brodalumab

Brodalumab
  • 文章类型: Journal Article
    白细胞介素-17(IL-17)抑制剂的应用,包括苏金单抗,ixekizumab,Brodalumab,还有bimekizumab,与念珠菌病的风险升高有关。这些药物会干扰IL-17通路,这对于维持粘膜屏障和协调针对念珠菌物种的免疫反应至关重要。观察数据和临床试验表明,用IL-17抑制剂治疗的个体中念珠菌病的发病率增加。Brodalumab和bimekizumab在引发念珠菌病方面比苏金单抗具有更大的风险,而关于ixekizumab的数据是模棱两可的.IL-17抑制剂的较高剂量和延长的治疗持续时间通过损害针对念珠菌物种的免疫应答而增加念珠菌病的风险。在开IL-17抑制剂之前,医疗保健专业人员应全面评估患者的病史并评估其危险因素。应对患者进行念珠菌病的体征和症状的教育,以利于早期发现和干预。未来的研究应集中在确定接受IL-17抑制剂的患者与念珠菌病相关的危险因素。需要进行前瞻性研究和长期监测,以探索特定抑制剂对念珠菌病发病率和严重程度的影响,并评估联合治疗的有效性。例如同时使用IL-17抑制剂和预防性抗真菌药物。
    The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients\' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.
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  • 文章类型: Journal Article
    白细胞介素17A(IL-17A)是IL-17细胞因子家族的主要成员,主要由T辅助17(Th17)细胞产生。其他细胞,如CD8+T细胞,γδT细胞,自然杀伤T细胞和先天淋巴样细胞也可以产生IL-17A。在健康的个体中,IL-17A具有宿主保护能力,但IL-17A的过度升高与自身免疫性疾病和癌症的发展有关。靶向IL-17A的单克隆抗体(mAb)(例如,ixekizumab和苏金单抗)或IL-17A受体(IL-17RA)(例如,brodalumab)将作为这些疾病的潜在治疗方法进行研究。目前,IL-17A靶向药物在自身免疫性疾病中的应用将为肿瘤的治疗提供新的思路,其与免疫检查点抑制剂的联合应用已成为研究热点。本文综述了IL-17A的作用机制以及抗IL-17A抗体的应用,重点介绍了IL-17A在结直肠癌(CRC)等多种肿瘤中的作用机制和治疗性阻断的研究进展,肺癌,胃癌和乳腺癌。此外,我们还包括癌症领域治疗性阻断的结果以及IL-17A信号调节的最新进展。
    Interleukin 17A (IL-17A) is a major member of the IL-17 cytokine family and is produced mainly by T helper 17 (Th17) cells. Other cells such as CD8+ T cells, γδ T cells, natural killer T cells and innate lymphoid-like cells can also produce IL-17A. In healthy individuals, IL-17A has a host-protective capacity, but excessive elevation of IL-17A is associated with the development of autoimmune diseases and cancer. Monoclonal antibodies (mAbs) targeting IL-17A (e.g., ixekizumab and secukinumab) or IL-17A receptor (IL-17RA) (e.g., brodalumab) would be investigated as potential treatments for these diseases. Currently, the application of IL-17A-targeted drugs in autoimmune diseases will provide new ideas for the treatment of tumors, and its combined application with immune checkpoint inhibitors has become a research hotspot. This article reviews the mechanism of action of IL-17A and the application of anti-IL-17A antibodies, focusing on the research progress on the mechanism of action and therapeutic blockade of IL-17A in various tumors such as colorectal cancer (CRC), lung cancer, gastric cancer and breast cancer. Moreover, we also include the results of therapeutic blockade in the field of cancer as well as recent advances in the regulation of IL-17A signaling.
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  • 文章类型: Multicenter Study
    目的:评估布罗达鲁单抗的长期疗效和安全性,完全人抗白细胞介素17受体A单克隆抗体,中轴脊柱关节炎(axSpA)患者。
    方法:在该多中心的16周双盲期间接受皮下brodalumab210mg的患者,在日本进行的第三阶段研究,在为期52周的开放标签扩展中,韩国和台湾继续如此,而接受安慰剂的患者在第16周改用brodalumab210mg。评价疗效(脊柱炎国际协会[ASAS]40和ASAS20反应率;使用C-反应蛋白[ASDAS-CRP]的强直性脊柱炎疾病活动评分相对于基线的变化)和安全性。
    结果:总体而言,145名患者(brodalumab,n=77;安慰剂,n=68)在开放标签扩展期间接受了brodalumab。ASAS40反应率(95%置信区间[CI])为56.3%(44.7%,67.3%)和57.4%(44.1%,70.0%)在brodalumab和安慰剂组中实现,分别,第68周两个治疗组在第68周达到的ASAS20反应率(95%CI)相似(brodalumab,71.3%[60.0%,80.8%];安慰剂,78.7%[66.3%,88.1%])。第68周时ASDAS-CRP的最小二乘平均变化(95%CI)提示临床上重要的改善(变化,≥1.1)在两个治疗组(brodalumab,-1.528[-1.737,-1.319];安慰剂,-1.586[-1.815,-1.357])。治疗引起的不良事件(TEAE)和药物相关TEAE的暴露校正事件发生率(每100名患者年)分别为255.9和147.9;鼻咽炎(35.6)和上呼吸道感染(14.7)是最常见的TEAE。
    结论:Brodalumab在axSpA患者68周内表现出持续疗效和一致的安全性。
    背景:ClinicalTrials.gov,https://clinicaltrials.gov,NCT02985983。
    To evaluate the long-term efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA).
    Patients receiving subcutaneous brodalumab 210 mg during the 16-week double-blind period of this multicentre, phase 3 study conducted across Japan, Korea and Taiwan continued the same during the 52-week open-label extension, whereas patients receiving placebo switched to brodalumab 210 mg at week 16. Efficacy [Assessment of SpondyloArthritis International Society (ASAS) 40 and ASAS 20 response rates; change from baseline in AS Disease Activity Score using CRP (ASDAS-CRP)] and safety were evaluated.
    Overall, 145 patients (brodalumab, n = 77; placebo, n = 68) received brodalumab during the open-label extension. ASAS 40 response rates (95% CI) of 56.3% (44.7%, 67.3%) and 57.4% (44.1%, 70.0%) were achieved in the brodalumab and placebo groups, respectively, at week 68. ASAS 20 response rates (95% CI) achieved at week 68 in both treatment groups were similar [brodalumab, 71.3% (60.0%, 80.8%); placebo, 78.7% (66.3%, 88.1%)]. The least squares mean change (95% CI) in ASDAS-CRP at week 68 suggested a clinically important improvement (change, ≥1.1) in both treatment groups [brodalumab, -1.528 (-1.737, -1.319); placebo, -1.586 (-1.815, -1.357)]. The exposure-adjusted event rates (per 100 patient-years) for treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 255.9 and 147.9, respectively; nasopharyngitis (35.6) and upper respiratory tract infection (14.7) were the most common TEAEs.
    Brodalumab demonstrated sustained efficacy and a consistent safety profile in patients with axSpA over 68 weeks.
    ClinicalTrials.gov, https://clinicaltrials.gov, NCT02985983.
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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: Journal Article
    To evaluate the therapeutic efficacy and safety of anti-IL-17 agents in the treatment of psoriasis, we performed a systemic review and meta-analysis of the relevant published clinical trials, collectively referred to as secukinumab, ixekizumab and brodalumab. 2668 patients in eight eligible trials with psoriasis were selected for the present meta-analysis. The estimated pooled PASI75, PSAI90, physician\'s global assessment (PGA; clear) showed significant improvements for psoriasis patients who received biotherapy compared with placebo. The results of headache, upper respiratory tract infection and infections demonstrated that there was no significant difference between the biotherapy and placebo groups. But the results of nasopharyngitis demonstrated that there was a significant difference for biotherapy group. The results showed that anti-IL-17 agents were effective and safe for psoriasis patients.
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