Treatment in the COVID era – What do DMTs do to immunity?
There are now over a dozen DMTs to treat MS and more are coming soon. These drugs affect the immune system in somewhat different ways – which can have a bearing on how the body combats the CoV-2 virus (Brownlee and colleagues. Neurology 2020;94:949-952).
Copaxone (and generics) induces a slight shift in the immune response to a less inflammatory profile. It isn’t associated with a risk of infections, so it can be safely started or continued during the pandemic. (As a general rule, all DMTs should be stopped if you are diagnosed with COVID.) The interferons (Avonex, Rebif, Betaseron/Extavia, Plegridy) have modest effects on the immune response, but also have some antiviral effects, so they appear to be safe. It’s important to note that a common side effect of interferons is flu-like symptoms (e.g. fever, headache, breathlessness), which can be confused with COVID symptoms (Hamdy and colleagues. Ther Clin Risk Manag 2020:16 651-662).
Tecfidera shifts the immune system to a less inflammatory response, but it’s not an immunosuppressant so it doesn’t appear to increase the risk of infection. It can be safely started or maintained during the pandemic. One effect of the drug is to reduce the number of immune cells. This isn’t usually associated with infections, but you may need to take a break from treatment if immune cell counts get too low. Aubagio specifically targets immune cells so it too can lower blood cell counts. But this doesn’t appear to be associated with a significant infection risk. It’s safe to start or continue with Aubagio during the pandemic. The drug will need to be actively eliminated from your body, however, if you develop COVID-19.
The situation is a little different with DMTs that have more potent effects on the immune system. Gilenya (and its generics) acts by significantly reducing the number of immune cells (called T cells) that work as “first responders” when there’s a viral infection. This T cell impairment remains for as long as the person is taking the drug. As a result, it’s generally recommended not to start this treatment during the pandemic. People who are already on the medication are advised to continue with it, in part because abruptly stopping the drug can cause a flare-up of MS. Periodic blood tests may be needed to ensure that blood cell counts don’t get too low.
Tysabri doesn’t suppress the immune response and the risk of infections is generally low so it can be safely started and continued during the pandemic (Zito and colleagues. ECTRIMS 2020; LB1235). The main concern with Tysabri is a risk of PML, a serious brain infection, in people infected with the JC virus. Some doctors are recommending taking the drug less often (every 5-8 weeks instead of every month) to reduce the risk of PML. Like Gilenya, Tysabri should not be stopped abruptly because of the risk of an MS flare-up.
The final three drugs are called ‘cell-depleting’ – they all control MS by eliminating immune cells. Mavenclad reduces the number of T cells, but its main effect is on B cells, which are “second responders” in fighting infection. B cells also produce antibodies, which confer immunity against re-infection (see Part 3 for more on antibodies and the COVID vaccine). The most vulnerable time with Mavenclad is the 2-3 months after dosing, which is when immune cell counts are at their lowest, so it may be prudent to take extra precautions for a few months after a course of treatment. People scheduled for a second course of treatment (in year 2) can safely delay therapy for up to six months without worsening their MS.
Lemtrada profoundly reduces immune cell counts; B cells recover within a few months but T cell counts can remain lower for years. So many doctors have been reluctant to start this drug during the pandemic. People who have already taken one course of treatment are likely to be advised to take extra precautions against infection (such as strict self-isolation) and delay taking the second course.
Ocrevus targets B cells, resulting in profoundly lower B cell counts for as long as you’re on treatment. Recent studies have raised a number of concerns about this class of therapy (called anti-CD20 agents) during the pandemic. A few studies have now reported that people taking these medications have a higher risk of getting COVID-19 (Kieseier and colleagues. ECTRIMS 2020; LB1252; Zabalza 2020). And the largest study to date found that there was a higher risk of severe COVID (requiring admission to hospital or the ICU) if a person became infected during treatment (Simpson-Yap and colleagues. ECTRIMS 2020; SS02.04). If you’re already taking Ocrevus, you may be able to postpone your next infusion for six months or so without running the risk of your MS getting worse.
According to the most recent information, it appears that people with MS who get COVID-19 do better overall if they are taking an MS medication rather than remaining untreated (Zabalza 2020). So it’s important to stay with the medication you’re on, at least until you’ve talked to your doctor about your safest options for your particular circumstances. In Part 2 we’ll look at other factors that can affect your risk of COVID.
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