Predictors of Infliximab Failure After Azathioprine Withdrawal in Crohn's Disease Treated With Combination Therapy

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 <= 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.