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

Abstract

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.

Keywords:

• Rheumatoid arthritis
• Japan
• Abatacept
• Subcutaneous injection
• Intravenous infusion

Acknowledgement

The authors would like to thank the investigators and medical personnel involved in this study at the following sites in Japan: Hokkaido University Hospital, Hokkaido; Sapporo City General Hospital, Hokkaido; Taga General Hospital, Ibaraki; National Hospital Organization Utsunomiya National Hospital, Tochigi; Jichi Medical University Hospital, Tochigi; Gunma University Hospital, Gunma; Saitama Medical University Hospital, Saitama; Saitama Medical Center, Saitama; Keio University Hospital, Tokyo; Tokyo Medical and Dental University Hospital Faculty of Medicine, Tokyo; Yokohama Rosai Hospital, Kanagawa; National Hospital Organization Sagamihara National Hospital, Kanagawa; Nagano Red Cross Hospital, Nagano; Seirei Hamamatsu General Hospital, Shizuoka; Kanzaki Municipal General Hospital, Hyogo; Matsubara Mayflower Hospital, Hyogo; Higashi-Hiroshima Memorial Hospital, Hiroshima; National Hospital Organization Kyushu Medical Center, Fukuoka; University of Occupational and Environmental Health Hospital, Fukuoka; National Hospital Organization Hokkaido Medical Center, Hokkaido; Inoue Hospital, Gunma; Kitasato Institute Medical Center Hospital, Saitama; Japanese Red Cross Narita Hospital, Chiba; Tokyo Metropolitan Police Hospital, Tokyo; Yokohama Minami Kyousai Hospital, Kanagawa; Osaka Rehabilitation Hospital, Osaka; Medical Corporation Matsubara Clinic, Hyogo; Kurashiki Kosai Hospital, Okayama; St. Mary's Hospital, Fukuoka; Hokkaido Medical Center for Rheumatic Diseases, Hokkaido; Shizuoka Kosei General Hospital, Shizuoka; Izumihara Rheumatoid Arthritis and Internal Medicine Clinic, Kagoshima; Hirose Clinic, Saitama.

Professional medical writing and editorial assistance was provided by Justine Lau and MaiLee Wong, at Caudex Medical, and was funded by Bristol-Myers Squibb K.K.

Conflict of interest

M. Iwahashi has received lecture fees from Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd, Pfizer Japan Inc., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Abbott Japan Co., Ltd, Astellas Pharma Inc., Santen Pharmaceutical Co., Ltd and Asahi Kasei Pharma Corporation. K. Amano has received lecture fees from AbbVie GK., Astellas Pharma Inc., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd, Mitsubishi Tanabe Pharma Corporation, Eisai Co., Ltd and Pfizer Japan Inc. T. Nakano has received lecture fees from Eisai Co., Ltd, Pfizer Japan Inc., Abbott Japan Co., Ltd, Daiichi Sankyo Company Limited, Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd, UCB Japan Co. Ltd and Mitsubishi Tanabe Pharma Corporation. T. Takeuchi has received grants from Abbott Japan Co., Ltd, Astellas Pharma Inc., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Company, Limited, Eisai Co., Ltd, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Sanofi K.K., Santen Pharmaceutical Co., Ltd, Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, AbbVie GK., Asahi Kasei Pharma Corporation and Taisho Toyama Pharmaceutical Co., Ltd; lecture fees from Abbott Japan Co., Ltd, Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd, Eisai Co., Ltd, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Takeda Pharmaceutical Company Limited., Astellas Pharma Inc. and Daiichi Sankyo Company Limited; consulting fees from AstraZeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Corporation, Asahi Kasei Pharma Corporation, AbbVie GK and Daiichi Sankyo Company Limited. A. Yamazaki is a paid employee of Bristol-Myers K.K. and owns Bristol-Myers Squibb stock. C. Karyekar is a paid employee of Bristol-Myers Squibb and owns Bristol-Myers Squibb stock. H. Inoue, T. Matsubara, T. Tanaka, T. Kanamono, S. Uchimura and T. Izumihara have nothing to disclose.

Sources of support: This study was funded by Bristol-Myers K.K.