@article{6d0e68df93bd416084d6aec583a12376,
title = "Long-term safety and efficacy of eculizumab in generalized myasthenia gravis",
abstract = "Introduction: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy. Methods: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients. Results: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001). Discussion: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019.",
author = "{for the Regain Study Group} and Srikanth Muppidi and Kimiaki Utsugisawa and Michael Benatar and Hiroyuki Murai and Barohn, {Richard J.} and Isabel Illa and Saiju Jacob and John Vissing and Burns, {Ted M.} and Kissel, {John T.} and Nowak, {Richard J.} and Henning Andersen and Carlos Casasnovas and {de Bleecker}, {Jan L.} and Vu, {Tuan H.} and Renato Mantegazza and O'Brien, {Fanny L.} and Wang, {Jing Jing} and Fujita, {Kenji P.} and Howard, {James F.} and Mazia, {Claudio Gabriel} and Miguel Wilken and Fabio Barroso and Juliet Saba and Marcelo Rugiero and Mariela Bettini and Marcelo Chaves and Gonzalo Vidal and Garcia, {Alejandra Dalila} and {Van den Abeele}, Guy and {de Koning}, Kathy and {De Mey}, Katrien and Rudy Mercelis and D{\'e}lphine Mahieu and Linda Wagemaekers and {Van Damme}, Philip and Annelies Depreitere and Caroline Schotte and Charlotte Smetcoren and Olivier Stevens and {Van Daele}, Sien and Nicolas Vandenbussche and Annelies Vanhee and Sarah Verjans and Jan Vynckier and Ann D'Hondt and Katsuhisa Masaki and Dai Matsuse and Takuya Matsushita and Taira Uehara",
note = "Funding Information: Abbreviations: AChR+, antiacetylcholine receptor antibody-positive; aHUS, atypical hemolytic uremic syndrome; CI, confidence interval; gMG, generalized myasthenia gravis; IST, immunosuppressive therapy; IVIg, intravenous immunoglobulin; MG, myasthenia gravis; MG-ADL, Myasthenia Gravis Activities of Daily Living; MGC, Myasthenia Gravis Composite scale; MGFA, Myasthenia Gravis Foundation of America; MG-QOL15, Myasthenia Gravis Quality of Life 15; PNH, paroxysmal nocturnal hemoglobinuria; QMG, Quantitative Myasthenia Gravis scale Key words: eculizumab; MG-ADL; MGC; MG-QOL15; myasthenia gravis; QMG Funding: This work was funded by Alexion Pharmaceuticals Conflicts of Interest: S. Muppidi has served as a paid consultant for Alnylam Pharmaceuticals and Alexion Pharmaceuticals. K. Utsugisawa has served as a paid consultant for Alexion Pharmaceuticals. M. Benatar has received support from Eli Lilly and Company and has served as a paid consultant for Alnylam Pharmaceuticals, Ra Pharmaceuticals, Voyager Therapeutics, UCB Pharma, Denali Therapeutics, Mitsubishi Tanabe Pharma, Biogen, and Avexis and as a site investigator for Alexion Pharmaceuticals, Cytokinetics, Neuraltus Pharmaceuticals, and Orphazyme. H. Murai has served as a paid consultant for Alexion Pharmaceuticals and has received speaker honoraria from Japan Blood Products Organization. R. J. Barohn has served as a consultant for NuFactor and Momenta Pharmaceuticals and receives research support from PTC Therapeutics, Ra Pharma, Orphazyme, and Sanofi Genzyme. I. Illa has served as a paid consultant for Alexion Pharmaceuticals and UCB Pharma. S. Jacob has served as a paid consultant for Alnylam Pharmaceuticals and Alexion Pharmaceuticals. J. Vissing has received support from and/or served as a paid consultant for Sanofi/Genzyme and Santhera Pharmaceuticals and has served as a paid consultant for Sarepta Therapeutics, Audentes Therapeutics, NOVO Nordisk, Alexion Pharmaceuticals, and Stealth Biotherapeu-tics. T. M. Burns has served as a paid consultant for Argenx and CSL Behring. J. T. Kissel has received support from Alexion Pharmaceuticals, aTyr Pharma, Cytokinetics Novartis, Sanofi Genzyme, BioMarin, Ionis Pharmaceuticals, and AveXis. R. J. Nowak has received support from Alexion Pharmaceuticals, Genentech, Grifols, and Ra Pharmaceuticals and has served as a paid consultant for Alexion Pharmaceuticals, Momenta, Ra Pharmaceuticals, Shire, and Grifols. H. Andersen has received research and travel support and speaker honoraria and has served as consultant for Octapharma, CSL Behring, NMD Pharma, Pfizer, Eisai, Sanofi Genzyme and UCB Pharma. C. Casasnovas has served as a paid consultant for Alexion Pharmaceuticals, Pharma-next, and CSL Behring. J. L. De Bleecker has served on the scientific advisory boards of Sanofi Genzyme and Pfizer and has received travel funding/speaker honoraria from Sanofi Genzyme and limited research funding from CSL Behring and CAF Belgium. T. H. Vu serves as a site principal investigator and on speaker bureaus for Alexion Pharmaceuticals, on speaker bureaus for CSL Behring, Allergan, and MT Pharma, and is the site principal investigator for clinical trials sponsored by Ra Pharmaceuticals, Argenx, and UCB Pharmaceuticals. R. Mantegazza has received support from Sanofi Genzyme, Teva Pharmaceutical Industries, Bayer and BioMarin and has served as a paid consultant for BioMarin, Alexion Pharmaceuticals, and Argenx BVBA. F. L. O{\textquoteright}Brien and K. P. Fujita are employees of and own stock in Alexion Pharmaceuticals. J. J. Wang is a former employee of and owns stock in Alexion Pharmaceuticals. J. F. Howard Jr reports research support from Alexion Pharmaceuticals; grants from Alexion Pharmaceuticals and UCB Pharma; honoraria from Alexion Pharmaceuticals; and nonfinancial support from Alexion Pharmaceuticals, Argenx, Ra Pharmaceuticals, and Toleranzia. Funding Information: The authors thank the patients who took part in REGAIN and the open-label extension study as well as their families; all of the investigators and collaborators for their contributions to the completion of the study; Angela Kaya, PhD, and Gus Khursigara, PhD, (formerly of Alexion Pharmaceuticals) and R{\'o}is{\'i}n Armstrong, PhD, Diaa Diab, MBBS, and Kelley Capocelli, MD, (Alexion Pharmaceuticals) for critical review of the manuscript, and Cindy Lane, MS, (Alexion Pharmaceuticals) for clinical study oversight. We acknowledge Vicky Sanders, PhD, and Ruth Gandolfo, PhD (Oxford PharmaGenesis, Oxford, UK), who provided medical writing support in the production of this manuscript (funded by Alexion Pharmaceuticals). All members of the REGAIN study group are listed in the Supporting Information materials. Publisher Copyright: {\textcopyright} 2019 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.",
year = "2019",
month = jul,
doi = "10.1002/mus.26447",
language = "English",
volume = "60",
pages = "14--24",
journal = "Muscle and Nerve",
issn = "0148-639X",
publisher = "John Wiley and Sons Inc.",
number = "1",
}