Efficacy of Delayed-Release Mesalamine in the Prevention of GI Symptoms Following Acute Diverticulitis: Results of the DIVA Trial

Purpose: Diverticular disease is the fift h most common reason for outpatient GI visits, and is one of the most common GI indications for hospitalization. No pharmacologic intervention is currently approved in North America or Europe for diverticular disease, although there is increasing (uncontrolled) evidence that anti-inflammatory agents such as mesalamine may play a therapeutic role. We present the results of the first US randomized controlled trial (RCT) of mesalamine after CT-documented diverticulitis. The primary outcome was to determine if once daily administration of 2.4 gm delayed-release mesalamine (6 x 400 mg tablets) is effective in diminishing GI symptoms and complications following acute diverticulitis. Methods: The DIVA (DIVerticulitis Assessment) trial was a 3-arm, multicenter, 12-week, randomized, double-blind, double-dummy, placebo-controlled study to assess the safety and efficacy of a 12-week treatment with delayed-release mesalamine, with and without probiotic supplementation (Bifidobacterium infantis 35624) vs. placebo, followed by a 9-month treatment- free observation period. The study enrolled 54% of its original target; 117 subjects were randomized within 7 days after CT-scan confirmed acute diverticulitis, for which all subjects received standard antibiotics. Efficacy was assessed using a patient-determined global symptom score (GSS) of the maximal severity for 10 GI symptoms on a 0-6 Likert scale. The primary endpoint was the decrease in GSS at 12 weeks for mesalamine vs. placebo. Results: Mesalamine reduced GSS by 2.9 points vs. placebo at 12 weeks (p=0.38). Subgroup analysis for the mesalamine-only group demonstrated improvement in complete symptom response (Likert=0) at 12 weeks vs. placebo (28.1% vs. 13.8%; total n=61, p=0.083) which persisted at 52 weeks (40.7 vs. 18.2%; total n=49, p=0.045). Higher efficacy was noted with regard to rectosigmoid-specific symptoms (urgency, tenesmus, diarrhea, constipation) in which complete symptom response rates were (mesalamine vs. placebo) 56.3% vs. 17.2% (p=0.001) and 59.3% vs. 27.3% (p=0.013) at 12 and 52 weeks respectively. There were no differences in diverticulitis recurrent rates, surrogate markers, or safety outcomes. The efficacy of mesalamine in diverticulitis did not appear to be augmented by dietary supplementation with a probiotic. Conclusion: A 12-week treatment course with 2.4gm/day of mesalamine after an episode of CT-confirmed diverticulitis resulted in an overall trend towards improved GI symptoms at 12 weeks compared to placebo. Statistical significance was achieved in rectosigmoid-specific symptoms, with persistent improvement noted at 12 months.