Neuromyelitis Optica Spectrum Disorder (NMOSD)

Significant advances have been made in the treatment of neuromyelitis optica spectrum disorders (NMOSDs) during the past 2 years. The US Food and Drug Administration (FDA) approved 3 medications–satralizumab, eculizumab, and inebilizumab–between 2019 and 2020, each with a different mechanism of action.¹ Here we focus on satralizumab, an interleukin-6 (IL-6) pathway inhibitor, and tocilizumab, another potential NMOSD therapeutic agent with the same mechanism of action.

Enspryng™ (Satralizumab-mwge) 

Enspryng is an IL-6 receptor antagonist indicated for the treatment of adult patients who have NMOSD with anti-aquaporin-4 (anti-AQP4) antibodies. It remains unknown why Enspryng is effective for treating anti-AQP4-positive NMOSD, but its mechanism of action is presumed to involve the inhibition of IL-6-mediated signaling through binding to soluble and membrane-bound IL-6 receptors. 

Enspryng comes in a preloaded syringe containing 120 mg/mL. It is administered by subcutaneous injection at a recommended loading dose of 120 mg given at weeks 0, 2, and 4. This is followed by a maintenance dose of 120 mg given every 4 weeks.² 

Enspryng was approved following the publication of 2 randomized placebo-controlled clinical trials (study 1 and study 2) of seropositive patients who received no concomitant immunosuppressive therapy (study 1) and seropositive patients who received concomitant immunosuppressive therapy (study 2).² 

In study 1, the time to the first relapse was significantly longer in the patients treated with Enspryng than in the patients who received placebo (risk reduction, 55%; hazard ratio [HR], 0.45; P=0.0184). In the anti-AQP4 antibody-positive population, a 74% risk reduction was noted (HR, 0.26; P=0.0014), whereas no evidence of a benefit was found in the anti-AQP4 antibody-negative patients. In study 2, the time to the first confirmed relapse was also significantly longer in the patients treated with Enspryng than in the patients who received placebo (risk reduction, 62%; HR, 0.38; P=0.0184). In the anti-AQP4 antibody-positive population, the risk reduction rate was 78% (HR, 0.22; P=0.0143). No evidence of benefit was found in the anti-AQP4 antibody-negative patients.² 

Enspryng is contraindicated in patients with active hepatitis B infection or with active or untreated tuberculosis. Patients should be screened for tuberculosis and hepatitis B before starting therapy. Enspryng should not be administered to patients with known allergies to satralizumab or any other ingredient of Enspryng. Caution should be exercised in patients with ongoing infections, and Enspryng should not be initiated until resolution. The administration of live or live attenuated vaccines is not recommended during treatment with Enspryng. The most common adverse reactions (incidence of at least 15%) are nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue, and nausea.² 

Data on the use of Enspryng in pregnant or lactating women, children, and patients older than 65 years are insufficient to make any recommendations.  

Read more about Enspryng

Actemra® (Tocilizumab)

Actemra is also an IL-6 receptor antagonist that is administered intravenously or subcutaneously; however, it is not FDA-approved for the treatment of NMOSD. It is currently approved to treat rheumatoid arthritis, giant cell arteritis, systemic sclerosis-associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, and cytokine release syndrome.³   

Numerous studies, including a phase 1/2 trial (TANGO) have evaluated the safety and efficacy of tocilizumab in both adult and pediatric patients who are either seropositive or seronegative for AQP4 antibodies.⁴ Tocilizumab significantly reduced the annual relapse rate (ARR) in all studies. In the open label, randomized phase 2 TANGO trial, tocilizumab was more effective than azathioprine at preventing relapse, with a median time to first relapse of 78.9 weeks vs 56.7 weeks, respectively, in the full analysis set (P=0.0026). At the end of the study, which lasted 60 weeks, 89% of patients in the per-protocol group taking tocilizumab were relapse-free vs 56% of patients in the azathioprine group (P <0.0001). In addition, the rate of treatment-associated adverse events was lower in the tocilizumab group (61% vs 83%), suggesting that tocilizumab is better tolerated than azathioprine.⁵ 

Actemra reduces the ability to fight infection, and life-threatening infections may develop, especially when the drug is used concomitantly with immunosuppressive therapy. Patients should be tested for tuberculosis before therapy is initiated and monitored during therapy. Serious cases of hepatic injury and intestinal perforation have also been observed.³

References

1. Neuromyelitis optica: new therapies offer hope. Mayo Clinic Neurology and Neurosurgery. Published June 19, 2021. Accessed March 17, 2022.

2. ENSPRYNG^TM (satralizumab-mwge) injection, for subcutaneous use. Genentech. Revised August 2020.

3. ACTEMRA® (tocilizumab) injection, for intravenous or subcutaneous use. Genentech. Revised March 2021.

4. Lotan I, McGowan R, Levy M. Anti-IL-6 therapies for neuromyelitis optica spectrum disorders: a systematic review of safety and efficacy. Curr Neuropharmacol. 2021;19(2):220. doi:10.2174/1570159X18666200429010825

5. ​​Zhang C, Zhang M, Qiu W, et al. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. 2020;19(5):391-401. doi:10.1016/S1474-4422(20)30070-3

Reviewed by Harshi Dhingra, MD, on 3/21/2022.

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Kyle Habet, MD

Kyle Habet, MD, is a physician at Belize International Institute of Neuroscience where he is a member of a multidisciplinary group of healthcare professionals involved in the care of patients with an array of neurological and psychiatric diseases. He is a published author, researcher and instructor of neuroscience and clinical medicine at Washington University of Health and Science.