Savarino 2013.

Methods	Study design: RCT, single Setting: Italy; University Hospital of Genoa; 2008 to 2010
Participants	Inclusion: Adult patients with ileal or ileocolonic CD within 4 weeks of resection of macroscopically diseased bowel with anastomosis between normal ileum and colon. Exclusion: Patients with (i) more than 10 years of CD requiring first resective surgery for short (10 cm) fibrostenotic stricture, (ii) macroscopically active disease not resected at the time of surgery, and (iii) presence of a stoma. Age (IG1 / IG2) median (range): not reported, overall > 18 years; 45 (22 to 66 years) versus 46 (25 to 65 years) Sex (M:F): 25:26 overall; (8:8) versus (9:8) versus (8:10) Type of surgery: not reported Previous surgery (IG1+IG2): one‐40 (12/15/13); two‐9 (3/2/4); three‐2 (1/0/1) Start of intervention after surgery: 2 to 4 weeks Medication use (IG1+ IG2): Not reported Smoker (IG1 / IG2): 19 (9/4/6) Number randomised (N = 51): 16/17/18 Number analysed (N = 51): (16) versus (17) versus (18) Post‐randomisation exclusion (n = 5): (1/16 ) versus (2/17) versus (2/18) (unclear)
Interventions	Group 1: Adalimumab subcutaneous injections 160 / 80 mg at 0 and 2 weeks, followed by 40 mg every 2 weeks for 2 years Group 2: Azathioprine (Azafor, Sofar S.P.A., Milan, Italy), at the dose of 2 mg / kg every day for 2 years Group 3: Mesalamine (Pentasa, Ferring S.P.A., Milan, Italy), at the dose of 3 g / day divided in 3 doses for 2 years All participants: Patients on antibiotics or immunomodulators at entry into the study discontinued these medications 12 weeks before surgery. Continuous use of nonsteroidal anti‐inflammatory drugs was not allowed during the study. No other medications were prescribed except for occasional tablets of paracetamol or tramadol. Patients were subjected to endoscopy at 12 and 24 months; small bowel enteroclysis or magnetic resonance imaging at 12 and 24 months; physical examination with interviews, together with an extensive battery of blood tests weekly for the first 4 weeks and then every 2 months, and completed an IBD‐Q at 1 month before surgery and at 12 and 24 months aft er surgery. The CDAI was determined at each study visit. In addition, adverse events were ascertained at each visit
Outcomes	Duration of study: 2 years 1. Clinical recurrence d defined as a score of ≥ 2 on the clinical recurrence grading scale 1‐4 proposed by Hanauer et al. 2. Clinical recurrence based on CD activity index (CDAI) was calculated for each patient and recurrence was set in case of a score > 200, whereas clinical remission was defined by a CDAI score of < 150 2. Endoscopic recurrence defined by a Rutgeerts score of ≥ i2 3. Radiologic recurrence defined as a score of ≥ 2 on the radiographic recurrence grading scale (where 1 indicates normal; 2, mucosal edema / aphthoid ulcers; 3, linear ulcers / cobblestoning; and 4, strictures / fistulas / inflammatory mass) 4. Health‐related quality of life 5. Median Lémann Index 5. Adverse events
Notes	Funding source: supported by research funds of the university Conflict of interest: Authors declare no conflict of interest Power calculation: we considered reasonable to hypothesize an endoscopic recurrence rate of ˜ 80 % and 15 % and a clinical recurrence rate of ˜ 65 % and 5 % for the mesalamine and ADA groups, respectively, at 2 years of follow‐up. This estimation has been supported by the results shown in previous trials on postoperative CD relapse. Thus, based on these data, 13 patients per treatment group resulted to be sufficient to detect a difference of at least 65 % for endoscopic recurrence and 60 % for clinical recurrence in favour of the ADA group with a power of 80 % (global type I error of 5 % ). Th e number of patients in each group was increased to 16 to compensate for an anticipated dropout rate of 15 % .
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Eligible and consenting patients were assigned randomly using a computer‐generated sequence (www. randomizer.org) to a regimen of…” Comment: Computer generated random sequence
Allocation concealment (selection bias)	Low risk	Quote: "Patient allocation was concealed and performed by an independent nurse not involved with the trial" Comment: Probably done
Blinding of participants and personnel (performance bias) All outcomes	High risk	Study is open‐label design
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "“A blinded investigator (P.D.) reviewed each patient's video‐recorded procedure and provided a separate endoscopic score” and “At the conclusion of the study, the principal investigator (E.S.) rescored each patient by re‐reviewing the video recordings in a random and blinded manner” Comment: Assessors were blinded for endoscopic assessments only. However, no information on clinical assessment of relapse
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: “Statistical analysis was conducted according to the intention‐to‐treat principle.” Comment: ITT analysis applied. Withdrawals and reasons reported
Selective reporting (reporting bias)	Low risk	Trial registration not available, however, all outcomes stated in the method section reported
Other bias	Low risk	Quote: “Characteristics were similar for sex, age, smoking, duration of CD, disease behavior, disease location, prior medication exposure, including IFX, and prior surgical resection” Comment: Groups well balanced at baseline; no other apparent sources of bias detected