Longterm Safety, Efficacy, and Inhibition of Structural Damage Progression Over 5 Years of Treatment with Abatacept in Patients with Rheumatoid Arthritis in the Abatacept in Inadequate Responders to Methotrexate Trial

Objective. Evaluate the safety and efficacy of longterm abatacept (ABA) treatment over 5 years in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). Methods. Patients from the 1-year, double-blind Abatacept in Inadequate Responders to Methotrexate (AIM) study (NCT00048568) received open-label ABA (∼10 mg/kg) in the longterm extension (LTE). Safety was assessed for patients who received ≥ 1 ABA dose, and efficacy for patients randomized to ABA and treated in the LTE. Radiographs were evaluated for changes in Genant-modified Sharp scores. Results. Out of 652 patients, 539 entered the LTE (ABA, n = 378; placebo, n = 161). At Year 5, 72.4% were ongoing; discontinuation rates declined over time. Incidence rates of serious adverse events, serious infections, malignancies, and autoimmune events were 13.87, 2.84, 1.45, and 0.99 events/100 patient-years exposure, respectively. American College of Rheumatology 20 response was 82.3% (n = 373) and 83.6% (n = 268) at years 1 and 5, respectively. Disease Activity Score 28 C-reactive protein (DAS28-CRP) < 2.6 and ≤ 3.2 were achieved by 25.4% and 44.1% of patients at Year 1 (n = 370), and 33.7% and 54.7% at Year 5 (n = 267), respectively. Mean changes in DAS28-CRP and Health Assessment Questionnaire–Disability Index at Year 1 [–2.83 (n = 365) and −0.68 (n = 369)] were maintained at Year 5 [−3.14 (n = 264) and −0.77 (n = 271)] for patients continuing treatment. Of them, 59.5% (n = 291) and 45.1% (n = 235) remained free from radiographic progression at years 1 and 5, respectively. Conclusion. In MTX-refractory patients with RA, longterm ABA treatment was well tolerated and provided consistent safety and sustained efficacy, with high patient retention. Radiographic progression continued to be inhibited with ongoing treatment.