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Immunotherapy in myasthenia gravis in the era of biologics

Nature Reviews Neurology volume 15, pages 113–124 (2019)Cite this article

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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.

Key points

  • In myasthenia gravis (MG), the clinical phenotype and the type of circulating antibodies that are present have the greatest influence on therapeutic decisions and outcomes.

  • Targeted immunotherapy seems to be the most promising therapeutic approach in MG because it can effectively overcome the limitations of current nonspecific immunotherapies and has the potential to induce remission.

  • Biologics that are relevant to treating MG target B cells, molecules associated with T cell activation, complement, the neonatal crystallizable fragment of immunglobulin G antibodies, and cytokines associated with antibody production.

  • The checkpoint inhibitors that are used for the treatment of advanced malignancies have a paradoxical effect that means they can trigger MG that requires early recognition and prompt immunotherapy.

  • In the era of biologics, more-effective therapies are creating a need for new criteria that define clinical responses and remission, and for better outcome measures and biomarkers to assess clinical benefits.

  • Several outdated or unverified views, including unsubstantiated concerns that exercise or administration of common drugs, such as antibiotics or statins, can worsen MG symptoms, need to be revisited.

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Fig. 1: The main cells and pathways in the immune network of myasthenia gravis and their potential as therapeutic targets.

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  1. Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA

    Marinos C. Dalakas

  2. Neuroimmunology Unit, National and Kapodistrian University of Athens Medical School, Athens, Greece

    Marinos C. Dalakas

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Dalakas, M.C. Immunotherapy in myasthenia gravis in the era of biologics. Nat Rev Neurol 15, 113–124 (2019). https://doi.org/10.1038/s41582-018-0110-z

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