Targeting B Cells to Modify MS, NMOSD, and MOGAD: Part 1

Jonas Graf1, Jan Mares1, Michael Barnett1

  • 1From the Department of Neurology (J.G., O.A., P.A., H.-P.H.), University Hospital, Medical Faculty Heinrich-Heine-University, Düsseldorf, Germany; Department of Neurology (J.M.), Palacky University, Olomouc, Czech Republic; Department of Neurology (M.B., H.-P.H.), Brain and Mind Centre, Department of Neurology, University of Sydney, New South Wales, Australia; and UCSF Weill Institute of Neurosciences (S.S.Z.), Department of Neurology, University of California at San Francisco.

Ocrelizumab, rituximab, ofatumumab, ublituximab, inebilizumab, and evobrutinib are immunotherapies that target various B cell-related proteins. Most of these treatments have proven efficacy in relapsing and progressive forms of MS and neuromyelitis optica spectrum disease (NMOSD), or are in advanced stages of clinical development. Currently, ocrelizumab, ofatumumab, and inebilizumab are licensed for treatment of MS and NMOSD, respectively. This review focuses on the current state of knowledge about the role of B lymphocytes in immune-mediated pathophysiology and its implications for the mode of action. To understand the significance of this breakthrough in the context of the current MS therapeutic armamentarium, this review more closely examines the clinical development of CD20 depletion and the pioneering contribution of rituximab. Phase 3 and the recently published postmarketing studies will be highlighted to better understand the relevant efficacy data and safety aspects of long-term B-cell depletion.