P538 Pooled safety analysis of long-term, once-daily multimatrix mesalazine use
S. Da Silva Sanchez*1, H. Wan2, P. Streck3, D. Willshire4, J.B. Raskin5
1Shire, Medical Affairs, Brussels, Belgium, 2Shire, Biostatistics, Wayne, PA, United States, 3Shire, Global Clinical Development, Wayne, PA, United States, 4Shire, Medical Affairs, North Ryde, Australia, 5University of Miami Health System, Gastroenterology and Internal Medicine, Miami, FL, United States
Mesalazine, the recommended first-line treatment for mild-to-moderate ulcerative colitis (UC), has also been examined for prevention of recurrent diverticulitis (DV). In this study, safety data from 6 clinical trials evaluating long-term multimatrix mesalazine use (2.4-4.8 g/d for up to 24 mo) in patients (pts) with UC or a history of DV were analyzed.
Results from 2 trials examining mesalazine for prevention of recurrent DV (NCT00545740, NCT00545103) and 4 trials examining mesalazine for maintenance of UC remission (NCT00151944, NCT00151892, NCT00446849, NCT01124149) were pooled. Pts in the DV trials had prior acute DV that resolved without surgery and were administered 1.2, 2.4, or 4.8 g/d mesalazine for 24 mo. Pts in the UC trials had quiescent symptoms or complete or partial remission (defined using a combination of qualifying symptom and endoscopy scores), and were given 2.4 g/d mesalazine for 6 to 12 mo; in some trials, remission was initially achieved via 8 wks of acute treatment with 4.8 g/d mesalazine. Safety was analyzed in the following groups: pts in all trials, pts on high-dose (4.8 g/d) mesalazine from the DV trials, and only UC pts.
Across all 6 trials, ≥1 dose of mesalazine was given to 2,859 pts (880 from DV trials, with 299 on 4.8 g/d; 1,979 from UC trials), and 1,542 (54%) reported treatment emergent adverse events (TEAEs). TEAEs leading to discontinuation were observed in 9% of pts. The most common TEAEs were abdominal pain (5%), headache (5%), diarrhoea (4%), UC (4%), nasopharyngitis (4%), and urinary tract infection (3%). Maximum severity of TEAEs was mild in 23% of pts, moderate in 24%, and severe in 7%. Serious TEAEs were reported by 5%; the most common was UC (1%). Treatment-related AEs included diarrhoea (2%), abdominal pain (1%), UC (1%), and headache (1%). For high-dose pts in the DV trials, 71% (211/299) experienced TEAEs; the most common were abdominal pain (11%), diarrhoea (10%), headache (9%), back pain (6%), and urinary tract infection (6%). In this subgroup, treatment-related AEs included diarrhoea (3%), headache (2%), nausea (2%), and abdominal pain (2%). For pts in the UC trials only, 45% (897/1,979) experienced TEAEs; the most common were UC (6%), headache (4%), ineffective drug (4%), and nasopharyngitis (3%). For UC pts, treatment-related AEs included UC (2%), headache (1%), diarrhoea (1%), and abdominal pain (1%).
At doses up to 4.8 g/d, multimatrix mesalazine was well-tolerated for up to 24 mo. Most TEAEs were mild or moderate in severity. Differences in treatment duration (24 mo vs 6-12 mo) and dosing (4.8 vs 2.4 g/d) may, in part, contribute to the higher incidence of TEAEs observed in the high-dose DV subgroup compared with UC pts.