Small Molecules Show Efficacy in Ulcerative Colitis

Novel small molecule therapies appear promising for the induction and maintenance of clinical remission in ulcerative colitis (UC) and improvement of health-related quality of life (HRQoL) but require additional rigorous studies and trials to ensure safety and more fully prove their efficacy, according to new research presented at the American College of Gastroenterology scientific meeting in Philadelphia.

The research was presented by Mahek Fatima, MBBS, from Osmania General Hospital and Medical College in Hyderabad, Telangana, India.

The investigators searched PubMed, PMC, Google Scholar, Cochrane Library, and clinicaltrials.gov for the period June 2014-June 2024 for studies that were randomized and conducted with adult subjects diagnosed with UC.

Among 6845 pooled patients from 9 randomized controlled trials, the small molecules upadacitinib, tofacitinib, ritlecitinib, brepocitinib, filgotinib and etrasimod proved superior to placebo in the management of UC for induction as well as maintenance of remission. They were effective in inducing early clinical remission, as determined by the assessment of total Mayo score and endoscopic normalization; these therapies also helped patients achieve corticosteroid-free remission.

Further assessment showed significantly improved HRQoL and Inflammatory Bowel Disease Questionnaire outcomes. Infections and infestations, mild anemia, headaches, and herpes zoster infection were tfrequently reported adverse effects (AEs). Elevated creatinine kinase levels with tofacitinib and sinus bradycardia with etrasimod were the noteworthy AEs.

Small molecules appear promising for the induction and maintenance of clinical remission in UC. They significantly improve the HRQoL index and reduce corticosteroid dependence. Tofacitinib has been thoroughly studied and established as an effective agent with minimal safety concerns; other agents should receive additional study to clarify their risk-benefit profiles.

Reference:

Fatima M, Priyadarsini A, Gaddam AR, et al. P0829 - Efficacy and safety profile of small molecules for induction and maintenance of remission in ulcerative colitis: a systematic review of randomised control trials. Presented at: the American College of Gastroenterology. October 27, 2024. Philadelphia, Pennsylvania.