No Impact of Concomitant Medications on Efficacy and Safety of Biologics and Small Molecules for Ulcerative Colitis.

BACKGROUND & AIMS: Although participants with inflammatory bowel diseases in clinical trials of biologics and small molecule drugs (henceforth, advanced therapies) frequently receive several medications concomitantly, it is unclear how they modify treatment effect.

METHODS

Through an individual patient data pooled analysis of 10 clinical trials of advanced therapies for moderate-to-severe ulcerative colitis, we assessed whether concomitant exposure to corticosteroids, immunomodulators, mesalamine, proton pump inhibitors, histamine receptor antagonists, opiates, antidepressants, and antibiotics modified the effect of the intervention on treatment efficacy and safety outcomes, using modified Poisson regression model.

RESULTS

Of 6044 patients (4280 receiving intervention, 1764 receiving placebo), several received concomitant corticosteroids (47%), immunomodulators (28%), mesalamine (68%), proton pump inhibitors (14%), histamine receptor antagonists (2%), opiates (7%), antidepressants (6%), and/or antibiotics (5%). After adjusting for confounders and examining treatment efficacy of intervention versus placebo, we observed no impact of concomitant exposure to corticosteroids (ratio of relative risk of drug vs placebo with vs without concomitant exposure: ratio of risk ratio [RRR], 0.81 [95% confidence interval, 0.63-1.06]), mesalamine (RRR, 1.04 [0.78-1.39]), proton pump inhibitors (RRR, 0.87 [0.61-1.22]), histamine receptor antagonists (RRR, 1.72 [0.97-14.29]), opiates (RRR, 0.90 [0.54-1.49]), antidepressants (RRR, 1.02 [0.57-1.83]), and antibiotics (RRR, 0.72 [0.44-1.16]) on likelihood of clinical remission. Concomitant exposure to immunomodulators was associated with lower likelihood of achieving clinical remission (RRR, 0.73 [0.55-0.97]), particularly with non-tumor necrosis factor antagonists.

CONCLUSIONS

In clinical trials of advanced therapies for ulcerative colitis, baseline concomitant exposure to multiple commonly used class of medications does not impact treatment efficacy or safety. These findings directly inform design of regulatory clinical trials with respect to managing concomitant medications at baseline.