Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (32 mg vs. 54 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.)

The main disease mechanism in myasthenia gravis (MG) is a humoral immune attack on the acetylcholine receptor (AChR), leading to the characteristic defect transmission in the neuromuscular junction.¹ In addition, heart and skeletal muscles are also speculated to be autoimmune targets in MG.² It is known that some patients with MG have focal collections of mononuclear cells in the skeletal muscles.³ This subclinical phenomenon, known as lymphorrhages, does not cause clinically defined myopathy.^2,3 Zamecnik et al⁴ concluded that the lymphocytic infiltrations of MG muscles did not represent a true autoimmune myositis, but reflected an infiltration by naive lymphocytes derived from lymphocyte-rich thymomas. However, inflammatory myopathies, ie, autoimmune-mediated myocarditis and/or myositis, developed in a few patients with MG, especially thymoma-associated MG.^2,5-8 Inflammatory myopathies not only lead to the deterioration of muscular weakness, but also were the most serious complications in the disease course of patients with MG.^2,5-8 Because inflammatory myopathies in patients with MG are rare, the clinical characteristics of case series have not been described.

Objectives To evaluate the ability of tacrolimus to reduce the corticosteroid dose in patients with myasthenia gravis (MG) and the drug's safety in a double-blind, placebo-controlled, parallel group study. Methods Patients being treated with oral prednisolone at doses equivalent to 10–20 mg/day, and with stable symptoms, were randomised to tacrolimus or placebo in a 28-week double-blind study. The dose of corticosteroid was tapered with the procedures specified in the protocol. The primary efficacy endpoint was the mean daily prednisolone dose given in the last 12 weeks of the study. Results Eighty patients received the study drug (40 patients in each group) and were included in the full analysis set. In the full analysis set, there was no significant difference in the primary efficacy endpoint between the two groups (p=0.078). However, some secondary analyses suggested the steroid-sparing effect of tacrolimus. Tacrolimus was well tolerated, and no safety concerns were noted. Conclusions This study suggests that tacrolimus has a potential advantage as a steroid-sparing agent in the treatment of MG patients. Clinical trial registration number NCT00309088. Name of the trial registry: FK506 Phase 3 Study: A Study for Steroid Non-Resistant MG Patients.