Introduction
Rystiggo (rozanolixizumab-noli) is a neonatal Fc receptor (FcRn) blocker approved by the FDA in June 2023 for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. It represents a novel therapeutic approach in the management of this chronic autoimmune neuromuscular disorder.
Mechanism of Action
Rystiggo is a humanized monoclonal antibody that binds to the neonatal Fc receptor (FcRn) with high affinity. By blocking FcRn, it reduces the recycling of immunoglobulin G (IgG) antibodies, including pathogenic autoantibodies, and accelerates their catabolism. This mechanism decreases circulating IgG levels, including the autoantibodies responsible for the pathophysiology of myasthenia gravis, thereby improving neuromuscular transmission and clinical symptoms.
Indications
FDA-approved for the treatment of generalized myasthenia gravis in adult patients who are anti-AChR or anti-MuSK antibody positive.
Dosage and Administration
Recommended dosage: 7 mg/kg administered by subcutaneous infusion once weekly Route: Subcutaneous infusion using an infusion pump Duration: Each infusion should be administered over approximately 90 minutes Special populations:- Renal impairment: No dosage adjustment recommended
- Hepatic impairment: No dosage adjustment recommended
- Elderly: No dosage adjustment recommended
- Pregnancy: Use only if potential benefit justifies potential risk
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Bioavailability is approximately 82% following subcutaneous administration Distribution: Volume of distribution is approximately 6.5 L Metabolism: Expected to be metabolized via proteolytic pathways similar to other IgG antibodies Elimination: Terminal half-life is approximately 8-12 days Special populations: No clinically significant differences observed based on age, sex, race, or body weightContraindications
- History of severe hypersensitivity reactions to rozanolixizumab-noli or any of its excipients
- Active infection requiring intravenous antimicrobial therapy
- Known immunoglobulin A (IgA) deficiency with antibodies against IgA
Warnings and Precautions
Infections: Increased risk of infections due to decreased IgG levels. Monitor for signs and symptoms of infection Hypersensitivity reactions: May occur during or after infusion. Monitor patients closely Immunization: Live vaccines are not recommended during treatment Fetal/Neonatal harm: Based on mechanism of action, may cause fetal harm IgA deficiency: Use with caution in patients with known IgA deficiencyDrug Interactions
Live vaccines: Avoid concurrent administration Other immunosuppressants: May increase risk of infections IgG-containing products: May interfere with Rystiggo's mechanism of actionAdverse Effects
Most common adverse reactions (≥10%):- Headache
- Infections (including upper respiratory tract infections)
- Diarrhea
- Fever
- Nausea
- Hypersensitivity reactions
- Serious infections
- Anaphylaxis and hypersensitivity reactions
Monitoring Parameters
Baseline:- Complete blood count with differential
- Quantitative immunoglobulins (IgG, IgA, IgM)
- Infection screening
- Pregnancy testing in women of childbearing potential
- Signs and symptoms of infection
- Hypersensitivity reactions during and after infusion
- Clinical response using validated MG assessment scales
- IgG levels (monthly monitoring recommended)
- Liver function tests
- Immunoglobulin levels
- Infection surveillance
- Neurological status
Patient Education
- Report any signs of infection (fever, cough, sore throat) immediately
- Inform healthcare providers about all medications being taken
- Understand the risk of hypersensitivity reactions during infusion
- Avoid live vaccines during treatment
- Use effective contraception during treatment and for several months after discontinuation
- Report pregnancy or planning pregnancy to healthcare provider
- Keep all scheduled appointments for monitoring
- Understand that clinical improvement may take several weeks
References
1. FDA prescribing information: Rystiggo (rozanolixizumab-noli) injection 2. Bril V, et al. Safety and efficacy of rozanolixizumab in patients with generalized myasthenia gravis: A phase 2 randomized controlled trial. Neurology. 2021 3. Howard JF Jr, et al. Long-term efficacy and safety of rozanolixizumab in generalized myasthenia gravis: Phase 3 study results. Muscle Nerve. 2023 4. Dalakas MC. FcRn antagonists: A novel approach to treat autoimmune neurology. Nat Rev Neurol. 2021 5. ClinicalTrials.gov: NCT03971422 and NCT04650893 6. Product monograph: Rystiggo (UCB, Inc.) 7. Myasthenia Gravis Foundation of America treatment guidelines. 2020