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Immunotherapy in myasthenia gravis in the era of biologics.
Nat Rev Neurol. 2019 Feb;15(2):113-124. doi: 10.1038/s41582-018-0110-z.
Dalakas MC1,2.
Abstract
No consensus has been reached on the ideal therapeutic algorithm for myasthenia gravis (MG).
Most patients with MG require induction therapy with high doses of corticosteroids and maintenance with an immunosuppressant.
Severe cases and acute worsening require intravenous immunoglobulin or plasmapheresis before oral immunosuppressants start having an effect.
However, biologics are emerging as important therapeutic tools that promise to provide better corticosteroid sparing effects than standard treatments and can even induce remission.
In particular, eculizumab, a monoclonal antibody against complement C5, has been approved by the FDA for refractory MG on the basis of a phase III trial.
Rituximab, an anti-CD20 monoclonal antibody that depletes peripheral B cells, has also been effective in many large uncontrolled series, although was not in a small phase III trial.
Whether the newer anti-CD20 agents ocrelizumab, ofatumumab, obinutuzumab, ublituximab or inebilizumab will be more effective remains unclear.
Belimumab, an antibody against the B cell trophic factor BAFF, was ineffective in phase III trials, and efgartigimod, which depletes antibodies, was effective in a phase II study.
Some anti-cytokine agents relevant to MG immunopathogenesis also seem promising.
Checkpoint inhibitors can trigger MG in some patients, necessitating early intervention.
Increased availability of new biologics provides targeted immunotherapies and the opportunities to develop more specific therapies.
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