No Superiority of Tacrolimus Suppositories vs Beclomethasone Suppositories in a Randomized Trial of Patients With Refractory Ulcerative Proctitis

Abstract

BACKGROUND & AIMS: Ulcerative proctitis (UP) refractory to 5-aminosalicylic acid (5-ASA) suppositories is a challenge to treat, often requiring step up to immunomodulator or biological therapy. Topical tacrolimus is effective and safe in patients with refractory UP. However, it is not clear how tacrolimus suppositories fit into in the treatment algorithm of UP. METHODS: We performed a randomized controlled, double-blind study at 8 hospitals in The Netherlands and Belgium from 2014 through 2017. Eighty-five patients with refractory UP (65% women) were randomly assigned to groups given once daily tacrolimus suppositories (2mg, n=43) or beclomethasone (3mg, n=42) for 4 weeks. The primary outcome was clinical response (decrease in Mayo score of 3 or more). Secondary outcomes included clinical remission, endoscopic response and remission, adverse events and quality of life. Outcomes were compared using Fisher's exact test and Mann-Whitney U test. RESULTS: Proportions of patients with clinical responses were 63% in the tacrolimus group and 59% in the beclomethasone group (P=.812); proportions of patients in clinical remission were 46% and 38%, respectively (P=.638). Proportions of patients with an endoscopic response were 68% and 60% in the tacrolimus group and in the beclomethasone group (P=.636); proportions in endoscopic remission rates were 30% and 13%, respectively (P=.092) Median increases in the inflammatory bowel disease questionnaire score were 18.0 in the tacrolimus group and 20.5 in the beclomethasone group (P=.395). Adverse event rates did not differ significantly between groups. CONCLUSIONS: In a 4-week randomized controlled trial, tacrolimus and beclomethasone suppositories induce comparable clinical and endoscopic responses in patients with UP refractory to 5-ASA. There were no significant differences in adverse events rates. Tacrolimus and beclomethasone suppositories are therefore each safe and effective treatment options for 5-ASA refractory disease. EUDRACT 2013-001259-11; Netherlands Trial Register NL4205 / NTR4416.