Myasthenia gravis (MG) is a relatively rare disease, characterized by weakness, particularly of the eyelids, face, and upper extremities. It is an autoimmune disease that compromises the function at the neuromuscular junction. The hallmark feature of MG is weakness that improves with rest and worsens with recurring movement.
The treatment strategies are twofold: one focuses on immune suppression, and the other is directed at the action of the neuromuscular junction. The targeted treatment with anti-cholinesterase agents is generally accompanied by immunosuppression with steroids, intravenous immunoglobulin (IVIG), or plasmapheresis. Thymectomy reduces some of the autoimmune activity, and is often considered in the treatment plan for patients who have MG.
New approaches in the treatment of MG
Overall, MG has a reasonably good prognosis, although some patients have recurrent symptoms requiring ongoing or periodic treatment. There are a few new treatments for MG that appear to have an immunologic mechanism of action and may also have a more direct effect on the action of acetylcholine on the neuromuscular junction than steroids, IVIG, and plasmaphoresis.
Tacrolimus has emerged as an alternative in the treatment of MG. An immunosuppressant medication, its mechanism of action is thought to be related to the inhibition of T lymphocyte activation. According to Cruz and colleagues,1 “tacrolimus may also improve excitation-contraction coupling early after treatment initiation, perhaps due to potentiation of the ryanodine receptor, which is responsible for release of calcium ions from the sarcoplasmic reticulum in muscle cells.” Tacrolimus can be taken as a daily oral medication for the treatment of MG. So far, several studies have shown that Tacrolimus may improve symptoms and may allow reduction of steroid use, which can prevent the development of some of the adverse effects of steroids.
Soliris® (eculizumab) was approved by the FDA in October 2017 for the treatment of MG in patients who are anti-acetylcholine receptor (AchR) antibody-positive. Eculizumab may affect the mechanism by which acetylcholine antibodies cause neuromuscular junction dysfunction by inhibiting the terminal part of the complement cascade.2 In the Phase 3 REGAIN study and its ongoing open-label extension study, Soliris was shown to be beneficial for patients with anti-AchR antibody-positive gMG who had failed immunosuppressive treatment and continued to suffer from symptoms of MG.3
Do you think the available treatments are adequate to control symptoms of MG or are new and better treatment options needed?
1. Howard JF Jr, Freimer M, O'Brien F, et al. QMG and MG-ADL correlations: Study of eculizumab treatment of myasthenia gravis. Muscle Nerve. 2017;56:328-330.
2. Cruz JL, Wolff ML, Vanderman AJ, Brown JN. The emerging role of tacrolimus in myasthenia gravis. Ther Adv Neurol Disord. 2015;8:92-103.
3. Howard JF, Wang JJ, O'Brien F, Mantegazza R and the REGAIN study group. Efficacy of eculizumab is maintained beyond 26 weeks in patients with AChR+ refractory generalized myasthenia gravis (gMG). Poster (Abstract 211), Annual Meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), September 14, 2017.