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Efficacy and safety of rituximab in Japanese patients with relapsed chronic immune thrombocytopenia refractory to conventional therapy

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Abstract

Primary immune thrombocytopenia (ITP) is an autoimmune disease mediated by the production of auto-antibody against platelets. Rituximab, an anti-CD20 antibody, is reported to be useful for treatment of ITP. In Japan, however, robust evidence on this treatment has not been accumulated. Hence, we conducted this open-label phase III clinical trial to confirm the efficacy and safety of rituximab, administered at 375 mg/m2 once per week at weekly intervals for 4 consecutive weeks in Japanese patients with chronic ITP, who had relapsed and were refractory to conventional therapy. The primary endpoint was defined as the percentage of patients with a platelet count above 50 × 109/L at week 24 after the first dose of rituximab, which was 30.8 % of 26 patients (95 % confidence interval 14.3–51.8 %). Although the lower confidence limit of primary endpoint failed to meet the pre-specified threshold of 20 %, the clinical efficacy of rituximab is substantial in consideration of the 2 % response rate in the placebo arm in other clinical studies in patients with chronic ITP. We conclude that rituximab is clinically useful and safe in the treatment of Japanese patients with chronic ITP, achieving the goal of maintaining platelet count and reducing risk of bleeding while minimizing treatment-related toxicity.

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Acknowledgments

This study is a research project of the Ministry of Health, Labour, and Welfare (MHLW) Scientific Research Project. The authors are gratefully indebted to Zenyaku Kogyo Co., Ltd. for the supply of the investigational product and support for preparation of the manuscript, and to Quintiles Transnational Japan Inc. for support in conducting the clinical trial and in preparation of the manuscript, and Center for Clinical Trials, Japan Medical Association (JMACCT) for financial support. We also appreciated CTD Inc. for providing professional advises to our study group.

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Authors and Affiliations

  1. Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyamamachi, Iruma-gun, Saitama, 350-0495, Japan

    Yoshitaka Miyakawa

  2. Department of Hematology and Oncology, Hiroshima University, Hiroshima, Japan

    Shinya Katsutani

  3. Hematology, Internal Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan

    Takahiro Yano

  4. First Department of Internal Medicine, Kansai Medical University Hirakata Hospital, Osaka, Japan

    Shosaku Nomura

  5. Department of Oncology and Hematology, The Jikei University School of Medicine, Kashiwa Hospital, Chiba, Japan

    Kaichi Nishiwaki

  6. Department of Blood Transfusion, Osaka University Hospital, Osaka, Japan

    Yoshiaki Tomiyama

  7. Department of Hematology, Kitasato University Hospital, Kanagawa, Japan

    Masaaki Higashihara

  8. Department of Hematology and Oncology, Tokai University Hospital, Kanagawa, Japan

    Yukari Shirasugi

  9. Clinical Research Support Center, Mie University Hospital, Mie, Japan

    Masakatsu Nishikawa

  10. Division of Hematology, Jichi Medical University, Tochigi, Japan

    Katsutoshi Ozaki

  11. Center for Clinical Research, Keio University School of Medicine, Tokyo, Japan

    Takayuki Abe & Kayoko Kikuchi

  12. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan

    Yuzuru Kanakura

  13. Yasuda Women’s University, Hiroshima, Japan

    Kingo Fujimura

  14. Faculty of Science and Engineering, Waseda University, Tokyo, Japan

    Yasuo Ikeda

  15. Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Shinichiro Okamoto

Authors
  1. Yoshitaka Miyakawa
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  2. Shinya Katsutani
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  3. Takahiro Yano
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  4. Shosaku Nomura
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  5. Kaichi Nishiwaki
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  6. Yoshiaki Tomiyama
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  7. Masaaki Higashihara
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  8. Yukari Shirasugi
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  9. Masakatsu Nishikawa
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  10. Katsutoshi Ozaki
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  11. Takayuki Abe
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  12. Kayoko Kikuchi
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  13. Yuzuru Kanakura
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  14. Kingo Fujimura
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  15. Yasuo Ikeda
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  16. Shinichiro Okamoto
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Corresponding author

Correspondence to Yoshitaka Miyakawa.

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Conflict of interest

Dr. Miyakawa reports non-financial support from Zenyaku Kogyo, grants from Japan Medical Association Center for Clinical Trials (JMACCT), during the conduct of the study; grants and personal fees from Alexion pharmaceutical, personal fees from Daiichi Sankyo, personal fees from Fuji film, personal fees from GlaxoSmithKline, personal fees from Kyowa-Hakko Kirin, personal fees from Ono pharmaceuticals, outside the submitted work; Dr. Kanakura reports grants from Chugai Pharmaceutical Co. Ltd., personal fees from Zenyaku-Kogyo, during the conduct of the study; grants and personal fees from Kyowa-Hakkyo Kirin Co. Ltd., grants and personal fees from Otsuka Pharmaceutical Co. Ltd., grants from Takeda Pharmaceutical Co. Ltd., grants from Teijin Pharma, grants from Janssen Pharmaceutical Co. Ltd., grants and personal fees from Alexion Pharmaceutical Co. Ltd., personal fees from Shire Co. Ltd., grants from Bristol-Myers Squibb Co. Ltd., outside the submitted work; Dr. Yano has nothing to disclose. Dr. Shirasugi reports personal fees from Kyowa-Hakko Kirin, personal fees from Pfizer, personal fees from Ono pharmaceutical, personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from GlaxoSmithKline, outside the submitted work; Dr. Higashihara reports grants and personal fees from Chugai pharmaceutical, during the conduct of the study; grants and personal fees from Kyowa-Hakko Kirin, grants from MSD, grants from Jannsen pharmaceutical, grants from Takeda, personal fees from Sumitomo Dainippon pharma, grants from Teijin, grants from Astellas pharma, personal fees from GlaxoSmithKline, outside the submitted work; Dr. Nishiwaki reports grants from Zenyaku Kogyo Company, Limited, grants from Chugai Pharmaceutical, grants from Novartis Pharma K.K., outside the submitted work; Dr. Okamoto reports grants from Chugai pharmaceuticals, during the conduct of the study; personal fees from KyowaHakkoKirin, personal fees from Takeda, personal fees from Bristol-Myers Squibb, personal fees from Janssen pharmaceutical, personal fees from Celgene, personal fees from Alexion, personal fees from Eisai, grants from GlaxoSmithKline, outside the submitted work; Dr. Katsutani has nothing to disclose. Dr. Nomura has nothing to disclose. Dr. Kikuchi has nothing to disclose. Dr. Abe has nothing to disclose. Dr. Nishikawa has nothing to disclose. Dr. Ozaki reports grants from Japan Medical Association Center for Clinical Trials, during the conduct of the study; personal fees from Nippon Shinyaku, personal fees from Janssen pharmaceutical companies, personal fees from Chugai pharmaceutical, personal fees from Celgene, personal fees from Kyowa-Hakko Kirin pharmaceutical, outside the submitted work; Dr. Ikeda reports personal fees from Chugai pharmaceuticals, during the conduct of the study; personal fees from Novartis, personal fees from Sanofi, personal fees from Daichi Sankyo, outside the submitted work; Dr. Tomiyama reports grants from JMACCT, during the conduct of the study; personal fees from GSK, personal fees from Novartis, personal fees from Kyowa-Hokko Kirin, personal fees from Eisai, personal fees from Sysmex, outside the submitted work; Dr. Fujimura reports non-financial support from Kyowa-Hakko Kirin, during the conduct of the study; non-financial support from Medical support, outside the submitted work.

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Miyakawa, Y., Katsutani, S., Yano, T. et al. Efficacy and safety of rituximab in Japanese patients with relapsed chronic immune thrombocytopenia refractory to conventional therapy. Int J Hematol 102, 654–661 (2015). https://doi.org/10.1007/s12185-015-1887-9

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  • DOI: https://doi.org/10.1007/s12185-015-1887-9

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