Patient Safety: Complement inhibitors in treatment of myasthenia gravis

From the Quality and Patient Safety Committee

39-year-old woman is evaluated for increased weakness, shortness of breath and difficulty swallowing. Three years ago, she developed diplopia and excessive fatigue and was diagnosed with anti-AchR-seropositive generalized myasthenia gravis treated initially with pyridostigmine 60 mg tid and prednisone up to 60 mg qd due to increased weakness. This was followed by additions of azathioprine up to 150 mg qd, and was then switched to mycophenolate up to 1500 mg bid due to poor efficacy. Intravenous immunoglobulins were not effective. Despite attempts to control the disease she had 4 hospital admissions with exacerbations of myasthenia gravis. Due to refractoriness of myasthenia gravis, treatment with complement inhibitors was recommended.

Question: Prior to starting treatment with complement inhibitors, the patient will have to complete following?

A. Hepatitis B vaccination
B. HIV serology
C. Meningococcal vaccination
D. Quantiferon testing

Explanation:

Correct answer: 3. Meningococcal vaccination.

Complement inhibitors are used for treatment of anti-AChR-seropositive generalized myasthenia gravis and other complement-mediated neurologic disorders like neuromyelitis optica (NMO). Complement inhibition is not used in treatment of anti-MuSK and seronegative myasthenia gravis, as anti-MuSK antibodies do not activate complement cascade. Currently, three FDA-approved complement inhibitors include eculizumab, ravulizumab and Zilucoplan, and other medications may follow.

Complement inhibition is associated with a greatly increased risk of potentially fatal meningococcal infections (1,000 to 2,000-fold) as is infection with other encapsulated organisms.

Meningococcal vaccination is a mandatory step and recent guideline requires that the patient complete primary vaccination schedule for both MenACWY and Men B . Enrollment of prescribing practitioners in the Risk Evaluation and Mitigation Strategy (REMS) programs is strongly recommended by FDA.  Meningococcal vaccination must include both quadrivalent (MenACWY) and Men B vaccines. If treatment with complement inhibitors is continued, booster revaccinations are required after several years (MenACWY every 5 years; MenB 1 year after initial series, then every 2-3 years). As vaccination does not eliminate the risk of infection with meningococci, continued alertness is required.

There is also an increased risk of infections with other encapsulated organisms as well (e.g. Haemophilus influenzae, Strep. pneumoniae), but additional vaccinations are not required.

Authors: Sasha Zivkovic, MD, PhD; Urvi Desai, MD

Sources:

1. Mbaeyi S et al. Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States,2020. MMWR Recomm Rep. 2020 Sep 25;69(9):1-41.  doi: 10.15585/mmwr.rr6909a1. PMID: 33417592. DOI: 10.15585/mmwr.rr6909a1.
2. Suh J et al. Safety and outcomes of eculizumab for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice. Muscle Nerve. 2022 Sep;66(3):348-353. doi: 10.1002/mus.27656. Epub 2022 Jun 27. PMID: 35684980
3. Narayanaswami P  et al . International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology. 2021 Jan 19;96(3):114-122. doi: 10.1212/WNL.0000000000011124. Epub 2020 Nov 3.PMID: 3314451.