Nikolaus 2003.

Methods	Randomised, double blind, intra‐individual, dose escalating study
Participants	17 adult patients with moderately active UC defined by a UCSS score of 6‐10, with a proctosigmoidoscopy score of 2 Group 1: n=10, M:F = 4:6, median age = 42.2 yrs (32‐68), median disease duration 9.8 yrs (2.6‐14.2), median UCSS score = 9 (7‐10), left sided colitis n=5 Group 2: n=7, M:F = 2:5, median age = 35 yrs (30‐63), median disease duration 9.0 yrs (2.6‐40.3), median UCSS score = 9 (7‐12), left sided colitis n=5
Interventions	Group 1: IFN‐β‐1a by SC injection t.i.w. at variable dose for a variable duration of treatment. Started at 22mcg (t.i.w.) Improvement was defined as a decrease of 1 point in the combined score of UCSS symptoms and PGA. If no improvement was observed after six injections, dose increased to 44 mcg t.i.w., and increased further to 88 mcg t.i.w., if no improvement was observed after six injections at 44 mcg dose If improvement was observed after six injections at any dose, the patient entered a maintenance treatment phase of 6‐12 injections at that dose If no improvement was observed after six injections at 88 mcg, or if remission occurred at any point, treatment was stopped Group 2: placebo The maximum duration of treatment was eight weeks, and the minimum duration was four weeks
Outcomes	Efficacy end points were treatment response and remission Treatment response was defined as a decrease of at least 3 points from baseline in the UCSS symptoms score and PGA (without the proctosigmoidoscopic score) during treatment Remission was defined as complete resolution of clinical symptoms (all clinical UCSS subscores equal to 0), with a proctosigmoidoscopy score of 0 or 1 at any time during treatment Secondary end points included overall treatment and end point responses, and clinical end point responses Safety data were also collected
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Eligible patients were randomised by means of a computer generated list Randomisation was stratified by centre with block size of three (2:1 IFN‐β‐1a: placebo)
Allocation concealment (selection bias)	Unclear risk	Details were not provided in the published report
Blinding (performance bias and detection bias) All outcomes	Unclear risk	The trial is double blind in design but the methods used for blinding were not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	All enrolled patients (n=18) were accounted for. One patients was excluded a priori (before the code was broken) from the analysis, because of misallocation of study drug. 6/10 (60%) of IFN‐β‐1a group and 2/7 (28.6%) of control group stopped the treatment early
Selective reporting (reporting bias)	Low risk	All outcomes were reported
Other bias	Low risk	No other issues were identified