New evidence offers some reassurance on inflammatory bowel disease risk with IL-17 inhibitors in hidradenitis suppurativa, but researchers say dermatologists should still take a gastrointestinal history and monitor for symptoms.
IL-17 inhibitors do not appear to significantly increase the risk of inflammatory bowel disease in patients with hidradenitis suppurativa, according to a new systematic review and meta-analysis.
The findings may provide some reassurance for dermatologists using the increasingly important drug class in moderate-to-severe HS.
However, the researchers cautioned that the small number of IBD events and inconsistent reporting meant the risk could not be ruled out.
“In this systematic review and meta-analysis, IBD events during IL-17 inhibitor therapy for HS were uncommon, with higher incidence rates in nonrandomised studies compared with RCTs, although events remained rare overall,” the researchers wrote.
“In a systematic review of IL-17 inhibitor-associated IBD not specific to HS, the median (range) time to onset of gastrointestinal symptoms was 2.9 (0.5-48.0) months, with most cases occurring within the first six months of therapy.
“Combined with our findings, these data suggest that the period of greatest risk may be during the first few months of treatment, although IBD can develop at any point during IL-17 inhibitor therapy.”
The analysis, published this month in JAMA Dermatology, included 24 studies comprising 10 randomised clinical trials, 11 nonrandomised studies, and three case reports, that examined IBD outcomes among patients with HS treated with IL-17 inhibitors.
Across the 10 RCTs, six of 2572 patients receiving an IL-17 inhibitor developed new-onset IBD during the placebo-controlled period to week 16, an incidence of 0.23%. There were no cases among 1066 patients receiving placebo.
The difference was not statistically significant, with a risk difference of 0.002 (95% CI −0.003 to 0.007).
Four of the six events occurred in patients receiving bimekizumab and two in those receiving secukinumab. No IBD events were reported through week 16 with sonelokimab or izokibep.
The picture was somewhat different outside the tightly controlled trial setting.
Seven new-onset IBD events occurred among 469 patients in nonrandomised studies, giving a crude incidence of 1.49%. The pooled incidence was 3.9% (95% CI 2.3%-6.5%).
The researchers said the higher rate in observational studies could reflect broader inclusion criteria, longer follow-up, and less stringent exclusion of people with previous IBD.
RCTs may also underestimate rare adverse events because they tended to be shorter and excluded higher-risk patients, they said.
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The distinction is particularly relevant in HS because patients already have an increased background risk of IBD, making it difficult to establish whether IL-17 blockade causes disease or unmasks an underlying predisposition.
That question has taken on greater clinical importance as targeting the IL-17 pathway has become an established treatment strategy for moderate-to-severe HS. Secukinumab targets IL-17A, while bimekizumab inhibits both IL-17A and IL-17F.
Concerns about IBD have nevertheless persisted. IL-17 has a role in maintaining intestinal epithelial barrier integrity, and previous studies have raised signals for new or worsening IBD with IL-17 inhibition. Current expert recommendations advise against the drugs in patients with concomitant active IBD.
Across the RCTs, long-term extension studies, and nonrandomised studies included in the new analysis, researchers identified 17 new-onset IBD cases and four flares. Seven events occurred by week 16, eight between weeks 16 and 52, and three after week 52, while timing was unavailable for three.
The researchers said the findings supported a low absolute risk of IBD with IL-17 inhibitor treatment in HS but did not justify abandoning clinical vigilance.
For patients without known IBD, they recommended taking a thorough gastrointestinal history before starting an IL-17 inhibitor and monitoring for gastrointestinal symptoms during treatment.
The evidence also remained limited by the rarity of events, inconsistent documentation of baseline personal and family IBD history, differences in follow-up and dosing, and the predominance of adult patients, the researchers said.
“In this systematic review and meta-analysis, IBD events observed during IL-17 inhibitor therapy for HS were rare in clinical trials as well as nonrandomised studies,” they concluded.
“Although the absolute risk appears low, interpretation is constrained by the low events and inconsistent reporting of IBD outcomes and baseline status.
“Improved standardisation in reporting of IBD across larger trials and studies in the community setting is needed to better estimate risk and strengthen the interpretation of safety data.”
