Introduction
Enspryng (satralizumab) is a humanized monoclonal antibody targeting the interleukin-6 receptor (IL-6R) approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive. As a novel therapeutic option, it represents a significant advancement in the management of this rare autoimmune disorder affecting the central nervous system.
Mechanism of Action
Satralizumab binds to both soluble and membrane-bound IL-6 receptors, inhibiting IL-6-mediated signaling. IL-6 is a key proinflammatory cytokine implicated in the pathogenesis of NMOSD, contributing to inflammation, demyelination, and astrocyte damage. By blocking IL-6 signaling, Enspryng reduces the inflammatory cascade that drives NMOSD pathology, including the production of AQP4-IgG by plasmablasts and the breakdown of the blood-brain barrier.
Indications
Enspryng is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.
Dosage and Administration
Initial loading dose: 120 mg subcutaneous injection administered at weeks 0, 2, and 4 Maintenance dose: 120 mg subcutaneous injection every 4 weeksAdministration:
- Administer subcutaneously in the abdomen, thigh, or back of upper arm
- Rotate injection sites
- Allow refrigerated medication to reach room temperature (30 minutes) before injection
- Do not shake the prefilled syringe
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Not studied; use with caution
- Elderly: No specific dosage adjustment recommended
Pharmacokinetics
Absorption: Bioavailability approximately 80% following subcutaneous administration Distribution: Steady-state volume of distribution is approximately 5.3 L Metabolism: Satralizumab is expected to be metabolized via proteolytic enzymes throughout the body Elimination: Elimination half-life is approximately 30 days Time to steady state: Approximately 20 weeksContraindications
- Active hepatitis B infection
- Active or untreated latent tuberculosis
- History of hypersensitivity to satralizumab or any component of the formulation
- Active serious infections
Warnings and Precautions
Infections: Increased risk of serious infections including tuberculosis, invasive fungal infections, and other opportunistic infections. Screen for TB before initiation. Hepatotoxicity: Monitor liver enzymes; may cause elevated transaminases Neutropenia: May cause decreased neutrophil counts; monitor complete blood count Hypersensitivity reactions: Anaphylaxis and other hypersensitivity reactions may occur Vaccinations: Avoid live vaccines during treatment Fetal risk: May cause fetal harm based on mechanism of action; advise women of reproductive potential to use effective contraceptionDrug Interactions
- CYP450 substrates: IL-6 inhibition may reduce metabolism of CYP450 substrates; monitor drugs with narrow therapeutic index
- Immunosuppressants: Concurrent use may increase risk of infections
- Live vaccines: Contraindicated during treatment
- Tocilizumab: Avoid concomitant use with other IL-6 inhibitors
Adverse Effects
Most common adverse reactions (≥10%):- Headache
- Fatigue
- Arthralgia
- Upper respiratory tract infections
- Rash
- Nausea
- Injection site reactions
- Serious infections (including opportunistic infections)
- Anaphylaxis and hypersensitivity reactions
- Neutropenia
- Thrombocytopenia
- Elevated liver enzymes
Monitoring Parameters
- Before initiation: Complete blood count, liver function tests, hepatitis B screening, tuberculosis screening
- During treatment: CBC with differential (monitor for neutropenia), liver function tests (monthly for first 6 months, then as clinically indicated)
- Infection monitoring: Monitor for signs and symptoms of infection throughout treatment
- Clinical response: Neurological assessments, relapse rate, disability progression
- Immunogenicity: Anti-drug antibodies (may affect efficacy)
Patient Education
- Instruct patients on proper subcutaneous injection technique and rotation of injection sites
- Educate about signs and symptoms of infection and when to seek medical attention
- Advise patients to avoid live vaccines during treatment
- Inform about potential side effects including injection site reactions
- Discuss importance of adherence to prescribed dosing schedule
- Counsel women of reproductive potential about pregnancy prevention and planning
- Advise patients to inform all healthcare providers about their Enspryng therapy
- Provide information on storage and handling of medication
References
1. Yamamura T, Kleiter I, Fujihara K, et al. Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019;381(22):2114-2124. 2. Enspryng [package insert]. South San Francisco, CA: Genentech, Inc.; 2020. 3. Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402-412. 4. FDA Approval Letter: Enspryng (satralizumab). August 2020. 5. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019;381(7):614-625.