title: Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the ACQUIRE trial.
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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
authors.forename: César Pacheco
authors.initials: CP
authors.lastname: Tena
authors.forename: Arturo
authors.initials: A
authors.lastname: Covarrubias
authors.forename: Gustavo
authors.initials: G
authors.lastname: Leon
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mysler
authors.forename: Mauro
authors.initials: M
authors.lastname: Keiserman
authors.forename: Robert
authors.initials: R
authors.lastname: Valente
authors.forename: Peter
authors.initials: P
authors.lastname: Nash
authors.forename: J Abraham
authors.initials: JA
authors.lastname: Simon-Campos
authors.forename: Jane
authors.initials: J
authors.lastname: Box
authors.forename: Clarence William
authors.initials: CW
authors.lastname: Legerton
authors.forename: Evgeny
authors.initials: E
authors.lastname: Nasonov
authors.forename: Patrick
authors.initials: P
authors.lastname: Durez
authors.forename: Ingrid
authors.initials: I
authors.lastname: Delaet
authors.forename: Julie
authors.initials: J
authors.lastname: Teng
authors.forename: Rieke
authors.initials: R
authors.lastname: Alten
mesh_terms: D000069594:Abatacept; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000009:adverse effects; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D020714:Maximum Tolerated Dose; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010147:Pain Measurement; D061214:Patient Safety; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D018796:Immunoconjugates; D000069594:Abatacept; D008727:Methotrexate
keywords: ABATACEPT; ACQUIRE; LONGTERM SAFETY; RHEUMATOID ARTHRITIS