Biologic intolerance/failure & subsequent response

December 9, 2024

Issue 24

Clinical Question

Does prior biologic intolerance predict poor response to subsequent biologics?

Editor’s Bottom Line

Not all forms of biologic failure are equal. Non-response and intolerance should be considered differently in clinical practice and in clinical trials.

Reference

Samnani S, Wong ECL, Hamam H, et al. Outcomes of patients with prior biologic intolerance are better than those with biologic failure in clinical trials of inflammatory bowel disease. J Crohns Colitis. Epub ahead of print Sept 20, 2024. https://academic.oup.com/ecco-jcc

Synopsis

This post-hoc analysis included data from 1,178 ulcerative colitis (UC) patients and 1,439 Crohn’s disease (CD) patients in the pivotal trials for ustekinumab (UNITI and UNIFI) and vedolizumab (GEMINI-1 and GEMINI-2).

Among the UC patients, 66.8% were biologic-naïve, while 27.8% had failed to respond to one prior biologic treatment (or had lost initial response) and 5.4% could not tolerate adverse effects of a prior biologic. Among the CD patients, 39.2% were biologic-naïve, 45.2% had prior failure and 15.6% were biologic-intolerant previously.

Analysis showed that clinical and endoscopic outcomes among biologic-intolerant patients with UC were similar to those among biologic-naïve patients in the study. Biologic-intolerant UC patients were numerically but not statistically more likely than those with prior biologic failure to experience a clinical response (54.7% vs. 38.8%; adjusted Odds Ratio [aOR]: 1.87; 95% Confidence Interval [CI], 0.93–3.73). However, biologic-intolerant UC patients were both numerically and statistically more likely than those with prior biologic failure to experience clinical remission (25% vs. 11%; aOR: 2.84; 95% CI, 1.47–5.49) and endoscopic improvement (40.6% vs. 24.8%; aOR: 2.76; 95% CI, 1.28–5.94).

Among CD patients, while biologic-intolerant individuals were numerically as likely as those with prior biologic failure to experience a clinical response to the study drug (34.2% vs. 32.8%), after adjusting for potential confounders—such as disease duration, C-reactive protein, albumin, and Crohn’s Disease Activity Index scores—those with prior biologic intolerance had a higher likelihood of clinical response than those with a prior biologic failure (aOR: 1.67; 95% CI, 1.09–2.55). Multivariate analysis found the likelihood of clinical remission was statistically similar between biologic-intolerant patients and those who had failed to respond to prior treatment (aOR: 1.48; 95% CI, 0.88–2.49).

 

Details

Study Design: Post-hoc analysis of pivotal trials
Funding: Not stated
Allocation: Not applicable
Setting: Multicenter
Level of Evidence: 2a