Feagan 2013.

Methods	Phase III, RCT, double‐blinded
Participants	Ulcerative colitis, moderately‐to‐severely active disease (Mayo Clinic score of 6 to 12, with a sigmoidoscopy subscore of at least 2, and disease that extended ≥ 15 cm or more from the anal verge). No response to or unacceptable side effects from ≥ 1 of the following: glucocorticoids, immunosuppressive agents, or TNF antagonists Exclusion criteria: previously treatment with vedolizumab, natalizumab, efalizumab, or rituximab; received TNF antagonists within 60 days before enrollment or cyclosporine, thalidomide, or investigational drugs within 30 days before enrollment; participants with toxic megacolon, abdominal abscess, symptomatic colonic stricture, stoma, a history of colectomy, an increased risk of infectious complications, clinically meaningful laboratory abnormalities, pregnancy or lactation, an unstable or uncontrolled medical disorder, an anticipated requirement for major surgery, colonic dysplasia or adenomas, and malignant neoplasms A total of 895 participants enrolled in the study and were randomised in a 3:2 ratio to received DB placebo (n = 149), DB vedolizumab (n = 225) or open‐label vedolizumab (n= 521) 300 mg at week 0 and week 2. At week 6, participants who demonstrated clinical response (reduction in Mayo Clinic score of ≥ 3 and a decrease of ≥ 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 or an absolute rectal bleeding subscore of 0 or 1) were then randomly assigned in a 1:1:1 ratio to receive DB vedolizumab every 8 weeks (n = 122), vedolizumab every 4 weeks (n = 125), or placebo (n = 126), for up to 52 weeks. Participants who did not have a clinical response at week 6 to vedolizumab induction therapy received vedolizumab at a dose of 300 mg every 4 weeks, for up to 52 weeks (n = 330). Age [Mean(SD) years): placebo 41.2 (12.5); vedolizumab DB induction therapy 40.1(13.1); vedolizumab open‐label induction therapy 40.1(13.3) Gender: placebo (92 males, 57 females); vedolizumab DB induction therapy (132 males; 93 females); vedolizumab open‐label induction therapy (301 males; 220 females) Disease duration [Mean(SD) years]: placebo 7.1 (7.2); vedolizumab DB induction therapy 6.1 (5.1); vedolizumab open‐label induction therapy 7.2 (6.6) Disease status [Mean(SD) Mayo Clinical score]: placebo 8.6 (1.7); vedolizumab DB induction therapy 8.5 (1.8); vedolizumab open‐label induction therapy 8.6 (1.8) Loss to follow‐up for maintenance phase: placebo (n = 78); vedolizumab maintenance therapy (300 mg every 8 weeks) (n = 45); vedolizumab maintenance therapy (300 mg every 4 weeks) (n = 41)
Interventions	Vedolizumab maintenance therapy Dosing regimen: a) 300 mg every 8 weeks; b) 300 mg every 4 weeks Mode of delivery: Intravenous infusion Duration: Six weeks DB or open‐label vedolizumab, followed by up to 52 weeks of randomised vedolizumab. Setting of trial: 211 medical centres (15 centres discontinued enrollment) in 34 countries worldwide Comparision treatment: placebo (double‐blind placebo intravenous infusions at week 0 and week 2, followed by every 4 weeks from week 6) Co‐interventions: Not reported
Outcomes	Fatigue was assessed using the IBDQ subcomponent 'fatigue' and 'energy level' (Rubin 2018). Quality of life was assessed using the IBDQ. Adverse events were assessed according to the Medical Dictionary for Regulatory Activities, version 15. Other outcomes assessed: Clinical remission, CRP, clinical response, glucocorticoid‐free clinical remission; durable clinical remission Assessment time points: Baseline, week 2, week 4, week 6 in the trial of induction therapy and every 4 weeks thereafter during the trial of maintenance therapy until week 52. IBDQ was assessed at week 6, week 30 and week 52.
Notes	3‐arm trial (2 experimental, 1 control) The study was supported by Millennium Pharmaceuticals. Additional study information request from Takeda Oncology (formally Millennium Pharmaceuticals) via the Vivli Platform, was declined as fatigue was considered a tertiary endpoint in the study, thus, not meeting the eligibility criteria for this review (primary or secondary outcome).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was performed centrally with the use of computer‐generated randomization schedules".
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Participant, Care Provider and Investigator were blinded to treatment assignment throughout the maintenance phase of the study".
Blinding of outcome assessment (detection bias) All outcomes	High risk	The investigators and participants were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss to follow‐up relatively similar across the groups and reasons comparable
Selective reporting (reporting bias)	High risk	Fatigue and quality of life outcomes assessed but not reported in full‐text publication or available upon request
Other bias	Low risk	"No clinically important differences in baseline characteristics". No apparent sources of bias evident