Safety and Efficacy of Inebilizumab in AQP4+ NMOSD Participants with History of Immunosuppression Treatment Prior to N-MOmentum Study
Friedemann Paul1, Roman Marignier2, John Lindsey3, Ho Jin Kim4, Dewei She5, Daniel Cimbora5, Kristina Patterson5, Bruce Cree6
1Charite Universitatsmedizin in Berlin, 2Hospices Civils de Lyon, 3University of Texas Health Science Center At Houston, 4National Cancer Center, 5Horizon Therapeutics plc, 6UCSF, Multiple Sclerosis Center
Objective:

To evaluate long-term outcomes of inebilizumab treatment in AQP4+ NMOSD participants from the N-MOmentum trial with a history of immunosuppressant therapy as compared to those without.

Background:
Inebilizumab (anti-CD19 B-cell-depleting antibody) is approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults seropositive for aquaporin-4 antibody (AQP4+). Immunosuppressants were prohibited during the N-MOmentum pivotal trial, although many participants had a history of immunosuppressant therapy before enrolment.
Design/Methods:

N-Momentum (NCT02200770) was a 28-week-randomized-phase-2/3 trial of inebilizumab vs placebo, with an optional Open-Label-Extension (OLE) (>2 years).  Immunosuppressant medication for the prevention or treatment of NMOSD relapses was allowed prior to dosing on Day 1. In this analysis, AQP4+ participants who received inebilizumab (through OLE) were grouped by no history of immunosuppression therapy beyond treatment of acute NMOSD attacks (naïve), or prior azathioprine (AZA) and/or mycophenolate mofetil (MMF) therapy. Outcomes included annualized relapse and hospitalization rates, as well as safety assessments.

Results:

Among inebilizumab participants, 94 received prior-AZA/MMF and 103 were immunosuppressant-naïve. The total patient-years of inebilizumab treatment in the prior-AZA/MMF group was 300.35 and for immunosuppressant-naïve participants, 335.7. The annualized relapse rate (95% confidence interval [CI]) for participants with prior-AZA/MMF was 0.11 (0.07, 0.17), compared to 0.08 (0.05, 0.14) for naïve. The annualized NMOSD-related inpatient hospitalization rate (annualized rate [95% CI]) for prior-AZA/MMF was 0.15 (0.08, 0.27), and 0.12 (0.06, 0.22) for naïve. The percentage of participants with ≥1 study drug-related-treatment-emergent-adverse-event (TEAE) was 30.9% (29/94) in prior-AZA/MMF and 46.6% (49/103) of naïve; 4.3% (4) of prior-AZA/MMF and 5.8% (6) of immunosuppressant-naïve reported ≥1 study drug-related-serious-adverse-event. Most adverse events were infection-related for both groups; (72.3% (68/94) for prior-AZA/MMF and 76.7% (79/94) for naïve).

Conclusions:
This post hoc analysis evaluating long-term outcomes of inebilizumab in AQP4+ NMOSD participants treated with prior AZA/MMF therapy demonstrated a similar efficacy and safety profile as participants without prior immunosuppressant therapy.
10.1212/WNL.0000000000202412