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Rituximab in neurological disease: principles, evidence and practice
  1. Daniel H Whittam1,
  2. Emma C Tallantyre2,3,
  3. Stephen Jolles4,5,
  4. Saif Huda1,
  5. Robert J Moots6,
  6. Ho Jin Kim7,
  7. Neil P Robertson2,3,
  8. Bruce A C Cree8,
  9. Anu Jacob1,9
  1. 1Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK
  2. 2Helen Durham Centre for Neuroinflammation, University Hospital or Wales, Cardiff, UK
  3. 3Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
  4. 4Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
  5. 5School of Medicine, Cardiff University, Cardiff, UK
  6. 6Department of Musculoskeletal Diseases, Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool, UK
  7. 7Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea
  8. 8Weill Institute for Neurosciences, University of California, San Francisco, California, USA
  9. 9School of Medicine, University of Liverpool, Liverpool, UK
  1. Correspondence to Dr Anu Jacob, The Walton Centre NHS Foundation Trust, Lower Ln, Liverpool L9 7LJ, UK; anu.jacob{at}thewaltoncentre.nhs.uk

Abstract

Rituximab is a widely used B-cell-depleting monoclonal antibody. It is unlicensed for use in neurological disorders and there are no treatment guidelines. However, as a rapidly acting, targeted therapy with growing evidence of efficacy and tolerability in several neuroinflammatory disorders, it is an attractive alternative to conventional immunomodulatory medications. This practical review aims to explain the basic principles of B-cell depletion with therapeutic monoclonal antibodies. We present the evidence for using rituximab in neurological diseases, and describe the practical aspects of prescribing, including dosing, monitoring, safety, treatment failure and its use in special circumstances such as coexisting viral hepatitis, pregnancy and lactation. We provide an administration guide, checklist and patient information leaflet, which can be adapted for local use. Finally, we review the safety data of rituximab and ocrelizumab (a newer and recently licensed B-cell-depleting therapy for multiple sclerosis) and suggest monitoring and risk reduction strategies.

  • rituximab
  • ocrelizumab
  • Bcell
  • monoclonal antibody

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Footnotes

  • Contributors DHW drafted the manuscript and subsequent revisions. All authors critically appraised, revised the manuscript for important intellectual content and approved the final version of the article. AJ conceived and designed the review.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests ECT has received honoraria and support to attend educational meetings from Merck, support to attend educational meetings from Biogen and salary as a UK MS Registry fellow from Biogen. SJ has received advisory board, consulting, meeting attendance, speaker, study, author and project support from CSL Behring, Shire, LFB, Biotest, Binding Site, UCB Pharma, Grifols, Octapharma, SOBI, GSK, Sanofi, BPL, Zarodex, Weatherden and Uptodate. SH has previously received funding from the NIHR Oxford Biomedical Research Centre, the Watney Trust and Myaware. RJM has acted as consultant to, or received support for speaking at or chairing meetings, or received grant funding for research from AKL Pharma, BMS, Cellgene, Chugai, Eli Lilly, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma. HJK has received speaking and/or consulting support from Bayer Schering Pharma, Biogen, Celltrion, Eisai, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok and UCB; research support from Ministry of Science & ICT, Sanofi Genzyme, Teva-Handok and UCB. He is a steering committee member for MedImmune, and coeditor/associated editor of MS Journal-Experimental, Translational and Clinical, and Journal of Clinical Neurology. NPR has received personal fees and other from Biogen, grants from Novartis, grants and other from Genzyme, Roche and Teva, and personal fees from Merck. BACC has received personal compensation for consulting for AbbVie, Biogen, EMD Serono, GeNeuro, Novartis and Sanofi Genzyme. AJ has received compensation for advisory board, consulting, meeting attendance and speaking from Biogen, Terumo-BCT, Genentech, Shire and Chugai Pharmaceuticals.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; externally peer reviewed by Jackie Palace, Oxford, UK; Neil Scolding, Bristol, UK; and Jon Sussman, Manchester, UK.

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