In patients with neuromyelitis optica spectrum disorder (NMOSD), treatment with the selective anti-CD19 B-cell–depleting monoclonal antibody inebilizumab (INEB) for
3.5 years was not associated with a meaningful decrease in vaccine titers, according to study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023, held in San Diego, California, from
February 23 to 25.
The agent, INEB, has been approved for the treatment of adults with aquaporin-4 seropositive NMOSD. Use of the agent was associated with a robust depletion of circulating B cells that impact NMOSD after 4 weeks in the phase 2/3 N-MOmentum trial (ClinicalTrials.gov Identifier: NCT02200770), with the response maintained for 4 or more years with continuous dosing every 6 months.
For this post hoc analysis of N-Momentum, researchers evaluated whether selective B-cell depletion over the long-term affects antibody titers from previous measles, mumps, rubella, varicella-zoster, and tetanus toxoid vaccinations. They determined the effect of long-term depletion of CD19+ B cells on childhood vaccine-generated humoral responses in participants from N-MOmentum.
All of the study participants were randomly assigned in a 3:1 ratio to treatment with intravenous INEB 300 mg or placebo (PBO) on days 1 and 15 of a 28-week randomized, controlled period, then every 6 months during the optional open-label period. Measles, mumps, rubella, and varicella immunoglobulin G (IgG) levels were measured in a central laboratory via utilization of a sandwich enzyme-linked immunosorbent assay (ELISA). Anti-tetanus toxoid IgG levels were measured in a central laboratory via use of an enzyme immunoassay. The median percent change from baseline (% CFB) at week 156 was assessed for measles, mumps, rubella, and varicella (IgG mg/dL for all), and for tetanus toxoid (IgG IU/mL).
The median (minimum, maximum) % CFB values to week 156 were as follows:
- Measles: 3.4% (–97.1%, 204.7% [n=47]) for INEB; –5.4% (–92.7%, 69.2% [n=10]) for PBO
- Mumps: 5.9% (–59.3%, 158.2% [n=47]) for INEB; 11.3% (–26.1%, 94.8% [n=12]) for PBO
- Rubella: 3.9% (–69.2%, 204.1% [n=55]) for INEB; –19.7% (–86.1%, 111.1% [n=15]) for PBO
- Varicella: 9.6% (–86.3%, 280.6% [n=40]) for INEB; 11.5% (–25.9%, 133.6% [n=13]) for PBO
- Tetanus toxoid: –1.0% (–92.9%, 160.7% [n=65]) for INEB; –17.2% (–61.3%, 45.2% [n=20]) for PBO
IgG levels decreased over the duration of the study, with a median (minimum, maximum) decrease of –13.2% (–81.1%, 21.8%) at week 52 (P =.005) and a median decrease of –20.5% (–81.1%, 21.8%) at week 156 (P =.0004) in the INEB group.
“Vaccine titers did not show a meaningful reduction after 3.5 years of INEB treatment even with near complete peripheral B cell depletion throughout this period,” the researchers concluded.
This article originally appeared on Neurology Advisor
Hartung H, Weinshenker B, Pittock S, et al. Effect of inebilizumab on vaccine-generated antibody titers in NMOSD participants: results from N-MOmentum study. Presented at: ACTRIMS Forum 2023; February 23-25; San Diego, CA. Poster 316.