Immunotherapy in myasthenia gravis in the era of biologics
- 20 December 2018
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Neurology
- Vol. 15 (2), 113-124
- https://doi.org/10.1038/s41582-018-0110-z
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.Keywords
This publication has 100 references indexed in Scilit:
- Myasthenia gravis and neuromyelitis optica spectrum disorderNeurology, 2012
- Complement and cytokine based therapeutic strategies in myasthenia gravisJournal of Autoimmunity, 2011
- Increased serum interleukin‐17 levels in patients with myasthenia gravisMuscle & Nerve, 2011
- Response of patients with refractory myasthenia gravis to rituximab: a retrospective studyTherapeutic Advances in Neurological Disorders, 2011
- A systematic review of population based epidemiological studies in Myasthenia GravisBMC Neurology, 2010
- Practical considerations on the use of rituximab in autoimmune neurological disordersTherapeutic Advances in Neurological Disorders, 2010
- Disequilibrium of T helper type 1, 2 and 17 cells and regulatory T cells during the development of experimental autoimmune myasthenia gravisImmunology, 2009
- Recapitulation of IVIG Anti-Inflammatory Activity with a Recombinant IgG FcScience, 2008
- Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response programThe Journal of Experimental Medicine, 2007
- Preliminary Results of a Double-Blind, Randomized, Placebo-Controlled Trial of Cyclosporine in Myasthenia GravisThe New England Journal of Medicine, 1987