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  • Less frequent rituximab retreatment maintains remission of neuromyelitis optica spectrum disorder, following long-term rituximab treatment

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Less frequent rituximab retreatment maintains remission of neuromyelitis optica spectrum disorder, following long-term rituximab treatment
  1. Su-Hyun Kim,
  2. Yeseul Kim,
  3. Gayoung Kim,
  4. Na Young Park,
  5. Hyun-Min Jang,
  6. Hyun-June Shin,
  7. Jae-Won Hyun,
  8. Ho Jin Kim
  1. Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea
  1. Correspondence to Dr Ho Jin Kim, Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang 410-769, South Korea; hojinkim{at}ncc.re.kr

https://doi.org/10.1136/jnnp-2018-318465

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    Introduction

    Rituximab, a chimeric monoclonal antibody that selectively targets CD20+ B cells, has exhibited robust efficacy and an acceptable safety profile in neuromyelitis optica spectrum disorder (NMOSD).1–3 Previously, we reported that the therapeutic response of B cell depletion varied among 100 patients with NMOSD, which resulted from multiple factors including Fc gamma polymorphism, and that monitoring CD27+ memory B cell appears to improve treatment outcomes via individualised treatment.2 Our treatment strategy has also proven to effectively prevent relapse at a lower cumulative dose, compared with the fixed maintenance therapy every 6 months, in a French cohort.4 Currently, we have a group of patients with NMOSD who have undergone long-term rituximab treatment for more than 7 years. We found that retreatment interval became significantly prolonged over time when we targeted depletion of memory B cells. Here, we analysed clinical outcomes and changes in B cell reconstitution over time, following long-term repeated rituximab treatment.

    Methods

    Through December 2017, sixty-eight patients with NMOSD had been treated with rituximab for at least 7 years. Twenty-one patients who had been treated with mitoxantrone, prior to rituximab, were excluded; the remaining 47 patients were included. Written informed consent was obtained from all patients. After induction therapy, patients received a single infusion of rituximab, at a dose of 375 mg/m2, as maintenance therapy; this was performed whenever the frequency of re-emerging CD27+ memory B cells in peripheral blood mononuclear cells (PBMC) exceeded 0.05% as revealed by flow cytometry for the initial 2 years, and, subsequently, when the frequency exceeded …

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    Footnotes

    • Contributors HJK and S-HK had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: HJK, S-HK. Acquisition of data: HJK, S-HK, GK, NYP, H-MJ, H-JS, J-WH. Analysis and interpretation of data: HJK, S-HK, GK, NYP, H-MJ, H-JS, J-WH. Drafting of the manuscript: S-HK, HJK. Critical revision of the manuscript for important intellectual content: HJK, S-HK, GK, NYP, H-MJ, H-JS, J-WH. Statistical analysis: S-HK. Study supervision: HJK.

    • Funding This work was supported by the National Research Foundation of Korea (Grant No NRF-2016R1D1A1A09916480) and by the Bio and Medical Technology Develop­ment Program (M3A9B6069339) through the Ministry of Science and ICT, Republic of Korea.

    • Competing interests S-HK has received a grant from the National Research Foundation of Korea. S-HK has lectured, consulted and received honoraria from Bayer Schering Pharma, Biogen, Celltrion, Eisai, Genzyme, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Teva-Handok and UCB; received a grant from the Ministry of Science and ICT; accepted research funding from Genzyme, Kael-GemVax, Merck Serono, Teva-Handok and UCB; serves on a steering committee for MedImmune; is a coeditor for the Multiple Sclerosis Journal-Experimental, Translational and Clinical, and an associated editor for the Journal of Clinical Neurology.

    • Patient consent Obtained.

    • Ethics approval This study was approved by the Institutional Review Board of the National Cancer Center.

    • Provenance and peer review Not commissioned; externally peer reviewed.