Adalimumab-treated Patients with Moderate to Severe Crohnʼs Disease Experienced Reductions in Extraintestinal Manifestations: Data from CHARM

Abstract

Purpose: Crohn's disease (CD) is associated with extraintestinal manifestations (EIMs) in approximately 25% of patients. We assessed the effect of adalimumab therapy on EIMs in patients treated in CHARM, a 56-week, double-blind, Phase III trial of adalimumab for maintenance of clinical response and remission in patients with moderately to severely active CD. Methods: All patients received open-label (OL) adalimumab induction therapy of 80 mg/40 mg at Weeks 0/2 and were randomized at Week 4 to adalimumab 40 mg every other week (eow), adalimumab 40 mg weekly, or placebo. From Week 12, patients with flares or nonresponse could receive OL adalimumab 40 mg eow (weekly if flares/nonresponse continued). The presence of EIMs was evaluated at baseline, and patients could have multiple EIMs. Assessment of EIMs was based on Question 4 of the Crohn's Disease Activity Index, which evaluates the presence of manifestations related to CD including arthritis/arthralgia, iritis/uveitis, and erythema nodosum/pyoderma gangrenosum/aphthous stomatitis. Of patients with EIMs at baseline, resolution of EIMs at Weeks 26 and 56 was compared between treatment groups in a double-blinded fashion. Nonresponder imputation was used if patients discontinued the study or moved to OL adalimumab. Results: Of the 778 patients randomized in CHARM, 420 (54.0%) had arthritis/arthralgia symptoms at baseline. Thirty-eight patients (4.9%) had baseline erythema nodosum, pyoderma gangrenosum, or aphthous stomatitis; these EIMs were not further analyzed because of the small sample size. Of patients with arthritis/arthralgia at baseline, resolution occurred in a significantly greater percentage of patients who received adalimumab compared with placebo (table). The absence of arthritis/arthralgia symptoms was evident at Week 26 and continued through Week 56. Conclusion: Adalimumab therapy was effective in reducing the presence of baseline arthritis/arthralgia EIMs in patients with moderately or severely active CD in CHARM. Disclosure: Dr schwartz - 1) P & G: Speakers bureau and grant support 2) Abbott: Speakers bureau, grant support, consultant 3) Centocor: Speaker's bureau 4) Salix: Speakers bureau 5) UCB: Speakers bureau and grant support 6) Prometheus: Speakers bureau 7) Cellerix: Consultant 8) Shire: Speakers bureau Dr Lofberg - Consulting and research funding: Abbott Labs, Asahi, Astra Zeneca, Celltech, Centocor, Connexion, Cosmo, Elan, InDex Pharmaceuticals, Meda, Otsuka, Pharmacia-Pfizer, Schering Plough, Schering AG, Serono, UCB. Dr Pollack - Employee of Abbott Laboratories; Stockholder: Abbott, Johnson & Johnson (Janssen), Human Genome Sciences Mr Chen - Employee: Abbott Dr Mulani - Employee, stocks: Abbott Dr Chao - Employee, stocks: Abbott This research was funded by Abbott Laboratories, Abbott Park, IL.Table: Patients with resolution of arthritis/arthralgiaa