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

Research output: Contribution to journalArticle

113 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)511-522
Number of pages12
JournalNew England Journal of Medicine
Volume375
Issue number6
DOIs
StatePublished - Aug 11 2016

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Thymectomy
Myasthenia Gravis
Prednisone
Azathioprine
Cholinergic Receptors
Immunosuppressive Agents
Random Allocation
Immunosuppression
Multicenter Studies
Therapeutics
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wolfe, G. I., Kaminski, H. J., Aban, I. B., Minisman, G., Kuo, H. C., Marx, A., ... 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

Randomized trial of thymectomy in myasthenia gravis. / 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.; Barboi, A. C.; Amato, A. A.; Shaibani, A. I.; Katirji, B.; Lecky, B. R F; Buckley, C.; Vincent, A.; Dias-Tosta, E.; Yoshikawa, H.; Waddington-Cruz, M.; Pulley, M. T.; Rivner, M. H.; Kostera-Pruszczyk, A.; Pascuzzi, R. M.; Jackson, C. E.; Garcia Ramos, G. S.; Verschuuren, J. J G M; Massey, J. M.; Kissel, J. T.; Werneck, L. C.; Benatar, M.; Barohn, R. J.; Tandan, R.; Mozaffar, T.; Conwit, R.; Odenkirchen, J.; Sonett, J. R.; Jaretzki, A.; Newsom-Davis, J.; Cutter, G. R.

In: New England Journal of Medicine, Vol. 375, No. 6, 11.08.2016, p. 511-522.

Research output: Contribution to journalArticle

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
Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A et al. Randomized trial of thymectomy in myasthenia gravis. New England Journal of Medicine. 2016 Aug 11;375(6):511-522. https://doi.org/10.1056/NEJMoa1602489
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. ; Barboi, A. C. ; Amato, A. A. ; Shaibani, A. I. ; Katirji, B. ; Lecky, B. R F ; Buckley, C. ; Vincent, A. ; Dias-Tosta, E. ; Yoshikawa, H. ; Waddington-Cruz, M. ; Pulley, M. T. ; Rivner, M. H. ; Kostera-Pruszczyk, A. ; Pascuzzi, R. M. ; Jackson, C. E. ; Garcia Ramos, G. S. ; Verschuuren, J. J G M ; Massey, J. M. ; Kissel, J. T. ; Werneck, L. C. ; Benatar, M. ; Barohn, R. J. ; Tandan, R. ; Mozaffar, T. ; Conwit, R. ; Odenkirchen, J. ; Sonett, J. R. ; Jaretzki, A. ; Newsom-Davis, J. ; Cutter, G. R. / Randomized trial of thymectomy in myasthenia gravis. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 6. pp. 511-522.
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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.",
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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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