The IBD risk among patients with hidrandentitis suppurtiva treated with IL-17 inhibitors: Low but not nothing

Interleukin (IL)-17 inhibitors such as Cosentyx (secukinumab) and Bimzelx (bimekizumab) have become mainstays of treatment of hidradenitis suppurativa. But they come with a catch, because of evidence that suggests that they might entail a risk of developing inflammatory bowel disease (IBD). But results of the review published in JAMA Dermatology earlier this month may assuage those concerns. It found no significant increase in IBD cases among patients treated with IL-17 inhibitors. The researchers left the door slightly ajar, though, noting the relatively small numbers and inconsistency of reporting of cases “limited interpretation.”

“The findings of our study support a low risk of IBD in patients with HS [hidradenitis suppurtiva] treated with IL-17 inhibitors,” wrote corresponding author Ahuva Cices, M.D., an assistant professor at the Icahn School of Medicine at Mount Sinai, and her colleagues in the discussion section of the paper. Patients with hidradenitis suppurativa can also have an IBD, and Cices noted that current guidelines say to avoid prescribing IL-17 inhibitors to patients with IBD. They recommended the clinicians get a full gastrointestinal history on patients with hidradenitis suppurativa without known IBD before starting treatment with an IL-17 inhibitor and that be monitored for gastrointestinal symptoms.

It is biologically plausible that IL-17 inhibition might lead to IBD, explain Cices and her colleagues in the introduction of the paper. IL-17 is active in the gut, contributing to antimicrobial defense and the integrity of epithelial tissue. Inhibiting the interleukin could, therefore, imperil the normal, healthy functioning of the gut and seed the occurrence of IBD.

Cices and her colleagues conducted their review in ways similar to how other researchers conduct such reviews. They sifted through the PubMed, Embase and Cochrane Center Register of Controlled Trials databases to identify studies related to hidradenitis suppurativa and IL-17 inhibitors. They organized their search into randomized clinical trials, nonrandomized trials and case reports. After applying various criteria, their review ended up including 10 randomized clinical trials, 11 nonrandomized trials and three case reports. They pooled results of the randomized clinical trials and the nonrandomized trials into two separate meta-analyses.

The randomized clinical trials meta-analysis included three trials that evaluated Bimzelx and two that evaluated Costenyx. It also included trials of evaluating two drugs that are still in development that are not on the market yet, three of Moonlake Immunotherapies’ sonelokimab and two of Affibody’s izokibep.

When Cices and her colleagues pooled the results of the randomized clinical trials together, setting week 16 as common duration, the results showed that six of the 2,572 patients with hidradenitis suppurativa treated with one of those four IL-17 inhibitors developed IBD, while none of the 1,066 randomly selected to receive the placebo did. That difference, though, did not meet the customary statistical standards for a true difference. Cices and her colleagues noted that after week 16 of the trials, between weeks 16 and 52, there were two new cases of IBD in the patients treated with Bimzelx and one new case among those treated with Cosentyx.

Collectively, the 11 nonrandomized studies included a total of 469 patients. The study durations ranged from 16 to 32 weeks, and the number of patients enrolled ranged from 5 to 132. Cices and her colleagues pointed out that most of the studies did not exclude patients with pre-existing IBD. The pooled results from the meta-analysis found a total of seven new cases of IBD, five in patients treated with Costentyx, one in a patient treated with Bimzelx and one in a patient treated with Izokibep.

Siliq (brodalumab), which is approved for plaque psoriasis but not hidradenitis suppurativa, was among the IL-I7 inhibitors evaluated in the nonrandomized trials. No patients taking Siliq developed IBD.

In two of the three case reports that Cices and her colleagues included their review, patients treated with Cosentyx developed colitis.

Cices and her colleagues commented on the pros and cons of the randomized and nonrandomized trials for painting a true picture of the risk of IBD from the IL-17 inhibition. The nonrandomized trials show a higher incidence rate but have broader exclusion criteria and less strict exclusion of patients with prior IBD. On the other hand, they said, randomized trials may underestimate the risk because they are relatively short and have criteria that might exclude patients who might be prone to developing IBD.