Multiple Sclerosis and Covid-19
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was in fact withdrawn from the market in Italy following serious adverse reactions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 lymphopenia
We 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.