Sandborn 2012.

Methods	Randomized, double‐blind, placebo‐controlled trial
Participants	Inclusion criteria: adult patients (≥ 18 years) with at least a 3‐month history of Crohn's disease and a score of 220 to 450 points on the CDAI were included in the induction phase. CERTIFI participants had moderate to severe Crohn's disease that was resistant to TNF‐α antagonists. Participants with a response to ustekinumab at 6 weeks of the induction phase were included in the maintenance phase (N = 145). Exclusion criteria: previous therapy specifically targeting interleukin‐12 or interleukin‐23
Interventions	Group 1: Placebo (N = 73) Group 2: Subcutaneous ustekinumab at weeks 8 and 16 (weeks 1 and 9 of maintenance phase), 90 mg (N = 72)
Outcomes	Primary outcome: Clinical response (≥ 100‐point decrease in CDAI) at week 6 Secondary outcomes: Clinical remission (CDAI < 150 points) at week 6 Clinical response at week 4 Clinical remission at week 22 among participants with a response to ustekinumab at week 6
Duration of follow‐up	Induction phase: 8 weeks Maintenance phase: 36 weeks
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central randomization was performed based on investigative site and the induction dose using Pocock and Simon's (1975) randomization method.
Allocation concealment (selection bias)	Low risk	Centralized randomization
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo administrations will have the same appearance as the respective ustekinumab administrations.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Treatment assignment blinding was maintained for investigative sites, site monitors, and participants in the study until the week 36 analyses were completed.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dropouts were balanced across interventions with similar reasons for withdrawal.
Selective reporting (reporting bias)	Low risk	All expected outcomes were reported.
Other bias	Low risk	The study appears to be free of other sources of bias.

CDAI: Crohn's Disease Activity Index; TNF‐α: tumor necrosis factor‐alpha