Deng Zhenzhen, Wang Shengfeng, Wu Cuifang, Wang Chunjiang
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Front Pharmacol. 2023 Mar 23;14:1124628. doi: 10.3389/fphar.2023.1124628. eCollection 2023.
Few real-world studies have shown clear association between interleukin (IL)-17 inhibitors and inflammatory bowel disease (IBD) onset. This study investigated the reporting prevalence and evaluated the clinical features and management of IL-17 inhibitor-related IBD events. We used the US FDA Adverse Event Reporting System database and retrieved data, from 2015 to 2022, on IL-17 inhibitors to identify gastrointestinal inflammatory events and conduct disproportionality analyses by estimating the reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs). Furthermore, case reports and case series, from 2015 to 30 November 2022, on IBD induced by IL-17 inhibitors were collected for retrospective analysis. A total of 388 cases of primary suspected IL-17 inhibitor-associated gastrointestinal events were reported (268 IBD and 120 colitis), including 348 cases involving secukinumab (SEC), 36 cases involving ixekizumab (IXE), and 4 cases involving brodalumab (BRO). Statistically significant reporting rates of total IBD events were observed for SEC and IXE (ROR = 2.13, 95% CI [1.96-2.30] and ROR = 2.79, 95% CI [2.39-3.27], respectively), whereas BRO did not trigger a safety signal. Twenty-nine studies, which included 34 cases, showed evidence of IBD, following SEC (79.4%) and IXE (20.6%) treatment. The median age was 42 years; typical initial symptoms included diarrhea (90.9%), abdominal pain (57.6%), bloody diarrhea (51.5%), and fever (36.4%). The median time to onset of IBD symptoms was 2.9 months. Some cases were accompanied by elevated white blood cell (WBC) count (87.5%), erythrocyte sedimentation rate (ESR; 85.7%), C-reactive protein (CRP; 100%), and fecal calprotectin (FC; 100%). Cessation of IL-17 inhibitors plus treatment with corticosteroids and TNF antagonists, as either monotherapy or in combination, could lead to complete clinical remission. The median time to remission after IL-17 inhibitor discontinuation was 4 weeks. IL-17 inhibitor treatment is associated with exacerbation and new onset of IBD and colitis. Obtaining a detailed patient history before initiation of treatment and monitoring gastrointestinal symptoms and intestinal inflammatory biomarkers during IL-17 inhibitor treatment is important for safe use of these drugs.
很少有真实世界研究表明白细胞介素（IL）-17抑制剂与炎症性肠病（IBD）发病之间存在明确关联。本研究调查了报告患病率，并评估了IL-17抑制剂相关IBD事件的临床特征及管理情况。我们使用美国食品药品监督管理局（FDA）不良事件报告系统数据库，检索2015年至2022年期间关于IL-17抑制剂的数据，以识别胃肠道炎症事件，并通过估计报告比值比（ROR）和相应的95%置信区间（CI）进行不成比例分析。此外，收集了2015年至2022年11月30日期间关于IL-17抑制剂诱发IBD的病例报告和病例系列进行回顾性分析。共报告了388例原发性疑似IL-17抑制剂相关胃肠道事件（268例IBD和120例结肠炎），其中348例涉及司库奇尤单抗（SEC），36例涉及依奇珠单抗（IXE），4例涉及布罗达单抗（BRO）。观察到SEC和IXE的IBD事件总报告率具有统计学意义（ROR分别为2.13，95%CI[1.96 - 2.30]和ROR为2.79，95%CI[2.39 - 3.27]），而BRO未引发安全信号。29项研究（包括34例病例）显示，在接受SEC（79.4%）和IXE（20.6%）治疗后出现IBD证据。中位年龄为42岁；典型的初始症状包括腹泻（90.9%）、腹痛（57.6%）、便血（51.5%）和发热（36.4%）。IBD症状出现的中位时间为2.9个月。部分病例伴有白细胞（WBC）计数升高（87.5%）、红细胞沉降率（ESR；85.7%）、C反应蛋白（CRP；100%）和粪便钙卫蛋白（FC；100%）升高。停用IL-17抑制剂并加用皮质类固醇和TNF拮抗剂进行单一或联合治疗可导致临床完全缓解。停用IL-17抑制剂后缓解的中位时间为4周。IL-17抑制剂治疗与IBD和结肠炎的加重及新发有关。在开始治疗前获取详细的患者病史，并在IL-17抑制剂治疗期间监测胃肠道症状和肠道炎症生物标志物，对于安全使用这些药物很重要。
