Infliximab, azathioprine, or combination therapy for Crohn's disease.
BACKGROUND
The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.


METHODS
In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50.


RESULTS
Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P=0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P=0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group.


CONCLUSIONS
Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)
Colombel
Jean Frédéric
JF
Hôpital Claude Huriez and Centre d'Investigation Clinique, Centre Hospitalier Universitaire de Lille, Université Lille Nord de France, Lille, France. jfcolombel@chru-lille.fr
Sandborn
William J
WJ
Reinisch
Walter
W
Mantzaris
Gerassimos J
GJ
Kornbluth
Asher
A
Rachmilewitz
Daniel
D
Lichtiger
Simon
S
D'Haens
Geert
G
Diamond
Robert H
RH
Broussard
Delma L
DL
Tang
Kezhen L
KL
van der Woude
C Janneke
CJ
Rutgeerts
Paul
P
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D007262:Infusions, Intravenous; D016015:Logistic Models; D008297:Male; D012074:Remission Induction
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D000069285:Infliximab; D001379:Azathioprine