With this post, I would like to conclude the short excursion on pathogens, our immune system and the immunotherapy of MS in times of a pandemic. I hope I have succeeded in explaining some important backgrounds to you (even if it might have been a bit complicated at some places), which will help you to understand connections better and form an opinion. I will only write about MS and Corona virus again when there are really reliable data and news – which will certainly be the case again soon. And of course, it would be a pleasure for me to report on an effective medication or to motivate you to get vaccinated against SARS-CoV2 in the fall – let’s hope for the best.
What is my personal conclusion or what are my personal answers to the frequently asked questions about MS and immunotherapy in times of Corona?
I do not consider MS per se to be a risk for infection with SARS CoV2 or for a complicated or even fatal course, especially in young, otherwise healthy individuals. However, I too would advise MS patients who are already advanced in age, have internal comorbidities and/or are severely physically impaired and in need of care to exercise increased caution and strictly follow general protective measures.
As for therapy with interferon preparations (Avonex, Plegridy, Rebif, Betaferon, Extavia), I have no concerns. This medication, due to its antiviral properties, certainly has no negative effect in the current situation and can be started and continued at any time. The same applies to Glatirameracetat (Copaxone, Clift). The effect of this medication is very specific in MS and uses the healthy immune system to develop tolerance towards CNS tissue (to put it simply) – here too, there is no negative impact on the immune system and defense against infection. Therefore, neither the start nor the continuation of therapy with Glatirameracetat is currently disadvantageous.
As for the oral first-line therapy Teriflunomide (Aubagio), although the mechanism of action consists in a reduction of lymphocytes, the main actors of adaptive immunity, within clinical trials and also in subsequent registry studies, infections were never a problem. Accordingly, it can probably be assumed that Teriflunomide (Aubagio) at the dosage used for MS is unproblematic. You might also be reassured to know that there are basic scientific studies on Teriflunomide that prove an antiviral effect of the substance.
I currently see neither a problem with starting nor continuing therapy with Dimethylfumarate (Tecfidera). However, a small proportion of Tecfidera patients develop quite pronounced lymphocytopenia at the start of therapy, which persists. To identify this group, regular checks of the differential blood count are therefore recommended, especially at the beginning of therapy, which is sometimes done rather scantily. If a decrease in lymphocytes is shown, I tend to switch my patients to another preparation sooner rather than later – among other things because of a higher risk for opportunistic infections (although there was no correlation between lymphocyte count and infections in the licensing studies – one must say this in all fairness). A once too low lymphocyte value should always be checked first before any action is taken – please do not panic.D
Now I come to the stronger second-line preparations. The drug that currently worries me least is Natalizumab (Tysabri). Natalizumab acts very specifically on the transmigration of T cells into the brain, so it has less importance in virus defense and did not attract attention in its approval studies due to increased infections. Tysabri is highly effective and therefore certainly a good choice when it comes to starting treatment for (highly) active patients. I would consider this regardless of the JCV status, because the risk of PML only becomes relevant in the 2nd year of therapy and by then you can switch back to your desired preparation. For those who are currently using Tysabri, the medication can of course also be continued without problems.
The mode of action of Fingolimod is to retain inflammatory cells in the lymph nodes – that’s why patients with Fingolimod also measure reduced lymphocytes in peripheral blood. This lymphopenia worries me less, because the cells are still in the body and also reactive. However, in the clinical studies, there was a higher incidence of respiratory diseases in patients treated with Fingolimod. I checked again in the FREEDOMS study, infections of the lower respiratory tract and lung occurred in 6% of placebo patients and 9.6% of patients with Fingolimod 0.5 mg – so there was a difference, but it’s not as if measures have to be taken in view of this. Especially since discontinuation of Fingolimod carries the risk of a return of relapse activity (rebound), it is sensible and pragmatic to continue the therapy and observe the general protective measures.
Alemtuzumab (Lemtrada) and Cladribin (Mavenclad) are drugs that deplete T and B cells – the main actors of our adaptive immunity. These drugs are very innovative and enrich MS therapy – but at present they are not my first choice due to cell depletion. Personally, I am currently refraining from putting patients on Alemtuzumab or Cladribin – we need more data first.
But what about the patients who are already being treated and are possibly waiting for the next cycle? Fortunately, there are probably very few patients with Lemtrada, since we have hardly started any new treatments due to the §20 procedure of the EMA last year. But probably quite a lot of patients are waiting for the next Mavenclad cycle. If there are no serious other reasons (comorbidity, significant lymphocytopenia, active infection) against it, this should also be carried out, but it would probably be sensible to protect yourself well against infections in the first weeks after ingestion. Those who have last taken Alemtuzumab or Cladribin months ago can be relaxed – the critical phase should be over here.
Ocrelizumab is the last drug I want to comment on. Ocrelizumab also depletes cells, but predominantly CD20 positive B cells, and these mainly in the bloodstream. Here, only about 2% of the lymphocytes are located, meaning that the vast majority of immune cells are located in the lymphatic organs, where the antibody only gets to a limited extent. This means that even after an infusion, there are still enough B cells present. In addition, B cells do not play the main role in primary virus defense. Therefore, I would personally be rather relaxed – but this is primarily a theoretical consideration. In practice, more upper respiratory tract infections were found under Ocrelizumab during the approval study than in the interferon group (15.2% vs. 10.5%), so it is quite understandable to worry. The Ocrelizumab infusion can certainly be pushed back a bit, probably 1 -2 months are no problem, but at some point one has to act, otherwise there are problems with the MS. Therefore, we continue the therapy and also start new treatments if the disease requires it.
My assessments and recommendations are – as you can see – mainly based on the recommendations of the Competence Network MS (KKNMS) and the DMSG, which I would like to refer to again here (dmsg.de/multiple-sklerose-news/dmsg-aktuell/news-article/News/detail/update-empfehlungen-fuer-multiple-sklerose-erkrankte-zum-thema-corona-virus-aktualisiert/?no_cache=1&cHash=1f45cc65c79272dae37d6e2827278143). I think it is important not to lose sight of MS despite all the worries and therefore to continue therapy consistently – in mutual consultation. Therefore, we also have to be there for you in the outpatient clinics and take care of your therapies and questions – if not in person, then at least by phone and email.
My greatest wish now is that our health system is so strong that we will survive this crisis well – and that all of you stay healthy and do not lose courage.