Subgroup analysis of the placebo-controlled CHARM trial: increased remission rates through 3 years for adalimumab-treated patients with early Crohn's disease.
OBJECTIVE
We examined the impact of disease duration on clinical outcomes and safety in a post hoc analysis of a remission maintenance trial with adalimumab in patients with moderate to severe CD.


METHODS
Patients in the CHARM trial were divided into 3 disease duration categories: <2 (n=93), 2 to <5 (n=148), and ≥5 years (n=536). Clinical remission and response rates at weeks 26 and 56 were compared between adalimumab and placebo subgroups, and assessed through 3 years of adalimumab treatment in the ADHERE follow-on trial. Logistic regression assessed the effect of disease duration and other factors on remission and safety.


RESULTS
At week 56, clinical remission rates were significantly greater for adalimumab-treated versus placebo-treated patients in all 3 duration subgroups (19% versus 43% for <2 years; P=0.024; 13% versus 30% for 2 to <5 years; P=0.028; 8% versus 28% for ≥5 years, P<0.001). Logistic regression identified shorter duration as a significant predictor for higher remission rate in adalimumab-treated patients. Patients with disease duration <2 years maintained higher remission rates than patients with longer disease duration through 3 years of treatment. The incidence of serious adverse events in adalimumab-treated patients was lowest with disease duration <2 years.


CONCLUSIONS
Adalimumab was superior to placebo for maintaining clinical remission in patients with moderately to severely active CD after 1 year of treatment regardless of disease duration. Clinical remission rates through 3 years of treatment were highest in the shortest disease duration subgroup in adalimumab-treated patients, with a trend to fewer side effects.
Department of Medicine I, University Hospital Schleswig-Holstein, Kiel, Christian-Albrechts University, Germany. s.schreiber@mucosa.de
S
S
Schreiber
W
W
Reinisch
J F
JF
Colombel
W J
WJ
Sandborn
D W
DW
Hommes
A M
AM
Robinson
B
B
Huang
K G
KG
Lomax
P F
PF
Pollack
D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D000068879:Adalimumab