Format

Send to

Choose Destination
N Engl J Med. 2016 Aug 11;375(6):511-22. doi: 10.1056/NEJMoa1602489.

Randomized Trial of Thymectomy in Myasthenia Gravis.

Collaborators (303)

Cutter GR, Aban IB, Minisman G, Feese M, Kuo HC, Newsom-Davis J, Wolfe GI, Kaminski HJ, Jaretzki A 3rd, Sonett JR, Mazia C, Saluto V, Rosenberg M, Alvarez V, Rey L, King J, Butzkueven H, Goldblatt J, Carey J, Pollard J, Reddel S, Handel N, McCaughan B, Pallot L, Waddington-Cruz M, Novis R, Boasquevisque C, Dias-Tosta E, Morato-Fernandez R, Ximenes M, Werneck L, Scola R, Soltoski P, Chalk C, Moore F, Mulder D, Wadup L, Oger J, Mezei M, Evans K, Jiwa T, Schaffar A, White C, Toth C, Gelfand G, Wood S, Pringle E, Zwicker J, Maziak D, Shamji F, Sundaresan S, Seely A, Cea G, Verdugo R, Aguayo A, Jander S, Zickler P, Klein M, Marx A, Ströbel P, Weis CA, Melms A, Bischof F, Aebert H, Ziemer G, Nix W, Thümler B, Wilhem-Schwenkmezger T, Mayer E, Schalke B, Pöschel P, Hieber G, Wiebe K, Antonini G, Clemenzi A, Ceschin V, Rendina E, Venuta F, Morino S, Bucci E, Durelli L, Tavella A, Clerico M, Contessa G, Borasio P, Evoli A, Servidei S, Granone P, Mantegazza R, Berta E, Novellino L, Spinelli L, Motomura M, Matsuo H, Nagayasu T, Yoshikawa H, Takamori M, Oda M, Matsumoto I, Furukawa Y, Noto D, Motozaki Y, Iwasa K, Yanase D, Ramos GG, Cacho B, de la Garza L, Kostera-Pruszczyk A, Lipowska M, Kwiecinski H, Potulska-Chromik A, Orlowski T, Silva A, Feijo M, Freitas A, Heckmann J, Frost A, Pan EL, Tucker L, Rossouw J, Drummond F, Illa I, Diaz J, Leon C, Yeh JH, Chiu HC, Hsieh YS, Witoonpanich R, Tunlayadechanont S, Attanavanich S, Verschuuren J, Straathof C, Titulaer M, Versteegh M, Pels A, Krum Y, Buckley C, Leite M, Vincent A, Hilton-Jones D, Ratnatunga C, Newsom-Davis J, Farrugia ME, Petty R, Overell J, Kirk A, Gibson A, McDermott C, Hopkinson D, Lecky B, Watling D, Marshall D, Saminaden S, Davies D, Dougan C, Sathasivam S, Page R, Marshall D, Sussman J, Ealing J, Krysiak P, Amato A, Salajegheh M, Jaklitsch M, Roe K, Ashizawa T, Smith RG, Zwischenberg J, Stanton P, Barboi A, Jaradeh S, Tisol W, Gasparri M, Haasler G, Yellick M, Dennis C, Barohn R, Pasnoor M, Dimachkie M, McVey A, Gronseth G, Dick A, Kramer J, Currence M, Herbelin L, Belsh J, Li G, Langenfeld J, Mertz MA, Benatar M, Harrison T, Force S, Usher S, Beydoun S, Lin F, DeMeester S, Akhter S, Malekniazi A, Avenido G, Crum B, Milone M, Cassivi S, Fisher J, Ciafaloni E, Heatwole C, Watson T, Hilbert J, Smirnow A, Distad B, Weiss M, Wood D, Haug J, Ernstoff R, Cao J, Chmielewski G, Welsh R, Duris R, Gutmann L, Pawar G, Graeber GM, Altemus P, Nance C, Gutmann L, Jackson C, Grogan P, Calhoon J, Kittrell P, Myers D, Kaminski H, Hayat G, Naunheim K, Eller S, Holzemer E, Katirji B, Alshekhlee A, Robke J, Karlinchak B, Katz J, Miller R, Roan R, Forshew D, Kissel J, Elsheikh B, Ross P, Chelnick S, Lewis R, Acsadi A, Baciewicz F, Masse S, Massey J, Juel V, Onaitis M, Lowe J, Lipscomb B, Mozaffar T, Thai G, Milliken J, Martin V, Karayan R, Muley S, Parry G, Shumway S, Oh S, Claussen G, Lu L, Cerfolio R, Young A, Morgan M, Pascuzzi R, Kincaid J, Kesler K, Guingrich S, Michaels A, Phillips L, Burns T, Jones D, Fischer C, Pulley M, Berger A, D'Agostino H, Smith L, Rivner M, Pruitt J, Landolfo K, Hillman D, Shaibani A, Sermas A, Ruel R, Ismail F, Sivak M, Goldstein M, Camunas J, Bratton J, Tandan R, Panitch H, Leavitt B, Jones M, Wolfe G, Muppidi S, Vernino S, Nations S, Meyer D, Gorham N.

Author information

1
From the Department of Neurology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo (G.I.W.), the Department of Neurology, University of Rochester Medical Center, Rochester (E.C.), and the Section of General Thoracic Surgery, Columbia University Medical Center, New York (J.R.S., A.J.) - all in New York; the Department of Neurology, George Washington University School of Medicine and Health Sciences, Washington, DC (H.J.K.); the Department of Biostatistics, University of Alabama at Birmingham, Birmingham (I.B.A., G.M., H.-C.K., G.R.C.); the Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Mannheim (A.M.), the Institute of Pathology, University of Göttingen, Göttingen (P.S.), and the Department of Neurology, Johannes Gutenberg University, Mainz (W.N.) - all in Germany; the Department of Neurology, University of Buenos Aires, Buenos Aires (C.M.); the Division of Neurology, University of British Columbia, Vancouver (J. Oger), and the Department of Neurology, McGill University, Montreal (C.H.C.) - both in Canada; the Department of Neurology, University of Chile, Santiago (J.G.C.); the Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa (J.M.H.); the Department of Neurology, Catholic University (A.E.), and the Department of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome (G.A.) - both in Rome; the Division of Neurology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (R.W.); the Department of Neurology, University of Melbourne, Melbourne, VIC, Australia (J.O.K.); the Department of Neurology, University of Southern California, Los Angeles (S.R.B.), and the Department of Neurology, University of California Irvine Medical Center, Orange (T.M.) - both in California; the Department of Neurology, Medical College of Wisconsin, Milwaukee (A.C.B.); the Department of Neurology, Harvard Medical School, Boston (A.A.A.); Nerve and M

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. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).

PMID:
27509100
PMCID:
PMC5189669
DOI:
10.1056/NEJMoa1602489
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center