Effects of Inebilizumab on Attack Severity and Biomarkers of Disease Activity in Neuromyelitis Optica Spectrum Disorder (NMOSD): N-Momentum Study

Background: NMOSD typically presents with optic neuritis and myelitis, which can result in accumulated, irreversible disability and blindness. Inebilizumab is an anti-CD19 antibody which is approved for adults with NMOSD who are seropositive for AQP4 autoantibodies. About 80% of patients with NMOSD have autoantibodies to the aquaporin-4 protein on the surface of astrocytes. Destruction of the astrocytes releases proteins including glial fibrillary acidic protein (GFAP). Neuroaxonal damage can result in the release of neurofilament light chain (NfL).

Objectives: To examine the relationship of attack severity with sGFAP and sNfL and to assess the effect of inebilizumab on attack severity and serum biomarkers.

Methods: N-MOmentum (NCT02200770) was a Phase 3, double-blind trial with a 28 week randomized placebo-controlled period (RCP). Adjudicated attacks were graded by the opticospinal impairment scale (OSIS) as major or minor based on subdomain changes in neurologic function. sGFAP and sNfL were assessed using single-molecule arrays (SIMOA).

Results: A total of 43 attacks occurred during the RCP (20 optic neuritis, 27 myelitis, 2 brain/brainstem, and 6 affected >1 domain). Of these attacks, 6/21 (29%) in the inebilizumab group were major and 15 (71%) were minor, whereas 10/22 (45%) attacks in the placebo group were major and 12 (55%) were minor (p=0.35). sGFAP was significantly higher during major vs minor attacks (p=0.023). At the time of attack, sGFAP concentration increased significantly from baseline in placebo (p=0.001) but not in inebilizumab‐treated participants (p = 0.31). Overall, sNfL was higher for major vs minor attacks (p=0.032); however, sNfL did not correlate with severity of optic neuritis attacks. While sNfL was not different during attacks for inebilizumab vs placebo (p=0.40), sNfL was higher for placebo vs inebilizumab treatment at the end of the RCP (week 26, p=0.03).

Conclusions: Attacks were less severe in patients receiving inebilizumab vs. placebo. sGFAP and sNfL were significantly higher in major vs minor attacks and increases in sGFAP occurred only in the placebo group.