A multicenter, randomized study to evaluate the efficacy and safety of mesalamine suppositories 1 g at bedtime and 500 mg Twice daily in patients with active mild-to-moderate ulcerative proctitis.

摘要

BACKGROUND: Ulcerative proctitis (UP) is a prevalent condition associated with increased morbidity and mortality. Topical mesalamine (5-aminosalicylic acid [5-ASA]) inhibits inflammatory processes in UP. METHODS: We evaluated effects of mesalamine 1-g suppository administered QHS compared with 500-mg suppository administered BID on UP activity (e.g., disease extension/mucosal appearance), remission, onset of response, safety and compliance in 97 patients with UP. A 6-week, randomized, multicenter, parallel-group, noninferiority study was conducted (and published) with Disease Activity Index (DAI) at week 6 as the primary efficacy variable and individual components of DAI at week 6 (i.e., stool frequency, rectal bleeding, mucosal appearance, global assessment) as secondary variables. Unreported outcomes were remission (DAI < 3 at weeks 3 and 6), disease extension, and complete response to treatment (DAI = 0; post-hoc, exploratory analysis). RESULTS: DAI values after 6 weeks were significantly reduced (+/-SD) from 6.6 +/- 1.5 to 1.6 +/- 2.3 (500-mg BID); and from 6.1 +/- 1.5 to 1.3 +/- 2.2 (1-g QHS). Mucosal appearance significantly improved from baseline after 3 and 6 weeks of treatment from 1.8 +/- 0.5 to 0.8 +/- 0.7 and 0.5 +/- 0.7 (500-mg BID; P 70%) after 6 weeks in both groups. Mesalamine was well tolerated. Compliance was >96%. CONCLUSIONS: Mesalamine 500-mg BID and 1-g QHS suppositories are safe and effective for patients with UP. Most patients reported significant improvement within 3 weeks and UP remission and reduced disease extension after 6 weeks of treatment. Validity of QHS administration was confirmed.