An update on biologic treatments for neuromyelitis optica spectrum disorder

ABSTRACT

Introduction

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system mediated by antibodies targeting the aquaporin-4 (AQP4) water channel expressed on astrocytes. The binding of specific antibodies to AQP4 causes complement-dependent cytotoxicity, leading to inflammation and demyelination. Several recent phase 2 and 3 randomized placebo-controlled trials showed the efficacy and safety of monoclonal antibody therapies targeting B-cells, interleukin-6 receptor, and complement.

Areas covered

Current biologic treatments for NMOSD and developments therein, and unresolved issues in NMOSD treatment.

Expert opinion

New biologic treatments demonstrate high efficacy and good safety for patients with AQP4-IgG-positive NMOSD. The optimal therapeutics for seronegative NMOSD, pediatric patients, and female patients who are pregnant or wish to be are unclear, and further research is needed. Also, real-world studies of new biological agents and the data on the durability of their beneficial effects and their long-term safety are required. Effective rescue therapy for an acute attack is critical given permanent disability in NMOSD is attack-related, and biologic agents that treat acute attack are emerging. If such treatments are to become widely applied, studies on the most cost-effective treatment strategies are needed.

KEYWORDS:

• Eculizumab
• inebilizumab
• intravenous immunoglobulin
• monoclonal antibody
• neuromyelitis optica spectrum disorder
• ravulizumab
• rituximab
• satralizumab
• tocilizumab

Article highlights

• NMOSD is an AQP4-IgG-medicated autoimmune disease characterized by unpredictable attacks that often cause irreparable neurological disability

• Several immunosuppressive therapies, such as azathioprine, mycophenolate mofetil, rituximab, and tocilizumab have been used off-label for prevention of relapses in NMOSD patients

• Three monoclonal antibodies (eculizumab, inebilizumab and satralizumab) targeting specific inflammatory pathways demonstrated the efficacy and safety in recent controlled trials, and have been approved for preventing relapses in AQP4-IgG seropositive NMOSD

• To achieve maximum effectiveness and safety in treating NMOSD, therapeutic options must be carefully chosen based on meticulous patient stratification

• Real-world studies of new biological agents and the data on the durability of their beneficial effects and their long-term safety are required

Declaration of interest

Kim HJ has received a grant from the National Research Foundation of Korea; consultancy/speaker fees or research support from Alexion, Aprilbio, Altos Biologics, Biogen, Celltrion, Daewoong, Eisai, GC Pharma, HanAll BioPharma, Handok, Horizon Therapeutics (formerly Viela Bio), Kolon Life Science, MDimune, Mitsubishi Tanabe Pharma, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva-Handok, and UCB; and is a coeditor for the Multiple Sclerosis Journal and an associated editor for the Journal of Clinical Neurology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer declares: honoraria for presentations and the assembly of educational material from Alexion, Angelini, Bristol-Myers Squibb, Biogen, Boehringer, Horizon, Immunic, Janssen, Merck, Novartis, Pfizer and Sanofi and is a member of scientific advisory boards of Alexion, Bristol-Myers Squibb, Biogen, Boehringer, Novartis and Sanofi. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by the National Research Foundation of Korea (Grant No. 2018R1A5A2023127)