Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4–immunoglobulin G–seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial

Abstract

Background: Efficacy and safety of inebilizumab for treatment of neuromyelitis optica spectrum disorder in adults seropositive for aquaporin-4 (AQP4)–immunoglobulin (Ig) G were demonstrated in the 28-week randomized controlled period of the N-MOmentum study. Objective: To assess efficacy and safety of long-term inebilizumab treatment. Methods: Post hoc analysis was performed in 75 AQP4–IgG–seropositive participants receiving inebilizumab for ⩾4 years in the randomized controlled period and open-label extension of the N-MOmentum study. Results: Eighteen attacks occurred in 13 participants during inebilizumab treatment (annualized attack rate, 0.052 attacks/person-year). Twelve attacks occurred during the first year of treatment, and two each occurred in years 2–4. Disability scores remained stable throughout ⩾4 years of treatment. Inebilizumab was well tolerated, with two (2.7%) serious treatment-emergent adverse events related to inebilizumab and no deaths. Immunoglobulin G levels decreased over time; however, correlation between severe infections and low IgG levels could not be determined because of their small numbers. Conclusion: These results from the N-MOmentum study continue to support use of inebilizumab for treatment of neuromyelitis optica spectrum disorder. Furthermore, the findings suggest that efficacy of inebilizumab may be enhanced after the first year of treatment, warranting additional long-term investigation.

Use of B-Cell–Depleting Therapy in Women of Childbearing Potential With Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

“…For ofatumumab, postinjection systemic inflammatory reactions can occur but are very mild and generally do not require pretreatment. The depletion of circulating B cells also leads to risk of infection, and some studies, 8 though not all, 9 suggest that this can arise particularly in the setting of hypogammaglobulinemia. In addition to IgG depletion, depletion of IgM and IgA can also occur 10 (vide infra, section on breastfeeding).…”

Roles of microglia/macrophage and antibody in cell sheet transplantation in the central nervous system

“…Just as CLP can be used to deplete microglia and macrophage populations, it is also possible to deplete immunoglobulin-producing plasmacytes. For example, inebilizumab, a monoclonal antibody (mAb), binds to and depletes CD19 + B cells, including plasmablasts and plasmacytes [ 28 ], leading to immunoglobulin depletion.…”

Antibody-mediated cell depletion therapies in multiple sclerosis

“…Inebilizumab treatment in NMOSD patients induced a robust depletion of CD20-positive B cells, that was maintained for at least 4 years ( 76 ). In a phase I study on 21 MS patients treated with different doses of inebilizumab, rapid B-cell depletion was observed at all dosing regimens except the 60-mg subcutaneously dose; the extent and duration of the B-cell depletion were dose-dependent, with most dose groups maintaining 90% depletion throughout the 24-week follow-up period ( 40 ).…”

“…As an unwanted on-target effect, concentrations of IgG, IgM, IgA, and IgE decreased over time during treatment with inebilizumab. Most participants (76%) maintained normal IgG levels, and no significant associations were observed between the lowest reported IgG categories and severe infections, although the relatively small number of the participants could have prevented from finding significant correlations ( 76 ). In a phase I study on MS patients, total Ig levels at week 24 showed a mean percentage decrease of 10.5% from baseline, rising to 15.0% at the 18-month follow-up ( 40 ).…”

“…R-FS was higher in the inebilizumab group compared to the placebo group, being at day 197 86.7% and 59.9%, respectively (hazard ratio, HR 0.27, 95% CI 0.15 – 0.50; p<0.0001), and the treatment effect was similar in the AQP4-positive subgroup. At week 52 of the OLE, R-FS was 84% in the group receiving continuative treatment with inebilizumab and 51% in the placebo-inebilizumab group ( 133 ), and interim analyses of a subgroup of 75 AQP4-positive participants who had received inebilizumab for at least 4 years show an R-FS of 83%, and stabilization of the mean EDSS score in the overall cohort ( 76 ).…”