Podcasts about il 17a

In this special live episode of Derms and Conditions, recorded at the Fall Clinical Dermatology 2024 Meeting, host Dr James Q. Del Rosso welcomes Dr April Armstrong, chief of dermatology at UCLA, to discuss key highlights from the conference. Together, they cover the latest in psoriasis treatments, promising developments for vitiligo, advances in hidradenitis suppurativa, and much more. The discussion kicks off with psoriasis, where exciting progress in oral TYK2, IL-23, and IL-17A inhibitors is providing potential for effective, safe options for moderate-to-severe cases. For atopic dermatitis, they review the recent approval of lebrikizumab and the real-world efficacy of tralokinumab for head and neck involvement. They also spotlight OX40/OX40 ligand inhibitors—amlitelimab and rocatinlimab—as promising long-acting treatments currently in development. In prurigo nodularis, the newly approved nemolizumab, an IL-31 inhibitor, offers antifibrotic benefits and has notably not shown evidence of conjunctivitis risk seen with other biologics. For vitiligo, BET inhibitors are creating new opportunities by targeting epigenomics, and several JAK inhibitors are pending phase 3 data. For hidradenitis suppurativa, focus has shifted from TNF inhibitors to IL-17 inhibitors like secukinumab, with bimekizumab and oral JAK inhibitors, including povarcitinib, in late-stage development. They round out the episode with chronic hand eczema, where topical ruxolitinib and delgocitinib—a pan-JAK inhibitor recently approved in Europe—show encouraging results. Tune in to the full episode for a full recap of these developments and other breakthroughs from the Fall Clinical Dermatology 2024 Meeting!

In this episode of Derms and Conditions, Andy Blauvelt, MD, joins James Q. Del Rosso, DO, to discuss IL-17 inhibition, with a focus on bimekizumab as a treatment for psoriasis. Bimekizumab is unique for inhibiting both IL-17A and IL-17F, demonstrating higher efficacy and a favorable safety profile. Dr Blauvelt highlights the drug's mechanism of action and covers its approval process, global use, and notable data. He emphasizes its efficacy in achieving Psoriasis Area Severity Index 100 (PASI 100) clearance. The pair discusses bimekizumab's dosing schedule, with an induction dosing period of once a month for 16 weeks followed by maintenance dosing every 8 weeks, a unique feature compared with other IL-17 blockers. Dr Blauvelt emphasizes bimekizumab's exceptional efficacy, with rapid and sustained results, reaching close to 60% of patients achieving PASI 100 after a single dose and around 70% within a year. The discussion includes comparisons with other IL-17 blockers, addressing the drug's suitability for different patient profiles. Safety considerations, such as oral candidiasis, are explored, with Dr Blauvelt providing insights into managing these side effects. The conversation delves into additional areas of interest, such as ongoing studies for psoriatic arthritis (PsA) and hidradenitis suppurativa (HS). Regarding safety, they touch on topics like suicidal ideation and liver enzyme elevations. Dr Blauvelt emphasizes the importance of understanding the baseline risks associated with mental health issues in patients with psoriasis. The FDA's cautious approach is acknowledged, and Dr Blauvelt provides context, comparing bimekizumab with other biologics in terms of suicidal ideation data. In summary, Dr Blauvelt expresses enthusiasm for bimekizumab as a new and highly effective option for patients with psoriasis, citing its remarkable efficacy and potential future indications for PsA and HS. The episode concludes with a discussion on scalp psoriasis and bimekizumab's positive impact on treating this condition.

In episode 65 of Derms and Conditions, our host, James Q Del Rosso, DO, chats with Ted Rosen, MD, Professor of Dermatology at Baylor College of Medicine and Chief of Dermatology Service at Michael E. DeBakey Veterans Affairs Medical Center, to discuss new developments in psoriasis treatment. They begin by discussing the current psoriasis treatment landscape and the perception that with effective biologics now on the market, there are no longer any unmet needs in psoriasis treatment. They reflect on the importance of having a variety of treatment options with differing mechanisms of action, which can address variability in patient response. They highlight the novel mechanism of action of bimekizumab, which provides dual inhibition of both IL-17A and IL-17F. The pair then discuss the relationship between IL-17s and candidiasis, noting that while there is a broad spectrum of risk, it is usually minimal and manageable, typically presenting as oral thrush rather than serious systemic infections. Dr Rosen discusses how he counsels his patients about the increased risk of candidiasis when on an IL-17A-F blocker and the importance of balancing risk with the potential benefits. They also delve into the data on bimekizumab, highlighting the favorable PASI 75 results seen at 4 weeks and how it compared to adalimumab, ustekinumab, and secukinumab in pivotal studies. Dr Rosen also discusses how the patient conversation can differ when counseling a patient on an IL-23 blocker compared to a drug with a simplified dosing regimen with an early onset of action. The pair concludes by discussing the dosing regimen for bimekizumab, noting that it's possible to reduce injection frequency after the initial 16 weeks of treatment and still sustain the same level of efficacy. They also discuss evidence that may suggest adjustments to the bimekizumab dosing regimen may lower the risk of candidiasis. Tune in to this episode to learn more about bimekizumab and its impact on the psoriasis treatment landscape!

Summary: Check out our free downloads at nascentmc.com: Implementing AMA Style – 8 Things to Get Right in Your Next Project Needs Assessments – 7 Essentials for Getting Funded Working With Your Medical Writer – 8 Ways to Get the Most out of Them See the full write ups for today's episode at nascentmc.com/podcast   Here are the highlights: Pembrolizumab (Keytruda) has received FDA approval for the treatment of metastatic biliary tract cancer, both in combination with chemotherapy and as a monotherapy. The approval is based on the positive outcomes of the KEYNOTE-966 trial, where patients receiving pembrolizumab plus chemotherapy demonstrated a statistically significant improvement in overall survival compared to those receiving a placebo with chemotherapy. Common adverse reactions included hematologic abnormalities, pyrexia, fatigue, cholangitis, and hepatic enzyme elevations. Approval was granted to Merck. Secukinumab (Cosentyx) has gained FDA approval for the treatment of moderate-to-severe hidradenitis suppurativa (HS), making it the first FDA-approved IL-17A inhibitor for this condition. Approval is based on results from the SUNSHINE and SUNRISE trials, showing significant improvements in response rates in HS patients treated with secukinumab compared to placebo. Ustekinumab-auub (Wezlana) has been granted FDA approval as an interchangeable biosimilar for Stelara, offering treatment options for multiple inflammatory diseases. It is indicated for moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis in adult patients, as well as pediatric patients with plaque psoriasis and psoriatic arthritis. Vonoprazan (Voquezna) has received FDA approval for the treatment of erosive esophagitis (GERD). As a potent potassium-competitive acid blocker (PCAB), it offers an alternative to proton pump inhibitors (PPIs). Approval is based on the PHALCON-EE study, where vonoprazan demonstrated noninferiority to lansoprazole in healing GERD. Abatacept (Orencia) has been expanded for use in pediatric patients aged 2 years and older to treat psoriatic arthritis. Originally approved for rheumatoid arthritis in adults in 2005, abatacept was also approved for adult psoriatic arthritis in 2017. Exa-cel, a CRISPR-based therapy developed by CRISPR Therapeutics and Vertex, is under FDA review for sickle cell disease. The advisory panel has found it safe for clinical use, with potential approval expected in December. Exa-cel aims to alleviate sickle cell symptoms through gene editing technology Intro and outro music Garden Of Love by Pk jazz Collective  

Go online to PeerView.com/MYV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Hidradenitis suppurativa (HS) is a chronic and recurrent inflammatory dermatologic condition that can take a long time to diagnose because of its relative rarity and long list of differential diagnoses. In the meantime, the pain and embarrassment caused by discharge and disfiguration severely decrease the quality of life for people who are impacted. Fortunately, there are a number of biologic therapies that are approved to treat HS or are in Phase 2 and 3 trials, such as inhibitors of IL-1, IL-17F and IL-17A. This activity is designed to reduce the time to diagnosis, educate clinicians on the burden their patients face, and understand the need for emerging therapies with greater efficacy. Two faculty experts will walk you through HS management and treatment protocols, with a focus on improving your knowledge and competence to incorporate new and emerging therapies into the management of this complex disease. Upon completion of this activity, participants should be better able to: Identify signs, symptoms, and diagnostic challenges to make a timely and accurate diagnosis of hidradenitis suppurativa; Describe the burdens of disease and impact on quality of life for patients with hidradenitis suppurativa; Recognize the limitations of current therapies for hidradenitis suppurativa; and Apply clinical safety and efficacy data on emerging novel treatments for patients with hidradenitis suppurativa

Go online to PeerView.com/MYV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Hidradenitis suppurativa (HS) is a chronic and recurrent inflammatory dermatologic condition that can take a long time to diagnose because of its relative rarity and long list of differential diagnoses. In the meantime, the pain and embarrassment caused by discharge and disfiguration severely decrease the quality of life for people who are impacted. Fortunately, there are a number of biologic therapies that are approved to treat HS or are in Phase 2 and 3 trials, such as inhibitors of IL-1, IL-17F and IL-17A. This activity is designed to reduce the time to diagnosis, educate clinicians on the burden their patients face, and understand the need for emerging therapies with greater efficacy. Two faculty experts will walk you through HS management and treatment protocols, with a focus on improving your knowledge and competence to incorporate new and emerging therapies into the management of this complex disease. Upon completion of this activity, participants should be better able to: Identify signs, symptoms, and diagnostic challenges to make a timely and accurate diagnosis of hidradenitis suppurativa; Describe the burdens of disease and impact on quality of life for patients with hidradenitis suppurativa; Recognize the limitations of current therapies for hidradenitis suppurativa; and Apply clinical safety and efficacy data on emerging novel treatments for patients with hidradenitis suppurativa

Go online to PeerView.com/MYV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Hidradenitis suppurativa (HS) is a chronic and recurrent inflammatory dermatologic condition that can take a long time to diagnose because of its relative rarity and long list of differential diagnoses. In the meantime, the pain and embarrassment caused by discharge and disfiguration severely decrease the quality of life for people who are impacted. Fortunately, there are a number of biologic therapies that are approved to treat HS or are in Phase 2 and 3 trials, such as inhibitors of IL-1, IL-17F and IL-17A. This activity is designed to reduce the time to diagnosis, educate clinicians on the burden their patients face, and understand the need for emerging therapies with greater efficacy. Two faculty experts will walk you through HS management and treatment protocols, with a focus on improving your knowledge and competence to incorporate new and emerging therapies into the management of this complex disease. Upon completion of this activity, participants should be better able to: Identify signs, symptoms, and diagnostic challenges to make a timely and accurate diagnosis of hidradenitis suppurativa; Describe the burdens of disease and impact on quality of life for patients with hidradenitis suppurativa; Recognize the limitations of current therapies for hidradenitis suppurativa; and Apply clinical safety and efficacy data on emerging novel treatments for patients with hidradenitis suppurativa

Go online to PeerView.com/MYV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Hidradenitis suppurativa (HS) is a chronic and recurrent inflammatory dermatologic condition that can take a long time to diagnose because of its relative rarity and long list of differential diagnoses. In the meantime, the pain and embarrassment caused by discharge and disfiguration severely decrease the quality of life for people who are impacted. Fortunately, there are a number of biologic therapies that are approved to treat HS or are in Phase 2 and 3 trials, such as inhibitors of IL-1, IL-17F and IL-17A. This activity is designed to reduce the time to diagnosis, educate clinicians on the burden their patients face, and understand the need for emerging therapies with greater efficacy. Two faculty experts will walk you through HS management and treatment protocols, with a focus on improving your knowledge and competence to incorporate new and emerging therapies into the management of this complex disease. Upon completion of this activity, participants should be better able to: Identify signs, symptoms, and diagnostic challenges to make a timely and accurate diagnosis of hidradenitis suppurativa; Describe the burdens of disease and impact on quality of life for patients with hidradenitis suppurativa; Recognize the limitations of current therapies for hidradenitis suppurativa; and Apply clinical safety and efficacy data on emerging novel treatments for patients with hidradenitis suppurativa

Go online to PeerView.com/MYV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Hidradenitis suppurativa (HS) is a chronic and recurrent inflammatory dermatologic condition that can take a long time to diagnose because of its relative rarity and long list of differential diagnoses. In the meantime, the pain and embarrassment caused by discharge and disfiguration severely decrease the quality of life for people who are impacted. Fortunately, there are a number of biologic therapies that are approved to treat HS or are in Phase 2 and 3 trials, such as inhibitors of IL-1, IL-17F and IL-17A. This activity is designed to reduce the time to diagnosis, educate clinicians on the burden their patients face, and understand the need for emerging therapies with greater efficacy. Two faculty experts will walk you through HS management and treatment protocols, with a focus on improving your knowledge and competence to incorporate new and emerging therapies into the management of this complex disease. Upon completion of this activity, participants should be better able to: Identify signs, symptoms, and diagnostic challenges to make a timely and accurate diagnosis of hidradenitis suppurativa; Describe the burdens of disease and impact on quality of life for patients with hidradenitis suppurativa; Recognize the limitations of current therapies for hidradenitis suppurativa; and Apply clinical safety and efficacy data on emerging novel treatments for patients with hidradenitis suppurativa

Go online to PeerView.com/MYV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Hidradenitis suppurativa (HS) is a chronic and recurrent inflammatory dermatologic condition that can take a long time to diagnose because of its relative rarity and long list of differential diagnoses. In the meantime, the pain and embarrassment caused by discharge and disfiguration severely decrease the quality of life for people who are impacted. Fortunately, there are a number of biologic therapies that are approved to treat HS or are in Phase 2 and 3 trials, such as inhibitors of IL-1, IL-17F and IL-17A. This activity is designed to reduce the time to diagnosis, educate clinicians on the burden their patients face, and understand the need for emerging therapies with greater efficacy. Two faculty experts will walk you through HS management and treatment protocols, with a focus on improving your knowledge and competence to incorporate new and emerging therapies into the management of this complex disease. Upon completion of this activity, participants should be better able to: Identify signs, symptoms, and diagnostic challenges to make a timely and accurate diagnosis of hidradenitis suppurativa; Describe the burdens of disease and impact on quality of life for patients with hidradenitis suppurativa; Recognize the limitations of current therapies for hidradenitis suppurativa; and Apply clinical safety and efficacy data on emerging novel treatments for patients with hidradenitis suppurativa

Join Professor Philip Mease and Dr Frank Behrens as they discuss the latest top research in PsA. In this edition, our Steering Committee members look at two key papers published in December 2022. The first of our papers discusses the latest trial of a novel scoring system for inflammation and tissue damage, whilst the second paper compares adjunctive therapy usage in patients treated with IL-17A inhibitors.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.18.520949v1?rss=1 Authors: Wang, Y., Kim, S. H., Klein, M. E., Chen, J., Gu, E., Smith, S. B., Bortsov, A., Slade, G. D., Zhang, X., Nackley, A. G. Abstract: Chronic primary pain conditions (CPPCs) affect over 100 million people, predominantly women. Yet, they remain ineffectively treated due, in large part, to lack of valid animal models with translational relevance. Here, we characterized a novel mouse model of CPPCs that integrated clinically-relevant genetic (catechol-o-methyltransferase; COMT knockdown) and environmental (stress and minor injury) factors. Compared to wildtype mice, COMT+/- mice undergoing the repeated swim stress and molar extraction surgery intervention exhibited pronounced multi-site body pain and depressive-like behavior lasting more than 3 months. The COMT+/- mice undergoing the intervention also exhibited enhanced activity of primary afferent DRG nociceptors innervating hindpaw and back sites and increased plasma levels of norepinephrine and the pro-inflammatory cytokines IL-6 and IL-17A. Notably, the pain and depressive-like behavior was of greater magnitude and longer duration (lasting at least 12 months) in females compared to males. Further, increases in anxiety-like behavior and IL-6 levels were female-specific. Intervention-induced body pain and nociception in COMT+/- mice was blocked by a beta-3 adrenergic antagonist, demonstrating predictive validity. Finally, the effect of COMT genotype x stress interactions on pain and IL-6 and IL-17A levels was observed in our clinical CPPC case-control cohort, demonstrating construct validity. Thus, our novel mouse model reliably recapitulates clinically- and biologically-relevant features of CPPCs and can be further implemented to test underlying mechanisms and discover new therapeutics. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

FDA 批准卡那单抗用于治疗成人Still病Lancet 苏金单抗与阿达木单抗治疗银屑病关节炎的头对头比较Arthri & Rheumatol重组腺苷脱氨酶可改善系统性硬化症模型的纤维化卡那单抗（canakinumab）上周一的心脏科专题中，我们聊到了冠心病的抗炎治疗最新进展，目前研究热点集中在IL-1β单克隆抗体卡那单抗和秋水仙碱。今天我们来聊一聊卡那单抗在免疫科中的应用。卡那单抗（canakinumab）最初于2009年被FDA批准用于治疗Cryopyrin相关周期性综合征（CAPS）、全身型幼年特发性关节炎以及三种少见的周期性发热综合征；2020年6月，卡那单抗被FDA批准用于治疗成人Still病。《卡那单抗用于治疗成人Still病以减少关节炎的表现：2期临床试验》Annals of Rheumatic Diseases，2020年8月 (1)这项多中心、双盲、随机、安慰剂对照试验，旨在评价其治疗成人Still病的有效性和安全性。研究纳入19名多关节受累的成人Still病患者，随机给予卡那单抗和安慰剂治疗。基线时，卡那单抗组和安慰剂组的平均疾病活动评分为5.4和5.3。在卡那单抗组中，61%的患者达到30%应答率，50%的患者达到50%应答率，28%的患者达到70%应答率；而对照组仅为20%、6.7%和0%（p=0.033，0.009和0.049)。卡那单抗组的两名患者经历了严重的不良事件。结论：卡那单抗治疗可改善多项成人Still病的疗效指标。银屑病性关节炎银屑病关节炎（psoriatic arthritis，PsA）是一种与银屑病有关的炎症性肌肉骨骼疾病。主要表现为受累关节疼痛和僵硬，可同时累及周围关节和中轴关节，常呈非对称性分布。70%的关节炎就诊时有银屑病病史，80-90%伴有甲病变。实验室检查没有特征性的变化，类风湿因子（RF）、抗核抗体（ANA）和抗瓜氨酸肽抗体（ACPA）大多呈阴性。《荟萃分析：银屑病关节炎关节外表现的患病率》Rheumatology，2020年9月 (2)研究的目的是评价银屑病关节炎关节外症状的流行情况（肌腱炎、指炎、指甲疾病、葡萄膜炎和炎症性肠病），及其对纵向疾病结局的影响。研究纳入65项研究，共计163 299例银屑病关节炎患者。在进行报道的文献中，肌腱炎平均发病率为30%，指炎平均发病率为25%，甲疾病发病率为60%，葡萄膜炎为3.2%，炎症性肠病3.3%。其中，合并指炎的患者影像学进展的可能性增加。结论：银屑病关节炎患者中，常合并肌腱炎、指炎和甲病；而葡萄膜炎和炎症性肠病不常见。《真实世界：银屑病或银屑病关节炎患者严重感染的风险》Annals of Rheumatic Diseases，2020年2月 (3)研究的目的是使用IL-17、IL-12/23或肿瘤坏死因子（TNF）抑制剂，是否与银屑病或银屑病关节炎患者严重感染风险的增加有关。研究共包括11560个新的治疗事件，9264人年的随访。研究共发现190例严重感染（占治疗期的2%），IL-17和TNF抑制剂的感染发生率相似，而IL-12/23抑制剂则明显降低（风险比0.59）。在曾经使用过生物制剂的患者中，各组感染风险无差异。结论：相对于TNF和IL-17抑制剂，IL-12/23抑制剂可以降低银屑病或银屑病关节炎患者的严重感染的风险。《纵向队列研究：银屑病性关节炎的DAPSA、颈动脉斑块和心血管事件》Annals of Rheumatic Diseases，2020年11月 (4)研究的目的是评价反映银屑病关节炎炎症成分的银屑病关节炎的疾病活动评分（DAPSA）是否能够预测心血管事件，而不依赖于传统的心血管危险因素和亚临床颈动脉粥样硬化。研究纳入189例银屑病关节炎患者，平均年龄48.9岁。平均9.9年的随访后，较高的银屑病关节炎的疾病活动评分与心血管事件的风险增加显著相关（风险比 1.04， p=0.009），在多变量模型中调整所有心血管风险后，这种关联仍然有统计学意义。亚组分析中，调整其他心血管风险后，颈动脉斑块与发生CV事件的风险增加显著相关（风险比 3.42）。结论：较高的DAPSA和CP的存在可以独立预测银屑病关节炎患者的心血管事件事件，这种风险不依赖于传统的心血管疾病风险。小羽点评：银屑病性关节炎不仅累及皮肤、关节，还可能增加感染和心血管疾病的发生风险，在临床实践中，需要对银屑病关节炎的患者进行多个系统的功能进行跟踪和随访。银屑病关节炎的治疗银屑病关节炎中，外周关节炎常使用NSAID治疗；若效果不佳，常采用传统改变病情的抗风湿药物（DMARD），如甲氨蝶呤（MTX）、来氟米特（LEF）；若多个关节侵蚀及功能受限，建议使用生物性DMARD，如TNF抑制剂为一线治疗（依那西普、阿达木单抗、英夫利西单抗、塞妥珠单抗和戈利木单抗）。一种TNF抑制剂无效时，可换用另一种TNF抑制剂；两种TNF抑制剂无效时，可使用IL-17抑制剂（苏金单抗、依奇珠单抗）、IL-12/23抑制剂（优特克单抗）、T细胞共刺激调节因子（阿巴西普）、JAK抑制剂（托法替尼）。累及骶髂关节和脊柱关节、附着点炎时，通常不推荐使用传统DMARD。银屑病关节炎患者一般应避免使用糖皮质激素，因为可能增加红皮病或脓疱型银屑病的几率。《回顾性队列研究：传统合成抗风湿药治疗银屑病性关节炎中，单药保留甲氨蝶呤优于柳氮磺胺吡啶》Rheumatology，2020年8月 (5)比较传统合成抗风湿药物的疗效和使用时间的研究有限，此研究的目的是比较一线传统合成抗风湿药物单药治疗的银屑病关节炎的药物保留和药物保留的预测因子。文章回顾性的研究了首次使用传统抗风湿药物作为单一药物治疗银屑病关节炎的187例患者，主要终点是治疗失败、停止用药或添加另一个抗风湿药物的时间。患者中单药使用甲氨蝶呤共163人，单药使用柳氮磺胺吡啶共21人，平均药物保留事件为31.8个月。其中甲氨蝶呤平均使用34.5个月，柳氮磺胺吡啶平均使用12.0个月（P =0.016）。使用甲氨蝶呤的患者中，随着年龄增长药物保留率逐渐增加。治疗失败的主要原因是无效(52%)和副作用(28%)。结论：在临床实践中，甲氨蝶呤单药治疗银屑病关节炎优于柳氮磺胺吡啶。《GO-DACT研究：治疗银屑病关节炎患者的指炎方面，戈利木单抗联合甲氨蝶呤优于单用甲氨蝶呤》Annals of Rheumatic Diseases，2020年4月 (6)戈利木单抗是一种抗肿瘤坏死因子α单抗，研究的目的是评价戈利木单抗联合甲氨碘呤和单用甲氨蝶呤治疗银屑病性关节炎指炎的疗效。这个多中心、随机、双盲、安慰剂对照、平行设计的3b期试验中，银屑病关节炎伴有活动性指炎的患者被分配到戈利木单抗或安慰剂组，两者均与甲氨蝶呤联合使用。24周后，与甲氨蝶呤单药治疗相比，戈利木单抗联合甲氨蝶呤显著改善指炎的临床症状（指炎严重程度评分变化分别为5和2，p = 0.026）。联合治疗组的指炎严重程度评分改善50%或70%的患者和Leeds指炎指数改善20%、50%或70%的患者比例显著高于单用甲氨蝶呤的患者。结论：戈利木单抗联合甲氨蝶呤作为一线生物抗风湿治疗银屑病指炎优于甲氨蝶呤单药治疗。《荟萃分析：生物制剂对银屑病关节炎患者外周关节影像学进展的影响》Rheumatology，2020年11月 (7)研究的目的是确定生物制剂在预防银屑病关节炎患者、外周关节影像学进展中的有效性。研究包括11项临床试验，涉及5382名患者，9种药物和18种治疗方法。与安慰剂相比，接受生物制剂的患者更有可能实现影像学无进展（优势比2.40，其中TNF抑制剂的优势比 2.94，IL抑制剂的优势比 2.15，阿巴西普的优势比 1.54）。生物制剂显著降低了外周关节影像学进展的风险（影像学进展评分平均下降-2.16，其中TNF抑制剂下降 -2.82，IL抑制剂下降 -1.60，阿巴西普下降 -0.40。生物制剂联合甲氨蝶呤的方案，并不优于单一生物制剂治疗的效果；尤特克单抗和苏金单抗的疗效，不受先前抗TNK治疗的影响。结论：与安慰剂相比，生物制剂可能在骨侵蚀和关节间隙狭窄方面延缓银屑病关节炎患者的影像学进展。甲氨蝶呤似乎没有额外的获益；先前的抗肿瘤坏死因子治疗似乎不会影响IL抑制剂的治疗效果。上一次的节目介绍了IL-17抑制剂（苏金单抗、依奇珠单抗）最近刚刚被FDA批准用于治疗中轴型脊柱关节炎，今天来和大家聊一聊IL-17A单抗在银屑病关节炎中的应用，以及比较这两个药物和肿瘤坏死因子抑制剂阿达木单抗的头对头研究。《Future 5研究：苏金单抗治疗银屑病性关节炎的3期研究结果》Rheumatology，2020年6月 (8)研究目的是评估苏金单抗治疗银屑病性关节炎52周后患者的影像学进展。纳入的银屑病性关节炎参与者，既往没有治疗过、或者TNF-α抑制剂无效，被随机分入苏金单抗 300mg组、150mg组、150mg无负荷给药组或安慰剂组，前4周q1w负荷给药，4周后q4w给药。其中300mg组有91.8%的患者52周后，没有出现影像学进展；在150mg组和150mg无负荷给药组中，这里比例分别是85.2%和87.2%。苏金单抗 300mg组、150mg组和150mg无负荷给药组中，影像学vdH-mTSS评分的随机斜率为-0.18、0.11和-0.20。临床疗效持续稳定，52周内没有报告新的或意料之外的安全事件。结论：苏金单抗 300mg、150mg和150mg无负荷剂量组，治疗银屑病性关节炎显示出持续稳定的低进展率。《SPIRIT-P1研究：依奇珠单抗治疗活动性银屑病关节炎患者的III期临床试验3年结果》Rheumatology，2020年2月 (9)研究的目的是评估长达156周的依奇珠单抗（IL-17A单抗）治疗银屑病关节炎的安全性和有效性。银屑病关节炎患者被随机分配到安慰剂组、阿达木单抗或依奇珠单抗q2w或q4w组。在第24周时，阿达木单抗和安慰剂组的患者被重新随机分配到依奇珠单抗q2w或q4w组，并继续延长治疗至第156周，共243例患者完成了为期3年的研究。依奇珠单抗q2w组患者治疗紧急和严重不良事件的发生率分别为38.0%和5.2%，依奇珠单抗q4w组患者为38.1%和8.0%。156周时，两组患者ACR响应≥20%的比例占69.8%和62.5%；响应≥50%的比例为51.8%和56.1%，响应≥70%的比例为33.4%和43.8%。银屑病面积和严重程度指数（PASI）缓解75%的占（63.5%和69.1）；缓解90%的展51.2%和64.5；缓解100%的占43.6%和60.5%。直至156周，在q2w组中的61%和q4w组中的71%的患者，影像学进展得到抑制。结论：依奇珠单抗治疗156周后，其安全性与之前的报道保持一致，并且观察到银屑病关节炎患者症状和体征的持续改善，包括影像学进展率持续较低。《EXCEED研究：头对头比较苏金单抗与阿达木单抗治疗银屑病关节炎疗效的3b期试验》Lancet，2020年5月 (10)EXCEED研究评估了苏金单抗与阿达木单抗作为一线生物单药治疗活动性银屑病关节炎患者的安全性和有效性。这个平行、双盲、多中心、主动对照的3b阶段的研究，招募18岁以上的、活动性银屑病关节炎患者，主要终点是52周时ACR反应标准至少改善20%（ACR20）。研究过程中853例患者完成了52周的研究，研究结束后，苏金单抗组14%和阿达木单抗组24%的患者选择停止使用研究中的治疗方案。第52周时，67%的苏金单抗组患者和62%的阿达木单抗组患者达到治疗的主要终点，两组间无统计学差异。苏金单抗组2%和阿达木单抗组1%的患者出现严重感染，苏金单抗出现一例与研究药物无关的死亡，其他的安全性与之前报道一致。结论：苏金单抗与阿达木单抗的疗效没有统计学差异，但是苏金单抗的治疗保留率更高。《SPIRIT研究：头对头比较依奇珠单抗和阿达单抗治疗银屑病关节炎的疗效和安全性》Annals of Rheumatic Diseases，2020年7月 (11)SPIRIT研究头对头的比较了依奇珠单抗（IL-17A单抗）和阿达单抗治疗银屑病关节炎的有效性和安全性。 研究纳入566例银屑病关节炎的患者，将患者随机分为依奇珠单抗和阿达单抗治疗组，评价标准是24周和52周时，患者ACR反应标准改善50%（ACR50）和银屑病面积和严重度评分改善100%（PASI100）。52周时，依奇珠单抗治疗组中同时达到ACR50和PASI100的患者的比例显著高于阿达木单抗 (39% vs 26%， p

FDA 批准卡那单抗用于治疗成人Still病Lancet 苏金单抗与阿达木单抗治疗银屑病关节炎的头对头比较Arthri & Rheumatol重组腺苷脱氨酶可改善系统性硬化症模型的纤维化卡那单抗（canakinumab）上周一的心脏科专题中，我们聊到了冠心病的抗炎治疗最新进展，目前研究热点集中在IL-1β单克隆抗体卡那单抗和秋水仙碱。今天我们来聊一聊卡那单抗在免疫科中的应用。卡那单抗（canakinumab）最初于2009年被FDA批准用于治疗Cryopyrin相关周期性综合征（CAPS）、全身型幼年特发性关节炎以及三种少见的周期性发热综合征；2020年6月，卡那单抗被FDA批准用于治疗成人Still病。《卡那单抗用于治疗成人Still病以减少关节炎的表现：2期临床试验》Annals of Rheumatic Diseases，2020年8月 (1)这项多中心、双盲、随机、安慰剂对照试验，旨在评价其治疗成人Still病的有效性和安全性。研究纳入19名多关节受累的成人Still病患者，随机给予卡那单抗和安慰剂治疗。基线时，卡那单抗组和安慰剂组的平均疾病活动评分为5.4和5.3。在卡那单抗组中，61%的患者达到30%应答率，50%的患者达到50%应答率，28%的患者达到70%应答率；而对照组仅为20%、6.7%和0%（p=0.033，0.009和0.049)。卡那单抗组的两名患者经历了严重的不良事件。结论：卡那单抗治疗可改善多项成人Still病的疗效指标。银屑病性关节炎银屑病关节炎（psoriatic arthritis，PsA）是一种与银屑病有关的炎症性肌肉骨骼疾病。主要表现为受累关节疼痛和僵硬，可同时累及周围关节和中轴关节，常呈非对称性分布。70%的关节炎就诊时有银屑病病史，80-90%伴有甲病变。实验室检查没有特征性的变化，类风湿因子（RF）、抗核抗体（ANA）和抗瓜氨酸肽抗体（ACPA）大多呈阴性。《荟萃分析：银屑病关节炎关节外表现的患病率》Rheumatology，2020年9月 (2)研究的目的是评价银屑病关节炎关节外症状的流行情况（肌腱炎、指炎、指甲疾病、葡萄膜炎和炎症性肠病），及其对纵向疾病结局的影响。研究纳入65项研究，共计163 299例银屑病关节炎患者。在进行报道的文献中，肌腱炎平均发病率为30%，指炎平均发病率为25%，甲疾病发病率为60%，葡萄膜炎为3.2%，炎症性肠病3.3%。其中，合并指炎的患者影像学进展的可能性增加。结论：银屑病关节炎患者中，常合并肌腱炎、指炎和甲病；而葡萄膜炎和炎症性肠病不常见。《真实世界：银屑病或银屑病关节炎患者严重感染的风险》Annals of Rheumatic Diseases，2020年2月 (3)研究的目的是使用IL-17、IL-12/23或肿瘤坏死因子（TNF）抑制剂，是否与银屑病或银屑病关节炎患者严重感染风险的增加有关。研究共包括11560个新的治疗事件，9264人年的随访。研究共发现190例严重感染（占治疗期的2%），IL-17和TNF抑制剂的感染发生率相似，而IL-12/23抑制剂则明显降低（风险比0.59）。在曾经使用过生物制剂的患者中，各组感染风险无差异。结论：相对于TNF和IL-17抑制剂，IL-12/23抑制剂可以降低银屑病或银屑病关节炎患者的严重感染的风险。《纵向队列研究：银屑病性关节炎的DAPSA、颈动脉斑块和心血管事件》Annals of Rheumatic Diseases，2020年11月 (4)研究的目的是评价反映银屑病关节炎炎症成分的银屑病关节炎的疾病活动评分（DAPSA）是否能够预测心血管事件，而不依赖于传统的心血管危险因素和亚临床颈动脉粥样硬化。研究纳入189例银屑病关节炎患者，平均年龄48.9岁。平均9.9年的随访后，较高的银屑病关节炎的疾病活动评分与心血管事件的风险增加显著相关（风险比 1.04， p=0.009），在多变量模型中调整所有心血管风险后，这种关联仍然有统计学意义。亚组分析中，调整其他心血管风险后，颈动脉斑块与发生CV事件的风险增加显著相关（风险比 3.42）。结论：较高的DAPSA和CP的存在可以独立预测银屑病关节炎患者的心血管事件事件，这种风险不依赖于传统的心血管疾病风险。小羽点评：银屑病性关节炎不仅累及皮肤、关节，还可能增加感染和心血管疾病的发生风险，在临床实践中，需要对银屑病关节炎的患者进行多个系统的功能进行跟踪和随访。银屑病关节炎的治疗银屑病关节炎中，外周关节炎常使用NSAID治疗；若效果不佳，常采用传统改变病情的抗风湿药物（DMARD），如甲氨蝶呤（MTX）、来氟米特（LEF）；若多个关节侵蚀及功能受限，建议使用生物性DMARD，如TNF抑制剂为一线治疗（依那西普、阿达木单抗、英夫利西单抗、塞妥珠单抗和戈利木单抗）。一种TNF抑制剂无效时，可换用另一种TNF抑制剂；两种TNF抑制剂无效时，可使用IL-17抑制剂（苏金单抗、依奇珠单抗）、IL-12/23抑制剂（优特克单抗）、T细胞共刺激调节因子（阿巴西普）、JAK抑制剂（托法替尼）。累及骶髂关节和脊柱关节、附着点炎时，通常不推荐使用传统DMARD。银屑病关节炎患者一般应避免使用糖皮质激素，因为可能增加红皮病或脓疱型银屑病的几率。《回顾性队列研究：传统合成抗风湿药治疗银屑病性关节炎中，单药保留甲氨蝶呤优于柳氮磺胺吡啶》Rheumatology，2020年8月 (5)比较传统合成抗风湿药物的疗效和使用时间的研究有限，此研究的目的是比较一线传统合成抗风湿药物单药治疗的银屑病关节炎的药物保留和药物保留的预测因子。文章回顾性的研究了首次使用传统抗风湿药物作为单一药物治疗银屑病关节炎的187例患者，主要终点是治疗失败、停止用药或添加另一个抗风湿药物的时间。患者中单药使用甲氨蝶呤共163人，单药使用柳氮磺胺吡啶共21人，平均药物保留事件为31.8个月。其中甲氨蝶呤平均使用34.5个月，柳氮磺胺吡啶平均使用12.0个月（P =0.016）。使用甲氨蝶呤的患者中，随着年龄增长药物保留率逐渐增加。治疗失败的主要原因是无效(52%)和副作用(28%)。结论：在临床实践中，甲氨蝶呤单药治疗银屑病关节炎优于柳氮磺胺吡啶。《GO-DACT研究：治疗银屑病关节炎患者的指炎方面，戈利木单抗联合甲氨蝶呤优于单用甲氨蝶呤》Annals of Rheumatic Diseases，2020年4月 (6)戈利木单抗是一种抗肿瘤坏死因子α单抗，研究的目的是评价戈利木单抗联合甲氨碘呤和单用甲氨蝶呤治疗银屑病性关节炎指炎的疗效。这个多中心、随机、双盲、安慰剂对照、平行设计的3b期试验中，银屑病关节炎伴有活动性指炎的患者被分配到戈利木单抗或安慰剂组，两者均与甲氨蝶呤联合使用。24周后，与甲氨蝶呤单药治疗相比，戈利木单抗联合甲氨蝶呤显著改善指炎的临床症状（指炎严重程度评分变化分别为5和2，p = 0.026）。联合治疗组的指炎严重程度评分改善50%或70%的患者和Leeds指炎指数改善20%、50%或70%的患者比例显著高于单用甲氨蝶呤的患者。结论：戈利木单抗联合甲氨蝶呤作为一线生物抗风湿治疗银屑病指炎优于甲氨蝶呤单药治疗。《荟萃分析：生物制剂对银屑病关节炎患者外周关节影像学进展的影响》Rheumatology，2020年11月 (7)研究的目的是确定生物制剂在预防银屑病关节炎患者、外周关节影像学进展中的有效性。研究包括11项临床试验，涉及5382名患者，9种药物和18种治疗方法。与安慰剂相比，接受生物制剂的患者更有可能实现影像学无进展（优势比2.40，其中TNF抑制剂的优势比 2.94，IL抑制剂的优势比 2.15，阿巴西普的优势比 1.54）。生物制剂显著降低了外周关节影像学进展的风险（影像学进展评分平均下降-2.16，其中TNF抑制剂下降 -2.82，IL抑制剂下降 -1.60，阿巴西普下降 -0.40。生物制剂联合甲氨蝶呤的方案，并不优于单一生物制剂治疗的效果；尤特克单抗和苏金单抗的疗效，不受先前抗TNK治疗的影响。结论：与安慰剂相比，生物制剂可能在骨侵蚀和关节间隙狭窄方面延缓银屑病关节炎患者的影像学进展。甲氨蝶呤似乎没有额外的获益；先前的抗肿瘤坏死因子治疗似乎不会影响IL抑制剂的治疗效果。上一次的节目介绍了IL-17抑制剂（苏金单抗、依奇珠单抗）最近刚刚被FDA批准用于治疗中轴型脊柱关节炎，今天来和大家聊一聊IL-17A单抗在银屑病关节炎中的应用，以及比较这两个药物和肿瘤坏死因子抑制剂阿达木单抗的头对头研究。《Future 5研究：苏金单抗治疗银屑病性关节炎的3期研究结果》Rheumatology，2020年6月 (8)研究目的是评估苏金单抗治疗银屑病性关节炎52周后患者的影像学进展。纳入的银屑病性关节炎参与者，既往没有治疗过、或者TNF-α抑制剂无效，被随机分入苏金单抗 300mg组、150mg组、150mg无负荷给药组或安慰剂组，前4周q1w负荷给药，4周后q4w给药。其中300mg组有91.8%的患者52周后，没有出现影像学进展；在150mg组和150mg无负荷给药组中，这里比例分别是85.2%和87.2%。苏金单抗 300mg组、150mg组和150mg无负荷给药组中，影像学vdH-mTSS评分的随机斜率为-0.18、0.11和-0.20。临床疗效持续稳定，52周内没有报告新的或意料之外的安全事件。结论：苏金单抗 300mg、150mg和150mg无负荷剂量组，治疗银屑病性关节炎显示出持续稳定的低进展率。《SPIRIT-P1研究：依奇珠单抗治疗活动性银屑病关节炎患者的III期临床试验3年结果》Rheumatology，2020年2月 (9)研究的目的是评估长达156周的依奇珠单抗（IL-17A单抗）治疗银屑病关节炎的安全性和有效性。银屑病关节炎患者被随机分配到安慰剂组、阿达木单抗或依奇珠单抗q2w或q4w组。在第24周时，阿达木单抗和安慰剂组的患者被重新随机分配到依奇珠单抗q2w或q4w组，并继续延长治疗至第156周，共243例患者完成了为期3年的研究。依奇珠单抗q2w组患者治疗紧急和严重不良事件的发生率分别为38.0%和5.2%，依奇珠单抗q4w组患者为38.1%和8.0%。156周时，两组患者ACR响应≥20%的比例占69.8%和62.5%；响应≥50%的比例为51.8%和56.1%，响应≥70%的比例为33.4%和43.8%。银屑病面积和严重程度指数（PASI）缓解75%的占（63.5%和69.1）；缓解90%的展51.2%和64.5；缓解100%的占43.6%和60.5%。直至156周，在q2w组中的61%和q4w组中的71%的患者，影像学进展得到抑制。结论：依奇珠单抗治疗156周后，其安全性与之前的报道保持一致，并且观察到银屑病关节炎患者症状和体征的持续改善，包括影像学进展率持续较低。《EXCEED研究：头对头比较苏金单抗与阿达木单抗治疗银屑病关节炎疗效的3b期试验》Lancet，2020年5月 (10)EXCEED研究评估了苏金单抗与阿达木单抗作为一线生物单药治疗活动性银屑病关节炎患者的安全性和有效性。这个平行、双盲、多中心、主动对照的3b阶段的研究，招募18岁以上的、活动性银屑病关节炎患者，主要终点是52周时ACR反应标准至少改善20%（ACR20）。研究过程中853例患者完成了52周的研究，研究结束后，苏金单抗组14%和阿达木单抗组24%的患者选择停止使用研究中的治疗方案。第52周时，67%的苏金单抗组患者和62%的阿达木单抗组患者达到治疗的主要终点，两组间无统计学差异。苏金单抗组2%和阿达木单抗组1%的患者出现严重感染，苏金单抗出现一例与研究药物无关的死亡，其他的安全性与之前报道一致。结论：苏金单抗与阿达木单抗的疗效没有统计学差异，但是苏金单抗的治疗保留率更高。《SPIRIT研究：头对头比较依奇珠单抗和阿达单抗治疗银屑病关节炎的疗效和安全性》Annals of Rheumatic Diseases，2020年7月 (11)SPIRIT研究头对头的比较了依奇珠单抗（IL-17A单抗）和阿达单抗治疗银屑病关节炎的有效性和安全性。 研究纳入566例银屑病关节炎的患者，将患者随机分为依奇珠单抗和阿达单抗治疗组，评价标准是24周和52周时，患者ACR反应标准改善50%（ACR50）和银屑病面积和严重度评分改善100%（PASI100）。52周时，依奇珠单抗治疗组中同时达到ACR50和PASI100的患者的比例显著高于阿达木单抗 (39% vs 26%， p

FDA 连续批准2个IL-17A单抗治疗中轴型脊柱关节炎Annals of Rheumatic Diseases 发表2篇真实世界的研究讨论TNF抑制剂在中轴型脊柱关节炎治疗中的疗效Science Advance 纳米颗粒包裹环孢素靶向治疗狼疮肾炎依奇珠单抗中轴型脊柱关节炎（axial spondyloarthritis，SpA）是慢性炎症性疾病，主要表现为背痛和进展性脊柱僵直。分成两种类型：影像学可见骶髂关节炎改变的称为强直性脊柱炎（ankylosing spondylitis，AS）；没有骶髂关节炎改变的称为影像学阴性的中轴型脊柱关节炎（nonradiographic axial spondyloarthritis，nr-axSpA）。常用的治疗药物包括非甾体类抗炎药和TNF-α抑制剂。依奇珠单抗（ixekizumab）是抗IL-17A的单克隆抗体，2016年被批准用于治疗银屑病和银屑病性关节炎；2020年6月适应症被扩展放射学阴性的中轴型脊椎关节炎、和强直性脊柱炎。《COAST-X研究：依奇珠单抗用于放射学阴性的中轴型脊椎关节炎的3期临床研究》Lancet，2020年1月 (1)COAST-X是一项52周、随机、双盲、安慰剂对照、平行组研究。共303名、活动性的、放射学阴性的中轴型脊椎关节炎的、对非甾体抗炎药效果不好的患者，被随机分配依奇珠单抗80mg q4w组，依奇珠单抗80mg q2w组或安慰剂组。第16周后，可根据情况开放标签。研究的主要终点设定为中轴型脊椎关节炎评估国际标准改善≥40%（ASAS40）。16周时，q4w组中35%的患者和q2w组中40%的患者病情缓解，安慰剂组仅19%。52周时，q4w组中30%的患者和q2w组中31%的患者病情缓解，安慰剂组仅13%。依奇珠单抗最常见的不良事件是鼻咽炎和注射部位反应，而且有1例出现严重感染。总的来说，三组的严重不良事件发生率都很低，没有肿瘤或死亡。结论：在治疗放射学阴性的中轴型脊椎关节炎方面，依奇珠单抗疗效优于安慰剂。《COAST-V和COAST-W研究：依奇珠单抗在治疗活动性强制性脊柱炎的有效性和安全性的3期临床研究》Annals of Rheumatology，2020年2月 (2)在2项3期临床研究中，旨在研究连续52周使用依奇珠单抗治疗活动性强制性脊柱炎的疗效和安全性，纳入研究的患者有的从未使用过生物抗风湿药（COAST-V），有的正在使用TNF抑制剂（COAST-W）。研究将患者随机分入依奇珠单抗q4w组，依奇珠单抗q2w组、安慰剂组或阿达木单抗组。在第16周时，安慰剂组和阿达木单抗组随机加用依奇珠单抗q2w或依奇珠单抗q4w，直至第52周。研究的主要终点设定为中轴型脊椎关节炎评估国际标准改善≥40%（ASAS40）。COAST-V研究中，在第16周和第52周达到ASAS40的比例分别为48%和53% （依奇珠单抗q4w），52%和51%（依奇珠单抗q2w），36%和51%（依奇珠单抗+阿达木单抗），19%和47%（依奇珠单抗+安慰剂）。COAST-W研究中，16周和52周达到ASAS40的比例分别为25%和34%（依奇珠单抗q4w），31%和31%（依奇珠单抗q2w），14%和39%（依奇珠单抗+安慰剂）。依奇珠单抗两种给药方案持续改善疾病活动度、患者身体功能、炎症的客观指标、生活质量、健康状况和整体功能达52周。依奇珠单抗52周安全性与16周的安全性一致。结论：对于未使用过生物制剂和曾经使用过TNF抑制剂的患者，依奇珠单抗的疗效从16周持续至52周。最初接受阿达木单抗治疗的患者换到依奇珠单抗后，有进一步改善。苏金单抗苏金单抗（secukinumab）是人源抗IL-17A的单克隆抗体。2015年被批准用于治疗银屑病和银屑病性关节炎；2020年6月适应症被扩展放射学阴性的中轴型脊椎关节炎。《苏金单抗治疗影像学阴性的中轴型脊椎关节炎的3期研究》Arthritis and Rheumatology，2020年8月 (3)研究旨在评估苏金单抗在治疗活动性、影像学阴性的中轴型脊椎关节炎的患者中的疗效。共555例患者，分别苏金单抗150mg负荷组，苏金单抗150mg无负荷组或安慰剂，前4周q1w负荷剂量给药，4周后q4w给药。20周后，允许切换到开放标签。研究的主要终点设定为国际中轴型脊椎关节炎评估国际标准改善≥40%（ASAS40）。16周时苏金单抗负荷组41.5%的患者，52周时非负荷组39.8%的患者出现病情缓解，安慰剂组仅为29.2%（P < 0.05)。没有新的安全发现报告。结论：苏金单抗治疗影像学阴性的中轴型脊椎关节炎优于安慰剂，疗效持续52周。中轴型脊柱关节炎中轴型脊柱关节炎的背痛的特点有：40岁以前出现背部不适、起病隐匿、随运动而改善、休息时无缓解、夜间痛。患者还可以伴有以下症状：交替性臀区疼痛、附着点炎导致的足跟痛、指炎、下肢非对称性关节炎、前葡萄膜炎（虹膜炎）、克罗恩病或溃疡性结肠炎、银屑病、疼痛对NSAID类药物反应良好、脊柱关节炎家族史。实验室检查包括HLA-B27阳性，和影像学骶髂关节炎。对于慢性背痛发病时3个月、后因无效而停用、并开始另一项抗风湿药物的患者，进行了一项回顾性队列研究。137例患者中，抗阿达木单抗抗体的存在并不能预测换用其他TNFi的药物反应性（敏感性/特异性 18%/75%），也不能预测非TNFi药物的反应性（敏感性/特异性 33%/70%）。阿达木单抗的血药浓度不能预测换用TNFi的药物反应性（敏感性/特异性 50%/52%），也不能预测非TNFi药物反应性（敏感性/特异性 32%/69%）。结论：对于抗阿达木单抗抗体或阿达木单抗血药浓度，作者无法找到二次使用TNFi或非TNFi药物反应的预测价值。《BSRBR-RA研究：抗TNF的早期反应预测长期获益》Rheumatology，2020年7月 (9)研究的目的是评估，类风湿关节炎患者在启动第一个抗TNF（TNF）的药物后，长期的疾病活动情况的轨迹。研究选取2001年至2013年首次使用抗TNF药物的类风湿关节炎患者，共14436例。类风湿关节炎活动评分的最低点出现在用药250天内。第180天时，已经出现了4种不同的、稳定的响应轨迹。55.3%的患者属于“适度”反应型；32.4%的患者属于“显著”反应型。其余的8.7%和3.6%分别符合“最大”和“最小”反应型。在2001-2008年和2010-2013年之间，达到“最大”反应的比例显著增加(P < 0.01)。结论：抗TNF药物使用6个月时，疾病活动的长期轨迹轮廓已经可以确定。大多数患者有持续的“适度”反应，维持中度的疾病活动；大约1/3的患者达到最大程度的缓解。《注册研究：一线TNF抑制剂与非TNF抑制剂生物制剂和靶向合成制剂在类风湿性关节炎患者中的疗效比较》Annals of Rheumatic Diseases，2020年7月 (10)本研究评估了TNF（TNF）抑制剂与非TNF抑制剂（生物疾病修饰抗风湿药物，bDMARDs）和靶向合成抗风湿药物（tsDMARDs）的疗效比较。TNF抑制剂治疗组和非TNF抑制剂治疗组在疗效评估方面无统计学差异。贫血的发生率上，TNF抑制剂组略优于非TNF抑制剂组（24.01 / 100人年，p=0.03)。结论：一线TNF抑制剂和一线非TNF抑制剂的疗效没有显著差异，支持指南中建议的“基于临床判断和考虑患者偏好的个体化治疗”。狼疮性肾炎《高效淋巴系统靶向纳米颗粒包裹的环孢霉素预防狼疮小鼠模型肾小球肾炎》Science Advance，2020年6月 (11)环孢素A是一种强大的免疫抑制剂，但由于其生物利用度低需要增加剂量，但大剂量又存在肾毒性，故它无法单独用于治疗系统性红斑狼疮。贝勒医学院的研究人员设计了一个以CD71为靶点的、生物可降解的聚酯纳米颗粒，直接向淋巴系统递送环孢素A。其中藤黄酸偶联纳米颗粒显著增加了纳米颗粒与CD3+或CD20+淋巴细胞以及肠道淋巴组织的结合率。在口服给药的小鼠模型中，经纳米颗粒包裹的环孢素A增加了4-18倍的淋巴给药量。环孢素A淋巴生物利用度的提高，与抗双链DNA抗体IgG滴度、血浆细胞因子和肾小球肾炎的缓解一致。结论：本研究证明了纳米颗粒增强淋巴组织靶向性的潜力。参考文献1.Deodhar A, van der Heijde D, Gensler LS, Kim TH, Maksymowych WP, Østergaard M, et al. 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Ann Rheum Dis. 2020;79(7):929-34.5.Abdelaziz MM, Gamal RM, Ismail NM, Lafy RA, Hetta HF. Diagnostic value of anti-CD74 antibodies in early and late axial spondyloarthritis and its relationship to disease activity. Rheumatology (Oxford). 2020.6.Jones GT, Dean LE, Pathan E, Hollick RJ, Macfarlane GJ. Real-world evidence of TNF inhibition in axial spondyloarthritis: can we generalise the results from clinical trials? Ann Rheum Dis. 2020;79(7):914-9.7.Koo BS, Oh JS, Park SY, Shin JH, Ahn GY, Lee S, et al. Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence. Ann Rheum Dis. 2020;79(10):1327-32.8.Ulijn E, den Broeder N, Wientjes M, van Herwaarden N, Meek I, Tweehuysen L, et al. Therapeutic drug monitoring of adalimumab in RA: no predictive value of adalimumab serum levels and anti-adalimumab antibodies for prediction of response to the next bDMARD. Ann Rheum Dis. 2020;79(7):867-73.9.Hamann PDH, Pauling JD, McHugh N, Hyrich K, Shaddick G. Early response to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA. Rheumatology (Oxford). 2020;59(7):1709-14.10.Pappas DA, St John G, Etzel CJ, Fiore S, Blachley T, Kimura T, et al. Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study. Ann Rheum Dis. 2020.11.Ganugula R, Arora M, Zou D, Agarwal SK, Mohan C, Kumar MNVR. A highly potent lymphatic system–targeting nanoparticle cyclosporine prevents glomerulonephritis in mouse model of lupus. Science Advances. 2020;6(24):eabb3900.

FDA 连续批准2个IL-17A单抗治疗中轴型脊柱关节炎Annals of Rheumatic Diseases 发表2篇真实世界的研究讨论TNF抑制剂在中轴型脊柱关节炎治疗中的疗效Science Advance 纳米颗粒包裹环孢素靶向治疗狼疮肾炎依奇珠单抗中轴型脊柱关节炎（axial spondyloarthritis，SpA）是慢性炎症性疾病，主要表现为背痛和进展性脊柱僵直。分成两种类型：影像学可见骶髂关节炎改变的称为强直性脊柱炎（ankylosing spondylitis，AS）；没有骶髂关节炎改变的称为影像学阴性的中轴型脊柱关节炎（nonradiographic axial spondyloarthritis，nr-axSpA）。常用的治疗药物包括非甾体类抗炎药和TNF-α抑制剂。依奇珠单抗（ixekizumab）是抗IL-17A的单克隆抗体，2016年被批准用于治疗银屑病和银屑病性关节炎；2020年6月适应症被扩展放射学阴性的中轴型脊椎关节炎、和强直性脊柱炎。《COAST-X研究：依奇珠单抗用于放射学阴性的中轴型脊椎关节炎的3期临床研究》Lancet，2020年1月 (1)COAST-X是一项52周、随机、双盲、安慰剂对照、平行组研究。共303名、活动性的、放射学阴性的中轴型脊椎关节炎的、对非甾体抗炎药效果不好的患者，被随机分配依奇珠单抗80mg q4w组，依奇珠单抗80mg q2w组或安慰剂组。第16周后，可根据情况开放标签。研究的主要终点设定为中轴型脊椎关节炎评估国际标准改善≥40%（ASAS40）。16周时，q4w组中35%的患者和q2w组中40%的患者病情缓解，安慰剂组仅19%。52周时，q4w组中30%的患者和q2w组中31%的患者病情缓解，安慰剂组仅13%。依奇珠单抗最常见的不良事件是鼻咽炎和注射部位反应，而且有1例出现严重感染。总的来说，三组的严重不良事件发生率都很低，没有肿瘤或死亡。结论：在治疗放射学阴性的中轴型脊椎关节炎方面，依奇珠单抗疗效优于安慰剂。《COAST-V和COAST-W研究：依奇珠单抗在治疗活动性强制性脊柱炎的有效性和安全性的3期临床研究》Annals of Rheumatology，2020年2月 (2)在2项3期临床研究中，旨在研究连续52周使用依奇珠单抗治疗活动性强制性脊柱炎的疗效和安全性，纳入研究的患者有的从未使用过生物抗风湿药（COAST-V），有的正在使用TNF抑制剂（COAST-W）。研究将患者随机分入依奇珠单抗q4w组，依奇珠单抗q2w组、安慰剂组或阿达木单抗组。在第16周时，安慰剂组和阿达木单抗组随机加用依奇珠单抗q2w或依奇珠单抗q4w，直至第52周。研究的主要终点设定为中轴型脊椎关节炎评估国际标准改善≥40%（ASAS40）。COAST-V研究中，在第16周和第52周达到ASAS40的比例分别为48%和53% （依奇珠单抗q4w），52%和51%（依奇珠单抗q2w），36%和51%（依奇珠单抗+阿达木单抗），19%和47%（依奇珠单抗+安慰剂）。COAST-W研究中，16周和52周达到ASAS40的比例分别为25%和34%（依奇珠单抗q4w），31%和31%（依奇珠单抗q2w），14%和39%（依奇珠单抗+安慰剂）。依奇珠单抗两种给药方案持续改善疾病活动度、患者身体功能、炎症的客观指标、生活质量、健康状况和整体功能达52周。依奇珠单抗52周安全性与16周的安全性一致。结论：对于未使用过生物制剂和曾经使用过TNF抑制剂的患者，依奇珠单抗的疗效从16周持续至52周。最初接受阿达木单抗治疗的患者换到依奇珠单抗后，有进一步改善。苏金单抗苏金单抗（secukinumab）是人源抗IL-17A的单克隆抗体。2015年被批准用于治疗银屑病和银屑病性关节炎；2020年6月适应症被扩展放射学阴性的中轴型脊椎关节炎。《苏金单抗治疗影像学阴性的中轴型脊椎关节炎的3期研究》Arthritis and Rheumatology，2020年8月 (3)研究旨在评估苏金单抗在治疗活动性、影像学阴性的中轴型脊椎关节炎的患者中的疗效。共555例患者，分别苏金单抗150mg负荷组，苏金单抗150mg无负荷组或安慰剂，前4周q1w负荷剂量给药，4周后q4w给药。20周后，允许切换到开放标签。研究的主要终点设定为国际中轴型脊椎关节炎评估国际标准改善≥40%（ASAS40）。16周时苏金单抗负荷组41.5%的患者，52周时非负荷组39.8%的患者出现病情缓解，安慰剂组仅为29.2%（P < 0.05)。没有新的安全发现报告。结论：苏金单抗治疗影像学阴性的中轴型脊椎关节炎优于安慰剂，疗效持续52周。中轴型脊柱关节炎中轴型脊柱关节炎的背痛的特点有：40岁以前出现背部不适、起病隐匿、随运动而改善、休息时无缓解、夜间痛。患者还可以伴有以下症状：交替性臀区疼痛、附着点炎导致的足跟痛、指炎、下肢非对称性关节炎、前葡萄膜炎（虹膜炎）、克罗恩病或溃疡性结肠炎、银屑病、疼痛对NSAID类药物反应良好、脊柱关节炎家族史。实验室检查包括HLA-B27阳性，和影像学骶髂关节炎。对于慢性背痛发病时3个月、后因无效而停用、并开始另一项抗风湿药物的患者，进行了一项回顾性队列研究。137例患者中，抗阿达木单抗抗体的存在并不能预测换用其他TNFi的药物反应性（敏感性/特异性 18%/75%），也不能预测非TNFi药物的反应性（敏感性/特异性 33%/70%）。阿达木单抗的血药浓度不能预测换用TNFi的药物反应性（敏感性/特异性 50%/52%），也不能预测非TNFi药物反应性（敏感性/特异性 32%/69%）。结论：对于抗阿达木单抗抗体或阿达木单抗血药浓度，作者无法找到二次使用TNFi或非TNFi药物反应的预测价值。《BSRBR-RA研究：抗TNF的早期反应预测长期获益》Rheumatology，2020年7月 (9)研究的目的是评估，类风湿关节炎患者在启动第一个抗TNF（TNF）的药物后，长期的疾病活动情况的轨迹。研究选取2001年至2013年首次使用抗TNF药物的类风湿关节炎患者，共14436例。类风湿关节炎活动评分的最低点出现在用药250天内。第180天时，已经出现了4种不同的、稳定的响应轨迹。55.3%的患者属于“适度”反应型；32.4%的患者属于“显著”反应型。其余的8.7%和3.6%分别符合“最大”和“最小”反应型。在2001-2008年和2010-2013年之间，达到“最大”反应的比例显著增加(P < 0.01)。结论：抗TNF药物使用6个月时，疾病活动的长期轨迹轮廓已经可以确定。大多数患者有持续的“适度”反应，维持中度的疾病活动；大约1/3的患者达到最大程度的缓解。《注册研究：一线TNF抑制剂与非TNF抑制剂生物制剂和靶向合成制剂在类风湿性关节炎患者中的疗效比较》Annals of Rheumatic Diseases，2020年7月 (10)本研究评估了TNF（TNF）抑制剂与非TNF抑制剂（生物疾病修饰抗风湿药物，bDMARDs）和靶向合成抗风湿药物（tsDMARDs）的疗效比较。TNF抑制剂治疗组和非TNF抑制剂治疗组在疗效评估方面无统计学差异。贫血的发生率上，TNF抑制剂组略优于非TNF抑制剂组（24.01 / 100人年，p=0.03)。结论：一线TNF抑制剂和一线非TNF抑制剂的疗效没有显著差异，支持指南中建议的“基于临床判断和考虑患者偏好的个体化治疗”。狼疮性肾炎《高效淋巴系统靶向纳米颗粒包裹的环孢霉素预防狼疮小鼠模型肾小球肾炎》Science Advance，2020年6月 (11)环孢素A是一种强大的免疫抑制剂，但由于其生物利用度低需要增加剂量，但大剂量又存在肾毒性，故它无法单独用于治疗系统性红斑狼疮。贝勒医学院的研究人员设计了一个以CD71为靶点的、生物可降解的聚酯纳米颗粒，直接向淋巴系统递送环孢素A。其中藤黄酸偶联纳米颗粒显著增加了纳米颗粒与CD3+或CD20+淋巴细胞以及肠道淋巴组织的结合率。在口服给药的小鼠模型中，经纳米颗粒包裹的环孢素A增加了4-18倍的淋巴给药量。环孢素A淋巴生物利用度的提高，与抗双链DNA抗体IgG滴度、血浆细胞因子和肾小球肾炎的缓解一致。结论：本研究证明了纳米颗粒增强淋巴组织靶向性的潜力。参考文献1.Deodhar A, van der Heijde D, Gensler LS, Kim TH, Maksymowych WP, Østergaard M, et al. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet. 2020;395(10217):53-64.2.Dougados M, Wei JC, Landewé R, Sieper J, Baraliakos X, Van den Bosch F, et al. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis. 2020;79(2):176-85.3.Deodhar A, Blanco R, Dokoupilová E, Hall S, Kameda H, Kivitz AJ, et al. Secukinumab improves signs and symptoms of non-radiographic axial spondyloarthritis: primary results of a randomized controlled phase III study. Arthritis Rheumatol. 2020.4.Renson T, Depicker A, De Craemer AS, Deroo L, Varkas G, de Hooge M, et al. High prevalence of spondyloarthritis-like MRI lesions in postpartum women: a prospective analysis in relation to maternal, child and birth characteristics. Ann Rheum Dis. 2020;79(7):929-34.5.Abdelaziz MM, Gamal RM, Ismail NM, Lafy RA, Hetta HF. Diagnostic value of anti-CD74 antibodies in early and late axial spondyloarthritis and its relationship to disease activity. Rheumatology (Oxford). 2020.6.Jones GT, Dean LE, Pathan E, Hollick RJ, Macfarlane GJ. Real-world evidence of TNF inhibition in axial spondyloarthritis: can we generalise the results from clinical trials? Ann Rheum Dis. 2020;79(7):914-9.7.Koo BS, Oh JS, Park SY, Shin JH, Ahn GY, Lee S, et al. Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence. Ann Rheum Dis. 2020;79(10):1327-32.8.Ulijn E, den Broeder N, Wientjes M, van Herwaarden N, Meek I, Tweehuysen L, et al. Therapeutic drug monitoring of adalimumab in RA: no predictive value of adalimumab serum levels and anti-adalimumab antibodies for prediction of response to the next bDMARD. Ann Rheum Dis. 2020;79(7):867-73.9.Hamann PDH, Pauling JD, McHugh N, Hyrich K, Shaddick G. Early response to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA. Rheumatology (Oxford). 2020;59(7):1709-14.10.Pappas DA, St John G, Etzel CJ, Fiore S, Blachley T, Kimura T, et al. Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study. Ann Rheum Dis. 2020.11.Ganugula R, Arora M, Zou D, Agarwal SK, Mohan C, Kumar MNVR. A highly potent lymphatic system–targeting nanoparticle cyclosporine prevents glomerulonephritis in mouse model of lupus. Science Advances. 2020;6(24):eabb3900.

How can you integrate decision-making resources into your clinical practice? In this resident takeover of the podcast, three dermatology residents — Dr. Daniel Mazori, Dr. Elisabeth Tracey, and Dr. Julie Croley — discuss clinical decision support tools such as scoring systems and other resources available for dermatologists. These tools should be used as a supplement, not as a substitute for one’s clinical judgment. “The optimal treatment for patients in a complex medical system requires not just coming to the correct diagnosis and using your clinical judgment to make a decision but effectively communicating that decision to the insurance companies [and] to the primary team that’s taking care of them on the inpatient service. ... Some objective data can really be useful in those situations,” advises Dr. Tracey. *   *   * Help us make this podcast better! Please take our short listener survey: https://www.surveymonkey.com/r/podcastsurveyOct2019 *   *   * We bring you the latest in dermatology news and research: 1. No tacrolimus/cancer link in atopic dermatitis in 10-year study 2. PASI-75 with ixekizumab approaches 90% in pediatric psoriasis study 3. NAM offers recommendations to fight clinician burnout *  *  *   Things you will learn in this episode: Evaluate for psoriatic arthritis with the Psoriasis Epidemiology Screening Tool (PEST). “It’s the kind of thing that I’ll use in addition to asking a patient with psoriasis questions about symptoms like joint pain and morning stiffness,” Dr. Mazori says. Consider UpToDate.com and VisualDx.com for clinical decision support, to formulate differential diagnoses, and as a resource for patient education. “The other day, I had a patient who was diagnosed with scabies,” Dr. Tracey explains. “We were counseling the patient on how to decontaminate their environment. I wanted to get the exact number of hours their belongings needed to be in a plastic bag or how to wash their clothes. So, we went on UpToDate and read it together in the clinic.” The SCORTEN system predicts hospital mortality from Stevens-Johnson syndrome/toxic epidermal necrolysis and is useful for the primary team. “I’ve found it useful ... as a measure of risk to communicate to the primary team, even the patient’s family,” Dr. Mazori says. But the SCORTEN isn’t perfect. “There are studies that have found it can overestimate or underestimate mortality,” he warns. To differentiate cellulitis from pseudocellulitis in adult patients, consider the ALT-70 score. “It gives me an objective measure of risk to communicate to the primary team in support of one diagnosis or another in addition to my clinical judgment,” advises Dr. Mazori. The Mohs Appropriate Use Criteria (AUC) helps guide decision making for Mohs micrographic surgery, but it has been scrutinized for classifying most primary superficial basal cell carcinomas as appropriate for treatment, omitting important European trials, and for having ratings that are based on expert opinion rather than evidence. The MyDermPath+ app can assist clinicians in forming differentials based on histopathologic patterns. Hosts: Elizabeth Mechcatie, Terry Rudd Guests: Daniel R. Mazori, MD (State University of New York Downstate Medical Center); Elisabeth (Libby) Tracey, MD (Cleveland Clinic Foundation); Julie Ann Amthor Croley, MD (University of Texas Medical Branch at Galveston) Show notes by: Jason Orszt, Melissa Sears, Elizabeth Mechcatie   For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgeDerm

O episódio de número 4 do Podcast Microbiando chegou para trazer as novidades da Microbiologia e Imunologia para vocês. E nele debatemos como uma população de células T, chamadas de gama delta, regulam a termogênese. Esse artigo foi publicado na revista Nature Immunology neste em 2018 e foi desenvolvido por um grupo da Universidade de Harvard nos EUA, em colaboração com a Universidade de Negev em Israel e com Trinity College na Irlanda e se chama “γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis”, algo em português como "Células T gama delta produtoras de IL-17A regulam a homeostase de células T reguladoras do tecido adiposo e a termogênese". No quadro Microlitros de Notícias: uma breve pipetada de novidades da Microbiologia e Imunologia temos algumas informações importantes sobre a Raiva; uma reportagem falando sobre o estado de dormência de algumas bactérias e a implicação em determinadas doenças; e também falaremos sobre o sistema CRISPR/Cas descoberto em alguns microrganismos e seu potencial como ferramenta de edição genética. E na Filogênia da Ciência, iremos trazer as descobertas da microbiologista Rebecca Lancefield.   Tópicos comentados nesse episódio Imunologia Células T Termogênese Tecido adiposo Gordura branca Gordura marrom Homeostase Vírus da Raiva Estado de dormência bacteriana Sistema CRISPR/Cas Rebecca Lancefield   Referências desse episódio Kohlgruber A. C. et al., γδ T cells producing IL-17A regulate adipose regulatory T cell homeostase and thermogenesis. Nat Immunol. 2018, 19:464-474. Chehimi M, Vidal H, Eljaafari A. Pathogenic Role of IL-17-Producing Immune Cells in Obesity, and Related Inflammatory Diseases. J Clin Med. 2017, 14;6(7): E68. Liang L, Hur J, Kang JY, Rhee CK, Kim YK, Lee SY. Effect of the anti-IL-17 antibody on allergic inflammation in an obesity-related asthma model. Korean J Intern Med. 2018, 19. Chen Y, Tian J, Tian X, Tang X, Rui K, Tong J, Lu L, Xu H, Wang S. Adipose tissue dendritic cells enhances inflammation by prompting the generation of Th17 cells. PLoS One. 2014, 9(3):e92450. Christine R. Fisher, Daniel G. Streicker e Matthias J. Schnell. (2018). The spread and evolution of rabies virus: conquering new frontiers. Nature Reviews MS (2018). Ministério da Saúde. Brasil tem segundo caso de pacientes que sobreviveram ao vírus da raiva humana. Protocolo para Tratamento de Raiva Humana no Brasil. 2009. Laboissiere, Paula. Pará tem 12 casos notificados de raiva humana. 2018. STUART, J. e JAY, L. Dormancy contributes to the maintenance of microbial diversity. PNAS, Novembro de 2009. BRADLEY, P. et al. The Bacterial Cytoplasm Has Glass-like Properties and Is Fluidized by Metabolic Activity. Cell, Novembro de 2013. MARTIN, G. e STEFAN, K. Mycobacterium tuberculosis: Success through dormancy. FEMS Microbiology Reviews, Maio de 2012. KOZARVOK, E. Bacterial invasion of vascular cell types: vascular infectology and atherogenesis. Future Cardiology, Janeiro de 2012. Rossi, Ciro C. ; Araujo-Alves, Amanda V. CRISPR, o sistema imune adaptativo bacteriano. Microbiologia In Foco, Soc Bras de Microbiologia, p. 15 - 18, 01 nov. 2016. Live Science. What Is CRISPR? Broad Institute. QUESTIONS AND ANSWERS ABOUT CRISPR Antonio Regalado. De Quem é a Maior Descoberta da Biotecnologia do Século? Gaudelli N. M., Komor A. C., Rees H. A., Packer M. S., Badran A. H., Bryson D. I., et al. (2017). Programmable base editing of A∙T to G∙C in genomic DNA without DNA cleavage. Nature 551, 464–471. Cox, D. B. T., Gootenberg, J. S., Abudayyeh, O. O., Franklin, B., Kellner, M. J., Joung, J., et al. (2017). RNA editing with CRISPR-Cas13. Science358, 1019–1027. Encyclopedia.com. Lancefield, Rebecca Craighill (1895-1981) Encyclopaedia Britannica. Rebecca Lancefield.   Sobre o Podcast Microbiando A ideia do Microbiando é discutir artigos científicos de ponta em tod...

Medicine Grand Rounds April 27, 2018 Daniela Čihakova, MD, PhD, D(ABMLI) Associate Professor of Immunology, Department of Pathology Johns Hopkins University School of Medicine Associate Professor, Department of Molecular Microbiology and Immunology Bloomberg School of Public Health, Johns Hopkins University Director, WHO Collaborating Center, Johns Hopkins University

Interleukin-17 (IL-17A) is a cytokine critical for the acute defence against extracellular bacterial and fungal infections. Excess production during chronic inflammation has been associated with many inflammatory and autoimmune disorders. In this podcast, the Editor-in-Chief of RMD Open Bernard Combe and Pierre Miossec (Department of Immunology and Rheumatology, University of Lyon, France) discuss a review paper about an update on IL-17A. The review concludes that the use of IL-17 inhibition in psoriatic arthritis (PsA) is easy to understand because of the role of IL-17 in bone destruction. However, the use of the same inhibitors for the treatment of ankylosing spondylitis (AS) implies another understanding. In fact, IL-17 specifically in combination with TNF, induces bone matrix formation by isolated osteoblasts. This is the case at the site of ligaments insertion, where osteoclasts are absent. Local bone formation leads to syndesmophytes. Professor Miossec also explains how these findings might impact clinical practice. For more details about this article, visit the RMD Open website: http://rmdopen.bmj.com/content/3/1/e000284.

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The parasite prophets solve the case of the Thai Man with Abdominal Distention, and discuss the finding that metastatic leishmaniasis dependent on a virus can be prevented by blocking IL-17A. Links for this episode: TWiP 27: Trematodes Leishmaniavirus and IL-17A dependent leishmaniasis (PLoS Path) Image credit Letters read on TWiP 117 This episode is sponsored by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and non­fiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/microbe and use the promo code MICROBE. This episode is also sponsored by Drobo, a family of safe, expandable, yet simple to use storage arrays. Drobos are designed to protect your important data forever. Visit www.drobo.com to learn more. Become a patron of TWiP. Case Study for TWiP 117 Woman 66 yo born in Guinea, grew up the moved to US past 10 years, just retired. Lives in Washington Heights. Mother having issues in Guinea, so went back for 3 months in 2016. Just came back a week ago, reporting headache, fever, feeling poorly. Staying in big city, with Mom (80s). Has own private toilet in nice home. No screens or bednets. Married for 40 years, recently divorces. Has had 10 children. Not sexually active. Starts with high fever, breaks, then 2 days later another for several hours, goes to ER. Given Ebola screening questions, negative, do some blood work, send her back out. 2-3 days later high fever, double vision, headache, comes to Columbia ER. No diarrhea, no urination discomfort. Has backache, feels that mouth is dry. Was admitted. Past med history: high bp, cholesterol, diabetes; not overweight; appendix out; has unknown reaction to novocaine. No smoking, drinking. Physical: 39.4 temp, 14-16 breath rate, heart rate over 100, rapid heartbeat, 2/6 systolic murmur with radiation to left carotid (flow murmur). No jugular venous distention. Abdomen right upper quadrant: slight enlargement of liver, not tender, can palpate spleen tip in left upper quadrant, slightly enlarged spleen. Normal bowel sounds, no rash. Blood: elevated white count, bands 9%. 0.1 eosinophils, platelets 79, hemoglobin 11. Bilirubin 1.5, bicarb 20, chest xray clear. Red cells: small, 79.4 mcv. Animals: don’t like animals! In middle of rainy season. Likes to walk outside in rain during day. No cats to keep out rodents. Food: all food is prepared in home. Eats all favorite foods: rice. No sick contacts, no exposure to health care setting, no bug bites.  Send your case diagnosis, questions and comments to twip@microbe.tv

Antimicrobial peptides (AMPs) are strongly expressed in lesional skin in psoriasis and play an important role as proinflammatory "alarmins" in this chronic skin disease. Vitamin D analogs like calcipotriol have antipsoriatic effects and might mediate this effect by changing AMP expression. In this study, keratinocytes in lesional psoriatic plaques showed decreased expression of the AMPs beta-defensin (HBD) 2 and HBD3 after topical treatment with calcipotriol. At the same time, calcipotriol normalized the proinflammatory cytokine milieu and decreased interleukin (IL)-17A, IL-17F and IL-8 transcript abundance in lesional psoriatic skin. In contrast, cathelicidin antimicrobial peptide expression was increased by calcipotriol while psoriasin expression remained unchanged. In cultured human epidermal keratinocytes the effect of different vitamin D analogs on the expression of AMPs was further analyzed. All vitamin D analogs tested blocked IL-17A induced HBD2 expression by increasing IkappaB-alpha protein and inhibition of NF-kappaB signaling. At the same time vitamin D analogs induced cathelicidin through activation of the vitamin D receptor and MEK/ERK signaling. These studies suggest that vitamin D analogs differentially alter AMP expression in lesional psoriatic skin and cultured keratinocytes. Balancing AMP "alarmin" expression might be a novel goal in treatment of chronic inflammatory skin diseases.