Long-term safety and efficacy of treatment with subcutaneous abatacept in Japanese patients with rheumatoid arthritis who are methotrexate inadequate responders.

OBJECTIVE: To assess the long-term safety, immunogenicity, and efficacy of subcutaneous (SC) abatacept in combination with methotrexate (MTX) in Japanese patients with rheumatoid arthritis who were MTX inadequate responders, in a long-term extension (LTE) to a double-dummy, double-blind study (NCT01001832). METHODS: Patients, who had previously received SC or intravenous (IV) abatacept with MTX (6-8 mg/week) for 24 weeks, received SC abatacept (125 mg/week) with MTX for an additional 52 weeks. Safety, immunogenicity, and efficacy were assessed. RESULTS: The LTE included 112 patients. SC abatacept was generally well tolerated in the LTE, with no new safety signals. American College of Rheumatology 20, 50, and 70 response rates, disease activity score 28 (C-reactive protein) remission rates (< 2.6), and Health Assessment Questionnaire-Disability Index response rates (≥ 0.3 improvement from baseline) achieved at the end of the double-blind period were maintained over the LTE and were comparable in patients who received SC or IV abatacept in the double-blind period. Seropositivity for immunogenicity occurred in 4 (3.6%) patients. Self-injection of SC abatacept was well controlled and not associated with additional safety events. CONCLUSIONS: SC abatacept had acceptable safety and was well tolerated and effective over the LTE (76 weeks in total), with low rates of immunogenicity in Japanese patients.

Efficacy, safety, pharmacokinetics and immunogenicity of abatacept administered subcutaneously or intravenously in Japanese patients with rheumatoid arthritis and inadequate response to methotrexate: a Phase II/III, randomized study.

OBJECTIVE: To evaluate efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept and background methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR). METHODS: Double-dummy, double-blind study (NCT01001832); 118 adults with ≥ 10 swollen joints, ≥ 12 tender joints and C-reactive protein (CRP) ≥ 0.8 mg/dL randomized 1:1 to SC abatacept (125 mg weekly) with IV loading (∼10 mg/kg on Day 1), or IV abatacept (∼10 mg/kg monthly) for 169 days, both also receiving MTX (6-8 mg/week). Primary endpoint was Day 169 American College of Rheumatology (ACR)20 response; other efficacy endpoints, safety and immunogenicity were assessed. RESULTS: Similar proportions of patients achieved ACR20 responses at Day 169 with SC (91.5% [95% CI 81.3, 97.2]) and IV abatacept (83.1% [71.0, 91.6]). ACR50/70 responses, adjusted mean changes from baseline in Health Assessment Questionnaire-Disability Index scores and remission rates (28-joint Disease Activity Score [CRP] < 2.6) were also comparable between groups. Serious adverse event frequencies (5.1% vs. 3.4%) were similar with both formulations. One patient per group tested seropositive for immunogenicity. Weekly SC abatacept dosing achieved mean serum concentrations > 10 µg/mL (minimum therapeutic target). CONCLUSIONS: SC abatacept demonstrated comparable efficacy and safety to IV abatacept, with low immunogenicity rates, in MTX-IR Japanese patients with RA.