Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn's disease.
OBJECTIVE
The effect of different treatment regimens on antibody responses to infliximab and their clinical significance was examined by using data from ACCENT I.


METHODS
Patients with Crohn's disease (n = 573) received 5 mg/kg infliximab (week 0) and then were randomly assigned to blinded infusions at weeks 2 and 6 and every 8 weeks until week 46 of placebo (group I), 5 mg/kg infliximab (group II), or 5 mg/kg infliximab at weeks 2 and 6, followed by 10 mg/kg thereafter (group III). At week 14 or later, patients losing response could cross over to episodic infliximab treatment increased by 5 mg/kg. Samples for antibody determination were collected before the first infusion and at weeks 14, 22, 54, 62, 72, and, if applicable, before and after crossover.


RESULTS
Through week 72, antibodies to infliximab were detected in 30%, 10%, and 7% of groups I, II, and III, respectively (P < 0.0001). Patients receiving immunomodulators had a lower incidence of antibodies compared with patients receiving infliximab alone (10% and 18%, respectively; P = 0.02). Antibodies were associated with a 12% absolute increase in infusion reactions but no increase in serious infusion reactions or serum sickness-like reactions. In the overall population, similar proportions of antibody-positive and antibody-negative patients achieved clinical response (64% and 62%, respectively; P = NS) or clinical remission (41% and 39%, respectively; P = NS) at week 54. Notably, 86% of patients responded to retreatment, and 63% were in clinical response at week 54; however, fewer antibody-positive group I patients attained clinical remission (31%) compared with those who were antibody negative (37%) or antibody inconclusive (54%) (P = NS).


CONCLUSIONS
Reduced antibody formation and greater clinical benefit were observed with an induction regimen followed by maintenance treatment compared with a single dose followed by episodic retreatment in Crohn's disease patients treated with infliximab.
Hanauer
Stephen B
SB
Department of Gastroenterology and Nutrition, University of Chicago Medical Center, IL 60637, USA. shanauer@uchicago.edu
Wagner
Carrie L
CL
Bala
Mohan
M
Mayer
Lloyd
L
Travers
Suzanne
S
Diamond
Robert H
RH
Olson
Allan
A
Bao
Warren
W
Rutgeerts
Paul
P
D000906:Antibodies / Q000032:analysis* / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000917:Antibody Formation / Q000187:drug effects; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000008:administration & dosage; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000906:Antibodies; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D000069285:Infliximab