Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the ACQUIRE trial

• Published in: Journal of rheumatology 2014-04, Vol.41 (4), p.629-639
• Main Authors: Genovese, Mark C, Tena, César Pacheco, Covarrubias, Arturo, Leon, Gustavo, Mysler, Eduardo, Keiserman, Mauro, Valente, Robert, Nash, Peter, Simon-Campos, J Abraham, Box, Jane, Legerton, 3rd, Clarence William, Nasonov, Evgeny, Durez, Patrick, Delaet, Ingrid, Teng, Julie, Alten, Rieke
• Format: Article
• Language: English
• Subjects: Abatacept; Adult; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - adverse effects; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunoconjugates - administration & dosage; Immunoconjugates - adverse effects; Injections, Intravenous; Injections, Subcutaneous; Male; Maximum Tolerated Dose; Methotrexate - administration & dosage; Methotrexate - adverse effects; Middle Aged; Pain Measurement; Patient Safety; Risk Assessment; Severity of Illness Index; Time Factors; Treatment Outcome
• ISSN: 0315-162X; 1499-2752
• DOI: 10.3899/jrheum.130112

Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA). The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported. Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8-44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA. These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).