Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder.

Abstract

BACKGROUND:

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system and is associated with autoantibodies to anti-aquaporin-4 (AQP4-IgG) in approximately two thirds of patients. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy of satralizumab added to immunosuppressant treatment in patients with NMOSD is unclear.

METHODS:

In a phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or seronegative for AQP4-IgG to receive either satralizumab, at a dose of 120 mg, or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter, added to stable immunosuppressant treatment. The primary end point was the first protocol-defined relapse in a time-to-event analysis. Key secondary end points were the change from baseline to week 24 in the visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores indicating more pain) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating more fatigue). Safety was also assessed.

RESULTS:

A total of 83 patients were enrolled, with 41 assigned to the satralizumab group and 42 to the placebo group. The median treatment duration with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo (hazard ratio, 0.38; 95% confidence interval [CI], 0.16 to 0.88). Multiple imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 (with corresponding P values of 0.01 to 0.04). Among 55 AQP4-IgG-seropositive patients, relapse occurred in 11% of those in the satralizumab group and in 43% of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 28 AQP4-IgG-seronegative patients, relapse occurred in 36% and 43%, respectively (hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the between-group difference in the change in the mean FACIT-F score was -3.10 (95% CI, -8.38 to 2.18). The rates of serious adverse events and infections did not differ between groups.

CONCLUSIONS:

Among patients with NMOSD, satralizumab added to immunosuppressant treatment led to a lower risk of relapse than placebo but did not differ from placebo in its effect on pain or fatigue. (Funded by Chugai Pharmaceutical; ClinicalTrials.gov number, NCT02028884.).

• Authors: Takashi Yamamura, Ingo Kleiter, Kazuo Fujihara, Jacqueline Palace, Benjamin Greenberg, Beata Zakrzewska-Pniewska, Francesco Patti, Ching-Piao Tsai, Albert Saiz, Hayato Yamazaki, Yuichi Kawata, Padraig Wright, Jerome De Seze
• Journal: The New England journal of medicine (N Engl J Med) Vol. 381 Issue 22 Pg. 2114-2124 (11 28 2019) ISSN: 1533-4406 [Electronic] United States
• PMID: 31774956 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Massachusetts Medical Society.

Chemical References

• Antibodies, Monoclonal, Humanized
• Aquaporin 4
• Autoantibodies
• Immunoglobulin G
• Immunosuppressive Agents
• Receptors, Interleukin-6
• satralizumab

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Aquaporin 4 (immunology)
• Autoantibodies (blood)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Immunoglobulin G (blood)
• Immunosuppressive Agents (therapeutic use)
• Male
• Middle Aged
• Neuromyelitis Optica (drug therapy, immunology)
• Receptors, Interleukin-6 (antagonists & inhibitors, immunology)
• Recurrence
• Young Adult