Ogata 2012.

Study characteristics
Methods	RCT Setting: multicentre hospitals in Japan Study period: August 2006 to February 2008 Trial/protocol registration and availability: protocol or trial registration not available
Participants	Inclusion criteria: active moderate/severe UC; left‐sided colitis and pancolitis; steroid resistance or steroid dependent; permitted medications (5‐ASA, steroids), without adjustments in the previous 2 weeks or throughout the study Exclusion criteria: positive Clostridium difficile on stool culture; hepatic/renal failure; pregnant or lactating women; AZA > 3 months before screening, and were permitted to continue taking AZA at an unchanged dose over the period beginning 3 months prior to the start of the study, until completion of the study; cytapheresis within 14 days; ciclosporin, biological therapies, 6‐MP, or other immunosuppressants Disease duration: NR Disease activity: DAI score mean: IG: 9.8 (SD 1.61); CG: 9.1 (SD 1.05) Extent of disease: NR Age: NR Sex (M/F): NR Concurrent therapies: NR Number randomised: 32/30 Number reaching end of study: 32/30
Interventions	IG: oral tacrolimus capsules contained 0.5 mg or 1 mg to achieve blood trough concentration of 10–15 ng/mL Tacrolimus therapy was initiated at a small dose of 1–2.5 mg per time, twice daily. Blood collection at 12 hours and 24 hours was required after the initial dose for determination of the trough concentration of tacrolimus. CG: placebo: pseudo‐dose adjusted After 2 weeks, the RCT was ended and all participants started receiving tacrolimus for the open‐label phase of the study.
Outcomes	Length of intervention: 2 weeks followed by a 10‐week open‐label phase Follow‐up points: week 0, week 2 and week 12 Primary outcomes: Definition of clinical improvement by study authors: clinical response defined as a reduction in DAI by ≥ 4 points and improvements in all categories (stool frequency, rectal bleeding, mucosal appearance and physician's overall assessment) Number of participants who achieved clinical improvement: IG: 16/32; CG: 4/30 Definition of remission by study authors: clinical remission defined as a DAI score ≤ 2, with an individual subscore 0 or 1, and mucosal healing was defined as an endoscopy subscore of 0 or 1 Number of participants who achieved remission: IG: 3/32; CG: 0/30 Secondary outcomes: Number of participants who required other rescue medication: NR Number of participants who underwent surgery: NR Adverse events: IG: 26; CG: 21 Related adverse events occurring in > 5% of participants in ≥ 1 of the treatment groups: Nausea: IG: 4; CG: 3 Headache: IG: 4; CG: 3 Numbness: IG: 4; CG: 0 Finger tremor: IG: 3; CG: 1 Dysmenorrhoea: IG: 3; CG: 1 Hot flushes: IG: 2; CG: 1 Abdominal pain upper: IG: 2; CG: 1 Back pain: IG: 2; CG: 1 Withdrawal due to adverse events: IG: 0; CG: 0 Serious adverse events: IG: 0; CG: 0
Notes	Author contact details: NR Conflict of interest: authors declared there were no conflicts of interest. Sponsor: industry funding (Astellas Pharma Inc., Japan)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation performed by the Control Center (Bellsystem 24), a third‐party organisation independent of study physicians and sponsor. However, not mentioned how it was performed and we received no response from authors.
Allocation concealment (selection bias)	Unclear risk	Not mentioned how it was performed and we received no response from authors. Quote: "to preserve the blindness of the study, blood trough levels were measured by SRL Inc. (a third party organisation independent of the study physicians or sponsor) and values were forwarded to Control Center (a third‐party organisation independent of the study physicians or sponsor)".
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo, double‐blind study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Placebo, double‐blind study.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomised participants finished the study.
Selective reporting (reporting bias)	Low risk	Authors stated outcomes in their methods were reflected in their results.
Other bias	Unclear risk	Insufficient information provided for baseline characteristics.

5‐ASA: 5‐aminosalicylic acid; 6‐MP: 6‐mercaptopurine; AZA: azathioprine; CAI: Clinical Activity Index; CG: control group; DAI: Disease Activity Index; eGFR: estimated glomerular filtration rate; F: female; GFR: glomerular filtration rate; IBDQ: Inflammatory Bowel Disease Questionnaire; IG: intervention group; IG H: intervention group high trough concentration; IG L: intervention group low trough concentration; IV: intravenous; M: male; MTX: methotrexate; NR: not reported; RCT: randomised controlled trial; SD: standard deviation; SEM: standard error of the mean; TNF: tumour necrosis factor; UC: ulcerative colitis; UP: ulcerative proctitis.