By: Lyana Sayilar PharmD. Candidate c/o 2022
Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder affecting 4,000 to 8,000 Americans. Adults with this disorder are often found to have anti-aquaporin-4 (AQP4)antibodies that primarily attack healthy cells and proteins in the optic nerves and spinal cord. The majority of patients have relapses within three years of the initial attack.¹,² In NMOSD, patients usually have occurrences of optic neuritis and experience eye pain and vision loss, of which approximately half of the patients have permanent visual impairment.¹ Transverse myelitis can also occur in a section of the spinal cord where myelin of neurons are damaged and lead to bladder dysfunction, loss of senses, and limb weakness. In addition, AQP4 antibodies can bind to aquaporin proteins of astrocytes along the blood brain barrier, causing disruption of the BBB and the release of cytokines and chemokines that recruit granulocytes, macrophages, and eosinophils. Further damage to oligodendrocytes, glial cells that produce myelin, lead to CNS damage. Additional symptoms of NMOSD include narcolepsy, hypotension, bradycardia, obesity, encephalopathy, and hypothermia. ²
The initial treatment of NMOSD is 1 gram IV methylprednisolone administered daily for three to five consecutive days. If patients experience severe symptoms or are unresponsive to methylprednisolone, then therapeutic plasma exchanges may be administered as second-line therapy every other day for a total of seven sessions. After treating the attacks, patients would require preventative therapy lifelong. The Food and Drug Administration-approved preventative therapy to treat NMOSD includes Soliris® (eculizumab), Uplizna® (inebilizumab-cdon), or Enspryng® (satralizumab-mwge). Additionally, immunosuppressants, including mycophenolate mofetil, azathioprine, and rituximab are off-label medications prescribed for preventative treatment for NMOSD. ³ IV eculizumab is a humanized monoclonal antibody that when bound to complement component C5 inhibits C5-mediated membrane attack complex. It is available under a restricted program, Risk Evaluation and Mitigation Strategies (REMS). The first four doses are administered at 900 mg weekly, followed by 1200 mg every two weeks thereafter. Patients should receive meningococcal vaccines and antibiotic prophylactic therapy if necessary, as eculizumab has the potential to increase the risk for meningitis. ²It is also worthy to note that eculizumab is contraindicated in patients with unresolved N. meningitidis infection. It can also cause upper respiratory tract infections, nausea, headache, and nasopharyngitis. ⁴ Inebilizumab-cdonis is a humanized antibody that suppresses the formation of lymphocytes from B cells upon binding to the CD19 antigen on B cells. Initially, 300 mg IV inebilizumab-cdon is given, followed by another 300 mg dose two weeks later. Patients receive 300 mg every six months thereafter; the first maintenance dose is given 6 months after the first 300 mg administration. Before every infusion, patients should receive pre-medications, consisting of a glucocorticoid, an antihistamine, and an antipyretic. Prior to receiving inebilizumab-cdon, patients should be screened for contraindications, such as hepatitis B and tuberculosis. ²
Satralizumab-mwge was the most recently approved humanized antibody for NMOSD that prevents IL-6-induced inflammation once bound to IL-6 receptors. In two Phase III, randomized, double-blind, placebo-controlled clinical trials, satralizumab-mwge was more effective than placebo in lowering NMOSD attacks. In the first clinical study, SAkuraStar, 95 adult patients participated, of which 64 patients had AQP4 antibodies. Satralizumab-mwge was found to be only effective in patients with AQP4 antibodies although patients who do not have AQP4 antibodies could still have the disorder. There was a statistically significant relapse risk reduction of 74% in those treated with satralizumab-mwge (95% CI [0.11, 0.63]; p= 0.0014). ⁵ At the end of week 48, 83% of AQP4 positive patients were relapse-free and at the end of week 96, 77% of AQP4 positive patients were relapse-free. Furthermore, in the second clinical trial, SAkuraSky, 76 adult patients participated; 52 of them were AQP4 antibody positive. In this trial, satralizumab-mwge and placebo were given alongside an immunosuppressant, such as azathioprine, mycophenolate mofetil, or oral corticosteroids. There was a statistically significant relapse risk reduction of 78% in those treated with satralizumab-mwge (95% CI [0.06, 0.82]; p=0.0143). At the end of weeks 48 and 96, 91% of the AQP4 positive patients were relapse-free. ⁵
Satralizumab-mwge is administered subcutaneously with a loading dose of 120 mg at weeks 0, 2, and 4, followed by 120 mg every four weeks. ² Adverse effects of satralizumab-mwge include an increase in the risk of infections, such as reactivating hepatitis B and tuberculosis. During treatment with satralizumab-mwge, patients should be monitored for changes in satralizumab-mwge, patients should be monitored for changes in liver enzymes and neutrophil counts. Common side effects include inflammation of stomach lining, common cold, upper respiratory tract infection, headache, joint and extremity pain, rash, fatigue, and nausea. Similar adverse effects are common with eculizumab and inebilizumab. Live-attenuated and live vaccines should not be administered while taking satralizumab-mwge, but can be given at least four weeks before treatment. ¹
- U.S. Food and Drug Administration. 2020.FDA Approves Treatment For RareDisease Affecting Optic Nerves, Spinal Cord. [online] Available at:https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-rare-disease-affecting-optic-nerves-spinal-cord. Accessed September 2, 2020.
- Uptodate.com. 2020. Uptodate. [online] Available at:https://www.uptodate.com/contents/neuromyelitis-optica-spectrum-disorders#H112826026. Accessed September 2, 2020.
- SRNA. 2020. NMOSD | Neuromyelitis Optica Spectrum Disorder | Prognosis &Management | SRNA. [online] Available at: https://wearesrna.org/living-with-myelitis/disease-information/neuromyelitis-optica-spectrum-disorder/prognosis-management/. Accessed September 2, 2020.
- Frampton JE. Eculizumab: A review in neuromyelitis optica spectrum disorder. Drugs. 2020;80(7):719-727.
- SAkuraStar & SAkuraSky Efficacy. Enspryng-hcp.com. https://www.enspryng-hcp.com/efficacy.html. Accessed October 2, 2020.