Attack Severity in Neuromyelitis Optica Spectrum Disorder With Inebilizumab

Presenting at CMSC 2022, researchers evaluated the relationship between attack severity with serum (s) GFAP and sNfL, and the effect of inebilizumab on attack severity and serum biomarkers.

In patients with neuromyelitis optica spectrum disorder (NMOSD) who are treated with inebilizumab, attacks are less severe than in individuals treated with placebo, according to study results presented at the 2022 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) held from June 1-4, in National Harbor, Maryland.

It is well known that individuals with NMOSD generally present with optic neuritis and myelitis, which can lead to accumulated, irreversible disability, and blindness. The anti-CD19 antibody inebilizumab has been approved for the treatment of adult patients with NMOSD who are seropositive for aquaporin-4 (AQP4) autoantibodies, with about 80% of individuals with NMOSD exhibiting autoantibodies to the AQP4 protein on the surface of astrocytes. When these astrocytes are destroyed, proteins are released, including glial fibrillary acid protein (GFAP), and neuroaxonal damage can lead to the release of neurofilament light chain (NfL).

The researchers sought to evaluate the relationship between attack severity and serum GFAP (sGFAP)/serum NfL (sNfL), as well as to examine the effect of inebilizumab on attack severity and biomarkers of disease activity.

N-Momentum, a phase 3, double-blind study ( identifier: NCT02200770) had a 28-week randomized, controlled period. The Opticospinal Impairment Scale was used to grade adjudicated attacks as major or minor, according to subdomain change in neurologic function. Single-molecule arrays were used to evaluate both sGFAP and SNfL. 

A total of 43 attacks were reported during the randomized, controlled period — 20 optic neuritis attacks, 27 myelitis attacks, and 2 brain/brainstem attacks. Of these attacks, 6 affected ≥1 domain. Overall, 29% (6 of 21) of attacks in the inebilizumab group were considered major and 71% (15 of 21) of attacks in the inebilizumab group were considered minor. In contrast, 45% (10 of 22) of attacks in the placebo group were considered major, whereas 55% (12 of 22) of attacks in the placebo group were considered minor (P =.35).

sGFAP concentration was statistically significantly higher during major vs minor attacks (P =.023). At the time of an attack, sGFAP level increased significantly from baseline in the placebo group (P =.001) but not in the inebilizumab group (P =.31). Although sNfL level was significantly higher in participants with major vs minor attacks, sNfL was not correlated with the severity of optic neuritis attacks.

Further, sNfL concentration did not differ with inebilizumab vs placebo during an attack (P =.40). sNfL was nevertheless significantly higher with placebo compared with inebilizumab at the end of the randomized, controlled period (ie, week 26; P =.03).

“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,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Bennett JL, Smith MA, Patterson KR, Weinshenker BG. Effects of inebilizumab on attack severity and biomarkers of disease activity in neuromyelitis optica spectrum disorder: N-MOmentum study. Presented at: CMSC 2022 Annual Meeting; June 1-4, 2022; National Harbor, Maryland. Abstract PSY05.