Randomized Trial of Thymectomy in Myasthenia Gravis

TLDR

Thymectomy is a common treatment for myasthenia gravis, yet its benefit remains unproven. The study aimed to compare thymectomy plus prednisone versus prednisone alone in patients with generalized nonthymomatous myasthenia gravis. The multicenter randomized trial enrolled 18‑65‑year‑old patients with disease duration <5 years and elevated acetylcholine‑receptor antibodies, assigning them to extended transsternal thymectomy plus alternate‑day prednisone or alternate‑day prednisone alone, with primary outcomes of time‑weighted average Quantitative Myasthenia Gravis score and prednisone dose over 3 years. Thymectomy lowered QMG scores (6.15 vs 8.99), reduced prednisone use (44 vs 60 mg), decreased azathioprine need (17% vs 48%) and hospitalizations (9% vs 37%), and produced fewer immunosuppressive symptoms and lower distress, while complication rates were similar. The trial was funded by the National Institute of Neurological Disorders and Stroke and registered at ClinicalTrials.gov (NCT00294658).

Abstract

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 (44 mg vs. 60 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.).