TY - JOUR
T1 - Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn's disease
AU - Hanauer, Stephen B.
AU - Wagner, Carrie L.
AU - Bala, Mohan
AU - Mayer, Lloyd
AU - Travers, Suzanne
AU - Diamond, Robert H.
AU - Olson, Allan
AU - Bao, Warren
AU - Rutgeerts, Paul
PY - 2004/7/1
Y1 - 2004/7/1
N2 - Background & Aims: 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.
AB - Background & Aims: 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.
KW - 6-MP
KW - 6-mercaptopurine
KW - ACCENT I
KW - ACR20/50
KW - ATTRACT
KW - American College of Rheumatology definition of 20% or 50% improvement
KW - a Crohn's disease clinical trial evaluating infliximab in a new long-term treatment regimen in patients with Crohn's disease
UR - http://www.scopus.com/inward/record.url?scp=3042579454&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042579454&partnerID=8YFLogxK
U2 - 10.1016/S1542-3565(04)00238-1
DO - 10.1016/S1542-3565(04)00238-1
M3 - Article
C2 - 15224278
AN - SCOPUS:3042579454
VL - 2
SP - 542
EP - 553
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 7
ER -