Safety and Efficacy of Abatacept Over 4 Years of Treatment in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate in the AIM Trial

OBJECTIVE: To present the safety and efficacy of abatacept over 4 years in the AIM trial. METHODS: AIM was a randomized, double-blind (DB), placebo-controlled trial of 12 months’ duration. Patients received a fixed dose of abatacept (~10 mg/kg) or placebo, plus methotrexate (MTX). Patients completing the DB period were eligible to enroll in the open-label long-term extension (LTE) period (fixed dose of abatacept ~10 mg/kg every 4 weeks plus MTX). Safety was assessed for all patients who received ≥1 dose of abatacept; incidence rates per 100 patient-years (pt-yrs) were calculated. Efficacy analyses included ACR 20, 50 and 70 responses, and are presented for all patients with data available at the visit of interest (as-observed analysis). RESULTS: A total of 433 and 219 patients were randomized and treated with abatacept or placebo, respectively; 378 and 161 of these patients entered the LTE period. In total, 414/539 (76.8%) patients who entered the LTE remained on treatment at the end of the 4 year study period. The types and incidence of adverse events (AEs) and serious adverse events (SAEs) were similar between the DB versus cumulative (combined DB + LTE) periods (303.4 vs 244.2/100 pt-yrs and 17.7 vs 14.7/100 pt-yrs, respectively). Incidence rates of infections and serious infections were 90.5 versus 69.0/100 pt-yrs and 4.2 versus 3.1/100 pt-yrs, in the DB versus cumulative periods, respectively. Malignancies, autoimmune events and tuberculosis (TB) were reported in 28 (4.7%), 45 (7.6%) and 3 (0.7%) patients, respectively, over 4 years. In the cumulative study period, 62 (10.4%) and 40 (6.7%) patients discontinued due to AEs and SAEs, respectively. The proportion of abatacept-treated patients who were ACR responders increased over 4 years; with no overlap of 95% CIs at 6 months and 4 years. CONCLUSION: In the LTE period of the AIM trial, the safety of abatacept remained consistent with the DB period, with no unique or unexpected events observed over 4 years. Retention rates remained high and abatacept provided durable improvements in ACR responses over 4 years of treatment.