Abstract and Introduction
Purpose of review: This article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and neuroelectrophysiological tests as diagnostic tools, to innovative and promising treatments based on biological drugs.
Recent findings: Novel studies performed by cell-based assays (CBAs) indicate an improvement in the chance of identifying serum autoantibodies in myasthenic patients. Clinical trials on the use of biological drugs were recently concluded, providing important data on safety and efficacy of eculizumab, efgartigimod and amifampridine phosphate: the first, a complement blocker, showed long-term safety and efficacy in acetylcholine receptor (AChR)-positive myasthenic patients with refractory generalized disease; the second, the neonatal Fc receptor blocker, was well tolerated and clinically effective in both AChR-specific and muscle-specific kinase receptor (MuSK)-positive patients; the third, a blocker of presynaptic potassium channels, was found to be well tolerated and effective in MuSK-positive patients.
Summary: CBAs can lead to a significant reduction of seronegative patients, improving myasthenia gravis diagnostic process. New biological drugs offer innovative approaches to treat myasthenic patients with generalized disease, promising to change the paradigm of treatment and to significantly enhance therapeutic success within a precision medicine framework.
Myasthenia gravis is an autoimmune disease causing neuromuscular junction (NMJ) impairment, characterized by weakness and easy fatigability on exertion involving different skeletal muscle districts. The autoimmune attack is mediated by autoantibodies targeting key functional and structural NMJ proteins: the acetylcholine receptor (AChR), the muscle-specific kinase receptor (MuSK) or the low-density lipoprotein receptor-related protein 4 (LRP4). In AChR-MG, morphological and functional changes (i.e. follicular hyperplasia and thymoma) of the thymus are pathologically relevant, and a wealth of data indicates that this organ is a main site of anti-AChR autosensitization, ultimately leading to autoantibody production and chronic autoimmunity. Myasthenia gravis diagnosis is clinical, instrumental and pharmacological; the latter particularly used in seronegative patients. Recently, recommendations for myasthenia gravis treatment have been published.[4,5] However, treatment improvement of myasthenic patients is still a medical need as a substantial proportion of them are refractory or intolerant.
The current article provides an update on the diagnostic and therapeutic strategies for myasthenia gravis in relationship with the clinical heterogeneity of the disease, highlighting how the introduction of novel biological agents and the development of precision medicine approaches, based on predictive biomarkers, could significantly improve therapeutic success in a cost/effective manner.
Curr Opin Rheumatol. 2019;31(6):623-633. © 2019 Lippincott Williams & Wilkins