A145 oral 5-asa for induction and maintenance of remission in ulcerative colitis

To assess the safety and efficacy of oral 5-aminosalicylic acid (5-ASA) for induction and maintenance of remission in patients with ulcerative colitis (UC). We searched MEDLINE, EMBASE, and CENTRAL from inception to May 2018. Randomized controlled trials (RCTs) with a minimum four-week treatment duration for induction studies and six-month treatment duration for maintenance studies were included. RCTs comparing oral 5-ASA to placebo, sulfasalazine (SASP) or other 5-ASA formulations were considered. RCTs comparing once daily 5-ASA treatment to conventional dosing of 5-ASA and 5-ASA dose ranging studies were also eligible. Data were analyzed on an intention-to-treat basis. Risk ratios (RR) and corresponding 95% confidence intervals (CI) were calculated for dichotomous outcomes. The primary outcomes included the proportion of patients who failed to enter and maintain clinical remission. Secondary outcomes included clinical improvement, endoscopic improvement, endoscopic remission, adherence to medication and adverse events. We used the Cochrane risk of bias tool to assess bias and GRADE to assess the overall quality of the evidence. Fifty-four RCTs (N=9612) of 5-ASA in active UC, and 43 RCTs (N=9791) of 5-ASA in quiescent UC were included. Seventy-one percent (1107/1550) of 5-ASA patients failed to enter remission at 4–12 weeks compared to 83% (695/837) of placebo patients (RR 0.86, 95% CI 0.82 to 0.89, P<0.001; high-quality evidence). Thirty-seven percent (335/907) of 5-ASA patients failed to maintain remission at 24–48 weeks compared to 55% (355/648) of placebo patients (RR 0.68, 95% CI 0.61 to 0.76, P<0.001; high-quality evidence), with a trend towards increased efficacy at higher doses. Adverse events were similar between the 5-ASA and placebo groups. Fifty-four (150/279) percent of SASP patients failed to enter remission at 4–12 weeks compared to 58% (144/247) of placebo patients (RR 0.90, 95% CI 0.77 to 1.04, P=0.15; moderate-quality evidence). Forty-eight percent (416/871) of 5-ASA patients failed to maintain remission at 48–72 weeks compared to 43% (336/784) of SASP patients (RR 1.14, 95% CI 1.03 to 1.27, P=0.01; high-quality evidence). SASP was associated with an increased rate of adverse events in induction studies, but not in maintenance studies. There was no statistically significant difference in efficacy, safety, or adherence, for once daily dosing compared to conventional 5-ASA dosing. There was no significant difference in efficacy or safety between the various 5-ASA formulations. 5-ASA was superior to placebo for both the induction and maintenance of ulcerative colitis. 5-ASA resulted in similar efficacy and fewer adverse events compared to SASP. There does not appear to be any difference in efficacy or safety between various 5-ASA formulations, nor between once daily and conventional dosing. Ferring Studentship Grant Award