Objectives: Whether all Crohn's disease (CD) patients should maintain long-term azathioprine treatment in combination with infliximab remains controversial. We analyzed the predictive factors of infliximab failure after azathioprine withdrawal.
Methods: This was an observational study from a single referral center. All patients with luminal CD in remission who stopped azathioprine after receiving infliximab in combination with azathioprine for at least 6 months were studied. Cumulative probabilities of infliximab failure-free survival were estimated by the Kaplan-Meier method from the date of azathioprine withdrawal to the date of infliximab failure or last known follow-up. Infliximab failure was defined by: (i) disease flare requiring shortening of the dosing interval or increasing the infliximab dose to 10 mg/kg, or switching to adalimumab; (ii) acute or delayed hypersensitivity reactions leading to infliximab discontinuation; or (iii) CD-related surgery.
Results: At last known follow-up, 35 out of 48 (73%) patients were infliximab failure free. The survival probabilities were 85% (+/-5%) at 12 months and 41% (+/-18%) at both 24 and 32 months. Cox proportional-hazards regression identified three predictors of infliximab failure: infliximab-azathioprine exposure duration of < or = 811 days (hazard ratio (HR)=7.46, P=0.01), C-reactive protein > 5 mg/l (HR=4.79, P=0.008), and platelet count > 298 10(9)/l (HR=4.75, P=0.02).
Conclusions: In CD in clinical remission under azathioprine-infliximab combination therapy, azathioprine withdrawal is associated with a high risk of relapse in patients with a duration of combination therapy of < 27 months and/or the presence of biological inflammation.