Neuromyelitis Optica Spectrum Disorder (NMOSD)


Overview

Before 2019,  no FDA-approved drugs were available for the treatment of neuromyelitis optica spectrum disorder (NMOSD). In 2019, Solaris (eculizumab) was the first drug to be approved; approval of Uplizna (inebilizumab-cdon) and Enspryng (satralizumab-mwge) followed in 2020.1–3 

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

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

Efficacy in Clinical Trials

Enspryng was approved following the publication of 2 randomized, placebo-controlled clinical trials (study 1 and study 2) of seropositive patients who received either no concomitant immunosuppressive therapy (study 1) or concomitant immunosuppressive therapy (study 2).4 

In study 1, the time to first relapse was significantly longer in the patients treated with Enspryng than in those who received placebo (risk reduction, 55%; hazard ratio [HR], 0.45; P=0.0184). A risk reduction of 74% was observed in the anti-AQP4 antibody-positive population (HR=0.26; P=0.0014), whereas no evidence of benefit was found in the anti-AQP4 antibody-negative patients. 

Access the Enspryng monograph page at MPR for full prescribing information.

In study 2, the time to first confirmed relapse was significantly longer in the patients treated with Enspryng than in those who received placebo (risk reduction 62%; HR: 0.38; P=0.0184). A 78% risk reduction was observed in the anti-AQP4 antibody-positive population (HR, 0.22; P=0.0143), whereas no evidence of benefit was found in the anti-AQP4 antibody-negative patients. 

Both trials concluded that Enspryng is an effective treatment for adults with NMOSD who are seropositive for AQP4 antibodies, both as monotherapy and as add-on therapy with immunosuppressive regimens. 

Adverse Events

Enspryng is contraindicated for 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 when a patient has an ongoing infection, and the initiation of Enspryng should be delayed until resolution. Vaccination with live or live attenuated vaccines is not recommended during treatment. The most common adverse reactions (incidence ≥15%) are nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue, and nausea.4 

During treatment, patients should be monitored frequently for infection, neutropenia, and elevated transaminases. Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin levels should be obtained before the start of therapy for monitoring. Transaminase levels should be checked every 4 weeks for the first 3 months of treatment, then every 3 months for 1 year. If liver enzymes are elevated to more than 5 times the upper limit of normal, immediate cessation of treatment is recommended. The neutrophil count should also be monitored for 4 to 8 weeks after the initiation of therapy and followed at regular, clinically determined intervals. If the neutrophil count is below 1.0 × 109/L, treatment should be interrupted to allow the count to recover. 

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

References

1. FDA approves new therapy for rare disease affecting optic nerve, spinal cord. News release. Food and Drug Administration. June 11, 2020.

2. FDA approves first treatment for neuromyelitis optica spectrum disorder, a rare autoimmune disease of the central nervous system. News release. Food and Drug Administration. June 27, 2019.

3. FDA Approves Treatment for Rare Disease Affecting Optic Nerves, Spinal Cord. News release. Food and Drug Administration. August 17, 2020.

4. ENSPRYNGTM (satralizumab-mwge) injection, for subcutaneous administration. RxList. Updated July 12, 2021. Accessed October 16, 2021. 

Reviewed by Harshi Dhingra, MD, on 10/17/2021.