Thymectomy for Myasthenia Gravis

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Thymectomy Effective in Myasthenia Gravis

by S. Andrew Josephson, MD, Professor; Senior Executive Vice Chairman, Department of Neurology, University of California, San Francisco, San Francisco, California

Update to Chapter 461: Myasthenia Gravis and Other Diseases of the Neuromuscular Junction

The mainstay of treatment for patients with autoimmune myasthenia gravis (MG) involves immunosuppressive medications along with the acetylcholinesterase inhibitor pyridostigmine. The thymus plays a central role in the pathogenesis of the disorder, with 10% of patients being found to harbor a thymoma that should be removed surgically in order to avoid metastatic disease. However, a majority of other patients with MG demonstrate thymic hyperplastic tissue, and whether removal of this tissue via thymectomy improves outcomes in MG remains a matter of debate. For more than a decade, Wolfe and colleagues (2016) have planned and executed a randomized trial of thymectomy in MG; the results of this study have been one of the most eagerly anticipated findings in the neuromuscular community.

The authors performed a multicenter, randomized, rater-blinded trial of patients with acetylcholine receptor antibody–positive generalized MG. Patients were eligible for enrollment if they were between 18 and 65 years of age with a disease duration of <5 years. Patients could be taking anticholinesterase treatment as well as glucocorticoids but could not be on other immunotherapies. Patients were randomized to thymectomy via sternotomy plus a standardized prednisone regimen versus a standardized prednisone regimen alone. The standardized regimen involved escalating alternate-day dosing until minimal symptoms were achieved (e.g., no functional limitation with some muscle weakness allowed on examination) followed by weaning as tolerated. The dual primary outcomes examined were the time-weighted average Quantitative Myasthenia Gravis score and the average required dose of prednisone during 3 years of follow-up as scored by raters blind to treatment group.

A total of 126 patients were randomized between 2006 and 2012 at 36 centers. The median age was around 33 years, and more than two-thirds were women. The patients assigned to surgery were found to have significantly lower Quantitative Myasthenia Gravis scores at month 36 than those assigned to medical therapy (6.15 vs 8.99; p<.001), while the thymectomy patients were also found to have a lower dose requirement for alternate-day prednisone (44 mg vs 60 mg; p<.001).

Secondary outcomes included significantly fewer patients requiring additional immunosuppressive medications in the thymectomy group and significantly fewer hospitalizations for exacerbations in the thymectomy group (9% vs 37%; p<.001). Treatment-associated complications did not differ between the two groups, but patients receiving thymectomy reported significantly lower treatment-associated symptoms and the stress related to these symptoms.

This extremely important trial supports the routine use of thymectomy in patients with autoimmune MG and should be practice-changing. At issue remains the most appropriate age cut-off for the procedure. The trial included patients up to age 65, but expert opinion differs on whether patients in the seventh decade of life or older should receive this invasive surgery. Another important point involves the procedure itself. Surgeons in the study went through standard training, and all performed thymectomy using the classic median sternotomy approach. Whether less invasive techniques, which have been shown to likely result in more retained thymic tissue, can be equally effective with less morbidity remains an important question not addressed in high-quality randomized trials. For now, clinicians caring for MG patients who meet the entry criteria for this trial should consider referral for thymectomy in order to improve their long-term disease control.

– Josephson SA. Thymectomy Effective in Myasthenia Gravis. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo JL. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015. Accessed September 27, 2016.


Wolfe GI et al.: Randomized trial of thymectomy in myasthenia gravis. N Engl J Med 375:511, 2016 [Free full-text N Engl J Med article PDF | PubMed® abstract]

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