Systematic review with meta‐analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies

• Published in: Alimentary pharmacology & therapeutics Vol. 49; no. 4; pp. 364 - 374
• Main Authors: Ma, Christopher, Guizzetti, Leonardo, Cipriano, Lauren E., Parker, Claire E., Nguyen, Tran M., Gregor, James C., Chande, Nilesh, Feagan, Brian G., Jairath, Vipul
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.02.2019
• Subjects: Adult; Aminosalicylic Acids - administration & dosage; Biological Products - therapeutic use; Biological Therapy; Canada; Clinical trials; Colitis, Ulcerative - drug therapy; Drug development; Heterogeneity; Humans; Immunosuppressive agents; Immunosuppressive Agents - therapeutic use; Inflammatory bowel disease; Meta-analysis; Patients; Prevalence; Randomized Controlled Trials as Topic; Ulcerative colitis; Canada
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.15090

Summary Background Aminosalicylates are the most frequently prescribed treatment for ulcerative colitis (UC). In the absence of empirical evidence, clinicians are uncertain whether to continue aminosalicylates in patients with UC after escalating therapy. Aims To quantify concomitant aminosalicylate use in UC randomised clinical trials (RCTs), identify factors associated with their use, and estimate treatment costs of concomitant aminosalicylate therapy. Methods MEDLINE, Embase, and CENTRAL were searched from inception to 1 March 2017 for placebo‐controlled RCTs of immunosuppressants, biologics, or oral small molecules in adults with UC. The proportion of patients prescribed concomitant aminosalicylates at trial entry was pooled using a random‐effects model. Meta‐regression was performed to assess trial‐level factors associated with aminosalicylate use. Treatment costs were estimated using 2018 formulary data from five Canadian provinces. Results Thirty‐two trials were included (23 induction only, nine induction, and maintenance trials). The pooled proportion of patients co‐prescribed aminosalicylates was 80.7% (95% CI 75.5%‐85.1%), with considerable observed heterogeneity (I2 = 95%). In univariable meta‐regression, aminosalicylate use was not associated with trial design, setting, year of publication, disease severity, disease duration, or drug class. The estimated direct annual treatment cost of concomitant aminosalicylates is ~$20 million for the Canadian UC population, assuming conservative estimates of UC prevalence, aminosalicylate use and dose, and the lowest cost formulation. Conclusions Approximately 80% of UC patients entering clinical trials of immunosuppressants, biologics, or oral small molecules continue to use aminosalicylates. An RCT is needed to inform the benefits and harms of continuing vs stopping aminosalicylates in patients escalating therapy.