Background Subcutaneous (SC) abatacept demonstrated comparable safety and efficacy to intravenous (IV) abatacept after 24 weeks in Japanese patients with active RA.1
Objectives To assess the long-term safety, immunogenicity and efficacy of SC abatacept after 52 additional weeks of treatment in Japanese patients with active RA and MTX inadequate response (MTX-IR) previously treated with SC or IV abatacept for 24 weeks (76 weeks in total).
Methods Patients with active RA and MTX-IR (≥10 swollen and ≥12 tender joints, C-reactive protein [CRP] ≥0.8 mg/dL) were initially randomized into two groups (1:1) during the double-blind (DB) period, and given either SC abatacept (125 mg weekly) with an IV abatacept loading dose (~10 mg/kg) on Day 1, or IV abatacept (~10 mg/kg, Days 1, 15, 29, and every 4 weeks thereafter) for 24 weeks, both with a background of MTX (6–8 mg/week). At 24 weeks, patients entered an open-label extension (OLE) in which they received SC abatacept for 52 additional weeks. In the OLE, safety, immunogenicity and efficacy, including ACR 20, 50, and 70 responses, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Disease Activity Score (DAS)28 (CRP) were assessed. Safety and efficacy were assessed in the intent-to-treat population, with safety data up to 56 days post-treatment.
Results During the DB period, 118 patients were randomized and treated (59 in each group), of whom 113 completed the first 24 weeks and 112 (56 from each group) entered the OLE. Baseline characteristics of the 112 OLE patients at entry into the DB period were similar to those treated continuously with SC treatment (SC group) compared with those who were switched from IV to SC administration (Switch group); mean (SD) values were: age 55.2 (12.9) years, disease duration 6.3 (8.1) years, DAS28 (CRP) 5.77 (0.88), and MTX dose 7.3 (0.9) mg/week. The frequency of serious adverse events (SAEs) in the OLE was 8.9%. No deaths were reported, and the incidence of malignancies was 1.8%. Infections and infestations occurred in 51.8% of patients, and serious infections in 1.8%. Local injection-site reactions occurred in 1.8% of patients; severity was mild. Overall AEs reported in the OLE were similar to that reported in the DB period, with no new safety signals identified. Immunogenicity was detected by electrochemiluminescence in 3.6% of each group in the OLE treatment period.
ACR response rates (95% CI) were maintained from Week 24 through Week 76; ACR 20/50/70 response rates for the SC and Switch groups at Week 76 were 94.2/78.8/57.7% and 96.1/90.2/60.8%, respectively. HAQ-DI response (improvement from baseline of ≥0.3) and DAS28 (CRP) remission (<2.6) were 78.8% and 63.5%, respectively, in the SC group and 60.8% and 62.7%, respectively, in the Switch group.
Conclusions During the OLE, the overall safety profile of SC abatacept was unchanged. The rate of immunogenicity was low in the OLE treatment period and did not appear to affect safety and efficacy. Improvement in RA signs and symptoms, disease activity, and physical function were maintained during long-term administration of SC abatacept.
Matsubara T, et al. Ann Rheum Dis 2012;71(Suppl3):197
Disclosure of Interest: K. Amano Consultant for: Bristol-Myers Squibb, T. Matsubara Grant/research support from: Santen Pharmaceutical, Bristol-Myers K.K., OTSUKA PHARMACEUTICAL CO., LTD., TAKEDA CHEMICAL INDUSTRIES, LTD., Eli-Lilly Japan K.K., Quintiles Transnational, H. Inoue: None Declared, M. Iwahashi: None Declared, A. Yamazaki Employee of: Bristol-Myers Squibb, C. Karyekar Employee of: Bristol-Myers Squibb, T. Takeuchi Grant/research support from: Abbott Laboratories, Centocor Research and Development, Inc., Chugai, Mitsubishi-Tanabe Pharma, Pfizer, Consultant for: Abbott Immunology Pharmaceuticals, Astellas, AstraZeneca, Bristol-Myers Squibb, Chugai, Janssen Pharma, Mitsubishi-Tanabe, Novartis Pharma, Pfizer Inc, Wyeth Pharmaceuticals, Speakers bureau: Abbott, Bristol-Myers Squibb KK, Chugai Pharma, Eisai Pharma, Jansen Pharma, Mitsubishi-Tanabe Pharma, Pfizer, Takeda Pharma, Wyeth KK