Myasthenia gravis: Historical achievements and the "golden age" of clinical trials

Abstract

Since the death of Chief Opechankanough >350 years ago, the myasthenia gravis (MG) community has gained extensive knowledge about MG and how to treat it. This review highlights key milestones in the history of treatment and discusses the current "golden age" of clinical trials. Although originally thought by many clinicians to be a disorder of hysteria and fluctuating weakness without observable cause, MG is one the most understood autoimmune neurologic disorders. However, studying it in clinical trials has been challenging due to the fluctuating nature of the medical condition which impacts MG clinical outcomes. Clinical trials must also account for the possibility of a placebo effect. Because MG is a rare incurable autoimmune disorder, it limits the number of potential patients available to participate in clinical trials. In the last 15 years, however, significant progress has been made with MG randomized clinical trials, resulting in a new drug (eculizumab) for physicians' treatment repertoire and an old technique (thymectomy) confirmed effective for MG. Some of the therapies (eg, thymectomy, corticosteroids, plasma exchange, and intravenous immunoglobulin [IVIg]) have survived the test of time. Others (eg, eculizumab and neonatal Fc receptor inhibitor) are novel and hold promise.

Keywords: Acetylcholine receptor antibodies; Autoantibody; Clinical trial; Complement-inhibition; Corticosteroids; FcRn antibodies; Immunoglobulin; Myasthenia gravis; Plasma exchange; Thymectomy.