Subgroup analysis of the placebo-controlled CHARM trial: increased remission rates through 3 years for adalimumab-treated patients with early Crohn's disease

J Crohns Colitis. 2013 Apr;7(3):213-21. doi: 10.1016/j.crohns.2012.05.015. Epub 2012 Jun 16.

Abstract

Background and aims: 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.

Trial registration: ClinicalTrials.gov NCT00077779 NCT00195715.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Crohn Disease / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Induction Chemotherapy
  • Kaplan-Meier Estimate
  • Logistic Models
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Adalimumab

Associated data

  • ClinicalTrials.gov/NCT00077779
  • ClinicalTrials.gov/NCT00195715