brodalumab

Brodalumab
  • 文章类型: Journal Article
    根据白细胞介素(IL)-17抑制剂的市场授权,已经报道了越来越多的IL-17抑制剂诱导的矛盾型银屑病(PsO)病例.我们的目的是介绍两例IL-17抑制剂诱导的反常性PsO,并系统地回顾类似病例的文献。总结和介绍相关数据。对先前提出的由IL-17抑制剂诱导的反常PsO病例进行了系统的文献综述。我们介绍了两名由苏金单抗(SEC)诱导的轴向脊柱关节炎(axSpA)和矛盾的PsO患者。一名患者的银屑病病变对辅助局部治疗反应良好,而另一名患者需要联合局部治疗和环孢素A才能成功治疗。SEC在这两种情况下都继续进行。我们还在文献综述中确定了35例IL-17抑制剂诱导的反常性PsO患者。最常见的矛盾PsO类型是掌足底脓疱和斑块PsO,而中位潜伏期为11周。大约三分之一的患者继续IL-17抑制剂的辅助治疗,主要是局部的,这在大多数患者中产生了令人满意的结果。几乎三分之二的患者停用了IL-17抑制剂,大多数患者转用另一种具有不同作用机制的生物制剂或开始其他全身性抗银屑病治疗,主要产生令人满意的结果。因此,IL-17抑制剂诱导的自相矛盾的PsO似乎在继续IL-17抑制剂并辅助治疗的患者和在转换为不同类别的生物制剂或开始其他全身性抗银屑病治疗时停用IL-17抑制剂的患者中反应良好.
    Following the market authorization of interleukin (IL)-17 inhibitors, a growing number of cases of IL-17 inhibitor-induced paradoxical psoriasis (PsO) have been reported. Our objectives were to present two cases of IL-17 inhibitor-induced paradoxical PsO and to systematically review the literature for similar cases, summarizing and presenting the relevant data. A systematic literature review of previously presented cases of paradoxical PsO induced by IL-17 inhibitors was conducted. We presented two patients with axial spondyloarthritis (axSpA) and paradoxical PsO induced by secukinumab (SEC). One patient\'s psoriatic lesions responded well to adjuvant topical treatment, while the other patient required a combination of topical treatment and cyclosporine Α for successful treatment. SEC was continued in both cases. We also identified 35 patients with IL-17 inhibitor-induced paradoxical PsO in the literature review. The most frequent types of paradoxical PsO were palmoplantar pustular and plaque PsO, while the median latency period was 11 weeks. Approximately one-third of patients continued IL-17 inhibitor treatment with adjunctive therapy, primarily topical, which produced satisfactory results in most patients. Almost two-thirds of the patients discontinued the IL-17 inhibitor, with the majority of patients switching to another biological agent with a different mechanism of action or initiating other systemic antipsoriatic treatments, resulting in mainly satisfactory outcomes. Therefore, paradoxical PsO induced by IL-17 inhibitors appears to respond well in both patients who continue IL-17 inhibitors with adjunctive treatment and those who discontinue IL-17 inhibitors while switching to a different class of biological agent or initiating other systemic antipsoriatic treatments.
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  • 文章类型: Review
    化脓性汗腺炎(HS)是一种慢性自身炎症性滤泡病,影响富含大汗腺的身体区域。中度至重度HS可能会严重损害患者的生活质量,这也是因为现有的治疗方法往往不能令人满意。一些证据表明,炎症细胞因子,例如肿瘤坏死因子-α(TNF-α)和白介素(IL)-17在HS的病理生理学中起关键作用。TNF-α抑制剂长期用于中度-重度形式的HS。然而,目前正在研究针对HS的几种针对IL-17亚型的单克隆抗体。我们报告了在各种TNF-α抑制剂失效后,用brodalumab治疗的50岁男性长期患有HS并伴有掌足底银屑病的病例。HS病变和患者的生活质量随着时间的推移而稳定改善,直到第136周。有趣的是,MRI评估的放射学改善证实了临床获益.我们的病例报告证明了Brodalumab在HS中的长期疗效和安全性,鼓励使用药物来抑制T辅助型17免疫轴,特别是在HS难以用TNF-α抑制剂治疗的情况下。
    Hidradenitis suppurativa (HS) is a chronic autoinflammatory follicular disease, affecting body areas that are rich in apocrine glands. Moderate-to-severe HS may severely impair patients\' quality of life also because the available therapies are often unsatisfactory. Several lines of evidence suggest that inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-17 play a pivotal role in the physiopathology of HS. TNF-α inhibitors have long been used with benefit in moderate-severe forms of HS. However, several monoclonal antibodies against IL-17 isoforms are currently being investigated for HS. We report the case of a 50-year-old man with long-standing HS and concomitant palmo-plantar psoriasis treated with brodalumab after failure of various TNF-α inhibitors. The HS lesions and the patient\'s quality of life improved steadily over time until week-136. Interestingly, the clinical benefit was confirmed by radiological improvement with MRI evaluation. Our case report demonstrates the long-term efficacy and safety of brodalumab in HS encouraging the use of drugs to inhibit the T helper-type 17 immune axis, especially in cases of HS refractory to therapy with TNF-α inhibitors.
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  • 文章类型: Review
    未经授权:脓疱型银屑病(PP)是一种罕见的银屑病亚型。总的来说,越来越多的证据-特别是对于急性全身性PP(3GPP)-支持它是具有特定致病途径的独立实体。白细胞介素(IL)-17/T辅助17(Th17)轴的参与可能在PP的病理生理中起重要作用。生物制品,通常需要达到临床缓解,改变了PP的处理方式。
    UNASSIGNED:我们为读者提供了在PP患者中使用基于抗体的靶向IL-17A疗法的所有可用证据的概述。
    UNASSIGNED:尽管这篇综述中报道的论文没有提供明确的证据(由于方法学上的限制)来支持使用IL-17抑制剂作为治疗PP的潜在一线药物,根据我们自己的经验和大多数报道的文献,靶向IL-17A,可能代表了这种特殊的银屑病临床谱中最好的治疗方法。
    Pustular psoriasis (PP) is a rare subtype of psoriasis. Overall, the growing evidence - in particular for acute generalized PP (GPP) - supports that it is a separate entity with a specific pathogenetic pathway. Interleukin (IL)-17/T-helper 17 (Th17) axis involvement may play an important role in the pathophysiology of PP. Biologicals, often required to achieve clinical remission, have changed the treatment of PP.
    We provide the reader with an overview of all the available evidence on the use of the antibody-based therapy targeting IL-17A in patients with PP.
    Although papers reported in this review do not provide definitive evidence (due to methodological limitations) to support the use of IL-17 inhibitors as potential first-line for the treatment of PP, based on our own experience and according to most of the reported literature, targeting IL-17A, may represent the best therapeutical approach in this peculiar clinical spectrum of psoriasis.
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  • 文章类型: Systematic Review
    背景:白细胞介素-17(IL-17)单克隆抗体药物在银屑病的治疗中越来越重要。但目前尚不清楚不同种族的疗效是否相同。
    目的:探讨IL-17抑制剂在白种人和亚洲人短期疗效的差异。
    方法:估计组间的合并对数风险比(logRR)。对logRR进行了荟萃回归分析,以白种人患者的比例为协变量。通过特异性IL-17抑制剂进行亚组分析。
    结果:在1,569项潜在相关研究中,纳入16项随机对照试验(RCTs).对于12周时的银屑病面积和严重程度指数75(PASI75)反应,亚洲组和高加索组的汇总logRR分别为2.81(95%CI:2.27-3.35,p<0.001)和2.93(95%CI:2.71-3.16,p<0.001),分别,表明亚洲人和白种人之间的疗效没有显着差异。荟萃回归分析未显示白种人的比例与效应大小相关(β=0.3203,p=0.334)。在亚组分析中,苏金单抗的比较结果与主要分析一致。
    结论:仅探讨了短期疗效。亚洲国家的数据有限。
    结论:IL-17抑制剂治疗银屑病的短期疗效在白种人和亚洲人之间无显著差异。
    背景:PROSPERO,标识符CRD42020201994,https://www.crd.约克。AC.英国/普华永道/。
    BACKGROUND: Interleukin-17 (IL-17) monoclonal antibody drugs have been increasingly significant in the treatment of psoriasis, but it is not clear whether the efficacy is equivalent across ethnicities.
    OBJECTIVE: To explore the differences of short-term efficacy of IL-17 inhibitors between Caucasians and Asians.
    METHODS: The pooled log risk ratio (logRR) between the groups was estimated. The meta-regression analysis on the logRR was performed, with the proportion of Caucasian patients as the covariate. The subgroup analysis was performed by specific IL-17 inhibitors.
    RESULTS: Of the 1,569 potentially relevant studies, sixteen randomized controlled trials (RCTs) were included. For the Psoriasis Area and Severity Index 75 (PASI 75) response at week 12, the pooled logRR of the Asian group and the Caucasian group was 2.81 (95% CI: 2.27-3.35, p < 0.001) and 2.93 (95% CI: 2.71-3.16, p < 0.001), respectively, indicating no significant difference of efficacy between Asians and Caucasians. The meta-regression analysis did not show an association of the proportion of Caucasians with the effect size (β = 0.3203, p = 0.334). In the subgroup analysis, the comparison results of secukinumab were consistent with the main analysis.
    CONCLUSIONS: Only the short-term efficacy was explored. The data from Asian countries were limited.
    CONCLUSIONS: The short-term efficacy of IL-17 inhibitors in the treatment of psoriasis has no significant difference between Caucasians and Asians.
    BACKGROUND: PROSPERO, identifier CRD42020201994, https://www.crd.york.ac.uk/prospero/.
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  • 文章类型: Case Reports
    完整且功能齐全的免疫系统在预防几种传染病中起着至关重要的作用。白细胞介素(IL)17显著参与口腔黏膜对多种抗原和微生物的免疫,包括白色念珠菌(CA)。在这里,我们介绍了3例与使用IL17A抑制剂治疗银屑病相关的口腔念珠菌病(OC)病例.3名牛皮癣患者用于评估与IL17A抑制剂的发作在时间上相关的广泛症状性口腔病变(两名患者为苏金单抗,一名患者为brodalumab)。临床检查显示,在红斑背景中部分可去除的白色斑块(病例#1)或弥漫性红斑病变(病例#2和3)涉及口腔粘膜的多个区域。细胞学涂片,在1号病例中进行组织病理学检查,证实了所有3例病例中OC的临床印象。所有患者均接受抗真菌治疗,临床反应满意。不建议停止抗银屑病治疗方案,但建议所有患者继续接受OC复发的监测.在过去的几年里,针对IL17的新型全身性生物制剂已被用于治疗各种免疫介导的疾病.很少有临床试验和罕见的病例报告表明,这些药物使个体处于发展念珠菌病的高风险中。我们建议使用这些药物治疗的患者应密切监测OC的发展,如果发生了,得到适当的管理。
    An intact and fully functional immune system plays a crucial role in the prevention of several infectious diseases. Interleukin (IL)17 is significantly involved in oral mucosa immunity against several antigens and microorganisms, including Candida albicans (CA). Herein, we present three cases of oral candidiasis (OC) related to the use of an IL17A inhibitor for psoriasis. Three psoriatic individuals presented for evaluation of widespread symptomatic oral lesions temporally correlated with the onset of IL17A inhibitors (secukinumab in two patients and brodalumab in one patient). Clinical examination revealed either partially removable white plaques in an erythematous background (case #1) or diffuse erythematous lesions (cases #2 and 3) involving several areas of the oral mucosa. Cytology smear, accompanied by histopathologic examination in case #1, confirmed the clinical impression of OC in all three cases. All patients received antifungal therapy with satisfactory clinical response. No discontinuation of the antipsoriatic regimen was recommended, but all patients were advised to remain under monitoring for possible OC relapses. During the last few years, new systemic biologic agents targeting IL17 have been used for the management of variable immune-mediated diseases. Few clinical trials and scarce case reports have shown that these medications place individuals at high risk of developing candidiasis. We propose that patients treated with these medications should be at close monitoring for the development of OC and, if it occurs, receive appropriate management.
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    文章类型: Journal Article
    UNASSIGNED: Interleukin (IL)-17 inhibitors are a newer class of biologic used to treat patients with moderate-to-severe plaque psoriasis and psoriatic arthritis.
    UNASSIGNED: We compared evidence-based clinical practice guidelines (CPGs) from leading dermatological organizations for the use of IL-17 inhibitors in psoriasis.
    UNASSIGNED: Guidelines from the Joint American Academy of Dermatology-National Psoriasis Foundation (AAD-NFP) Guidelines, British Association of Dermatologists guidelines (BAD), and European S3 group (ES3) were all reviewed and compared.
    UNASSIGNED: This analysis revealed significant overlap in the recommendations made by experts from each CPG. However, our review highlights differences in routine laboratory recommendations and the relative and absolute contraindications to use with IL-17 inhibitors.
    UNASSIGNED: IL-17 inhibitors are an effective treatment option for psoriasis. This analysis and review of guidelines for IL-17 inhibitor use highlights the consensus in treatment protocols and areas of disagreement between CPGs.
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  • 文章类型: Journal Article
    The IL-17 pathway is a potential therapeutic target shown to be implicated in hidradenitis suppurativa (HS), however, it remains unclear whether evidence from mechanistic studies may translate into clinical practice. This systematic review summarizes available treatment outcomes of IL-17 inhibitors in patients with HS. Embase, MEDLINE, PubMed, and clinicaltrials.gov were comprehensively searched on February 26, 2021 to include 16 original studies representing 128 patients with HS (mean age: 36.5 years; age range: 21-47 years; male: 50.0%). Treatment outcomes were reported for the following biologics: secukinumab (n = 105), brodalumab (n = 22), and ixekizumab (n = 1). Patients were classified as responders or non-responders according to achievement of a positive response/improvement based on criteria established for each included study. For secukinumab 57.1% (n = 60/105) of patients were responders in a mean response period of 16.2 weeks and 42.9% (n = 45/105) were non-responders; for brodalumab, 100.0% (n = 22/22) of patients were responders within 4.4 weeks; and the one patient treated with ixekizumab was a responder within 10 weeks. In conclusion, IL-17 inhibitors may serve as an effective therapeutic target in approximately two-thirds of patients with HS and can be considered in those who are refractory to other treatment modalities. We also stress the importance of consistent outcome measures to enhance evidence synthesis, decrease reporting bias, provide potential for future meta-analysis, and ultimately improve clinical outcomes for patients with HS.
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  • 文章类型: Journal Article
    白细胞介素17是一种促炎细胞因子,被认为在许多慢性免疫介导的疾病的免疫发病中起重要作用。白介素17抑制剂为银屑病患者提供了极好的治疗选择,银屑病关节炎,或者强直性脊柱炎.然而,白细胞介素17抑制剂已被怀疑恶化或引发新发炎症性肠病。
    进行了文献检索,直至2021年3月,以调查报告患病率,以及使用白介素17抑制剂治疗的患者的所有胃肠道不良事件的特征。纳入了106项临床随机试验,涉及40,053名患者。在暴露于白介素17抑制剂的患者中,有0.4%报告了炎症性肠病病例。其他最常见的胃肠道不良事件是腹泻(2.5%),恶心或呕吐(0.7%),和肠胃炎(0.2%)。纳入61项对照或回顾性研究,涉及16791名患者。报告了60例(0.36%)炎症性肠病病例,0.6%的患者报告了其他胃肠道不良事件。
    白细胞介素17抑制剂治疗银屑病安全有效,银屑病关节炎,强直性脊柱炎.已经报道了使用抗IL-17药物发展新发炎症性肠病或加重先前存在的炎症性肠病的低发病率。临床医生在考虑这种治疗时应该意识到这些问题的可能性。
    UNASSIGNED: Interleukin 17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of many chronic immune-mediated disorders. Interleukin 17 inhibitors provide an excellent treatment option for patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis. However, Interleukin 17 inhibitors have been suspected of worsening or triggering new-onset inflammatory bowel disease.
    UNASSIGNED: A literature search was conducted until March 2021 to investigate reporting prevalence, and characteristics of all gastroenterological adverse events in patients treated with Interleukin 17 inhibitors. One hundred and six clinical randomized trials were included, involving 40,053 patients. Inflammatory bowel disease cases were reported in 0.4% of patients exposed to Interleukin 17 inhibitors. The most frequent other gastrointestinal adverse events were diarrhea (2.5%), nausea or vomiting (0.7%), and gastroenteritis (0.2%). Sixty-one uncontrolled or retrospective studies were included, involving 16,791 patients. Sixty (0.36%) inflammatory bowel disease cases were reported, 0.6% of patients reported other gastrointestinal adverse events.
    UNASSIGNED: Interleukin 17 inhibitors are safe and effective in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Low incidence rate of developing new-onset inflammatory bowel disease or exacerbating preexisting inflammatory bowel disease with anti-IL-17 agents has been reported. Clinicians should be aware of the possibility of these concerns when considering this therapy.
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  • 文章类型: Journal Article
    The treatment of moderate to severe plaque psoriasis in patients with history of malignancy is challenging. To review the studies reporting the experience with IL-17A inhibitors in patients with psoriasis and history of malignancy; secondly, to investigate cancer recurrence in a series of patients with a prior malignancy and plaque psoriasis treated with IL-17A inhibitors. A systematic literature review and an observational retrospective analysis of patients with history of malignancy and plaque psoriasis treated with IL-17A inhibitors was performed. About 5 original articles out of 601 were retrieved, reporting a total of 10 patients with a median age of 59 years, interquartile range (IQR) 50-63. Seven patients were treated with secukinumab, one with ixekizumab and two with both sequentially. Although the stage ranged from in situ to IV stage, most of the cases were early-stage neoplasm. The IL-17A inhibitor was initiated after a median of 10 months, interquartile range (IQR) 5-30 (range 0-144) from the diagnosis of malignancy. In addition, a series of 12 patients with history of malignancy were identified from the University Hospital of Verona, including 9 cases with cancer in clinical remission and 3 with advanced disease at time of initiating IL-17 inhibitor. No malignancy recurrence was reported within a median of 12 (IQR 6-23) and 46 (IQR 36-48) months follow up in case series from literature and our experience, respectively. Data on use of IL-17A inhibitors in patients with chronic plaque psoriasis and history of malignancy are limited. Registries and proactive pharmacovigilance activities are needed to guide clinical practice.
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  • 文章类型: Journal Article
    With our aging population, an increasing number of psoriasis patients are classified as elderly. However, psoriasis treatment in older adults can be challenging, given an increased number of comorbid conditions and immunosenescence. Biologic agents present a solution to this treatment dilemma because of their high efficacy and favorable tolerability. The objective of this systematic review was to summarize the findings of clinical trial and real-world studies exploring the safety and efficacy of biologic agents in elderly patients with moderate-to-severe psoriasis. We searched MEDLINE, Embase, the Cochrane Library, and clinical trial databases. Studies analyzing biologics for psoriasis were included if elderly patients were the main population of interest or were a separate subgroup in their analysis. Eighteen articles met inclusion criteria after screening. Across all biologic classes, efficacy for biologics between nonelderly adult patient and elderly patients was similar. Adverse events (AEs) and infections occured at a similar frequency between both groups. However, serious AEs were more common in the elderly. The available literature on the safety and efficacy of biologic agents in elderly patients supports the use of these agents in this population. However, serious AEs and discontinuation due to AEs were more common in older patients. As elderly patients have a higher burden of comorbid conditions and an increased baseline vulnerability for AE, physicians should continue to be prudent in screening before initiating biologics and monitor patients more closely as AEs tend to be more severe.
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