Vol.23 No.4

Original Article

Tolerability and efficacy of abatacept in Japanese patients with rheumatoid arthritis: a phase I study

Authors

Tsukasa Matsubara1 , Seizo Yamana2 , Shigeto Tohma3 , Tsutomu Takeuchi4 , Hirobumi Kondo5 , Hitoshi Kohsaka6 , Shoichi Ozaki7 , Hiroshi Hashimoto8 , Nobuyuki Miyasaka6 , Ami Yamamoto9 , Masaki Hiraoka9 , Tohru Abe10

  • Department of Orthopedics, Matsubara Mayflower Hospital, 944-25 Fujita, Kato Hyogo, 673-1462, Japan
  • Centre for Rheumatic Diseases, Higashihiroshima Memorial Hospital, 2214 Yoshiyuki, Saijo-cho, Higashihiroshima Hiroshima, 739-0002, Japan
  • Department of Rheumatology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Minami-ku, Sagamihara Kanagawa, 252-0392, Japan
  • Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
  • Department of Internal Medicine, Kitasato University School of Medicine, 1-15-1, Kitasato, Sagamihara Kanagawa, 228-8555, Japan
  • Department of Medicine and Rheumatology and Global Center of Excellence, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
  • Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki Kanagawa, 216-8511, Japan
  • Department of Rheumatology, Juntendo Tokyo Koto Geriatric Medical Center, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan
  • Bristol-Myers KK, 6-5-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 163-1328, Japan
  • Division of Rheumatology, Clinical Immunology, Saitama Medical Center/School, 1981 Kamoda, Kawagoe Saitama, 350-8550, Japan
Received:

2 March 2012

Accepted:

2 July 2012

Published online:

26 July 2012

Full Text

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Abstract

Objective The primary objective of this study was to evaluate the tolerability of single and multiple doses of abatacept in Japanese patients with rheumatoid arthritis.
Secondary objectives included evaluating its pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy.
Methods This dose-escalation, single- and multiple-dose, multicenter, open-label study was conducted at nine sites in Japan. Seven patients were enrolled at each of three dose levels (2, 8 and 16 mg/kg) and received a single intravenous dose of abatacept on day 1 of the single-dose phase.
The multiple-dose phase, at the same dose, started once the patients had completed the single-dose phase and when it was confirmed that there were no safety issues.
Results Twenty patients started the single-dose phase. Single and multiple doses of abatacept were well tolerated,and adverse events were of mild to moderate intensity.
There were no discontinuations or deaths due to adverse events. The pharmacokinetics of abatacept were linear, with no notable accumulation. There were no immunogenic effects on the safety, efficacy, or pharmacokinetics of abatacept. Multiple doses of abatacept improved individual items of the American College of Rheumatology core set.
Conclusion Single and multiple doses of abatacept showed favorable tolerability and efficacy in Japanese patients with rheumatoid arthritis.

Key words

Abatacept, Immunogenicity, Phase I study, Rheumatoid arthritis, Tolerability