IL-17 inhibitor-associated inflammatory bowel disease: A study based on literature and database analysis

Abstract

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.

The Role of Interleukin 23/17 Axis in Psoriasis Management: A Comprehensive Review of Clinical Trials

“… 124 However, a database analysis by Deng et al, using the US FDA Adverse Event Reporting System database from 2015 to 2022, identified a significant reporting rate of IBD events among patients treated with secukinumab (ROR = 2.13, 95% CI [1.96–2.30]) and ixekizumab (ROR = 2.79, 95% CI [2.39–3.27]), while brodalumab did not trigger a safety signal (ROR = 1.48, 95% CI [0.48–4.6]). 125 In clinical trials for Crohn’s disease (CD), both secukinumab and brodalumab failed to demonstrate clinical benefits and were associated with an increased number of cases of worsening CD in patients with active CD compared with placebo. 126 , 127 Although a low incidence rate of developing new-onset IBD has been reported with anti-IL17 drugs, exacerbating pre-existing IBD is more common.…”

The Potential Role of Vitamin E and the Mechanism in the Prevention and Treatment of Inflammatory Bowel Disease

“…IL-2 controls intestinal epithelial cell proliferation and cell death by regulating the p52-SHCA and JAK3 signaling pathways, which are critical for maintaining mucosal homeostasis after injury repair [ 87 ]. IL-17 plays multiple roles in IBD, including promoting inflammation, affecting intestinal epithelial cells, activating other immune cells, and impairing the integrity of the intestinal mucosal barrier, which affect the development and severity of the disease [ 88 ]. Elevated levels of IL-17 have been detected in patients with autoimmune diseases, such as IBD [ 89 ].…”

Immunogenicity and Loss of Effectiveness of Biologic Therapy for Inflammatory Bowel Disease Patients Due to Anti-Drug Antibody Development

“…The FDA-approved for psoriasis IL-17 inhibitors, Cosentyx (secukinumab), Taltz (ixekizumab), and Siliq (brodalumab), can also lose their efficacy due to loss of response [ 67 , 68 ]. However, recently, an IL-17 inhibitor-associated IND was described [ 69 ].…”