Randomised clinical trial: mesalazine versus placebo in the prevention of diverticulitis recurrence

Abstract

SummaryBackgroundPrevious studies have reached conflicting conclusions regarding the efficacy of mesalazine in the prevention of recurrent diverticulitis.AimTo investigate the efficacy and safety of mesalazine granules in the prevention of recurrence of diverticulitis after acute uncomplicated diverticulitis.MethodsTwo phase 3, randomised, placebo‐controlled, double‐blind multicentre trials (SAG‐37 and SAG‐51) investigated mesalazine granules in patients with prior episodes (<6 months) of uncomplicated left‐sided diverticulitis. Patients were randomised to receive either 3 g mesalazine once daily or placebo (SAG‐37, n=345) or to receive either 1.5 g mesalazine once daily, 3 g once daily or placebo for 96 weeks (SAG‐51, n=330). The primary endpoint was the proportion of recurrence‐free patients during 48 weeks (SAG‐37 and SAG‐51) or 96 weeks (SAG‐51) of treatment.ResultsMesalazine did not increase the proportion of recurrence‐free patients over 48 or 96 weeks compared to placebo. In SAG‐37, the proportion of recurrence‐free patients during 48 weeks was 67.9% with mesalazine and 74.4% with placebo (P=.226). In SAG‐51, the proportion of recurrence‐free patients over 48 weeks was 46.0% with 1.5 g mesalazine, 52.0% with 3 g mesalazine and 58.0% with placebo (P=.860 for 3 g mesalazine vs placebo) and over 96 weeks 6.9%, 9.8% and 23.1% respectively (P=.980 for 3 g mesalazine vs placebo). Patients with only one diverticulitis episode in the year prior to study entry had a lower recurrence risk compared to >1 episode. Safety data revealed no new adverse events.ConclusionMesalazine was not superior to placebo in preventing recurrence of diverticulitis.

Effect of mesalazine on recurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease: a meta‐analysis with trial sequential analysis of randomized controlled trials

“…Searches of electronic databases identified 187 articles of which six RCTs , which enrolled a total of 1918 patients, were selected for this review. Overall, 1292 patients were included in the mesalazine group and 626 patients were included in the placebo group.…”

“…Four studies enrolling 1367 patients compared a mesalazine dose of > 2 g/day with placebo. The risk of recurrence of diverticulitis was higher in the mesalazine group (OR 1.28, 95% CI 1.02–1.62, P = 0.04).…”

Editorial: mesalazine to prevent recurrent acute diverticulitis—the final nail in the coffin. Authors’ reply

“…We thank Drs Gracie and Ford for their editorial on our study . We fully agree that the use of mesalazine for preventing recurrence of true diverticulitis cannot be recommended.…”

Current Controversies in the Management of Diverticulitis: A Review

“…The role of anti-inflammatory, aminosalicyclate (5 ASA) compounds to counteract this, including mesalazine has been investigated. However, multiple placebo controlled trials have shown that they neither reduce recurrent episodes nor improve symptomatology [23,24]. These findings are confirmed in a 2017 systematic review and meta-analysis of 8 randomised controlled trials.…”