Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis

2-year extension of the MGTX randomised trial

MGTX Study Group

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings: Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation: At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding: National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Original languageEnglish (US)
Pages (from-to)259-268
Number of pages10
JournalThe Lancet Neurology
Volume18
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Thymectomy
Myasthenia Gravis
Prednisone
National Institute of Neurological Disorders and Stroke
Edrophonium
Intention to Treat Analysis

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{33e262a42e184e198b4939dbc9299b88,
title = "Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial",
abstract = "Background: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings: Of the 111 patients who completed the 3-year MGTX, 68 (61{\%}) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74{\%}) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42{\%}) of 33 patients in the prednisone group, and 12 (34{\%}) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation: At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding: National Institutes of Health, National Institute of Neurological Disorders and Stroke.",
author = "{MGTX Study Group} and Wolfe, {Gil I.} and Kaminski, {Henry J.} and Aban, {Inmaculada B.} and Greg Minisman and Kuo, {Hui Chien} and Alexander Marx and Philipp Str{\"o}bel and Claudio Mazia and Joel Oger and Cea, {J. Gabriel} and Heckmann, {Jeannine M.} and Amelia Evoli and Wilfred Nix and Emma Ciafaloni and Giovanni Antonini and Rawiphan Witoonpanich and King, {John O.} and Beydoun, {Said R.} and Chalk, {Colin H.} and Barboi, {Alexandru C.} and Amato, {Anthony A.} and Shaibani, {Aziz I.} and Bashar Katirji and Lecky, {Bryan R.F.} and Camilla Buckley and Angela Vincent and Elza Dias-Tosta and Hiroaki Yoshikawa and M{\'a}rcia Waddington-Cruz and Pulley, {Michael T.} and Rivner, {Michael Harvey} and Anna Kostera-Pruszczyk and Pascuzzi, {Robert M.} and Jackson, {Carlayne E.} and Verschuuren, {Jan J.G.M.} and Massey, {Janice M.} and Kissel, {John T.} and Werneck, {Lineu C.} and Michael Benatar and Barohn, {Richard J.} and Rup Tandan and Tahseen Mozaffar and Silvestri, {Nicholas J.} and Robin Conwit and Sonett, {Joshua R.} and Alfred Jaretzki and John Newsom-Davis and Cutter, {Gary R.} and Gary Cutter and Inmaculada Aban",
year = "2019",
month = "3",
day = "1",
doi = "10.1016/S1474-4422(18)30392-2",
language = "English (US)",
volume = "18",
pages = "259--268",
journal = "The Lancet Neurology",
issn = "1474-4422",
publisher = "Lancet Publishing Group",
number = "3",

}

TY - JOUR

T1 - Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis

T2 - 2-year extension of the MGTX randomised trial

AU - MGTX Study Group

AU - Wolfe, Gil I.

AU - Kaminski, Henry J.

AU - Aban, Inmaculada B.

AU - Minisman, Greg

AU - Kuo, Hui Chien

AU - Marx, Alexander

AU - Ströbel, Philipp

AU - Mazia, Claudio

AU - Oger, Joel

AU - Cea, J. Gabriel

AU - Heckmann, Jeannine M.

AU - Evoli, Amelia

AU - Nix, Wilfred

AU - Ciafaloni, Emma

AU - Antonini, Giovanni

AU - Witoonpanich, Rawiphan

AU - King, John O.

AU - Beydoun, Said R.

AU - Chalk, Colin H.

AU - Barboi, Alexandru C.

AU - Amato, Anthony A.

AU - Shaibani, Aziz I.

AU - Katirji, Bashar

AU - Lecky, Bryan R.F.

AU - Buckley, Camilla

AU - Vincent, Angela

AU - Dias-Tosta, Elza

AU - Yoshikawa, Hiroaki

AU - Waddington-Cruz, Márcia

AU - Pulley, Michael T.

AU - Rivner, Michael Harvey

AU - Kostera-Pruszczyk, Anna

AU - Pascuzzi, Robert M.

AU - Jackson, Carlayne E.

AU - Verschuuren, Jan J.G.M.

AU - Massey, Janice M.

AU - Kissel, John T.

AU - Werneck, Lineu C.

AU - Benatar, Michael

AU - Barohn, Richard J.

AU - Tandan, Rup

AU - Mozaffar, Tahseen

AU - Silvestri, Nicholas J.

AU - Conwit, Robin

AU - Sonett, Joshua R.

AU - Jaretzki, Alfred

AU - Newsom-Davis, John

AU - Cutter, Gary R.

AU - Cutter, Gary

AU - Aban, Inmaculada

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings: Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation: At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding: National Institutes of Health, National Institute of Neurological Disorders and Stroke.

AB - Background: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings: Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation: At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding: National Institutes of Health, National Institute of Neurological Disorders and Stroke.

UR - http://www.scopus.com/inward/record.url?scp=85060438170&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060438170&partnerID=8YFLogxK

U2 - 10.1016/S1474-4422(18)30392-2

DO - 10.1016/S1474-4422(18)30392-2

M3 - Article

VL - 18

SP - 259

EP - 268

JO - The Lancet Neurology

JF - The Lancet Neurology

SN - 1474-4422

IS - 3

ER -