Long-term Comparative Efficacy of Inebilizumab in the AQP4+ Subpopulation from N-MOmentum Open-label Period Versus Azathioprine and Immunosuppressants and Versus Placebo in Patients with NMOSD
Bruce Cree1, Beatrice Suero2, Sarah Walsh2, Romain Marignier3, John Lindsey4, Ho Jin Kim5, Dewei She6, Daniel Cimbora6, Kristina Patterson6, Friedemann Paul7
1Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA, 2Eversana, Burlington, Ontario, Canada, 3Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuroinflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France, 4Division of Multiple Sclerosis and Neuroimmunology, University of Texas Health Science Center at Houston, Houston, TX, USA, 5Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea, 6Amgen Research, Amgen Inc, Thousand Oaks, CA, USA, 7Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Objective:

To evaluate the long-term comparative efficacy of inebilizumab (INEB) over N-MOmentum open label period (OLP) vs azathioprine and other immunosuppressants (AZA/IST) and vs historical-placebo (PBO) in participants with neuromyelitis optica spectrum disorder (NMOSD).

Background:
INEB, an anti-CD19 B cell-depleting antibody, is approved for the treatment of NMOSD in adults seropositive for aquaporin-4 antibody (AQP4+).  N-MOmentum (NCT02200770) consisted of a 28-week randomized-controlled period (RCP) and an optional OLP (>2 years) in which all participants received treatment with INEB.
Design/Methods:

Two historical comparator groups (HCGs) of participants who received AZA/IST (N=132) or PBO only (N=106) were derived using data from published NMOSD studies and were used to evaluate the comparative efficacy of INEB (N=208) over the OLP. Hazard ratios (HR) for INEB vs HCGs were estimated using a Cox proportional hazards (PH) regression. Time to NMOSD attack was analyzed using parametric and flexible survival (spline) models that were fit to INEB and HCGs. 

Results:

The HR (95% CI) of time to NMOSD attack for the N-MOmentum PBO group compared to historical-PBO groups was 1.15(0.67–1.91); P=0.58. The HR (95% CI) for time to NMOSD attack for INEB vs AZA/IST and PBO groups were 0.29(0.17,0.42); P<0.001 and 0.15(0.10,0.21); P<0.001, respectively. A time-varying spline with two internal knots and normal linear predictor provided the best fit.  At 4 years, the model estimated an attack-free probability (95% CI) of 77%(71,83) for INEB, 36%(27,46) for AZA/IST, and 12%(7,20) for PBO. Results indicate a greater difference in efficacy for INEB vs PBO compared to AZA/IST vs PBO, suggesting a significant reduction in risk of attack for INEB vs both AZA/IST and PBO.

Conclusions:

INEB was associated with a statistically significant reduction in risk of an NMOSD attack and provided a long-term attack-free probability over the OLP compared to the relative short-term benefit observed with AZA/IST. 

10.1212/WNL.0000000000204717