Bryan Lecky

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.).

We compared prednisolone (PRED) and azathioprine (AZA) versus prednisolone alone in the treatment of MG. Prednisolone alone or combined with azathioprine is widely used in the treatment of MG, but no randomized placebo-controlled comparative trial data are available. The prednisolone dose and clinical outcome were compared in a multicenter randomized double-blind study of 34 MG patients who were followed up for 3 years. One group (PRED + AZA) received prednisolone (on alternate days) plus azathioprine (2.5 mg/kg); the other group received prednisolone on alternate days plus placebo (PRED + PLAC). Initial high-dose prednisolone (1.5 mg/kg on alternate days) was tapered at remission to the minimal dose required to maintain remission. The prednisolone dose did not differ significantly between the two groups at 1 year (median values: PRED + AZA, 37.5 mg on alternate days; PRED + PLAC, 45 mg on alternate days) but was reduced at 2 and 3 years in the PRED + AZA group (median value at 3 years: PRED + AZA, 0 mg on alternate days; PRED + PLAC, 40 mg on alternate days; p=0.02). Relapses and failures to remit over the 3 years were more frequent in the PRED + PLAC group. There was a sharp rise in the anti-acetylcholine receptor (AChR) titers in the PRED + PLAC group at 2 years. Incidence of side effects was slightly less in the PRED + AZA group. Azathioprine as an adjunct to alternate day prednisolone in the treatment of antibody-positive generalized MG reduces the maintenance dose of prednisolone and is associated with fewer treatment failures, longer remissions, and fewer side effects.