B-Cell Targeted Treatments for Neuromyelitis Optica Spectrum Disorder: A Focus on CD19 and CD20

Figures & data

Table 1 Summary of B Cell Targeted Treatments for NMOSD

	Rituximab	Ocrelizumab	Ofatumumab	Ublituximab	Inebilizumab
Structure	Chimeric IgG1*	Humanized IgG1	Fully human IgG1	Glycoengineered chimeric IgG1	Glycoengineered humanized IgG1
Target	CD20+ B cells	CD20+ B cells	CD20+ B cells	CD20+ B cells	CD19+ B cells
Primary MOA	CDC*	ADCC*	CDC	ADCC	ADCC
Boxed warnings	● Fatal infusion reactions ● Tumor lysis syndrome ● Severe mucocutaneous reactions ● PML*	None	None	None	None
Effectiveness data in NMOSD	● >20 open-label and retrospective analyses ● Open-label RCT* ● Placebo-controlled and blinded RCT (RIN-1; n=38)	None reported	Case report	Open-label acute treatment trial (n=5)	Placebo-controlled and blinded RCT (n=230)
Dosing Regimen in NMOSD	Not standardized	No data in indication	Limited/no data in indication	Limited/no data in indication	300 mg IV q6 months, following 2 paired doses at initiation
Infusion reactions in NMOSD	37% in RIN-1 (none serious), compared to 0% on placebo	No data	No data	No data	9%; comparable to placebo in rate and severity
FDA-approval for NMOSD	No	No	No	No	Yes

Abbreviations: *IgG1, immunoglobulin-1; CDC, complement-dependent cytotoxicity; ADCC, antibody-dependent cellular cytotoxicity; PML, progressive multifocal leukoencephalopathy; RCT, randomized-controlled trial.

Figure 1 B cells migrate from from the peripheral circulation to the central nervous system after they are activated in lymph nodes. AQP4 antibodies are mostly produced by peripheral AQP4-reactive B cells but during a relapse, some plasmablasts make AQP4 antibody within the CNS.

Notes: Reproduced from: Kowarik MC, Astling D, Gasperi C, et al. CNS Aquaporin-4-specific B cells connect with multiple B-cell compartments in neuromyelitis optica spectrum disorder. Annals of Clinical and Translational Neurology. 2017; 4(6): 369–380.³ With permission from Dr. Bennett. Copyright © 2017 The Authors. Creative Commons Attribution‐NonCommercial‐NoDerivs (https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcode).

Kowarik MC, Astling D, Gasperi C, et al. CNS aquaporin-4-specific B cells connect with multiple B-cell compartments in neuromyelitis optica spectrum disorder. Ann Clin Transl Neurol. 2017;4(6):369–380. eCollection 2017 Jun. doi:10.1002/acn3.418

 Web of Science ®Google Scholar