What Is Neuromyelitis Optica?
Neuromyelitis Optica (NMO), or neuromyelitis optica spectrum disorder (NMOSD) aka Devic’s Disease (named after the doctor who initially discovered it), is a rare neurological autoimmune disease- meaning the body’s own immune cells begin to attack components of the nervous system, predominantly the optic nerve and spinal cord. NMOSD can also target areas of the brain. Historically, NMO has been misdiagnosed with multiple sclerosis (MS), another autoimmune disease of the central nervous system (CNS). Misdiagnosis can lead to either delay of appropriate treatment for NMO or inappropriate treatment, which can potentially exacerbate the disease.
NMOSD patients experience optic neuritis (causing eye pain and vision loss), transverse myelitis (leading to limb weakness and paralysis), as well as decreased sensation and loss of bladder and bowel control. Other symptoms can include intractable hiccuping, nausea and vomiting, sexual dysfunction, neuropathic pain, spasticity and chronic fatigue.
Mechanism of Disease
NMOSD is a distinct disease from multiple sclerosis (MS), typically sparing the brain and affecting a higher proportion of females to males (4:1). NMO can specifically lead to the formation of pathogenic (disease-causing) antibodies against aquaporin 4 (AQP4), or NMO-IgG, in the vast majority of patients, which is believed to be a mediator in spinal cord destruction. While nearly 80% of NMO subjects have these antibodies, NMO patients without NMO-IgG have similar spinal inflammation and destruction. Further diverging from MS, in which patients most often have mild attacks with good recovery, NMO attacks lead to severe disability, most often with incomplete recovery. Other subtypes of NMOSD can include MOG-seropositivity. MOG is protein that helps make up the CNS, and antibody formation against this protein can cause damage. Data show that patients can be either AQP4-IgG or MOG-IgG positive, but not both.
Common treatments for acute relapse include high dose intravenouse (IV) steroids, IV immunoglobulin (IVIG), and/or plasmapheresis. (See table below).
To Reduce/Prevent Relapse
There is no cure for NMO, but there are treatments used to reduce relapse.
As of June 2019, there is now 1 FDA-approved treatment for NMOSD, in adult patients who are positive for the AQP4 antibody. Alexion Pharmaceutical's Soliris (eculizumab) is a monoclonal antibody that targets C5a, a key component of an inflammatory immune cascade called the complement pathway. The drug was studied in AQP4+ NMOSD patients in the PREVENT clinical trial. The patients who received eculizumab demonstrated a significantly lower risk of NMO relapse compared to those who received placebo, with relapses occurring in 3 of 96 patients (3%) treated with eculizumab group and 20 of 47 (43%) treated with placebo. While there was no significant difference in measures of disability progression between the eculizumab or placebo-treated groups, the mean change in the EDSS score was –0.18 in the eculizumab-treated patients and 0.12 in the placebo-treated patients. Regarding safety outcomes, the clinical trial results show that upper respiratory tract infections and headaches were more common in the eculizumab-treated group, and one patient who had received the immunesuppressant azathioprine died from infectious pleural effusion after 108 weeks in the study. Learn more about the results of the clinical trial in the article published in the New England Journal of Medicine: https://www.nejm.org/doi/full/10.1056/NEJMoa1900866?query=featured_home. Click here for information on the FDA approval: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-neuromyelitis-optica-spectrum-disorder-rare-autoimmune-disease-central?fbclid=IwAR12905cJHuXXwIph-0D4NiVxxB_3SpjytQ7yl7u6aTqMA8d70i2ITl-A8M
You can also access the prescribing information aka label approved by the FDA for Soliris, which provides key safety information: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125166s431lbl.pdf
There are a number of immunosuppressive therapies that have been used to help reduce relapse which have not been formally studied in NMOSD and not FDA-approved for NMOSD. Because NMOSD is a rare disease, affecting about 15,000 in the United States, it has been granted Orphan status. An Orphan disease is one that affects less than 200,000 in the United States. For the NMOSD population, orphan drug designation has been granted to a number of immunosuppressive therapies. (See table below).