Progress in the therapy of myasthenia gravis: getting closer to effective targeted immunotherapies

Marinos C Dalakas
Current Opinion in Neurology 2020, 33 (5): 545-552

PURPOSE OF REVIEW: To provide an update on immunomodulating and immunosuppressive therapies in myasthenia gravis and highlight newly approved, or pending approval, therapies with new biologics.

RECENT FINDINGS: Preoperative IVIg is not needed to prevent myasthenic crisis in stable myasthenia gravis patients scheduled for surgery under general anesthesia, based on controlled data. Rituximab, if initiated early in new-onset myasthenia gravis, can lead to faster and more sustained remission even without immunotherapies in 35% of patients at 2 years. Biomarkers determining the timing for follow-up infusions in Rituximab-responding AChR-positive patients are discussed. Most patients with MuSK-positive myasthenia gravis treated with Rituximab have sustained long-term remission with persistent reduction of IgG4 anti-MuSK antibodies. Eculizumb in the extension REGAIN study showed sustained long-term pharmacological remissions and reduced exacerbations. Three new biologic agents showed promising results in phase-II controlled myasthenia gravis trials: Zilucoplan, a subcutaneous macrocyclic peptide inhibiting complement C5; Efgartigimod, an IgG1-derived Fc fragment binding to neonatal FcRn receptor; and Rozanolixizumab, a high-affinity anti-FcRn monoclonal antibody. Finally, the safety of ongoing myasthenia gravis immunotherapies during COVID19 pandemic is discussed.

SUMMARY: New biologics against B cells, complement and FcRn receptor, are bringing us closer to successful targeted immunotherapies in the chronic management of myasthenia gravis promising an exciting future for antibody-mediated neurological diseases.

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