PracticeUpdate Neurology Best of 2018

CONFERENCE COVERAGE 26

Thymectomy Continues to Be Successful for Myasthenia Gravis Thymectomy improves clinical outcomes, reduces immunosuppressant requirements and decreases side effects. R esults of the MGTX trial have pro- vided a definitive answer to questions about the efficacy of thymectomy for Dual primary outcomes were the time- weighted average of the Quantitative Myasthenia Gravis Score and prednisone dose over 3 years.

Dr. Wolfe concluded that extended trans- sternal thymectomy performed within the first 5 years of disease improves clinical outcomes, reduces immunosuppressant requirements, and decreases side effect burdens in generalized acetylcholine receptor antibody-positive individuals with myasthenia gravis without thymoma. This group represents the largest sub-popula- tion of individuals with myasthenia gravis. Richard J. Barohn, MD, of the University of Kansas Medical Center in Kansas City, dis- cussed MGTX in a presentation in which he stressed the central role that thymectomy was confirmed to play in the treatment of myasthenia gravis. The tumor should be removed in thymoma- tous myasthenia gravis. The entire thymus tissue should be removed along with the thymoma. Myasthenic symptoms may or may not improve. Controlled trials involving thoracic surgery for a rare disease are difficult, so high-qual- ity evidence about thymectomy remained scarce for decades. Surprisingly, the effects of thymectomy in MGTX were observed as early as 3 to 4 months and were maintained for the entire 3-year study. Individuals with persistent bulbar, respira- tory, or limb weakness should be treated with plasma exchange before surgery. Evidence does not support thymectomy in MuSK, LRP4, or agrin antibody-positive individuals. Individuals with myasthenia gravis with MuSK antibodies were not included but those with MuSK and those who are “double-negative” for antibodies have undergone thymectomy and have done well anecdotally. Similarly, limited evidence supports thymectomy in individuals with ocular myasthenia gravis. If the individual is refrac- tory and positive for acetylcholine receptor antibody, however, thymectomy may be considered. MGTX mandated a sternal splitting procedure. References: 1. Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized Trial of Thymectomy in Myasthenia Gravis. N Engl J Med 2016;375:511-22 2. Blalock A, Mason MF, Morgan HJ, et al. Myasthenia gravis and tumors of the thymic region: report of a case in which the tumor was removed. Ann Surg. 1939;110:544-61. www.practiceupdate.com/c/70778

myasthenia gravis. Fewer individuals who underwent thymectomy needed additional immunosuppression, and they experienced fewer adverse events and admissions for myasthenic crises. This outcome from the multicenter, randomized, prospective MGTX trial was reported at ICNMD 2018. Gil I. Wolfe, MD, of the University of Buf- falo in New York, and colleagues set out to determine whether the combination of alternate-day prednisone and extended trans-sternal thymectomy after 3 years versus an identical dosing protocol of pred- nisone alone would: 1 • Lead to better outcomes as measured by a time-weighted average of the Quanti- tative Myasthenia Gravis Score • Reduce time-weighted average alter- nate-day prednisone requirements • Reduce the burden of side effects that arise primarily from medications used to treat the disease Participants aged 18 to 65 years and suf- fering from generalized non-thymomatous acetylcholine receptor antibody-positive myasthenia gravis for <5 years and Myas- thenia Gravis Foundation of America Clinical Classification 2 to 4 were included.

A total of 126 participants with myasthe- nia gravis were randomized at 36 sites. Individuals who underwent thymec- tomy showed significant improvement in myasthenia gravis status (time-weighted average Quantitative Myasthenia Gravis Score 6.15 vs 8.99, P < .001) and reduced alternate-day prednisone requirement (32 vs 54 mg, P < .001) after 3 years with ben- efits observed as early as 9 to 12 months. The ability to withdraw from prednisone completely and remain off it after 3 years also favored surgery (58% vs 20%, P < .01). The ability to withdraw from prednisone correlated with neither duration of disease, age at onset of myasthenia gravis, nor trial enrollment. Histological analysis of thymic follicular hyperplasia, seen in 67% of surgical individ- uals, failed to correlate with time-weighted Quantitative Myasthenia Gravis Score or prednisone exposure. Intrathymic fat con- tent, however, correlated directly with time-weighted prednisone exposure (P = .004). In terms of secondary outcomes, fewer individuals who underwent thymectomy required immunosuppression with aza- thioprine (17% vs 48%, P < .001) or were hospitalized for exacerbations (9% vs 37%, P < .001). The number of individuals with treat- ment-associated complications did not differ significantly between groups, but the thymectomy group exhibited fewer treat- ment-associated symptoms (P < .001) and less symptom-related distress (P = .003). The Myasthenia Gravis Activities of Daily Living scale and proportion of individuals reaching minimal manifestation status also favored surgery significantly. Dr. Wolfe explained that the thymectomy trial in non-thymomatous generalized myasthenia gravis patients receiving corticosteroids (MGTX) was the first rand- omized, rater-blinded study of thymectomy in myasthenia gravis. The international trial addressed questions regarding the efficacy of thymectomy in non-thymomatous myasthenia gravis that had persisted for 75 years since the pro- cedure’s use was first reported by Blalock and colleagues in 1941. 2

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