Emerging Targeted Therapies for Neuromyelitis Optica Spectrum Disorders
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LEADING ARTICLE
Emerging Targeted Therapies for Neuromyelitis Optica Spectrum Disorders Cristina Valencia‑Sanchez1 · Dean M. Wingerchuk2 Accepted: 20 November 2020 © Springer Nature Switzerland AG 2020
Abstract Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, inflammatory disorder of the central nervous system that typically presents with recurrent episodes of optic neuritis, longitudinally extensive myelitis, brainstem, diencephalic, and cerebral syndromes. Up to 80% of NMOSD patients have a circulating pathogenic autoantibody that targets the water channel aquaporin-4 (AQP4-IgG). The discovery of AQP4-IgG transformed our understanding of the pathogenesis of the disease and its possible treatment targets. Monoclonal antibodies targeting terminal complement (eculizumab), CD19 (inebilizumab), and the interleukin-6 receptor (satralizumab) have demonstrated efficacy in NMOSD attack prevention in recent phase 3 trials and have gained subsequent regulatory approval in the USA and other countries. We aim to review the evidence supporting the efficacy of these new drugs.
Key Points
1 Introduction
Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune central nervous system astrocytopathy associated with a pathogenic autoantibody that targets the water channel aquaporin-4.
Neuromyelitis optica is an autoimmune, inflammatory central nervous system (CNS) disorder that typically presents with recurrent episodes of optic neuritis and longitudinally extensive myelitis. A broader range of manifestations has been recognized, including brainstem, diencephalic, and cerebral syndromes [1], and the current diagnostic criteria unify the clinical and neuroimaging characteristics of the disease under the term neuromyelitis optica spectrum disorders (NMOSD). [2] Acute NMOSD attacks are severe and recovery is often incomplete, leading to accumulation of disability with each additional attack. [3] NMOSD is more common in women, and its prevalence varies between populations and geographic location, ranging from 0.5 to 4.4 persons per 100,000 people [4], with a higher prevalence in non-white populations [5, 6]. Formerly thought to be a severe form of multiple sclerosis (MS), NMOSD is associated with the specific antibody aquaporin-4-IgG (AQP4-IgG), which targets the astrocyte water channel aquaporin-4 (AQP4), and is detectable in serum in up to 80% of clinically defined patients. AQP4IgG is rarely found in MS; using the best available cellbased assays, its specificity for NMOSD approaches 100%. Now considered a separate disease, NMOSD has distinct clinical, radiological, and pathological characteristics [7, 8]. Patients with an NMOSD clinical phenotype who are AQP4IgG seronegative are a heterogeneous group with several
Recent randomized controlled trials confirm the efficacy of three newly approved therapies (eculizumab, inebilizumab, and satralizumab) and confirm the relevance of their respective immune targets (terminal complement, CD19-expressing B lymphocytes, and the interleukin-6 pathway).
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