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. 2025 Sep;23(10):1786-1797.
doi: 10.1016/j.cgh.2024.08.040. Epub 2024 Oct 11.

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

Dhruv Ahuja  1 , Guangyong Zou  2 , Virginia Solitano  3 , Gaurav Syal  4 , Han Hee Lee  5 , Christopher Ma  6 , Vipul Jairath  7 , Siddharth Singh  8
Affiliations

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

Dhruv Ahuja et al. Clin Gastroenterol Hepatol. 2025 Sep.

Abstract

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.

Keywords: Concomitant Medications; Inflammatory Bowel Diseases; Trial Design; Ustekinumab; Vivli.

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Conflict of interest statement

  1. DA: No relevant disclosures

  2. GYZ: Consultancy/advisory board fees from Alimentiv Inc.

  3. VS: No relevant disclosures

  4. GS: has received research grant from Pfizer

  5. HHL: No relevant disclosures

  6. CM: Consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Roche, Sanofi; speaker’s fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; research support from Ferring, Takeda, Pfizer.

  7. VJ: Consultancy/advisory board fees from AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion; and speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi

  8. SS: has received research grants from Pfizer

Figures

Figure 1:
Figure 1:
Impact of baseline concomitant medications on clinical remission at the end of induction period in patients with moderate-to-severe ulcerative colitis treated with advanced therapies. [Abbreviations: 5-ASA=5-aminosalicylates; H2RA=Histamine receptor antagonists]
Figure 2:
Figure 2:
Impact of baseline concomitant medications on (A) endoscopic remission and (B) symptomatic remission based on patient reported outcomes at the end of induction period in patients with moderate-to-severe ulcerative colitis treated with advanced therapies. [Abbreviations: 5-ASA=5-aminosalicylates; H2RA=Histamine receptor antagonists; PRO2=Patient reported outcome-2]
Figure 3:
Figure 3:
Impact of baseline concomitant medications on (A) risk of serious adverse events and (B) risk of serious infections at the end of induction period in patients with moderate-to-severe ulcerative colitis treated with advanced therapies. [Abbreviations: 5-ASA=5-aminosalicylates; H2RA=Histamine receptor antagonists; PPI=Proton pump inhibitors]
See this image and copyright information in PMC

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