Munch 2016.

Methods	An initial 8‐week open‐label induction phase with budesonide therapy to achieve clinical remission was followed by a double‐blind, randomized, placebo‐controlled, parallel‐group, multicentre, 12‐month phase for maintenance of clinical remission. After this there was 6 months of treatment‐free follow‐up
Participants	A total of 148 patients were screened, all age ≥ 18 years Inclusion criteria: 1. Histologically established diagnosis of collagenous colitis, defined as thickened subepithelial collagen layer ≥10 mm on well‐orientated sections, and increased inflammatory cells indicating chronic inflammation in the lamina propria 2. Prescreening history of non‐bloody, watery diarrhea for ≥2 weeks in patients with newly diagnosed collagenous colitis, or a prescreening history of clinical relapse for ≥1 week in patients with previously established collagenous colitis 3. A mean of ≥3 stools/day, including a mean of ≥1 watery stool/day, during the week prior to baseline Exclusion criteria: 1. Diabetes mellitus, infection, glaucoma, tuberculosis, peptic ulcer disease or hypertension if careful medical monitoring was not ensured 2. Established cataract 3. Known hereditary problems of galactose or fructose intolerance, lactase deficiency, increased levels of anti‐transglutaminase 2 antibodies 4. Established osteoporosis with T‐score <−2.5 As per Figure 2: 110 met eligibility criteria and started the open‐label phase. 92 patients had achieved remission during the open‐label phase and were randomized for treatment in the double‐blind phase (44 budesonide, 48 placebo). 43 completed the 12‐month study visit (32 budesonide, 11 placebo). 36 patients at the end of the double‐blind phase (28 budesonide, 8 placebo) entered the follow‐up phase
Interventions	During the open‐label induction phase, all patients received once‐daily budesonide (Budenofalk 3 mg capsules) at a dose of 9 mg/day for 4 weeks, then 6 mg/day for 2 weeks, followed by alternate daily doses of 6 and 3 mg/day (mean 4.5 mg/day) for the final 2 weeks During the double‐blind phase, the active treatment group received once‐daily budesonide 6 and 3 mg/day on alternate days (mean 4.5 mg/day). The placebo group received two placebo capsules and one placebo capsule on alternate days, administered once daily After the final visit of the double‐blind phase (month 12), there was a 2‐week tapering‐off period, during which patients in the active treatment group received 3 mg/day budesonide for 1 week followed by 3 mg/day budesonide every second day for 1 week. Patients in the placebo group received one placebo capsule on the corresponding days Patients who remained in clinical remission at the end of the double‐blind phase received no further study drug after the 2‐week tapering‐off period During the treatment‐free follow‐up, no intervention was given
Outcomes	The primary endpoint was the proportion of patients remaining in clinical remission during the 12‐month double‐blind phase, with clinical remission defined as a mean of <3 stools/day, including a mean of <1 watery stool/day over 1 week The main secondary endpoints during the double‐label phase included health‐related quality of life using the Short Health Scale (SHS) and the Psychological General Well‐Being Index (PGWBI) Further secondary endpoints during the double‐blind phase were achievement of histological remission or histological improvement
Notes	During the entire study period, loperamide, anti‐inflammatory or immunosuppressant drugs were not permitted Prophylactic treatment of osteoporosis with calcium and vitamin D3 was strongly recommended and under the responsibility of the investigator
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Method of randomization was described as "a computer‐generated randomisation list using randomly permuted blocks"
Allocation concealment (selection bias)	Unclear risk	Allocation concealment not described
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blinding is mentioned, but not described in more detail. Placebo capsules were used
Incomplete outcome data (attrition bias) All outcomes	Low risk	Well described patient disposition in Figure 2 and had intention‐to‐treat analysis described. They accounted for attrition/exclusions with reasons given
Selective reporting (reporting bias)	Low risk	All primary outcomes were reported. Most secondary outcomes were reported with exception of histological outcomes Safety and adverse‐effect data was also presented, but not described as part of methods section
Other bias	Low risk	Study appeared to be free of other forms of bias