Ten RCTs were included in the review (3,410 patients). The number of patients per trial ranged from 20 to 1,023. Four trials scored 5 for quality on the Jadad scale, four trials scored 4, one trial scored 3, and one trial scored 2.
Efficacy of once-daily versus multiple-daily mesalamine for preventing relapse in quiescent ulcerative colitis: Intention-to-treat analysis revealed that 372 (26.3%) patients receiving once-daily doses of mesalamine relapsed compared with 384 (26.5%) patients receiving multiple doses a day; the difference between the groups was not statistically significant (RR 1.00, 95% CI 0.89 to 1.12; eight trials). Moderate statistical heterogeneity was shown (Ι²=41%). Similar results were shown with per-protocol analysis. Results of various sensitivity analyses were reported but did not materially alter the results of the analysis. No evidence of publication bias was found.
Efficacy of once-daily versus multiple-daily mesalamine for inducing remission in active ulcerative colitis: Intention-to-treat analysis revealed that remission was not observed in 82 (29.8%) patients receiving once-daily doses of mesalamine compared with 104 (37.8%) patients receiving multiple doses a day. Risk of failure to achieve remission was higher among multiple-daily patients compared with once-daily patients (RR 0.80, 95% CI 0.64 to 0.99; two trials), but this difference was of borderline statistical significance. Statistical heterogeneity was observed but was not substantial (Ι²=21.6%). Per-protocol analysis revealed this difference to be statistically non-significant.
Adverse events: No statistically significant differences were found between once-daily and multiple-daily regimens for the incidence of adverse events overall, serious adverse events, and discontinuations due to adverse events. Statistical heterogeneity for these analyses was not reported.
Compliance: No statistically significant difference was found between once-daily regimens and multiple-daily regimens for compliance.