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

Ustekinumab Vivli concomitant medications inflammatory bowel diseases trial design

Journal

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775

Informations de publication

Date de publication:
10 Oct 2024
Historique:
received: 25 06 2024
revised: 10 08 2024
accepted: 22 08 2024
medline: 13 10 2024
pubmed: 13 10 2024
entrez: 12 10 2024
Statut: aheadofprint

Résumé

While participants with inflammatory bowel diseases (IBD) 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. Through an individual patient data pooled analysis of ten clinical trials of advanced therapies for moderate-to-severe ulcerative colitis (UC), we assessed whether concomitant exposure to corticosteroids, immunomodulators, 5-aminosalicylates, proton pump inhibitors (PPIs), histamine receptor antagonists (H2RA), opiates, antidepressants, and antibiotics modified the effect of the intervention on treatment efficacy and safety outcomes, using modified Poisson regression model. Of 6044 patients (4280 receiving intervention, 1764 receiving placebo), several received concomitant corticosteroids (47%), immunomodulators (28%), 5-aminosalicylates (68%), PPIs (14%), H2RAs (2%), opiates (7%), antidepressants (6%), and/or antibiotics (5%). After adjusting for confounders and examining treatment efficacy of intervention vs. placebo, we observed no impact of concomitant exposure to corticosteroids (ratio of relative risk of drug vs. placebo with vs. without concomitant exposure: RRR, 0.81 [95% CI,0.63-1.06], 5-aminosalicylates (RRR, 1.04[0.78-1.39]), PPIs (RRR, 0.87 [0.61-1.22]), H2RAs (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-TNF antagonists. In clinical trials of advanced therapies for UC, 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.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
While participants with inflammatory bowel diseases (IBD) 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 METHODS
Through an individual patient data pooled analysis of ten clinical trials of advanced therapies for moderate-to-severe ulcerative colitis (UC), we assessed whether concomitant exposure to corticosteroids, immunomodulators, 5-aminosalicylates, proton pump inhibitors (PPIs), histamine receptor antagonists (H2RA), opiates, antidepressants, and antibiotics modified the effect of the intervention on treatment efficacy and safety outcomes, using modified Poisson regression model.
RESULTS RESULTS
Of 6044 patients (4280 receiving intervention, 1764 receiving placebo), several received concomitant corticosteroids (47%), immunomodulators (28%), 5-aminosalicylates (68%), PPIs (14%), H2RAs (2%), opiates (7%), antidepressants (6%), and/or antibiotics (5%). After adjusting for confounders and examining treatment efficacy of intervention vs. placebo, we observed no impact of concomitant exposure to corticosteroids (ratio of relative risk of drug vs. placebo with vs. without concomitant exposure: RRR, 0.81 [95% CI,0.63-1.06], 5-aminosalicylates (RRR, 1.04[0.78-1.39]), PPIs (RRR, 0.87 [0.61-1.22]), H2RAs (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-TNF antagonists.
CONCLUSIONS CONCLUSIONS
In clinical trials of advanced therapies for UC, 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.

Identifiants

DOI: 10.1016/j.cgh.2024.08.040 PMID: 39395572
pubmed: 39395572
pii: S1542-3565(24)00877-2
doi: 10.1016/j.cgh.2024.08.040
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Dhruv Ahuja (D)

Department of Medicine, Indira Gandhi Hospital, New Delhi, India.

Guangyong Zou (G)

Alimentiv Inc, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.

Virginia Solitano (V)

Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada; Division of Gastroenterology and Gastrointestinal Endoscopy, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan.

Gaurav Syal (G)

Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA.

Han Hee Lee (HH)

Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA; Division of Gastroenterology, Department of Internal Medicine, Yeouido St. Mary's Hospital College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Christopher Ma (C)

Alimentiv Inc, London, ON, Canada; Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada; Italy.

Vipul Jairath (V)

Alimentiv Inc, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada; Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada. Electronic address: vjairath@uwo.ca.

Siddharth Singh (S)

Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California, USA. Electronic address: sis040@ucsd.edu.

Classifications MeSH