Flourie 2013.

Methods	Multicentre, controlled, randomised, investigator‐blinded, comparative, non‐inferiority study
Participants	Adult patients (18 years or older) with newly diagnosed or relapsing mild‐to‐moderate ulcerative colitis, with disease extension beyond the rectum (N = 206)
Interventions	Mesalazine (4 g/day), either once daily with two sachets of 2 g mesalazine granules in the morning (n = 102) or twice daily with one 2 g sachet in the morning and one in the evening (n = 104) for 8 weeks
Outcomes	Primary outcome: percentage of patients in clinical and endoscopic remission after 8 weeks (defined as UC‐DAI score < 1) Secondary outcomes: complete remission at week 8 (clinical and endoscopic UC‐DAI = 0), clinical and endoscopic improvement at week 8 (decrease in UC‐DAI by at least 2 points), clinical remission at weeks 4, 8 and 12, determined by normal stool frequency, no bloody stools and no active disease by physician’s assessment, time to remission (based on patient’s diary with normal stool frequency and cessation of bleeding; estimated using Kaplan–Meier methodology), mucosal healing at 8 weeks (defined as an UC‐DAI endoscopic sub‐score of 0 or 1, or alternatively a Rachmilewitz endoscopic index of < 4), adherence, global patient’s acceptability and adverse events
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomised centrally via a computer‐generated randomisation system
Allocation concealment (selection bias)	Low risk	To maintain the investigator‐blind trial design, sealed treatment boxes were identical in size and weight, and contained written instruction about the dosing arm to which the patient was assigned; investigators were unaware of this information
Blinding (performance bias and detection bias) All outcomes	High risk	Only Investigators were blinded in this trial
Incomplete outcome data (attrition bias) All outcomes	Low risk	All patients involved with the study are accounted for
Selective reporting (reporting bias)	Low risk	Expected outcomes were reported
Other bias	Unclear risk	The study appeared to be free of other sources of biases