Inebilizumab for Treatment of Neuromyelitis Optica Spectrum Disorder

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by recurrent optic neuritis and transverse myelitis often resulting in severe disability. Anti–aquaporin-4–immunoglobulin (Ig) G is a pathogenic product of CD19-positive plasma cells found in most, but not all, individuals with NMOSD and is associated with immune-mediated neurologic injury. Inebilizumab, an afucosylated humanized IgG1 κ, anti-CD19 monoclonal antibody, may target pathogenic CD19-expressing B cells. In a Phase II/III trial, inebilizumab significantly reduced the proportion of participants experiencing an NMOSD attack and was well tolerated versus placebo. Fewer treated participants had worsening disability than those receiving placebo. Inebilizumab was approved in 2020 by the US FDA for treatment of anti–aquaporin-4 antibody positive NMOSD.

Treatment and Relapse Prevention of Typical and Atypical Optic Neuritis

“…Due to the sample’s inequality regarding seronegative patients among groups (only four participants were randomized to the placebo arm), efficacy could not be interpreted in the seronegative subset. Of note, the trial also confirmed that the efficacy of inebulizumab was consistent across the clinical presentations of myelitis and optic neuritis domains [ 138 , 139 , 140 ].…”

“…The wider expression of CD19 compared to CD20 on cells that constitute the B-cell lineage allows inebilizumab to target a broader range of pathogenic B cells not being targeted by anti-CD20 agents. Additionally, CD19-positive plasmablasts circulating in the peripheral blood of individuals with NMOSD may produce AQP4-IgG antibodies [ 138 ].…”

“…Inebilizumab can also cause hypogammaglobulinemia, resulting in recurrent or serious opportunistic infections, which may require the discontinuation of the treatment or IVIg administration. Additionally, B-cell-depleting therapies in general are associated with an increased risk for malignancy and infection, including PML [ 107 , 138 ].…”

The impact of monoclonal antibody drugs on healthcare economics in the treatment of multiple sclerosis and neuromyelitis optica spectrum disorders

“…The short dosing interval necessitates frequent hospital visits, and the risk of fatality from meningococcal infection necessitates careful patient selection. STZ and INZ are also highly efficacious in preventing relapse 39,40 ; however, they can potentially increase the risk of infection. It is prudent to exercise caution, bearing in mind both the safety and costeffectiveness of a particular drug, while treating elderly patients with a high degree of disability.…”

B cell targeted therapies in inflammatory autoimmune disease of the central nervous system

“…In the pro-B cell stage, the gene segments of the heavy chain are rearranged and ultimately expressed as a µ-chain. While the µ-chain represents the heavy chain of the final BCR product, the CD19 antigen is already expressed on the pro-B cell ( 15 ). In the pre-B cell stage, CD20 is already displayed on the cell surface and the light chain gene segments of the BCR are reorganized, however not yet integrated into the receptor.…”