key: cord-0815250-7lhi63tb authors: Peters, Bradley J.; Rabinstein, Alejandro A.; DuBrock, Hilary M. title: Use of Remdesivir in Myasthenia gravis and COVID‐19 date: 2021-04-27 journal: Pharmacotherapy DOI: 10.1002/phar.2524 sha: 54ce9610fd918ccb6cc29927dafde751a177cb15 doc_id: 815250 cord_uid: 7lhi63tb Myasthenia gravis and the associated pharmacologic management options could place patients at higher risk of contracting severe acute respiratory syndrome coronavirus 2 and exhibiting more severe manifestations of the novel coronavirus disease 2019 (COVID‐19). Multiple agents have been studied for the management of the COVID‐19, including remdesivir. To date, no published reports have evaluated the utilization of the antiviral remdesivir in patients with myasthenia gravis. We describe the first reported clinical course of three patients with myasthenia gravis who safely received remdesivir in combination with dexamethasone for the management of COVID‐19. Myasthenia gravis (MG) is an autoimmune disease that leads to fatigable skeletal muscle weakness. Antibodies targeting acetylcholine receptors, or functionally related molecules such as muscle-specific kinase or lipoprotein receptor-related receptor 4, in the postsynaptic membrane of the neuromuscular junction result in failure of neuromuscular transmission. 1 The ensuing weakness can vary from day to day and over the course of the day. It can be generalized or localized and is often associated with repetitive muscle use (ie, fatigability). Immunosuppressive agents, including but not limited to corticosteroids, antimetabolites, and calcineurin inhibitors, are effective for the treatment of MG. 1, 2 The immunosuppressive agents utilized for MG treatment may put these patients at higher risk of contracting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and exhibiting more severe manifestations of the novel coronavirus disease 2019 . 3, 4 Several classes of drugs, including some antibiotics and antiviral medications, have been associated with clinical worsening of MG. 5 Antivirals with reports of exacerbating MG include interferon alpha, hydroxychloroquine, and peramavir. 5, 6 Remdesivir has an alternative mechanism of action when compared to the previously listed antivirals. Remdesivir is an inhibitor of viral RNAdependent, RNA polymerase that is intended to reduce virus levels and subsequent lung damage in SARS-CoV-2 infection. [7] [8] [9] At the time of publication, there have been no published reports of the utilization of the antiviral remdesivir in patients with MG. Here, we describe the use of remdesivir and clinical outcomes in three patients with MG and SARS-CoV-2 infection. A 71-year-old male with MG was treated at baseline with mycophenolic acid monotherapy (Table 1) . His comorbidities included type 2 diabetes mellitus, hyperlipidemia, hypertension, and a prior stroke. The patient was a poor historian, and information regarding past MG exacerbations was limited. He was brought to an outside hospital emergency department after being found down at his assisted living facility. He was noted to be hypoxic and febrile, with hazy bilateral opacities on chest x-ray. Nasopharynx real-time reverse transcription polymerase chain reaction (RT-PCR) was positive for SARS-CoV-2. He was given 200 mg of intravenous (IV) remdesivir and 6 mg of IV dexamethasone and was transferred to our institution's intensive care unit (ICU) for management of hypoxemic respiratory failure. In our hospital, he received 10 total days of dexamethasone 6 mg/day and 4 additional days of IV remdesivir 100 mg/day. In addition to these therapies, the patient qualified for a clinical trial and received lenzilumab 600 mg every 8 h for 3 doses or placebo as per the study protocol. He continued his maintenance mycophenolic acid regimen for MG. He required continuous positive airway pressure (CPAP) and high-flow nasal cannula (HFNC) to maintain oxygenation, but did not have evidence of significant hypercapnia (arterial blood gas with pH of 7.43, partial pressure of carbon dioxide of 45 mmHg, and partial pressure of oxygen 56 mmHg). Due to progressively worsening hypoxemic respiratory failure, Neurology was consulted to ensure neuromuscular weakness was not contributing to his declining respiratory status. Neurologic examination was notable for absence of accessory respiratory muscle use and lack of paradoxical breathing pattern. He had preserved strength overall with no ptosis with sustained upward gaze and no evidence of bulbar weakness. Thus, MG was not felt to be contributing to his respiratory failure and he was ultimately diagnosed with an acute pulmonary embolism. After further goals of care discussions, the patient was transitioned to comfort-focused care measures and passed away in the hospital. A 41-year-old female had been diagnosed with MG in 1995. She had undergone thymectomy and was treated with mycophenolate mofetil, prednisone, and pyridostigmine at baseline. Comorbidities included A 59-year-old male had a recent diagnosis of MG in May 2020. Little is known about the use of remdesivir in patients with MG and COVID-19. In this case series, we describe the clinical course and outcomes of three patients with MG and COVID-19 pneumonia with hypoxemic respiratory failure who were treated with remdesivir in combination with dexamethasone. None of the patients experienced significant clinical worsening of MG after treatment with remdesivir. There is a concern that MG and the associated pharmacologic Remdesivir, an antiviral, was studied in a double-blind, randomized, placebo-controlled clinical trial (ACTT-1) and was found to be superior to placebo in shortening the time to recovery in hospitalized adults with COVID-19 and lower respiratory tract infection. 8 Although there is additional conflicting evidence regarding use of remdesivir in COVID-19, it is currently approved by the United States Food and Drug Administration for the treatment of COVID-19 in appropriate hospitalized patients requiring supplemental oxygen but are not requiring mechanical ventilation. 7, 9, 10 Remdesivir is an adenosine nucleotide prodrug that is rapidly converted to two initial metabolites (alanine metabolite and nucleoside monophosphate metabolite). 7, 11 The monophosphate metabolite is further phosphorylated to the active remdesivir triphosphate. The remdesivir tri- Since some antivirals and other classes of medications can worsen MG, we had initial hesitancy to prescribe remdesivir in these critically ill patients with SARS-CoV-2 infection. We reviewed the prescribing information and the mechanism of action which did not seem to be related to alterations of acetylcholine or the associated receptors and decided to proceed with remdesivir treatment. 5, 7, 8, 11, 12 All three patients were monitored for worsening neuromuscular weakness and respiratory failure for more than 10 days after receiv- In this case series, we describe three patients with MG and active SARS-CoV-2 infections who received remdesivir. In these critically ill patients with MG and COVID-19 pneumonia, the use of the antiviral remdesivir in combination with dexamethasone did not precipitate a MG exacerbation or crisis. The authors have no conflicts of interest to report. Bradley J. 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