Adalimumab Maintenance Therapy Is Associated with a Reduced Risk of Major Surgery

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Purpose: The majority of patients with Crohn's disease (CD) will undergo surgery during their lifetimes. In 2006, CD-related hospitalizations involving surgery were twice as costly as non-surgical hospitalizations with estimated annual costs of $49,4051. Adalimumab (ADA) is approved in the U.S. for use in the treatment of moderate to severe CD in adults. CHARM was a 56-week, Phase III, randomized, placebo-controlled trial that assessed the ability of ADA to maintain clinical remission in patients (pts) with moderate to severe CD. Methods: We evaluated the effects of ADA maintenance therapy on major CD-related surgery in pts who participated in the CHARM trial. At Week 4 of the study, 778 pts were randomized to 40 mg ADA every other week (eow), 40 mg ADA weekly, or placebo, and studies through 56 weeks. All pts were followed from Week 4 (ie, after randomization) until the first occurrence of the following events: switch to open-label therapy with ADA, withdrawal from the study, or end of trial. The numbers of major CD-related surgeries for each treatment group, as assigned by 2 authors (BGF and KGL), were compared through Poisson regression analysis. Major CD-related surgeries, excluding drainage of abscess and placement of a seton, were those performed in hospital, recorded as serious adverse events in the trial, and deemed to be major by the investigators. Kaplan–Meier estimates of CD-related surgical hospitalization rates were compared using log-rank test. Results: The rate of CD-related surgeries was significantly reduced by 80–90% in patients receiving ADA eow or weekly therapies versus patients on placebo. These rates were 0.4%, 0.8%, 0.6%, and 3.8% in the ADA eow, weekly, combined ADA, and placebo arm respectively (all P≤ 0.01 vs placebo). Based on Kaplan–Meier analysis, the 1-year actuarial CD-related surgical hospitalization rates for the eow, weekly, combined ADA, and the placebo groups were 0.7%, 1.2%, 1.0%, and 4.8%, respectively (all P < 0.05 vs placebo, log-rank test). Conclusion: Patients who received adalimumab maintenance therapy had a significant decreased risk for CD-related surgery and surgical hospitalization. These findings demonstrate the importance of effective maintenance therapy for altering the natural course of disease and have significant cost implications for society and third-party payers.