Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease Recurrence. A GETECCU Randomised Trial

J Crohns Colitis. 2017 Oct 27;11(11):1293-1301. doi: 10.1093/ecco-jcc/jjx051.


Background and aims: Postoperative recurrence of Crohn's disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting.

Methods: We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader.

Results: We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions.

Conclusions: ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. NCT01564823.

Keywords: Crohn’s disease; adalimumab; azathioprine.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adalimumab / therapeutic use*
  • Adult
  • Azathioprine / therapeutic use*
  • Crohn Disease / prevention & control*
  • Crohn Disease / surgery
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Postoperative Care / methods
  • Secondary Prevention / methods


  • Immunosuppressive Agents
  • Adalimumab
  • Azathioprine

Associated data