Abstract: Twelve studies (2146 participants) that compared 5-ASA to placebo were included. We did not identify any studies that compared sulphasalazine to placebo. Seven studies were judged to be at low risk of bias. The other studies were judged to have an unclear risk of bias for various items due to insufficient details to allow for a judgement. There was no statistically significant difference in relapse rates at 12 months. Fifty-three per cent (526/998) of 5-ASA patients (dose 1.6 g to 4 g/day) relapsed at 12 months compared to 54% (544/1016) of placebo patients (RR 0.98, 95% CI 0.91 to 1.07; 11 studies; 2014 patients; moderate-quality evidence). Sensitivity analyses based on an available case analysis and a random-effects model had no impact on the results. One study found no difference in relapse rates at 24 months. Fifty-four per cent (31/57) of 5-ASA patients (dose 2 g/day) relapsed at 24 months compared to 58% (36/62) of placebo patients (RR 0.94, 95% CI 0.68 to 1.29, 119 patients; low-quality evidence). One paediatric study found no statistically significant difference in relapse rates at 12 months. Sixty-two per cent (29/47) of paediatric 5-ASA patients (dose 50 mg/kg/day) relapsed at 12 months compared to 64% (35/55) of paediatric placebo patients (RR 0.97, 95% CI 0.72 to 1.31; 102 patients; moderate-quality evidence). There was no statistically significant difference in the proportion of patients who experienced an adverse event, withdrawal due to adverse events or serious adverse events. Thirty-four per cent (307/900) of 5-ASA patients had at least one adverse event compared to 33% (301/914) of placebo patients (RR 1.05, 95% CI 0.95 to 1.17; 10 studies; 1814 patients). Fourteen per cent (127/917) of 5-ASA patients withdrew due to adverse events compared to 13% (119/916) of placebo patients (RR 1.11, 95% CI 0.88 to 1.38; 9 studies; 1833 patients). One per cent (3/293) of 5-ASA patients had a serious adverse event compared to 0.7% (2/283) of placebo patients (RR 1.43, 95% CI 0.24 to 2.83; 3 studies; 576 patients). Common adverse events reported in the studies included diarrhoea, nausea and vomiting, abdominal pain, headache and skin rash. We found no evidence in this review to suggest that oral 5-ASA preparations are superior to placebo for the maintenance of medically-induced remission in patients with Crohn's disease. Additional randomised trials may not be justified.

Plain-language summary: We found 12 studies that included a total of 2146 participants. Eleven studies including 2014 adult participants compared oral 5-ASA to a placebo (i.e. inactive pills or tablets). One study including 132 children compared oral 5-ASA to a placebo. Eleven studies were conducted for 12 months and one study was conducted for 24 months. Seven studies were judged to be of high quality and the other studies were judged to be of unclear quality because insufficient details were reported to allow for a judgement about quality. The studies with insufficient details were generally older studies that were published 20 or more years ago. A combined analysis of eleven studies including 2014 adult participants found no difference between oral 5-ASA (at daily doses between 1.6 g to 4 g) and placebo in the proportion of participants who remained in remission at 12 months. Similarly, a study including 161 adult participants found no difference between oral 5-ASA (at a dose of 2 g per day) and placebo in the proportion of participants who remained in remission at 24 months. The study involving children found no difference between oral 5-ASA (at a daily dose of 50 mg/kg) and placebo in the proportion of participants who remained in remission at 12 months. There does not appear to be an increased risk of side effects in people who take oral 5-ASA compared to placebo. Common adverse events reported in the studies included diarrhoea, nausea and vomiting, abdominal pain, headache and skin rash. In conclusion, there is no evidence that oral 5-ASA is superior to placebo for helping people with Crohn's disease remain in remission that was achieved by medical therapy.