Randomized trial of thymectomy in myasthenia gravis

G. I. Wolfe; H. J. Kaminski; I. B. Aban; G. Minisman; H. C. Kuo; A. Marx; P. Ströbel; C. Mazia; J. Oger; J. G. Cea; J. M. Heckmann; A. Evoli; W. Nix; E. Ciafaloni; G. Antonini; R. Witoonpanich; J. O. King; S. R. Beydoun; C. H. Chalk; A. C. Barboi; A. A. Amato; A. I. Shaibani; B. Katirji; B. R F Lecky; C. Buckley; A. Vincent; E. Dias-Tosta; H. Yoshikawa; M. Waddington-Cruz; M. T. Pulley; M. H. Rivner; A. Kostera-Pruszczyk; R. M. Pascuzzi; C. E. Jackson; G. S. Garcia Ramos; J. J G M Verschuuren; J. M. Massey; J. T. Kissel; L. C. Werneck; M. Benatar; R. J. Barohn; R. Tandan; T. Mozaffar; R. Conwit; J. Odenkirchen; J. R. Sonett; A. Jaretzki; J. Newsom-Davis; G. R. Cutter

doi:10.1056/NEJMoa1602489

Randomized trial of thymectomy in myasthenia gravis

G. I. Wolfe, H. J. Kaminski, I. B. Aban, G. Minisman, H. C. Kuo, A. Marx, P. Ströbel, C. Mazia, J. Oger, J. G. Cea, J. M. Heckmann, A. Evoli, W. Nix, E. Ciafaloni, G. Antonini, R. Witoonpanich, J. O. King, S. R. Beydoun, C. H. Chalk, A. C. BarboiA. A. Amato, A. I. Shaibani, B. Katirji, B. R F Lecky, C. Buckley, A. Vincent, E. Dias-Tosta, H. Yoshikawa, M. Waddington-Cruz, M. T. Pulley, M. H. Rivner, A. Kostera-Pruszczyk, R. M. Pascuzzi, C. E. Jackson, G. S. Garcia Ramos, J. J G M Verschuuren, J. M. Massey, J. T. Kissel, L. C. Werneck, M. Benatar, R. J. Barohn, R. Tandan, T. Mozaffar, R. Conwit, J. Odenkirchen, J. R. Sonett, A. Jaretzki, J. Newsom-Davis, G. R. Cutter

Neurology

Research output: Contribution to journal › Article › peer-review

301 Scopus citations

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.

Original language	English (US)
Pages (from-to)	511-522
Number of pages	12
Journal	New England Journal of Medicine
Volume	375
Issue number	6
DOIs	https://doi.org/10.1056/NEJMoa1602489
State	Published - Aug 11 2016

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General Medicine

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Wolfe, G. I., Kaminski, H. J., Aban, I. B., Minisman, G., Kuo, H. C., Marx, A., Ströbel, P., Mazia, C., Oger, J., Cea, J. G., Heckmann, J. M., Evoli, A., Nix, W., Ciafaloni, E., Antonini, G., Witoonpanich, R., King, J. O., Beydoun, S. R., Chalk, C. H., ... Cutter, G. R. (2016). Randomized trial of thymectomy in myasthenia gravis. New England Journal of Medicine, 375(6), 511-522. https://doi.org/10.1056/NEJMoa1602489

Wolfe, GI, Kaminski, HJ, Aban, IB, Minisman, G, Kuo, HC, Marx, A, Ströbel, P, Mazia, C, Oger, J, Cea, JG, Heckmann, JM, Evoli, A, Nix, W, Ciafaloni, E, Antonini, G, Witoonpanich, R, King, JO, Beydoun, SR, Chalk, CH, Barboi, AC, Amato, AA, Shaibani, AI, Katirji, B, Lecky, BRF, Buckley, C, Vincent, A, Dias-Tosta, E, Yoshikawa, H, Waddington-Cruz, M, Pulley, MT, Rivner, MH, Kostera-Pruszczyk, A, Pascuzzi, RM, Jackson, CE, Garcia Ramos, GS, Verschuuren, JJGM, Massey, JM, Kissel, JT, Werneck, LC, Benatar, M, Barohn, RJ, Tandan, R, Mozaffar, T, Conwit, R, Odenkirchen, J, Sonett, JR, Jaretzki, A, Newsom-Davis, J & Cutter, GR 2016, 'Randomized trial of thymectomy in myasthenia gravis', New England Journal of Medicine, vol. 375, no. 6, pp. 511-522. https://doi.org/10.1056/NEJMoa1602489

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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 = "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",

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TY - JOUR

T1 - Randomized trial of thymectomy in myasthenia gravis

AU - Wolfe, G. I.

AU - Kaminski, H. J.

AU - Aban, I. B.

AU - Minisman, G.

AU - Kuo, H. C.

AU - Marx, A.

AU - Ströbel, P.

AU - Mazia, C.

AU - Oger, J.

AU - Cea, J. G.

AU - Heckmann, J. M.

AU - Evoli, A.

AU - Nix, W.

AU - Ciafaloni, E.

AU - Antonini, G.

AU - Witoonpanich, R.

AU - King, J. O.

AU - Beydoun, S. R.

AU - Chalk, C. H.

AU - Barboi, A. C.

AU - Amato, A. A.

AU - Shaibani, A. I.

AU - Katirji, B.

AU - Lecky, B. R F

AU - Buckley, C.

AU - Vincent, A.

AU - Dias-Tosta, E.

AU - Yoshikawa, H.

AU - Waddington-Cruz, M.

AU - Pulley, M. T.

AU - Rivner, M. H.

AU - Kostera-Pruszczyk, A.

AU - Pascuzzi, R. M.

AU - Jackson, C. E.

AU - Garcia Ramos, G. S.

AU - Verschuuren, J. J G M

AU - Massey, J. M.

AU - Kissel, J. T.

AU - Werneck, L. C.

AU - Benatar, M.

AU - Barohn, R. J.

AU - Tandan, R.

AU - Mozaffar, T.

AU - Conwit, R.

AU - Odenkirchen, J.

AU - Sonett, J. R.

AU - Jaretzki, A.

AU - Newsom-Davis, J.

AU - Cutter, G. R.

PY - 2016/8/11

Y1 - 2016/8/11

N2 - 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.

AB - 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.

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DO - 10.1056/NEJMoa1602489

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

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Randomized trial of thymectomy in myasthenia gravis

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