@article{2d3e1c3911ce4bd4bd5dc32a016b083a,
title = "Randomized trial of thymectomy in myasthenia gravis",
abstract = "BACKGROUND: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS: A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS: Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis.",
author = "Wolfe, {G. I.} and Kaminski, {H. J.} and Aban, {I. B.} and G. Minisman and Kuo, {H. C.} and A. Marx and P. Str{\"o}bel and C. Mazia and J. Oger and Cea, {J. G.} and Heckmann, {J. M.} and A. Evoli and W. Nix and E. Ciafaloni and G. Antonini and R. Witoonpanich and King, {J. O.} and Beydoun, {S. R.} and Chalk, {C. H.} and Barboi, {A. C.} and Amato, {A. A.} and Shaibani, {A. I.} and B. Katirji and Lecky, {B. R F} and C. Buckley and A. Vincent and E. Dias-Tosta and H. Yoshikawa and M. Waddington-Cruz and Pulley, {M. T.} and Rivner, {M. H.} and A. Kostera-Pruszczyk and Pascuzzi, {R. M.} and Jackson, {C. E.} and {Garcia Ramos}, {G. S.} and Verschuuren, {J. J G M} and Massey, {J. M.} and Kissel, {J. T.} and Werneck, {L. C.} and M. Benatar and Barohn, {R. J.} and R. Tandan and T. Mozaffar and R. Conwit and J. Odenkirchen and Sonett, {J. R.} and A. Jaretzki and J. Newsom-Davis and Cutter, {G. R.}",
note = "Funding Information: (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.) Supported by a grant (U01 NS042685) from the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, and by the Muscular Dystrophy Association and the Myasthenia Gravis Foundation of America. Dr. Wolfe reports receiving lecture fees and fees for serving on advisory boards from Grifols and Baxalta, consulting fees from Alpha Cancer Technologies, argenx, and UCB, and grant support from CSL Behring and Alexion Pharmaceuticals; Dr. Kaminski, receiving fees for serving on data and safety monitoring boards from Genentech and Novartis, consulting fees from Alnylam Pharmaceuticals, UCB, Chugai Pharma, Rubius Therapeutics, RA Pharmaceuticals, and Momenta Pharmaceuticals, receiving serum samples from Rubius Therapeutics, receiving study medication from Genentech, and holding a patent related to technology to focus a complement inhibitor on the neuromuscular junction for the treatment of myasthenia gravis (U.S. patent no. 8,961,981); Dr. Evoli, receiving fees for serving on an advisory board from CSL Behring and for serving as a scientific-award jury member from Grifols; Dr. Beydoun, receiving consulting and lecture fees from Grifols and Baxalta and grant support from GlaxoSmithKline, Alexion Pharmaceuticals, and CSL Behring; Dr. Vincent, receiving grant support from Glaxo SmithKline, and royalties from patents related to MuSK antibodies for diagnosis of myasthenia gravis (U.K. patent no., PCT/GB01/02661; licensed to Athena Diagnostics) and LGI1 and CASPR2 antibodies for autoimmune encephalitis (U.K. patent no., PCT/GB2009/051441; licensed to Euroimmun); Dr. Yoshikawa, receiving grant support from Astellas Pharma; Dr. Waddington-Cruz, receiving consulting fees from Pfizer, Genzyme, and Ionis Pharmaceuticals (formerly Isis), travel support from Pfizer, and grant support from Pfizer, Ionis Pharmaceuticals, and Alnylam Pharmaceuticals; Dr. Pulley, receiving personal fees from Grifols and Mallinckrodt Pharmaceuticals; Dr. Verschuuren, receiving consulting fees from Alexion Pharmaceuticals and Argenx, paid to his institution, and holding a patent (U.S. patent no. 14/486,400; royalties are paid to his institution) related to therapy for anti-MuSK myasthenia gravis; and Dr. Cutter, receiving fees for serving on data and safety monitoring boards from Biogen Idec, Teva Neuroscience, Pfizer, Sanofi, Celgene, Gilead Sciences, Neuren Pharmaceuticals, ModigeneTech, Opko Biologics, Ono Pharmaceuticals, Merck Serono, GlaxoSmithKline, Horizon Pharma, Reata Pharmaceuticals, and PTC Therapeutics, fees for serving on a steering committee from MedImmune, fees for serving on advisory boards from EMD Serono, Novartis, Questcor Pharmaceuticals, Genentech, and Janssen Pharmaceutica, consulting fees from Teva Neuroscience, Genzyme, Genentech, Transparency Life Sciences, Roche, Opexa Therapeutics, Somahlution, Savara Pharmaceuticals, and Nivalis Therapeutics, fees from a law firm for providing a legal opinion regarding a patent infringement case on behalf of Galderma, and grant support to his institution from Teva Neuroscience. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the members of the data and safety monitoring board (Steven Keller, M.D. [chair], Alan Dyer, Ph.D., Donald Schotland, M.D., John Winer, M.D., and Peter Gilbert, Sc.M. [ex officio]); Audrey Penn, M.D., of the NINDS, Johan Aarli, M.D., Robert Griggs, M.D., Robert Lisak, M.D., and Lewis Rowland, M.D., for advocating for the trial in its early stages; and the patients who participated in this trial and were willing to be randomly assigned to either a surgical group or a nonsurgical group and to adhere to a trial protocol that lasted for years. Publisher Copyright: Copyright {\textcopyright} 2016 Massachusetts Medical Society.",
year = "2016",
month = aug,
day = "11",
doi = "10.1056/NEJMoa1602489",
language = "English (US)",
volume = "375",
pages = "511--522",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "6",
}