivation behind the ocrelizumab trial was based on the rituximab trial; ocrelizumab is a follow-on and rituximab is more humanized, so that should come with fewer side effects like infusion reactions and anti-drug antibodies. In that rituximab trial, there was a subgroup of the population that responded. These were people that are younger and had MRI activity. So when we designed the ocrelizumab ORATORIO trial, we tried to enrich the study for young people and people that were more active, more enhancing lesions, and we did that. So the population is younger, and the proportion of patients with gadolinium-enhancing lesions at baseline was about a quarter of them. And we also made sure that all the patients had an abnormal CSF spinal fluid. The reason for that is in the Copaxone glatiramer acetate trial, patients who didn't have an abnormal CSF behaved very differently to those with an abnormal CSF, so we wanted to make sure that we had a homogeneous population. And we made sure they had oligoclonal bands or raised IgG in the spinal fluid simply because we we're trying to target a B cell response; so those that are CSF-negative may not be responsive to a B cell therapy. Lots of features of this trial that we try to wait to make it positive, so we're really, really excited about the results, that people on ocrelizumab had an approximately 25% reduction in confirmed disease progression on EDSS compared to patients on placebo. And it was an event-driven, so the trial wasn't designed to be a fixed time point, it was designed as soon as you got enough events; it was like an adaptive trial, so it was quite cleverly designed in that regard. So it's great news. Now whether the trial was positive because ocrelizumab is a more effective therapy than the others, or because it's targeting something special like the B cell, at the moment is not known. The only way we're going to find that out is if we do another primary-progressive trial with another highly effective therapy and see what happens there. But this is fantastic news for people with progressive MS. If you follow any patient forums or blogs or whatever, the most frustrated, depressed group is the primary-progressive patients; they've been neglected for years, decades. I think that's the big news, we now will have a therapy which we can offer them. The one unknown, though, is maybe this result has been driven by a particular subgroup, and I think the regulators and the payers will want to get that data from us. Because if it is driven by a particular subgroup, they may limit the license and the payment for that particular subgroup, the responder group. And so I can't talk to that yet, because most of the subgroup and post-hoc analyses haven't been done. But potentially maybe like the rituximab trial, there will be a proportion of the patients that have characteristic features that are more responsive to the drug, and drive the trial results compared to the other group. And if that is the case, then it's still good news regardless. MSDF As it stands now, it seems like the indication would be for people with abnormal CSF, oligoclonal bands, or elevated IgG. Is there any thought that this drug may work possibly by the same mechanism even if you're not seeing abnormal CSF? Dr. Giovannoni The spinal fluid tests aren't 100% perfect, so there are people who will have false-negative results. But I've always been a big proponent of the hypothesis that the oligoclonal response in the spinal fluid is something key to this disease. We see that response in infectious diseases like neurosyphilis, measles, rubella panencephalitis, herpes; it's really a signature of its common to infectious diseases, which is why I'm still a supporter of the hypothesis that MS may be an infectious disease. You do find that in a few other autoimmune diseases, particularly the paraneoplastic plastic syndromes, that it's a signature of an intrathecal B cell response. And this drug targets B cells. One thing it doesn't target, though, it's the long-lived plasma cell, and so CD20 actually stops being expressed, even on plasmablasts, so as soon as you go from the mature B cell to plasmablast to plasma cells, you don't deplete those with anti-CD20. So we know from rituximab data that the oligoclonal bands persist, so we need longer punctures, you don't get rid of those. But until we have long-term followup, we don't know. Maybe drugs that target the plasmablast and the plasma cell will be more effective than rituximab. We don't have any of those drugs available in MS yet. There's one that's being developed, it's anti-CD19; CD19 gets expressed onto the plasmablast and some plasma cells, and there are some specific markers for plasma cells. But if you gave those to people with MS, you'd probably deplete them of their antibody-producing cells and make them a gamma globulin anemic. Then you'd have to probably then start supplementing with gamma globulin, so it gets quite complicated. But at the moment, the drug will be licensed, I think, for continuous use every 6 months; it won't be induction therapy. Some of the data would suggest you could potentially use it as induction therapy, so, you know, do 2 years and then wait and see if the disease comes back. But the way the drug's been developed at the moment is for continuous maintenance use. There are some concerns; can you continue to use it in the B cell depletion forever? And that's going to have to be answered with the open-label extension studies. MSDF Since plasma cells persist and oligoclonal bands persist, if I understood you correctly, do you think that the pathology is mediated through antibody, or this depletion of B cells is acting in a different way, that the B cells are interacting either with T cells or on their own doing something? Dr. Giovannoni I mean, there is pretty good evidence from the pathology literature that antibodies are very important in MS. So whether or not you accept it, there is pathological classifications of the top 1 to 4. And there is antibody and complement activation in MS lesions, and there is emerging evidence that so-called grey matter lesions and subpial lesions on the surface are particularly driven by antibody and complement. So I do think they are pathogenic. And so you may get rid of the focal inflammatory lesions that appear to be T cell-driven, whereas the cortical subpial lesions may be antibody-driven. So you may be getting rid of one pathology and not all the pathologies, which is why I remain a little bit skeptical still about whether or not this anti-CD20-depleting antibody will be effective in the long-term. So we may need additional treatment to target plasma cells. And what you've got to ask yourself really is what's driving those oligoclonal bands. We know they are highly selected, so they're not just there. They're oligoclonal, they've undergone selection by hypermutation, so there's some antigen driving them. They respond to something, and we just haven't been able to find out what they respond to. They are pathogenic, and if we do find the cause of MS, that will almost certainly begins to cause the disease. An analogy would be herpes encephalitis; if somebody's had a herpes infection, then you take those oligoclonal bands out and you absorb them against the antigen from herpes, you remove almost all the antibodies. So they are antigen-specific in the infectious space. We've tried for years to find out what those bands react against in MS, and we haven't found it. There's several groups still working on it, and I would encourage them to continue working it, because that may be where the action is. MSDF The ORATORIO data was only begun to be analyzed very recently. You had mentioned that you were going to be doing subgroup analyses. Are there other analyses yet to come? Dr. Giovannoni I mean, the headline results are probably in main secondary outcomes, and there's less of tertiary outcomes. We need to do subgroup analyses trying to look at brain atrophy, the time course of the progressions. I'm very interested in second progressions, because I have this theory that early progressions in progressive disease is not driven by inflammation that occurs in this epoch, it's in the past; so inflammation a year or two ago is driving progression now. And so when you design these progressive trials, a large number of people progress early. And I think it's nothing to do with the trials because it's happened before the trial. So what you then need to do is look at progressions in the future to see if they flatline or stabilize. So there's lots of luck. I think we need to play around with the data, look at the first and second confirmed progressions, incorporate the brain MRI activity as the confounder. There's lots to do, tons to do. But it's good news. The excitement about those analyses are generated because you've got a positive result. MSDF Picking up on this idea that what you see today is the result of an insult that happened sometime before, what is the time course that you see using ocrelizumab in terms of benefit; is it so rapid that it questions whether what you said is what's operating? Dr. Giovannoni Yes, it's too rapid. When you see the survival curves, they go flat very early, so this is actually saying something else which is really surprising me, which is why I think some of the activity may be driven by an anti-inflammatory, because we know that anti-inflammatory drugs have an effect quite quickly. So that's why I'm suspicious that the positive result is driven by an inflammatory core of patients, and those with the more neurodegenerative or previous inflammation are unlikely to respond. That's my worry with the drug. But let's see what their subgroup analyses show. MSDF Anything we've missed or important to add on that? Dr. Giovannoni What I want to mention to people with the disease is they shouldn't overhype expectations. The simple reason is when you've got progressive disease you've already lost reserve, so that's why you're progressing. So in early relapsing disease, you make recovery from attacks because you've got ability to recover, a reserve. And so early on you stabilize or improve, and later on you slow down progression. So I'm trying to tell people with the disease if you do go into this therapy, don't expect to improve or get better. You're much more likely to progress more slowly, which you won't notice. It's hard in an individual to say they're progressing more slowly, or you'll plateau out and stabilize. I think that must be the expectation, rather than improvement. And I think we need to manage those expectations, that people may not at a personal level find a big dramatic response in terms of their disability on the drug. MSDF But this sounds like – getting back to the discussion of the Brain Health report – where you should diagnosis and treat rather quickly. At least now if someone comes in with primary-progressive, there may be at some point something to do from the start. Dr. Giovannoni Yeah. Well, it's like with any neurodegenerative disease, the sooner you treat the more you've got to protect, and the later you treat the less you've got to protect. So this would be a call to get primary-progressive disease diagnosed as soon as possible and treat as soon as possible. And if you look at the diagnostic delay in primary-progressive disease, it's probably worse than relapsing disease. People often go years before being diagnosed. So we're going to have to sharpen up the referral pathways and the diagnostic pathways in primary-progressive disease to get that timeless brain concept across there, too. [transition music] Thank you for listening to Episode Fifty-Six of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Heather McDonald curated the MSDF drug database updates. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. MSDiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller. [outro music]
Today in FirstWord:
Die Diagnose Multiple Sklerose riss Heike Röben erst den Boden unter den Füßen weg. Dann begleiteten sie Extavia, Copaxone und Rebif 44 eine ganze Zeit. Inklusive der Nebenwirkungen. Nach etwa drei Jahren Schubfreiheit entschloss sie sich gemeinsam mit ihrer Neurologin, … Weiterlesen →
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
[intro music] Hello, and welcome to Episode Twenty of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller. This week’s podcast features an interview with Dr. Jeffery Cohen about two clinical trials. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org. Genome-wide association studies are raising more questions than they answer for multiple sclerosis, according to new research. As the number of risky genetic variants grew, researchers began to wonder if many of those variants would be found in the murky waters of “noncoding DNA,” which comprises about 98% of the human genome. Those fears were confirmed in a study published last month in the journal Nature. According to the report, almost 90% of the risk variants fell within the noncoding region and 60% were found in areas known as enhancers or switches. These areas manage gene activity, though researchers are far from fully understanding how they work. While genome-wide association studies have been helpful to researchers, this study highlights that they are just a first step towards a better understanding of MS and the human genome. The International Progressive MS Alliance recently released a call for applications for their second round of grants. To go along with this announcement, Professor Alan Thompson, the head of the Alliance’s scientific steering committee, penned a post for our blog. In his post, he emphasizes the urgent need for more research into progressive MS. He notes that over one million people worldwide live with progressive MS, yet no specific treatments exist for this condition. You can read Professor Thompson’s post in the blog section of the News and Future directions tab at msdiscovery.org. To get more information about the grants from the Alliance, visit our “Funding Opportunities” section under the “Professional Resources” tab on our website. In addition to the latest funding opportunity from the Progressive MS Alliance, we also recently posted a long list of funding opportunities from the National MS Society. [transition music] Now to the interview. Dr. Jeffrey Cohen is a neurologist and director of the Mellen Center for multiple sclerosis at the Cleveland Clinic. He spoke with MSDF about two clinical trials, one examining the clinical use of stem cells, the other about a generic version of glatiramer acetate, Copaxone. Interviewer – Dan Keller First of all, what was the aim of the clinical stem cell trial and what phase was it done in? Interviewee – Jeffrey Cohen So we now have 11 medications approved to treat multiple sclerosis. They are all effective in the early, relapsing remitting stage of the disease, but there is a major unmet need for treatments that repair damage and might be effective in progressive MS. Our main goal was to explore cell-based therapies to treat multiple sclerosis, specifically to test the feasibility and safety of administering so-called mesenchymal stem cells. This was a Phase I study of mesenchymal stem cells. These are stem cells that are present in many tissues of the body. We isolated them from bone marrow which is probably the version that is the best studied previously. We grew them in the laboratory to increase their numbers, and then readministered them intravenously. We were focusing primarily on safety, as I said. We had fairly intense monitoring for any complications. Thankfully, we saw none. We also looked in a very preliminary way for benefit using clinical measures, a variety of imaging approaches and immunologic measures. MSDF What is the hypothesis here that they are doing? Do they actually get into the brain? You are infusing them IV. There is a blood-brain barrier, these are pretty big objects. Dr. Cohen There are actually a large number of studies in the laboratory and in animals that suggest that these cells have a number of properties that we think would be of use in a disease like multiple sclerosis. First of all, they seem to modulate the immune response. They dampen down inflammation. But more importantly, they appear to be able to produce a wide range of soluble factors, growth factors and other substances that we think promote repair. We think of them as the delivery system for growth factors that promote repair. We don't think that they themselves develop into brain tissue but will become neuro-cells, but rather that they create a milieu that is conducive for the natural intrinsic repair processes to remyelinate or restore neurologic function. The other property that is potentially very advantageous is that they appear to be attracted to areas of tissue damage or inflammation. They appear to have the ability to migrate within tissues, and in fact to migrate from either the cerebral spinal fluid into the brain or from the blood into the nervous system. So we think we can take advantage of that by administering them intravenously. MSDF Did you do dose-ranging here? Dr. Cohen: We did not. One of the things we learned from this study is that there are a lot of unknowns about cell-based therapies. What the appropriate dose is? Whether multiple doses are needed? What is the best route of administration? Whether there are nuances as to how you grow the cells in culture? What characteristics you want to augment? Dose-ranging in particular is something that has been very difficult to do in the field, particularly for some of these cells that are grown in culture; you usually have the dose that you have. That has been an issue that we have struggled with as have others in the field. MSDF How long did you follow these patients and what did you find? Dr. Cohen We followed them for two months prior to infusion. That is the time during which their cells were being cultured, and then for six months after infusion. So very reassuringly there were no serious or severe adverse events. In fact, there were very little, if any, side effects. Patients were not immunosuppressed. They had no premedication. The only side effect was that the culture media contains a chemical called DSMO. Some patients got a garlic taste in their mouth. If they don't like Italian food, they didn't like that. We also looked in a preliminary way for evidence of benefit with the caveat that this study was not really designed to look for benefit. We used this as an opportunity to explore a variety of measures that might show tissue repair. We saw enticing improvement in some measures in some patients, but for patients as a group, there was no clear-cut evidence of benefit. We have to be very careful how we interpret these results. MSDF Could you follow them in any way? Were they tagged or any other way that you know where they went? Dr. Cohen No. That is another aspect of the cell therapy field that is getting a lot of attention. At the moment it is largely a black box. After we administer the cells, knowing whether they survive and where they go and how long they live there. That is another line of research besides pursuing further clinical trials of these cells is also to develop methods to track them within the body. There are some promising approaches that we are in the process of developing. MSDF Now I take it these were not modified in any way, they were just cultured to multiply them? Dr. Cohen There were some growth factors in the culture media, but they were from the regulatory point of view, not very manipulated. That is the terminology that is used. That is another area of debate is some of the specifics of the culture approach, whether we should add other factors that might change the properties of the cells. Whether it is okay for them to be frozen, which we do largely for convenience because then we can schedule the infusion. Or whether they should be taken fresh from the culture and administered. There are arguments for both approaches. MSDF Many cells seem to hone right back to where they came from. Do these just go back to the bone marrow do you think, or do you think they actually went somewhere because that area needed repair? Dr. Cohen There have been a few studies in some other conditions where these cells have been given. One of the interesting properties is that you can administer these cells from another person and they are not rejected. They become, I wouldn't say the standard, but a very common treatment for what is called graft-versus-host disease, which is a very severe complication of allogeneic bone marrow transplant where the transplanted immune system attacks the recipient's body. That is where the immunomodulatory effects of mesenchymal stem cells were first observed. There are, unfortunately, have been a couple of instances where MSCs that were from another person of a different gender, were administered to someone with graft-versus-host disease who unfortunately, subsequently died of GVH. In those cases, these cells were found in a range of tissues including bone marrow. Probably a more important obstacle is for after intravenous administration is the lung because that is where the blood goes from the veins. These cells probably collect in the lung initially and then percolate out into the tissues. MSDF Do you have any concerns, any caveats about potential harms, limitations, from using this? Is it feasible on a large scale? Dr. Cohen We took a very conservative approach with the idea that there are so many unknowns of cell-based therapies, including precedence in multiple sclerosis where therapies had a different effect than we anticipated. We thought it was appropriate to take a very careful systematic approach starting with a small safety study and then building from there. At least within the limitations of our study, meaning that it was relatively short, and relatively small, we saw no indications of any complications. Some of the hypothetical concerns would be cancer. Stem cells share some properties that are similar to cancer cells, or ectopic tissue formation. Stem cells have the natural ability to develop into almost any kind of tissue. At least, presumably they could go to one tissue and develop into another type of cell, so bone within the heart or something like that. We really saw no indication of that. There are really no examples of that in the literature, but because of those sorts of concerns, we took a very careful approach. We feel comfortable now moving on to a bigger program. MSDF You had discussed some of the problems that arose using allogeneic cells. Just to clarify, this was using autologous cells? Dr. Cohen Correct. These were cells from the patient themselves. There is still some debate in the field, which approach is better. Whether to take cells from the person themselves or whether to take cells from someone who does not have the disease that you are treating. That again is an issue that has not been settled. I think some of the cell tracking we were talking about earlier may help with that. Rather than answering all of these questions one trial at a time, we may be able to adjudicate some of these questions by seeing whether cells traffic more effectively. MSDF Let’s shift to your other trial, the GATE trial using generic Copaxone. Is that available now and what was the point of the trial? Dr. Cohen The purpose of this trial was potentially to have a generic version of one of the established multiple sclerosis drugs come available. The incentive would be that presumably because of the lower development costs, that the generic version would save money for payers and for patients. The trial we just completed was of a generic version of glatiramer acetate, Copaxone, one of the initial drugs approved to treat MS, a drug that we have a great deal of experience with. It has established efficacy and a known good safety profile. This study tested a generic version of that with the intent of showing that it had equivalent efficacy, in this case, as tested by MRI and had equivalent safety and tolerability. MSDF These were all patients with relapsing, remitting MS? You had, what, about 735? Dr. Cohen Correct. This was in a patient population with relapsing, remitting MS; the population for which Copaxone is approved. MSDF What were the interventions, the test group? Dr. Cohen There were three groups in this trial. One group was treated with generic glatiramer acetate. One group was treated with the brand Copaxone and then there was also a small placebo group to demonstrate what is called study assay sensitivity. The purpose of which was to show for the trial overall that the generic glatiramer acetate is equivalent to the brand-name, the reference drug as it is called, but also that within this trial with this population, that both drugs were effective. MSDF Where was this done, and is that ethical? Dr. Cohen One of the things we have encountered increasingly in developing multiple sclerosis drugs is that there are ethical and practical issues to including placebo groups. At this point it has become extremely difficult to include a placebo group in a large Phase III study that goes on for several years. In this case, this was a short trial, with the advantage of using MRI as the endpoint. It was conducted to some extent in North America, but primarily in Eastern Europe and other countries where unfortunately, multiple sclerosis treatments are not as available. MSDF What did you find? Dr. Cohen The study was successful. It showed equivalent efficacy as measured by gadolinium-enhanced MRI, and also showed equivalent safety and tolerability as measured by adverse events and injection site tolerability. MSDF What would this mean for patients if someone brought out a generic? Dr. Cohen The hope would be, is that if this drug is approved, that it would be less expensive. Multiple sclerosis is an expensive disease to care for and a great part of that cost is medication costs. So the hope would be that this would be less expensive. The other caveat is that complicated molecules such as Copaxone are difficult to replicate. In addition to very extensive chemical and biophysical analyses, that is why a trial was conducted, because of the feeling that it would only be with clinical data that we could…we assure ourselves that this was in fact similar to Copaxone. MSDF I would take it, that this would only apply to the generic you tested. I mean generics have a certain tolerance level margin compared to the approved brand, so not all generics are the same. Dr. Cohen That is correct. It is actually quite tricky to develop a generic of a complicated molecule, either a complex mixture such as glatiramer acetate or a so-called biological like a monoclonal antibody. Each one has to be tested one at a time. MSDF Anything important that we have missed, or to add? Dr. Cohen This trial was designed with the assistance of, and discussions with EMA, the European Regulatory Agency. It has been somewhat more difficult in the United States. The FDA is still somewhat unclear on their policies and the procedures for testing complex generics and biosimilars. The status of this trial in the United States is still somewhat uncertain. MSDF Very good. Thank you. Dr. Cohen Thank you. [transition music] Thank you for listening to Episode Twenty of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. [outro music]
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Er medicinen til sclerosepatienter overhovedet god, og på hvilket grundlag træffer du og neurologen det rigtige valg? Hvorfor anbefales Rebif, Copaxone, Avonex og lign. stadig, selvom man har vidst i 4 år, at det ikke virker? Rix har mange provokerende spørgsmål og oplysninger fra bagsædet af denne Hyrevogn. Udsendelsen er både lang og stoffet indviklet, men uhyre relevant. Scleroseforeningen burde ifølge Rix undersøge to ting: - hvordan er sygdomsudviklingen hos de patienter som fravælger medicin? - er der overhovedet dokumentation for at de nye mediciner er bedre, eller bruger man stadig “den gamle” fremskrivningsmodel? Links til de undersøgelser der er nævnt i udsendelsen: https://bitly.com/bundles/o_l428721pu/2
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Peter på 38 og far til to er overbevist om at han har sclerose. I to år har han kæmpet for at få en diagnose. Lægesystemet har nærmest opgivet, men Peter er sikker på at det ikke er noget psykisk. Kan kroppen virkelig lave så overbevisende symptomer? Internettet har været en stor hjælp for Peter, men er det måske også for stor viden som spænder ben i mødet med systemet? Hør bl.a.: - kan man bilde sig alt ind? - hvad kunne du ønske for dig selv? - er dit liv sat på pause? Den problematiske ventetid mellem det første symptom og den endelige diagnose, kan være ligeså svær at tackle, som den første tid efter en alvorlig diagnose. Forskellen er den, at med en diagnose i hånden bliver man taget alvorligt, og pludselig er der masser af hjælp at hente fra systemet og fra ens pårørende. Hvorimod rollen som hypokonder er meget svær at blive sat i og at leve med. Hør også hvorfor Rix er skiftet fra Avonex til Copaxone, og hvad Rix pod har på programmet til efteråret. ... Dette podcast er publiceret med hjælp fra PodConsult.dk og Hindenburg.
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