Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

客观的：很少有真实世界的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。本研究调查了报告流行率并评估了 IL-17 抑制剂相关 IBD 事件的临床特征和管理。

方法：我们使用美国 FDA 不良事件报告系统数据库并检索了 2015 年至 2022 年关于 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，还收集了 2015 年至 2022 年 11 月 30 日关于 IL-17 抑制剂诱导的 IBD 的病例报告和病例系列，用于回顾性分析。

结果：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 例涉及苏金单抗（SEC），36 例涉及依克珠单抗（IXE），4 例涉及布达单抗（BRO） ). SEC 和 IXE 观察到总 IBD 事件的统计显着报告率（ROR = 2.13, 95% CI [1.96-2.30] 和 ROR = 2.79, 95% CI [2.39-3.27]），而 BRO 没有触发安全信号。二十九项研究，其中包括 34 个病例，在 SEC (79.4%) 和 IXE (20.6%) 治疗后显示出 IBD 的证据。中位年龄为 42 岁；典型的初始症状包括腹泻（90.9%）、腹痛（57.6%）、血性腹泻（51.5%）和发烧（36.4%）。IBD 症状发作的中位时间为 2.9 个月。部分病例伴有白细胞（WBC）计数（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 抑制剂加上皮质类固醇和 TNF 拮抗剂治疗，无论是单一疗法还是联合疗法，都可能导致临床完全缓解。停用 IL-17 抑制剂后至缓解的中位时间为 4 周。

结论：IL-17 抑制剂治疗与 IBD 和结肠炎的恶化和新发有关。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。