Adalimumab Rapidly Induces Clinical Remission and Response in Patients with Moderate to Severe Crohnʼs Disease Who Had Secondary Failure to Infliximab Therapy

Abstract

Purpose: To assess the safety and efficacy of adalimumab (ADA), a self-injectable, fully human anti-TNF monoclonal antibody, in the induction of clinical remission (CDAI < 150) and response in patients with active Crohn's disease (CD) who had secondary failure to infliximab (IFX) therapy. Methods: Patients with moderate to severe CD (CDAI 220–450) and secondary failure to IFX therapy were enrolled in GAIN, a Phase III, double-blind, placebo-controlled study, and were randomized to receive ADA, 160 mg sc at Wk 0 (BL) and 80 mg sc at Wk 2, or placebo (PBO) at both time points. Primary endpoint was remission at Wk 4. Secondary endpoints were clinical response (CR) defined as a decrease from BL CDAI of ≥70 or 100 (CR70/100) at Wk 4. Safety was assessed throughout the study. Results: Patients were randomized to receive ADA (N = 159) or PBO (N = 166). Baseline characteristics were similar between the two arms: mean age, 38 yrs; female, 65%; mean CDAI, 313 (± 62 SD); median CRP, 0.8 mg/dL; immunosuppressant use, 48%. Clinical remission and response rates observed in the ADA arm were significant vs. PBO. Serious adverse events (SAE) were observed in 4.8% of PBO patients (abscess, 3; sepsis, 1; CD flare, 1; dehydration, 1; abdominal pain, 1) and in 1.3% of ADA patients (CD flare, 1; dehydration, 1). No delayed-hypersensitivity (serum sickness) reactions or deaths occurred. The overall safety profile of ADA was consistent with prior CD trials and the existing RA database. Conclusions: Adalimumab rapidly and significantly induced clinical remission and response in patients with moderate to severe CD who had secondary failure to IFX. Adalimumab was well-tolerated.Table: Clinical Remission and Response in GAIN.