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P394. Pooled clinical trial analysis of MMX mesalazine safety: Focus on 4.8 g/d dose long-term exposure

S. Da Silva Sanchez1, M. Palmen2, P. Streck3, S. Inglis2, 1Shire, Medical Affairs, Brussels, Belgium, 2Shire, Clinical Development, Basingstoke, United Kingdom, 3Shire, Clinical Research & Development, Wayne, PA, United States

Background

Mesalazine (5-aminosalicylic acid) is standard first-line treatment for mild-to-moderate ulcerative colitis (UC), and has been studied for the treatment of diverticulitis (DV). Although there is some evidence of improved efficacy in induction of remission in UC with high-dose treatment, data are limited on the safety of long-term high-dose mesalazine treatment. This analysis examines the safety profile of high-dose (4.8 g/d) MMX mesalazine administered for 2 years to patients with DV, pooled from 2 studies.

Methods

Two Phase 3, randomized, double-blind, placebo-controlled, multicenter studies (PREVENT1, NCT00545740; PREVENT2, NCT00545103; sponsor, Shire Development LLC) evaluated the efficacy and safety of 3 dose regimens of once-daily MMX mesalazine (1.2 g, 2.4 g, or 4.8 g) versus placebo in the prevention of recurrent DV in adult patients over a period of 104 wks.

Results

A total of 1,182 total patients were enrolled in PREVENT1 and PREVENT2, and 301 were randomized to receive 4.8 g/d MMX mesalazine. Of these, 299 were administered ≥1 dose of MMX mesalazine (mean [SD] age, 55.6 [11.9] y; 46.8% male). Mean (SD) treatment exposure was 64.4 (42.7) wks. Among patients who received ≥1 dose of MMX mesalazine, 211 (70.6%) reported ≥1 treatment-emergent adverse event (TEAE; 1006 events reported); 59 (19.7%) patients experienced only mild TEAEs, 114 (38.1%) experienced TEAEs with a maximum severity of moderate, and 38 (12.7%) experienced severe TEAEs. Serious TEAEs were reported by 32 (10.7%) patients (38 events). A total of 51 (17.1%) patients experienced TEAEs determined to be related to study treatment (102 events), and 4 (1.3%) patients reported serious TEAEs related to study treatment (4 events). A total of 36 (12.0%) patients experienced TEAEs that led to withdrawal from their respective studies. The most frequently reported TEAEs (>5%) were abdominal pain (11.0%), diarrhoea (10.0%), headache (9.3%), back pain (6.3%), urinary tract infection (6.0%), nausea (5.3%), and upper respiratory tract infection (5.3%).

Conclusion

Pooled analysis of adverse event data from long-term exposure to MMX mesalazine 4.8 g/d in patients with a history of DV showed that high-dose MMX mesalazine was well-tolerated for 2 years.