Long-term effect of thymectomy in patients with non-thymomatous myasthenia gravis treated with prednisone: 2-year extension of the MGTX randomised tria

Background: The MGTX trial demonstrated that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status measured by the Quantitative MG (QMG) score in patients with non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods: A multicentre, rater-blinded 2-year extension study was conducted across 36 centres in 15 countries for patients who completed the MGTX randomised, controlled trial and were willing to participate. MGTX trial patients were aged 18 to 65 years at enrollment, had generalised non-thymomatous myasthenia gravis (MG) with disease duration less than 5 years and elevated (≥1.00 nmol/l; 0.50–0.99 nmol/l allowed if confirmed by positive edrophonium or electrophysiologic testing) acetylcholine receptor antibody titers.. All patients received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints were the time-weighted average of both the QMG and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention-to-treat. The trial was registered on clinicaltrials.gov, number NCT00294658. Findings: Of 111 subjects who completed the 3-year MGTX trial, 68 (61%) entered the extension study between September 1, 2009 and August 26, 2015 (33 prednisone alone; 35 prednisone plus thymectomy). Of the 68, 50 (74%) completed the 60-month assessment (24 prednisone alone; 26 prednisone plus thymectomy). At 5 years, patients randomised to thymectomy plus prednisone continued to demonstrate improved clinical status compared to patients in the prednisone alone group based on time-weighted average QMG (5.47±3.87 vs. 9.34±5.08; 95% CI for the difference 0.71–7.04; p=0.0007) and lower average alternate-day prednisone requirements (24 mg±21 mg vs. 48±29 mg; 95% CI for the difference 12–36 mg; p=0.0002). The proportion of patients requiring hospitalisation for MG exacerbation (6% vs. 30%; 95% CI for the difference 7.1–42.1%; p=0.0105) was lower in the thymectomy group. Other MEDRA-coded adverse events were infrequent, occurring at a rate of ≤6% in both groups and did not differ significantly between them. There were no treatment-related deaths. Interpretation: After 5 years, thymectomy continues to confer benefits in generalised non-thymomatous MG. Although caution in predicting benefit for all such patients is appropriate since the extension study included only half of MGTX trial subjects, results available through month 60 provide further evidence to support thymectomy in this large group of patients with generalised MG