Treatment/Prevention of Relapses

A curative treatment for NMOSD does not currently exist. The main treatment goals are remission, long-term stabilization of disease course by means of relapse prevention and residual symptom relief. Therapy initiation depends on the severity and remission of the first relapse and clinical course.4,7,24

Intravenous methylprednisolone is the first-line therapy for treatment of acute NMOSD. Plasma exchange is used as a second-line therapy. Treatment in the acute or early stages aims to improve relapse symptoms and restore neurological function (Table 4).7,20,25-32

Table 4. Common Treatments for NMOSD in the United States7,20,25-32


Acute Treatments
 
IV steroids, such as methylprednisolone● The first standard of care to treat transverse myelitis or optic neuritis attacks is to give high-dose IV steroids
● Methylprednisolone (1 g/day) is usually administered for 5 consecutive days ● Continued steroids for longer periods of time is based on the clinical course and MRI appearance
Plasma exchange● The second standard of care used for moderate to aggressive forms of transverse myelitis or optic neuritis, if there is no improvement from using IV steroids
● Works to deplete circulating AQP4-IgG
Immunosuppressants or immunomodulator agents● Use if no improvement is seen with the use of IV steroids or plasma exchange ● Can cause severe complications over a duration of time
Long-Term Treatments 
Azathioprine● Administered orally 2X a day
● Widely used and long history of use
● Originally FDA approved for organ transplant rejection prophylaxis; also approved for active rheumatoid arthritis
● If used, monitoring of liver enzymes with regular blood tests is recommended
● FDA Category D: should not be taken during pregnancy
Eculizumab● IV infusion as directed
● Indicated for NMOSD in patients who are AQP4 antibody positive
● Complement inhibitor that inhibits the C5 protein
● Warning for risk of life-threatening and fatal meningococcal infections
● Can increase the risk of serious infections
● Only available through a restricted program
Inebilizumab-cdon● A CD19-directed cytolytic antibody indicated for the treatment of NMOSD in adult patients who are AQP4- antibody positive
● Initial IV infusion should be followed by a second infusion 2 weeks later, and every 6 months thereafter
Mycophenolate mofetil● Administered orally 2X a dayUsed as an alternative if azathioprine is causing severe side effects and poor responses
● FDA approved for organ transplant rejection prophylaxis
● Shown to be more effective than azathioprine for maintaining remission for longer periods while reducing relapse frequency
● If used, monitoring of liver enzymes with regular blood tests is recommended FDA Category D: should not be taken during pregnancy
Rituximab● IV infusion, administered 2 times a year for 2 years (4 infusions total)
● Works to target and deplete B cells
● If used, blood tests are recommended to monitor the expression of CD20, a B cell differentiation antigen
● FDA Category C, but no official FDA reports of birth defects
Satralizumab-mwge● An interleukin-6 (IL-6) receptor antagonist indicated for the treatment of NMOSD in adult patients who are AQP4-antibody positive
AQP4, aquaporin-4 antibodies; FDA, US Food and Drug Administration; IV, intravenous

Since relapses occur in 90% of cases, it is generally thought that long-term treatment with medications that suppress the immune system is necessary to prevent future attacks.7,20 The 3 primary immunosuppressant treatments used in recent years in the United States are azathioprine, mycophenolate mofetil, and rituximab.20 These medications are not approved by the US Food and Drug Administration (FDA) for NMOSD. All 3 drugs carry a risk of infection, particularly upper respiratory infections and urinary tract infections. There is also a risk of developing a rare, potentially lethal brain infection called progressive multifocal leukoencephalopathy, which is caused by the reaction of the John Cunningham virus that lives in the kidneys.20 Oral prednisone can also be used as an immunosuppressant medication, but long-term steroid use is associated with a wide range of complications.20 Observational studies have revealed that using both prednisone and azathioprine reduced the frequency of relapses.4


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In June 2019, the FDA approved the monoclonal antibody eculizumab for NMOSD in adults who are AQP4-antibody positive. It is the first FDA-approved medication for NMOSD.25 Eculizumab has been tested in several clinical trials, including a multinational phase 3 study (N=143 adults) completed in July 2018.27,32 Eculizumab works to “turn off” a substance called complement component C5 that is produced following the biological effects of the AQP4-IgG antibody resulting in an exacerbated immune attack on the optic nerves, spinal cord, and brain.7,20,32 Eculizumab has shown a significant reduction in the frequency of relapses in patients who are AQP4-IgG positive.32

Since then, 2 other agents were FDA approved for NMOSD in patients who are AQP4-antibody positive: inebilizumab-cdon and satralizumab-mwge, which is the first subcutaneous treatment for this indication.28,31

Prognosis

In NMOSD, the likelihood of recurrence of disease activity is greater than 90%.3,20 Relapses are more frequent and more severe in NMOSD than in MS and the prognosis of relapsing NMOSD is poor in comparison with MS. The factors indicating a worse prognosis include the following: frequent relapses during the first 2 years of the disease, increased severity of the first attack, and coexistence of systemic lupus erythematosus or other nonorgan-specific autoimmune disorders or the presence of autoantibodies.4 The 5-year survival rate is 90% in monophasic patients and 68% in relapsing patients. Thus, ongoing treatments with medications to suppress the immune system are necessary.4

Rehabilitation prevents secondary complications of immobility and improves functional skills. Spasticity, fatigue, neuropathic pain, and urinary symptoms are commonly treated with prescription medications, but other pain management therapies can be utilized.33 Physical therapy and regular exercise/stretching may improve neurologic function. Working to strengthen muscles and incorporating daily tasks that build stamina and reduce stress can lessen fluctuations of symptoms.20

Heather P. Adams, MPAS, PA-C, is an associate professor in the Physician Assistant Department at Gannon University and a clinically practicing PA at Women’s Wellness and Gynecology, both in Erie, Pennsylvania. Heba Al-Sahlani, PA-S, is a student in the Master of Physician Assistant Studies program at Gannon University. Blake Hoppe, DO, MSMed, is associate director and assistant professor in the Physician Assistant Department at Gannon University.

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