COVID-19-associated risks and effects in myasthenia gravis (CARE-MG)
Authors: Srikanth Muppidi, Jeffrey T Guptill, Saiju Jacob, Yingkai Li, Maria E Farrugia, Amanda C Guidon, Jinny O Tavee, Henry Kaminski, James F Howard, Gary Cutter, Heinz Wiendl, Matthew B Maas, Isabel Illa, Renato Mantegazza, Hiroyuki Murai, Kimiaki Utsugisawa, Richard J Nowak, Amanda C Guidon, Alok Tyagi, Ana Paula Sousa, Anthony A Amato, Ashwin Pinto, Bhaskar Roy, Caroline Carmichael, Dubravka Dodig, Georgina Burke, Gary R Cutter, Henry J Kaminski, Heinz Wiendl, Hiroyuki Murai, Ikjae Lee, Isabel Illa, Jeffrey Guptill, James F. Howard, James Caress, Jane Pritchard, Jinny O Tavee, John Vissing, Kamla Best, Kimiaki Utsugisawa, Mahtab Ramezani, Mathew Maas, Maria E Farrugia, Michael K Hehir, Michelle Kaku, Natalia Jiménez Esquivel, Paul Gallagher, Paul Maddison, Philip A Ambrose, Renato E Mantegazza, Richard J Nowak, Rocio Vazquez Do Campo, Saiju Jacob, Sami Saba, Shahriar Nafissi, Shannon Itoyama, Srikanth Muppidi, Stuart Viegas Viegas, Victoria Marshall, Yingkai Li Li
Journal: The Lancet Neurology (2020)

During the COVID-19 pandemic, patients with neuromuscular disorders, especially patients with autoimmune myasthenia gravis, might be at greater risk of worse outcomes than otherwise healthy people because of an immunocompromised state related to immunotherapy and possible respiratory and bulbar muscular weakness. However, cessation of immunotherapy in neuroinflammatory disorders has severe risks as well.1Korsukewitz C Reddel SW Bar-Or A Wiendl H Neurological immunotherapy in the era of COVID-19—looking for consensus in the literature.Nat Rev Neurol. 2020; 16: 493-505Crossref PubMed Scopus (53) Google Scholar Moreover, infections are a well recognised trigger of symptom exacerbation in patients with myasthenia gravis, and some drugs used in therapeutic trials early in the pandemic, including hydroxychloroquine2Robberecht W Bednarik J Bourgeois P Van Hees J Carton H Myasthenic syndrome caused by direct effect of chloroquine on neuromuscular junction.Arch Neurol. 1989; 46: 464-468Crossref PubMed Scopus (53) Google Scholar and azithromycin,3Cadisch R Streit E Hartmann K Exacerbation of pseudoparalytic myasthenia gravis following azithromycin (Zithromax).Schweiz Med Wochenschr. 1996; 126 (in German).: 308-310PubMed Google Scholar can provoke symptom exacerbations. As there was no real-world evidence available at the onset of this pandemic and heightened concern existed for possible misinformation, an international group of neuromuscular physicians developed initial guidelines for managing myasthenia gravis, which were based on previous experience with viral illnesses in this patient population.4Jacob S Muppidi S Guidon A et al.Guidance for the management of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) during the COVID-19 pandemic.J Neurol Sci. 2020; 412116803Summary Full Text Full Text PDF PubMed Scopus (111) Google Scholar However, the need for data to answer key clinical questions was quickly recognised and a registry was created to capture high-quality information about outcomes for patients with myasthenia gravis and laboratory-confirmed, or clinically suspected, COVID-19. This physician-reported registry, COVID-19 Associated Risks and Effects in Myasthenia Gravis (CARE-MG), is a joint effort of the International MG/COVID-19 Working Group and neurologists who help to take care of patients with myasthenia gravis globally and was formally launched on April 9, 2020. Registry data elements, inclusion and exclusion criteria, and research study approval are available in the appendix (appendix pp 7–8). The registry is still open and active accrual continues through electronic-form or paper-form submission of case reports. Data entry for each case submission takes approximately 10 min. Additional study details and steps for case submission are available from the Myasthenia Gravis Foundation of America website.6Myasthenia Gravis Foundation of AmericaCARE-MG.https://myasthenia.org/For-Professionals/Resources-for-Professionals/CARE-MGDate accessed: October 26, 2020Google Scholar A total of 91 patients with myasthenia gravis were included at the time of interim analysis (Oct 5, 2020; appendix pp 10–12). Myasthenia gravis worsening or crisis requiring rescue therapy (eg, intravenous immunoglobulin, plasma exchange, or steroids) in the setting of COVID-19 was reported in 36 (40%) of 91 patients. Complete recovery or discharge to home was reported in 39 (43%) patients, whereas 22 (24%) patients died due to COVID-19. These preliminary data suggest that a global, physician-reported registry is feasible during times of crisis, even for rare diseases, such as myasthenia gravis. Current data, which might be biased toward poor outcomes reporting, show that patients with myasthenia gravis who are infected with severe acute respiratory syndrome coronavirus 2 are frequently admitted to hospital, have disease exacerbations, and have a higher mortality than the general population with COVID-19.5Wu Z McGoogan JM Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention.JAMA. 2020; 323: 1239-1242Crossref PubMed Scopus (12616) Google Scholar More neurologists and neuromuscular specialists from across the globe need to submit details of cases to the CARE-MG registry if it is to become more representative—in terms of contributing physicians, patients, and results—and provide the information necessary to enable evidence-based care for patients with myasthenia gravis during this pandemic. SM reports consultation fees for advisory board meetings from Alexion Pharmaceuticals, argenx, Ra Pharmaceuticals, unrelated to this Correspondence. JTG reports personal fees for advisory boards from Immunovant, Alexion Pharmaceuticals, Cabaletta Bio, Regeneron Pharmaceuticals, argenx, and Momenta Pharmaceuticals and grants from Ra Pharmaceuticals, unrelated to this Correspondence. SJ has served as an international advisory board member for Alexion Pharmaceuticals, Alnylam Pharmaceuticals, and Regeneron Pharmaceuticals; is currently an expert panel member of myasthenia gravis consortium for argenx, has worked as chief or principal investigator for myasthenia trials by Alexion Pharmaceuticals, argenx, Momenta Pharmaceuticals, and UCB and has received speaker fees from Terumo Blood and Cell Technologies and Eisai, unrelated to this Correspondence. ACG has received research support from the Myasthenia Gravis Foundation of America and Myasthenia Gravis Rare Disease Network; clinical trial funding and consultant fees or honoraria from Momenta Pharmaceuticals, Ra Pharmaceuticals, and Alexion Pharmaceuticals; and publishing royalties from Oakstone Publishing, unrelated to this Correspondence. JFHJ has received research support from Alexion Pharmaceuticals, argenx, the Centers for Disease Control and Prevention (Atlanta, GA, USA), the Muscular Dystrophy Association, the National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), Patient-Centered Outcomes Research Institute, Ra Pharmaceuticals; honoraria from Alexion Pharmaceuticals, argenx, Ra Pharmaceuticals, Regeneron Pharmaceuticals, and Viela Bio; and non-financial support from Alexion Pharmaceuticals, argenx, Ra Pharmaceuticals, and Toleranzia, unrelated to this Correspondence. GC reports personal fees from MedDay Pharmaceuticals during the conduct of the study; personal fees for data safety monitoring boards from AstraZeneca, Avexis, BioLineRx, BrainStorm Cell Therapeutics, Bristol Myers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Horizon Pharmaceuticals, Hisun Pharmaceuticals, Mapi Pharmaceuticals, Merck, Merck/Pfizer, Opko Biologics, Neurim, Novartis, Ophazyme, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, Viela Bio, Vivus, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, unrelated to this Correspondence; personal fees for consulting or advisory board from Biogen, Click Therapeutics, Sanofi Genzyme, Genentech, GW Pharmaceuticals, Klein-Buendel, MedImmune, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion Pharmaceuticals/CereXis, Roche, Somahlution, and TG Therapeutics; and personal fees from Pythagoras, unrelated to this Correspondence. HW reports grants and personal fees from Abbvie, Biogen, Merck Serono, Sanofi Genzyme; personal fees from Evgen, MedDay Pharmaceuticals, Novartis, Roche Pharmaceuticals, Immunic, Alexion Pharmaceuticals, Actelion, F Hoffmann-La Roche, Gemeinnützige Hertie-Stiftung, Lundbeck, Teva Pharmaceuticals, WebMD Global; grants from Federal Ministry for Education and Research, Deutsche Forschungsgesellschaft, Else Kröner Fresenius Foundation, EU, Fresenius Foundation, Hertie Foundation, North Rhine-Westphalia Ministry of Education and Research, Interdisciplinary Center for Clinical Studies Muenster, Rasmussen's Encephalitis Children's Foundation, Progressive Multifocal Leukoencephalopathy Consortium, Swiss Multiple Sclerosis Society, and GSK, unrelated to this Correspondence. MBM receives grant funding from the National Institutes of Health and the Agency for Healthcare Research and Quality, unrelated to this Correspondence. HM reports personal fees from Alexion Pharmaceuticals, argenx, Ra Pharmaceuticals, and UCB; and grants from Japan Blood Products Organization and Ministry of Health, Labour and Welfare, Japan, unrelated to this Correspondence. KU has served as a paid consultant for argenx, Ra Pharmaceuticals, UCB, and Viela Bio and has received speaker honoraria from the Japan Blood Products Organization and Alexion Pharmaceuticals, unrelated to this Correspondence. RJN has received research support from Alexion Pharmaceuticals, argenx, Genentech, Grifols, Immunovant, Momenta Pharmaceuticals, the Myasthenia Gravis Foundation of America, the National Institutes of Health (National Institute of Neurological Disorders and Stroke and National Institute of Allergy and Infectious Diseases), and Ra Pharmaceuticals; and consultancy fees from Alexion Pharmaceuticals, argenx, CSL Behring, Grifols, Immunovant, Momenta Pharmaceuticals, Ra Pharmaceuticals, Roivant Sciences, and Viela Bio, unrelated to this Correspondence. RM has received funding for travel or meeting attendance from Alexion Pharmaceuticals, argenx, Biomarin Pharmaceuticals, Novartis, Catalyst Pharmaceuticals, Merck Serono, and UCB and for advisory board participation from Alexion Pharmaceuticals, argenx, UCB, and Regeneron Pharmaceuticals. All other authors declare no competing interests. SM, JTG, and RJN contributed equally. Download .pdf (.23 MB) Help with pdf files Supplementary appendix