Analyzing Long-Term, End-Of-Study Results for Inebilizumab Treatment in NMOSD: Bruce Cree, MD, PhD, MAS, FAAN

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"It’s very interesting observation because it speaks to a biological impact of long-term B cell depletion in NMO (neuromyelitis optica) and resonates with the clinical experience that many of us have had when we have treated patients with other B-cell depleting therapies such as rituximab: once patients stabilized on treatment they tend to stay stable on treatment over the long term."

Inebilizumab (Uplizna; Amgen), an FDA-approved anti-CD19 B-cell-depleting antibody, has shown sustained efficacy and safety in patients with neuromyelitis optica spectrum disorder (NMOSD) according to newly published end-of-study results from the phase 2/3 N-MOmentum trial (NCT02200770). The end-of-study analysis of N-MOmentum, which included both the randomized controlled period and the open-label extension period, confirmed the long-term clinical benefits of inebilizumab treatment in patients with NMOSD.

In the trial, led by Bruce Cree, MD, PhD, MAS, FAAN, adults with NMOSD were randomly assigned in a 3:1 ratio to intravenous inebilizumab 300 mg (n = 174) or placebo (n = 56) on days 1 and 15 during the randomized period, which lasted up to 197 days. The primary end point of this period was the time to the onset of an adjudicated NMOSD attack by day 197. Patients who experienced an adjudicated attack, completed 197 days of the trial, or were in the randomized controlled period when enrollment stopped, were eligible to enter the open-label period. In this phase, patients who had initially received placebo (n = 51) started inebilizumab treatment, while those who had received inebilizumab (n = 165) continued the therapy. All participants received inebilizumab every 6 months for a minimum of 2 years.

The end-of-study analysis focused on time to adjudicated attack, annualized attack rate, and safety outcomes. Results showed that adjudicated NMOSD attacks occurred in 21% of treated patients (n = 225), with 63% of these attacks occurring in the first year of treatment. Of the patients who experienced an adjudicated attack while on inebilizumab, 77% (36 out of 47 patients) were attack-free by the end of 4 years. In terms of safety, 92% of treated patients reported at least 1 treatment-emergent adverse event (TEAE). The most common AEs were urinary tract infection, nasopharyngitis, and arthralgia.

In a recent interview, Cree, the clinical research director of the UCSF Multiple Sclerosis Center, sat down with NeurologyLive^® to discuss the significance of the changing hazard ratio for NMOSD attacks seen over time in the end-of-study analysis of N-MOmentum. He also spoke about how long-term B cell depletion therapy compares with other treatments like rituximab in terms of stability for patients with NMOSD. Furthermore, Cree shared some of the recommended practices for monitoring immunoglobulin G levels in patients undergoing B cell depleting therapy in clinical practice.

REFERENCES
1. Cree BAC, Kim HJ, Weinshenker BG, et al. Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial. Lancet Neurol. 2024;23(6):588-602. doi:10.1016/S1474-4422(24)00077-2