Wolfe et al. conducted the Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy (MGTX), an international, randomized, single-blind (rater-blinded) trial, to determine whether extended transsternal thymectomy combined with a standardized prednisone protocol would be superior to prednisone alone after 3 years, with respect to lessening myasthenic weakness, lowering the total dose of prednisone, and enhancing quality of life.
In patients with nonthymomatous myasthenia gravis, thymectomy plus prednisone was associated with better clinical outcomes than prednisone alone. Patients treated with thymectomy had fewer hospitalizations for exacerbations and required lower prednisone doses. A new Original Article explains.
• What has been the rationale for performing thymectomy in patients with myasthenia gravis?
Thymectomy for the treatment of myasthenia gravis is based on several lines of evidence that support a central role of the thymus in the pathogenesis of the disease. Thymomas are present in 10% of patients with myasthenia gravis, and thymectomy is considered to be mandatory to prevent further spread. Up to 70% of the remaining patients with myasthenia gravis have hyperplastic thymic changes that are not seen in healthy persons. However, the success of immunotherapy has raised questions regarding whether such an operation is necessary.
• What is known about the possible benefits of thymectomy in myasthenia gravis?
Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. The first reported use of thymectomy in patients with nonthymomatous myasthenia gravis was 75 years ago. Of six patients who underwent surgery, three had a favorable response. Subsequent retrospective studies have shown benefits of thymectomy in patients with nonthymomatous myasthenia gravis but with widely varying rates of clinical improvement or remission. A compilation of retrospective studies comparing surgery with medical management did not show a difference in remission rates. Two studies that showed clinical improvements after thymectomy indicated that benefit occurred in the first few years after the procedure, but after 5 years, rates of clinical improvement were similar among surgically treated patients and those who were treated medically. Observational studies have not shown benefits of thymectomy, perhaps because of the effectiveness of modern immunotherapeutic approaches. Despite calls for a randomized, controlled study, data are lacking, and uncertainty persists regarding the benefit of thymectomy and the clinical characteristics of the patients who should be offered the procedure.
Morning Report Questions
Q: Did the MGTX trial provide evidence supporting the role of thymectomy in myasthenia gravis?
A: The MGTX trial provides evidence supporting the use of thymectomy for improving clinical outcomes and reducing the need for immunosuppressive therapy in patients with myasthenia gravis. Over a period of 3 years, thymectomy was associated with a more favorable outcome than was prednisone alone, with a difference in Quantitative Myasthenia Gravis scores that correlated with clinically significant improvement. The time-weighted average required alternate-day prednisone dose was significantly lower in the thymectomy group than in the prednisone-only group.
Q: What other benefits were associated with thymectomy in the MGTX trial?
A: In the MGTX trial, fewer patients were hospitalized for exacerbations of myasthenia gravis in the thymectomy group than in the prednisone-only group (9% vs. 37%, P<0.001). Similarly, other findings favored thymectomy over prednisone alone, including the time-weighted average score on the Myasthenia Gravis Activities of Daily Living scale (2.24 vs. 3.41, P=0.008), azathioprine use (17% vs. 48% of participants, P<0.001), and the percentage of patients who had minimal-manifestation status at month 36 (67% vs. 47%, P=0.03). The survey regarding treatment-associated complications showed no significant difference between the two treatment groups over a period of 3 years (P=0.73).