Predictors of infliximab failure after azathioprine withdrawal in Crohn's disease treated with combination therapy.
OBJECTIVE
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.
Oussalah
Abderrahim
A
INSERM, U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.
Chevaux
Jean-Baptiste
JB
Fay
Renaud
R
Sandborn
William J
WJ
Bigard
Marc-André
MA
Peyrin-Biroulet
Laurent
L
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D016001:Confidence Intervals; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069285:Infliximab; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D017211:Treatment Failure; D016896:Treatment Outcome; D028761:Withholding Treatment; D055815:Young Adult
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D000069285:Infliximab; D001379:Azathioprine