NMOSD Management Enters New Phase With Approved Disease-Modifying Therapies

Imaging of the optic nerve tends show to show more severe thinning of the retinal nerve fiber layer (RNFL) and the ganglion cell layer in neuromyelitis optica spectrum disorder (NMOSD) compared with multiple sclerosis (MS). Since 2019, three new therapies have been approved targeting different mechanisms associated with NMOSD pathogenesis.ORLANDO, Fla. – Until recently, there were no disease-modifying therapies (DMTs) approved specifically for neuromyelitis optica spectrum disorder (NMOSD). In 2019 and 2020, three agents were approved in the U.S., each targeting a different pathogenic mechanism associated with the condition: complement C5 (eculizumab), CD19 B cells (inebilizumab), and interleukin-6 (satralizumab). At the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) here, a variety of sessions were presented to update attendees on the diagnostic criteria for NMOSD, clinical features, and the latest long-term safety and efficacy data for NMOSD therapies based on results from open-label extensions of the pivotal clinical trials.

NMOSD is a demyelinating condition affecting primarily the optic nerves and spinal cord. The disorder is now recognized to be distinct from multiple sclerosis (MS). NMOSD has a U.S. prevalence lower than that of MS, with between 4,000 and 8,000 persons affected (primarily women). However, it carries a high degree of disease burden. In addition to the typical symptoms of eye pain and vision loss, patients may present with transverse myelitis causing numbness, weakness, or paralysis of the arms and legs, as well as loss of bladder and bowel control. Most attacks occur in clusters, days to months to years apart, followed by partial recovery during periods of remission. Up to half of patients with a diagnosis of NMOSD have residual visual impairment and paralysis. Therapies for NMOSD have been shown to significantly reduce the rate of attacks and slow disease progression.

Distinguishing between NMOSD and MS is an important factor in the differential diagnosis, conference speakers said, because the treatments differ and some MS treatments may be detrimental in patients with NMOSD. In the current International Consensus Criteria for NMOSD, core clinical characteristics include optic neuritis, transverse myelitis, and symptoms related to area postrema lesions (vomiting, nausea, hiccups). Other brainstem or diencephalic lesions may be present. For patients without a positive anti-AQP4 antibody status, more stringent criteria are required for diagnosis, including additional neuroimaging findings.

The three newer therapies are approved for patients with NMOSD who are seropositive for autoantibodies against aquaporin QP4 (AQP4). Posters presented at CMSC included a study presented by lead author Benjamin Greenberg, MD, of the University of Texas Southwestern Medical School in Dallas. The poster summarized safety data from the open-label extension of inebilizumab, an agent that depletes CD19-expressing B cells, to determine if infection rates might be linked to dropping immunoglobulin (Ig) levels. Among 174 patients followed for period of 4.75 years of treatment, infection rates did not increase during the open-label phase, despite declining Ig levels. Nasopharyngitis and upper respiratory tract infection were the most commonly observed infections. Infection rates were similar regardless of whether Ig levels were below or above the lower limit of normal.