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Rituximab prolongs the time to relapse in patients with immune thrombotic thrombocytopenic purpura: analysis of off-label use in Japan

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Abstract

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by ADAMTS13 deficiency due to anti-ADAMTS13 autoantibodies. Rituximab, an anti-CD20 monoclonal antibody, is often used to suppress these autoantibodies. This retrospective study, conducted in an iTTP cohort in Japan, evaluated the long-term efficacy of rituximab as off-label treatment for refractory or relapsed cases. A total of 252 iTTP patients with severe ADAMTS13 deficiency (< 10%) and its inhibitor were enrolled, and 169 episodes in 156 patients were analyzed. Sixty-five episodes with relapse or resistance to conventional treatment were treated with rituximab, while 104 episodes received conventional treatment only. The rituximab group had a significantly higher inhibitor titer than the rituximab-untreated group. During the median follow-up period of 3.9 years, there were 8 relapses in the rituximab group and 17 relapses in the rituximab-untreated group. The median time to relapse in the rituximab group (2.9 years) was significantly longer than that in the rituximab-untreated group (1.2 years). Relapse-free survival at 2 years was significantly higher in the rituximab group than in the rituximab-untreated group. The incidence of relapse at 5 years did not differ between the 2 groups. Rituximab reduced the risk of relapse in refractory or relapsed iTTP patients for 2 years.

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Acknowledgements

This work was supported by research grants from the Ministry of Health, Labour and Welfare of Japan. We would like to thank the physicians at referring hospitals for providing blood samples and patient information.

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Authors and Affiliations

  1. Department of Blood Transfusion Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

    Masayuki Kubo, Kazuya Sakai, Yumi Yoshii, Masaki Hayakawa & Masanori Matsumoto

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  1. Masayuki Kubo
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  2. Kazuya Sakai
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  3. Yumi Yoshii
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  4. Masaki Hayakawa
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  5. Masanori Matsumoto
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Contributions

MK performed data collection, statistical analysis, interpreted the results and wrote the manuscript. KS performed data collection and statistical analysis. YY and MH performed data collection. MM designed the research, interpreted the data, and wrote the paper.

Corresponding author

Correspondence to Masanori Matsumoto.

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Conflict of interest

MM is an inventor of the ELISA used to assess ADAMTS13 activity. MM received research funds from Chugai Pharmaceutical. The other authors have no conflicts of interest.

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Kubo, M., Sakai, K., Yoshii, Y. et al. Rituximab prolongs the time to relapse in patients with immune thrombotic thrombocytopenic purpura: analysis of off-label use in Japan. Int J Hematol 112, 764–772 (2020). https://doi.org/10.1007/s12185-020-02974-y

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  • DOI: https://doi.org/10.1007/s12185-020-02974-y

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