Mark C Genovese1, César Pacheco Tena, Arturo Covarrubias, Gustavo Leon, Eduardo Mysler, Mauro Keiserman, Robert Valente, Peter Nash, J Abraham Simon-Campos, Jane Box, Clarence William Legerton, Evgeny Nasonov, Patrick Durez, Ingrid Delaet, Julie Teng, Rieke Alten. 1. From Stanford University, Palo Alto, California, USA; Universidad Autónoma de Chihuahua, Chihuahua; Unidad Reumatologica Las Americas S.C.P., Mérida, Mexico; Instituto De Ginecologia Y Reproduccion, Lima, Peru; Organización Médica de Investigación, Buenos Aires, Argentina; Pontificial Catholic University School of Medicine, Porto Alegre, Brazil; Physician Research Collaboration, Lincoln, Nebraska, USA; University of Queensland, Brisbane, Queensland, Australia; Centro De Especialidades Médicas/Universidad Marista, Mérida, Mexico; Box Arthritis and Rheumatology of the Carolinas, Charlotte, North Carolina; Low Country Rheumatology, Charleston, South Carolina, USA; Institute of Rheumatology, Moscow, Russia; Service et Pôle de Rhumatologie, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium; Bristol-Myers Squibb, Princeton, New Jersey, USA; and Schlosspark-Klinik, Teaching Hospital of the Charité University Medicine Berlin, Berlin, Germany.
Abstract
OBJECTIVE: Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA). METHODS: 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. RESULTS: 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. CONCLUSION: 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).
RCT Entities:
OBJECTIVE: Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA). METHODS: 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. RESULTS: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. CONCLUSION: 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).
Authors: R D Pawar; B Goilav; Y Xia; L Herlitz; J Doerner; S Chalmers; K Ghosh; X Zang; C Putterman Journal: Clin Exp Immunol Date: 2015-02 Impact factor: 4.330
Authors: Michael Schiff; Joe Koo; Erik Jin; Eric Schiller; Ashley Day; Rebecca Stevens; Christina Laskar Journal: Adv Ther Date: 2016-01-30 Impact factor: 3.845