Are multiple sclerosis therapies safe in severe acute respiratory syndrome coronavirus 2 times?

Sir, Following the activation of the cytokinic cascade due to the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) virus and the accumulation of fibrotic tissue, patients with multiple sclerosis face an additional complication to avoid worsening their disease.[1,2] There are many drugs approved for the treatment of MS that lead to good disease control and high patient adherence and compliance. Unfortunately, however, these drugs are not free from serious adverse reactions which in some cases are fatal. This is because there are little data on safety on newer drugs such as ocrelizumab. Alemtuzumab was in fact withdrawn from the market in Italy following serious adverse reactions with Cytomegalovirus reactivation. The decrease in lymphocytes in the blood is the cause of major complications after entry of the virus through the renin-angiotensin system [Figure 1]. Fingolimod leads to serious adverse rations, and the most frequent are infections. Teriflunomide and dimethyl fumarate lead to a slight reduction in white cell counts with growth risk of infection. Based on the present literature, postmarketing pharmacovigilance data and Summary of Product Characteristics, it is clear that there is an increased risk of infection associated with drugs for MS. The marked reduction in IgG and IgA leads to an increased risk of causing infection, and hence, the drugs for MS that cause a high reduction in IgG lead to a marked risk of infection for the patient. Drugs such as Ocrelizumab Cladribina should definitely be avoided because of their marked lymphocytopenia.[3,4,5]Figure 1: Increased risk is closely related to increased lymphopeniaWe have thoroughly reviewed and compared all the positions of scientific societies and regulatory agencies in different countries, trying to understand the individual position on whether to discontinue current treatment with MS drugs. In general, in Italy, there are currently no indications for discontinuing the various drugs used in MS and exposing the patient to the risk of reactivation of the disease. It is therefore recommended to continue treatment with the current therapy, particularly with all first-line treatments (interferons, glatiramer acetate, teriflunomide, dimethylfumarate). For named depletive therapies such as ocrelizumab or rituximab it should be considered on a case-by-case basis whether to postpone the start of treatment if the patient is already on therapy and therefore already immunosuppressed the cycle should be completed by recommending more precautions. Finally, in case of confirmed Sars-CoV-2 infection, suspend any line I and II therapy until the clinical picture is resolved or a specialist reassessment is made. Considering individual drugs and countries, the recommendations for natalizumab in Italy are that treatment can be started in patients or continued in patients who were already taking it, suspended in case of confirmed Sars- CoV-2 infection. In the United Kingdom, it is recommended to continue treatment. In Germany, natalizumab is not mentioned, in Canada, it is recommended to prescribe it normally also in case of Sars- CoV-2. For dimethylfumarate in Italy, doctors are recommended to carefully consider the benefits and risks for patients who need to isolate themselves as much as possible to avoid infection. In the UK treatment with dimethylfumarate is considered safe, in Germany, it is considered safe and the risk of infection should not increase and it is recommended not to interrupt the monitoring of leukocyte count. For NFI in Italy, it is recommended to continue treatment even in case of Sars- CoV-2 infection at the discretion of the treating physician, the continuation of NFI for any antiviral action data in the literature could be of added value. In the UK, it is considered safe to start or continue treatment with NFI and to stop treatment in case of Sars-cov-2 infection. In Germany, it is recommended that NFI can continue to be prescribed normally, in the USA and Canada it is recommended not to stop treatment. In Italy it is recommended to postpone the start of depletive therapy with ocrelizumab, alemtuzumab, rituximab and cladribine. In patients treated with anti-CD20, it is suggested to delay the infusion even beyond 6 months, if the B-lymphocytes are zero at the expected time of reinfusion. In the UK, patients already on ocrelizumab treatment are recommended to postpone treatment until the epidemic is resolved and for alemtuzumab and cladribine which are considered less safe than natalizumab and ocrelizumab it is recommended not to start them. In Germany, it is recommended to consider postponing the start of depletive therapy in older patients or those with concomitant cardiovascular lung disease and to stop in case of infection. Finally, for fingolimod teryflunomide and glatiramer is recommended to continue treatment in case of Sars-Cov-2 infection and to stop all treatments. In the United Kingdom, it is considered safe to start or continue treatment with glatiramer and teriflunomide and it is recommended to stop treatment in case of SARS-Cov-2 infection. Fingolimod probably moderately increases the risk of infection. In Germany, Glatiramer and teriflunomide may continue to be prescribed normally. Fingolimod may increase the risk of respiratory complications. In the United States and Canada, they may be prescribed and if you have an infection contact doctor. In recent years, drugs with increased immunosuppressive power have been developed for the treatment of MS. However, these drugs are not free from serious adverse reactions. In this period of global SARS- CoV-2 pandemic, the use of these new immunomodulatory drugs has raised even more the issue of safety and increased potential risks of infection. The question is: Can therapy with these drugs continue during this pandemic period? Or should it be discontinued? The positions of scientific societies and regulatory bodies in different countries, as described above, and given the complication of MS treatment, it would be appropriate to identify the decision-making process on the individual condition of the patient. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Acknowledgment The authors have nothing to say about ethical standards, ethical approval and funding. This manuscript is not a clinical trial and does not violate ethical rules. No funding has been received for its preparation.

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