Sandborn 2012.

Methods	Prospective, multicenter, double‐blind, double‐dummy, randomised, placebo‐controlled trial
Participants	Participants (N = 509) were recruited from 108 centres from North America (United States, Canada, Mexico) and India Non‐pregnant adult patients (age 18 ‐ 75 years) with mild to moderate UC as defined by an Ulcerative Colitis Disease Activity Index score of ≥ 4 and ≤ 10 (Sutherland 1987) were eligible A ≥ 2‐day wash out period for oral mesalamine or other 5‐ASA product was required Exclusion criteria: history of oral or rectal corticosteroid, immunosuppressant or biologic use within the preceding 4 weeks, 8 weeks and 3 months, respectively, patients with severe UC (UCDAI > 10 points) or those with disease limited to the rectum, severe anaemia, leukopenia, granulocytopenia, pregnancy or lactation, cirrhosis, liver or renal insufficiency, severe disease in other organs or systems, underlying conditions (other than UC) requiring corticosteroid therapy as well patients with type 1 diabetes or glaucoma The median age of the patients included in the final analysis was 42 years with a median disease duration of 3.3 years Approximately half of the enrolled patients were Caucasian and one third were Asian. 28.6% of enrolled patients had proctosigmoiditis, 29% had left‐sided colitis and 40.5% had extensive or pan‐colitis The median UCDAI score at study entry was 7.0
Interventions	Budesonide‐MMX® 9 mg (n = 123) Budesonide‐MMX® 6 mg (n = 121) Placebo (n = 121) Asacol® 2.4g/day (mesalamine 800mg 3 times daily) daily(n = 124) Placebo formulations were available for the Asacol and the Budesonide‐MMX® tablets
Outcomes	The primary outcome was combined clinical and endoscopic remission at 8 weeks. (UCDAI score ≤ 1, with sub‐scores of zero for rectal bleeding and stool frequency, no mucosal friability at colonoscopy and a reduction of ≥ 1 point in the endoscopic index score (Rachmilewitz 1989)). Secondary outcomes included clinical improvement (≥3 point reduction in UCDAI), endoscopic improvement, symptom resolution, histologic healing as well as an assessment of adverse effects and potential glucocorticoid side‐effects.
Notes	Modified intention‐to‐treat population was 489 The presence of confirmed active UC based on histologic findings was an eligibility criterion; however, there was a lag time from study enrolment to the availability of histology results and therefore participants with normal histology were excluded from the analysis The authors also excluded participants who had a diagnosis of infectious colitis which had not been recognised at the time of enrolment We contacted Dr Andy Barrett, Associate Director, Medical and Scientific Communications at Salix in order to clarify the authors decision to use a modified intention‐to‐treat analysis and we are in agreement with the authors decision to proceed with a modified intention‐to‐treat analysis Further details on the reasons for use of the modified intention‐to‐treat analysis are available in the FDA Review document produced by Dr Marjorie Dennis, available at http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203634_uceris_toc.cfm This trial was supported by Cosmo pharmaceuticals SpA, Italy, and Santarus manufacturers of budesonide‐MMX®
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	An interactive voice response system was responsible for randomising patients in blocks of 4 to each of the treatment arms
Allocation concealment (selection bias)	Low risk	An external contractor, located centrally, was responsible for the randomisation process.
Blinding (performance bias and detection bias) All outcomes	Low risk	Outcome assessors were blinded to the treatment allocation
Blinding (performance bias and detection bias) Treatment Allocation	Low risk	Physicians, patients and outcome assessors were blinded to the treatment allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	All patients were accounted for in the final analysis which was a modified intention‐to‐treat analysis. Outcome data appear to be complete. 349 of 489 (71.4%) patients completed the study The proportions of patients who did not complete the study as well as reasons for study discontinuation were similar across different treatment groups
Selective reporting (reporting bias)	Low risk	The published report includes all expected outcomes
Other bias	Low risk	No other sources of bias identified