Panes 2013.

Methods	Randomized, multi‐center, double‐blind, placebo‐controlled study performed in 31 Spanish hospitals over 76 weeks Data was analysed using an intention‐to‐treat approach The study was stopped because it met pre‐established futility criteria in the interim analysis
Participants	Patients (N = 131) aged 18‐70 years, diagnosed with established CD criteria within 8 weeks of screening irrespective of disease activity and use of corticosteroids at the time of screening Exclusion criteria: patients who had previously been treated with AZA, 6‐MP, methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, infliximab or adalimumab; an immediate need for surgery; previous surgery for CD; symptomatic stenosis; internal penetrating or perianal fistulizing disease; severe comorbidity; documented infection; malignancy; or history of drug abuse and pregnancy
Interventions	AZA 2.5 mg/kg/day, oral (n = 68) versus identically‐matched placebo (n = 63) Those receiving corticosteroids at randomization point had doses decreased by 10 mg/wk until a dosage of 20 mg/day was achieved; it was then decreased by 5 mg/wk until cessation Those previously receiving budesonide were tapered according to the following schedule: budesonide was tapered after completion of 6 weeks of treatment with 9 mg/day to 6 mg/day for 3 weeks and to 3 mg/day for 3 weeks thereafter Corticosteroids were allowed to treat flares during the study, (prednisone doses ranged 1 mg/kg/day to a maximum of 60 mg/day; budesonide dosage 9 mg/day), but were tapered using the above schedule No other medications used to treat CD were allowed, except antibiotics for suspected or demonstrated infection
Outcomes	Primary outcome was the rate of corticosteroid free clinical remission (CDAI < 150) at week 76 Secondary outcomes were rates at different time points; relapse‐free survival, mean CDAI and IBDQ scores, and CRP concentrations at each visit; requirement for corticosteroids; cumulative dose of corticosteroids; development of a fistula; requirements for hospitalization; and CD‐related surgery; and cumulative prednisone dose Safety data was also collected
Notes	Sustained corticosteroid‐free remission was defined as the presence of clinical remission (CDAI score <150 at each visit) in patients who had not been treated with corticosteroids during the entire study or patients who were treated with corticosteroids at baseline after the scheduled weaning of this treatment Relapse was defined as a CDAI score > 175 at week 12 or later Patients who did not achieve remission after randomization with a CDAI score > 175 at week 12 were categorized as in relapse
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization was performed centrally with the use of an adaptive randomization procedure stratified according to age (< 40 years) and use of systemic corticosteroids at the time of inclusion (yes or no)
Allocation concealment (selection bias)	Low risk	Centralized randomization
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind Patients, study site personnel, and study investigators were unaware of the treatment assignment The local investigator was not blinded; performed dose adjustment if bone marrow suppression was observed in the blood tests
Incomplete outcome data (attrition bias) All outcomes	Low risk	Any missing patient data is described and justified throughout the screening and study period Description of analysis as intention‐to‐treat, with missing data accounted for
Selective reporting (reporting bias)	Low risk	Primary and secondary endpoints described in the methods section were reported in the results section Post hoc analyses evaluating requirement of corticosteroids in patients under 40 years and the presence or perianal disease as predictors of disabling disease
Other bias	Low risk	The study appears to be free of other sources of bias