Adalimumab produces clinical remission and reduces extraintestinal manifestations in Crohn's disease: Results from CARE

Background: Data regarding the effectiveness of anti-tumor necrosis factor (TNF) agents for resolution of extraintestinal manifestations (EIMs) are scarce. The CARE study evaluated clinical effectiveness, EIM resolution, and safety of adalimumab in a large pan-European cohort of patients with moderate to severe Crohn's disease (CD). Methods: In all, 945 patients with a Harvey-Bradshaw Index (HBI) >= 7 enrolled in this multicenter, open-label phase IIIb trial. Patients received subcutaneous adalimumab, 160/ 80 mg at weeks 0/ 2, then 40 mg every other week. Dose adjustments were allowed for CD-related concomitant medications (from week 8) and adalimumab (from week 12). Clinical endpoints were analyzed through week 20 for all patients, and after stratification by prior infliximab exposure and by reason for discontinuing infliximab (primary nonresponse [ PNR] or other). Results: The remission rate (HBI < 5) at week 20 was 52% (95% confidence interval, 49%-55%) overall, and was higher for infliximab-nai ve versus infliximab-exposed patients (62% versus 42%, P < 0.001). Remission rates were similar for PNR (37%) and other reasons (43%; P 0.278). Of 497 patients with baseline EIMs, 51% were free of EIM signs and symptoms at week 20. Serious infectious adverse events were reported in 5% of patients. Opportunistic infections and malignancies were rare (>= 1%). There was one case of demyelinating disease, but no occurrences of lupus, tuberculosis, or death. Conclusions: In this large cohort of patients, adalimumab treatment resulted in rates of clinical remission and EIM resolution exceeding 50%, and substantial rates of effectiveness in patients who had PNR to infliximab. Adalimumab was well tolerated, with safety consistent with prior reports.