Predictors of infliximab failure after azathioprine withdrawal in Crohn's disease treated with combination therapy.

Abstract

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.

• Authors: Abderrahim Oussalah, Jean-Baptiste Chevaux, Renaud Fay, William J Sandborn, Marc-André Bigard, Laurent Peyrin-Biroulet
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 105 Issue 5 Pg. 1142-9 (May 2010) ISSN: 1572-0241 [Electronic] United States
• PMID: 20389296 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Immunosuppressive Agents
• Infliximab
• Azathioprine

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Azathioprine (administration & dosage, adverse effects)
• Cohort Studies
• Confidence Intervals
• Crohn Disease (diagnosis, drug therapy, mortality)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Infliximab
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Predictive Value of Tests
• Probability
• Proportional Hazards Models
• Recurrence
• Retrospective Studies
• Risk Assessment
• Severity of Illness Index
• Survival Rate
• Treatment Failure
• Treatment Outcome
• Withholding Treatment
• Young Adult