@article{c707801d23be4594a1b8943db4469e3a,
title = "Minimal manifestation status and prednisone withdrawal in the MGTX trial",
abstract = "ObjectiveTo examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG).MethodsThis study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18-65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone was compared between the thymectomy plus prednisone and prednisone alone groups.ResultsPatients with MG in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, p < 0.001) over the 5-year study period. Prednisone-Associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone.ConclusionsThymectomy benefits patients with MG by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone.Clinicaltrials.gov identifierNCT00294658.Classification of evidenceThis study provides Class II evidence that for patients with generalized MG with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone.",
author = "Ikjae Lee and Kuo, {Hui Chien} and Aban, {Inmaculada B.} and Cutter, {Gary R.} and Tarrant McPherson and Kaminski, {Henry J.} and Jon Sussman and Philipp Str{\"o}bel and Joel Oger and Gabriel Cea 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 Marcia Waddington-Cruz and Pulley, {Michael T.} and Rivner, {Michael H.} and Anna Kostera-Pruszczyk and Pascuzzi, {Robert M.} and Jackson, {Carlayne E.} and Verschuuren, {Jan J.G.} 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 Robin Conwit and Greg Minisman and Sonett, {Joshua R.} and Wolfe, {Gil I.}",
note = "Funding Information: Supported by NINDS U01 NS042685, MDA, MGFA, NCATS UL1TR001417, NCATS UL1TR000001, NCATS UL1TR001412, NCATS UL1TR001120, and NCATS 8UL1TR000149 UT. Funding Information: I. Lee: Alexion Pharmaceuticals advisory boards. H. Kuo served as master level statistician in the data coordinator center for the MGTX study; received funding from the MGTX study, which was completed; and receives support from the Myasthenia Gravis Foundation of America. I. Aban reports no disclosures relevant to the manuscript. G. Cutter: data and safety monitoring boards: AMO Pharmaceuticals, Biolinerx, Brainstem, Horizon Pharmaceuticals, Hisun Pharmaceuticals, Merck, Merck/Pfizer, Opko Biologics, Neurim, Novartis, Ophazyme, Sanofi-Aventis, Reata Pharmaceuticals, Receptos/Celgene, Teva Pharmaceuticals, NHLBI (protocol review committee), NICHD (OPRU oversight committee); consulting or advisory boards: Biogen, Argenix, Brainstorm Cell Therapeutics, Charleston Labs Inc, Click Therapeutics, Genzyme, Genentech, GW Pharma, Klein-Buendel Incorporated, Medimmune, Medday, Novartis, Perception Neurosciences, Roche, Scifluor, Somahlution, Teva Pharmaceuticals, TG Therapeutics, UT Houston; employed by the University of Alabama at Birmingham; and President of Pythagoras, Inc., a private consulting company located in Birmingham. T. McPherson: grant support from the Myasthenia Gravis Foundation of America. H. Kaminski: consulting fees from Alnylam Pharmaceuticals, UCB, Biocatalyst, RA Pharmaceuticals, and Momenta Pharmaceuticals; receives grant support from the Muscular Dystrophy Association; and holds a patent related to technology for the treatment of myasthenia gravis (US patent no. 8,961,981). J. Sussman, P. Strobel, J. Oger, G. Cea, and J. Heckmann report no disclosures relevant to the manuscript. Amelia Evoli served as a member of the advisory board for Alexion and is a scientific award jury member for Grifols and a safety data monitor for UCB. W. Nix reports no disclosures relevant to the manuscript. E. Ciafaloni received personal compensation for serving on advisory boards and/or as a consultant for Sarepta, Biogen, Santhera, Strongbridge, Avexis, PTC, and Pfizer, and has received research support from MDA, CureSMA, PPMD, PTC, Sarepta, Santhera, NIH, FDA, CDC, and PCORI. G. Antonini received travel grants and conference honoraria from Kedrion SpA and Sanofi-Genzyme. R. Witoonpanich and J. King report no disclosures relevant to the manuscript. S. Beydoun: grant support from Argenx, Catalyst, Mallinckrodt, Pfizer, and UCB; advisory/speaker of Akcea, Alexion, Alnylam, CSL, Grifols, MT Pharma, and Takeda. C. Chalk and A. Barboi report no disclosures relevant to the manuscript. A. Amato: Associate Editor for Neurology{\textregistered} and served on medical advisory boards for Alexion and Acceleron. A. Shaibani, B. Katirji, B. Lecky, and C. Buckley report no disclosures relevant to the manuscript. A. Vincent: coinvestigator with Werner Hoch of MuSK antibody testing for myasthenia gravis, patented by the University of Oxford, and licensed by Athena Diagnostics; O.U. and A.V. receive a proportion of royalties. E. Dias-Tosta, H. Yoshikawa, and M. Waddington-Cruz report no disclosures relevant to the manuscript. M. Pulley served on medical advisory boards for Alexion, MT Pharma, Grifols, CSL Behring, and Catalyst. M. Rivner served as a speaker for Alexion and Allergan; and participated in research studies for Alexion, UCB Pharma, Momenta, Orion, Mallinckrodt ARD, Inc, Seikagaku Corporation, Biohaven Pharmaceuticals, and Catalyst Pharmaceuticals, Inc. A. Kostera-Pruszczyk serves as a PI for IVIg study in MG by Grifols and ARGX study in MG. R. Pascuzzi reports no disclosures relevant to the manuscript. C. Jackson received grant support from Cytokinetics, NIH, and Flex Pharma; served as a consultant for Argenx, Cytokinetics, ITF Pharma, Alexion, and Strongbridge Pharmaceuticals; speakers bureau for CSL Behring, Cytokinetics, Strongbridge Pharmaceuticals, and Avanir; and serves on data safety monitoring boards for Brainstorm, Mallinckrodt, and Anelixis. J. Verschuuren has been involved in MG research sponsored by the Princes Beatrix Fonds, NIH, FP7 European grant (#602420), consultancies for Argen-X, Alexion, and Ra Pharma, and patents pending on the use of MuSK antibodies; all reimbursements were received by the LUMC; J. Verschuuren had no personal financial benefit from these activities. The LUMC receives royalties for MuSK antibody assays. J. Massey: Revance Therapeutics, PI–Clinical trial in Cervical Dystonia. J. Kissel and L. Werneck report no disclosures relevant to the manuscript. M. Benatar: Ra Pharma, UCB. R. Barohn: NuFactor and Momenta Pharmaceutical and receives research support from PTC Therapeutics, Ra Pharma, Orphazyme, Sanofi Genzyme, FDA OOPD, NIH, and PCORI. R. Tandan reports no disclosures relevant to the manuscript. T. Mozaffar served on advisory boards for aTyr, Alnylam, Alexion, Amicus, Argenx, Audentes, Sanofi-Genzyme, Sarepta, Spark Therapeutics, MT-Pharma, and Ultragenyx; in relation to these activities, he has received travel subsidies and honoraria; he has also served on the speaker's bureau for Alexion, CSL, Grifols, and Sanofi-Genzyme. Dr. Mozaffar has received research funding from the Myositis Association, the Muscular Dystrophy Association, the NIH, and the following sponsors: Alexion, Amicus, Argenx, aTyr, Bristol-Myers-Squib, Idera, Ionis, Grifols, Momenta, Ra Pharmaceuticals, Sanofi-Genzyme, Spark Therapeutics, UCB, Ultragenyx, and Valerion; he serves on the data safety monitoring board for Acceleron and Avexis. R. Conwit, G. Minisman, and J. Sonett report no disclosures relevant to the manuscript. G. Wolfe: Grifols, Takeda, and Alexion advisory boards; CSL Behring, ArgenX, Alexion, Ra, and Immunovant research support. Go to Neurology.org/N for full disclosures. Publisher Copyright: {\textcopyright} American Academy of Neurology.",
year = "2020",
month = aug,
day = "11",
doi = "10.1212/WNL.0000000000010031",
language = "English (US)",
volume = "95",
pages = "E755--E766",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "6",
}