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.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).

Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial

“…Demographic data and clinical characteristics at baseline for patients treated in the LTE period were similar to those observed in the DB period 10 : 74.5% white, 82.4% female, mean age of 49.7 years, and RA mean duration of 7.6 years. At entry into the LTE period, 99.1% of patients were receiving ≥ 15 mg/week MTX (99.9% orally) and < 1% a concomitant non-MTX DMARD.…”

“…As during the DB and 3-year LTE period 10,13 , the presence of a positive antibody seroconversion response did not appear to affect the efficacy (including ACR20, 50, and 70, DAS28-CRP ≤ 3.2, DAS28-CRP < 2.6, and HAQ-DI) or safety of ABA during the 5-year LTE period of our study. A review of the ACR20 responses in patients with anti-ABA neutralizing antibodies did not reveal any trends toward lessening efficacy following the occurrence of neutralizing antibodies (data not shown), consistent with the immunogenicity results found at 3 years 10 .…”

“…The ACQUIRE study (NCT00559585) design and inclusion/exclusion criteria have been published in detail 10,13 . Briefly, at study entry, patients were aged ≥ 18 years with active RA, and had inadequate response to ≥ 3 months of MTX treatment, ≥ 10 swollen joints, ≥ 12 tender joints, and C-reactive protein (CRP) levels ≥ 0.8 mg/dl.…”

“…Briefly, at study entry, patients were aged ≥ 18 years with active RA, and had inadequate response to ≥ 3 months of MTX treatment, ≥ 10 swollen joints, ≥ 12 tender joints, and C-reactive protein (CRP) levels ≥ 0.8 mg/dl. In the DB period, patients were randomized (1:1) to receive SC ABA (125 mg/wk) on Day 1 (with addition of a single IV infusion of 10 mg/kg on Day 1) and weekly thereafter, or IV ABA (10 mg/kg) on days 1, 15, and 29, and every 4 weeks thereafter 10,13 . Patients continued MTX at the same dose they were receiving at randomization (min 15 mg/wk, orally or parenterally as clinically indicated); low-dose stable oral corticosteroids (< 10 mg/d prednisone equivalent) and stable dose nonsteroidal antiinflammatory drugs (NSAID) were also permitted.…”

“…Longterm safety and efficacy of the IV formulation of ABA has been shown, with several studies demonstrating that both efficacy and safety were maintained up to 7 years in patients with an inadequate response to methotrexate (MTX) 3,4,5,6,7,8 , and to 5 years in patients with an inadequate response to tumor necrosis factor inhibitors 4 . However, the longterm safety and efficacy of SC ABA are less well characterized 9,10,11,12 . An integrated analysis of safety data from the double-blind (DB) and open-label periods of 5 clinical trials, including a total of 1879 patients with 4214.6 patient-years (PY) of exposure, showed that treatment with SC ABA (mean length of exposure 2.3 yrs) was associated with a low incidence of serious infections, malignancies, autoimmune events, and injection-site reactions 12 .…”