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BOSTON -- Thymectomy combined with prednisone therapy in patients with nonthymomatous (no thymus tumor) myasthenia gravis (MG) resulted in better three-year patient outcomes than steroid therapy alone in a randomized trial, researchers reported here.

MG is a rare autoimmune disease that results from a disruption of communication between nerve and muscle. Patients can develop a variety of symptoms, including droopy eyelids, blurred vision, muscle weakness, and difficultly speaking, swallowing, and breathing. It is estimated that the disease affects about 60,000 Americans.

Research as far back as the late 19th century has suggested MG is associated with various abnormalities of the thymus gland, and the first use of thymectomy in patients with nonthymomatous myasthenia gravis was reported by Alfred Blalock, MD, and colleagues in the Journal of the American Medical Association in 1941. As reported in that article, of the six patients who underwent the surgery, three had a favorable response.

"Since Blalock's report, thymectomy has been used, but there's always been a question of what we get out of it," said Gil I. Wolfe, MD, of the University of Buffalo Jacobs School of Medicine and Biomedical Sciences, and lead author of a paper reporting on the randomized trial. Wolfe summarized the trial results at a plenary session here at the American Academy of Neurology's annual meeting.

"This was a trial that was 15 years in the making and designed to address a question that has persisted for 75 years," said Wolfe.

According to Wolfe, while a consensus has been established in favor of thymectomy among this group of patients, "that consensus is based on non-randomized case series and no class one or class two evidence." And while there have been repeated calls for randomized trials, they've never materialized.

Wolfe also pointed out -- based on nationwide inpatient sample from about 1,000 hospitals -- that the thymectomy rate fell from 7% to 1.5% between 2000 and 2005, suggesting that doctors and patients could have been waiting to see the results of this trial or because of the availability of alternative therapies for MG.

In this trial, Wolfe and his colleagues addressed three questions: Compared with a prednisone protocol alone does thymectomy plus prednisone therapy result in:

• Greater improvement in strength (as measured by a time weighted average Quantitative Myasthenia Gravis score)?
• A lower prednisone requirement?
• Enhanced quality of life?

Patients 18 to 65 years of age who had generalized nonthymomatous MG with a disease duration of less than five years were included in the trial if they had Myasthenia Gravis Foundation of America clinical class II-IV disease. A total of 126 patients were included in the study and randomized from 2006 to 2012 to undergo thymectomy plus the standardized prednisone protocol or to receive that steroid regimen alone.

Wolfe and colleagues found that patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a three-year period than those receiving prednisone alone (6.15 vs. 8.99), and also needed about a third-less prednisone to control their disease.

Wolfe and his colleagues also found no significant differences between the two treatment groups regarding treatment associated complications, but did find that patients who underwent thymectomy had fewer treatment-associated symptoms related to immunosuppressive medications and lower distress levels related to symptoms.

"We also say benefits across several subgroups -- by age, sex and prednisone exposure -- as well," Wolfe added.

"This is class one evidence that extended transsternal thymectomy has a favorable impact on acetylcholine-receptor antibody positive generalized MG, based on clinical outcomes, through the quantitative MG score, corticosteroid exposure, and adverse events," Wolfe concluded.