A Low Risk of Inflammatory Bowel Disease with IL-17 Inhibition Save

Inhibitors of interleukin-17 (IL-17) have proven to be effective in spondyloarthritis and psoriatic disease but not rheumatoid arthritis or inflammatory bowel disease (IBD).  More importantly, there have been reports of either colitis onset or worsening concurrent with either of the new IL-17 inhibitors, ixekizumab (IXE) and secukinumab (SEC). 

A recent analysis of the IXE database and 7 randomized controlled and uncontrolled trials sought to report adjudicated IBD cases (Crohn's disease [CD] and ulcerative colitis [UC]) in patients exposed to ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A.

With 4209 patients (6480 patient-exposure years) were exposed to ixekizumab. There were 19 cases of suspected CD or UC; and all 19 were adjudicated as definite/probable IBD (CD, N = 7, incidence rate = 1.1/1000 patient-exposure years; UC, N = 12, incidence rate = 1.9/1000 patient-exposure years).

Also in the trials there were 16 patients with reported IBD history; 12 of these havenot had an IBD treatment-emergent AE/serious AE to date.

A similar analysis was reported Dr. Atul Deodhar at the 2016 ACR meeting in Washington, DC (Abstract #962).

Dr. Deodhar presented data from trials of 3430, 974, and 571 patients taking secukinumab for psoriasis, PsA, and AS, respectively. The exposure adjusted incidence rates for CD were 0.11, 0.07 and  0.77 per 1000 pt-yrs in the Pso, PsA and AS trials respectively. The exposure adjusted incidence rates for UC were 0.15, 0.14 and  0.29 per 1000 pt-yrs in the Pso, PsA and AS trials respectively. Overall, there was no dose dependency with respect to the incidence of CD or UC with secukinumab, and no pattern in time-to-onset; suggesting either no or a very low risk of such events. 

The SEC product label states, "Caution should be used when prescribing COSENTYX to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in COSENTYX treated patients during clinical trials." New onset inflammatory bowel disease cases occurred in clinical trials wherein patients received secukinumab.

 Overall, the risk of CD and UC with IL-17 inhibition are quite uncommon (<1%).