How do MS medications work?
The current pandemic and the drive to vaccinate against COVID-19 have focused attention on the importance of maintaining an adequate immune response to protect against infection. An early concern among people with multiple sclerosis was whether the immune abnormalities seen in MS would increase the risk of contracting COVID-19. This does not appear to be the case, although extra precautions are needed for older individuals, and those with significant disability or other medical conditions.
The second issue that arose during the pandemic was whether the immune-modulating medications used to treat MS would put people at risk of severe COVID or impair their response to COVID vaccines. So it may be helpful to review how the different categories of MS disease-modifying therapy (DMT) affect the immune response (Zheng and colleagues. CNS Drugs 2020;34:879-896). Of particular interest is how treatments affect the two main types of immune cells – the T cells and the B cells.
1. Treatments that make the immune response less inflammatory: When T cells become activated, medications can induce them to be less inflammatory, which can reduce the amount of tissue damage caused by inflammation. This is primarily how the injectable MS medications work, such as the interferons (Avonex, Betaseron/Extavia, Rebif, Plegridy) and Copaxone (Kieseier BC. CNS Drugs 2011;25:491-502).
Oral medications also reduce the inflammatory response but by different mechanisms. Aubagio prevents activated T cells from proliferating. The fumarates (Tecfidera, Vumerity) induce the body’s antioxidant response, which blocks the formation of inflammatory molecules (Gold and colleagues. Clin Immunol 2012;142:44-48). Treatment can reduce the number of T cells to some degree but this does not appear to be associated with a risk of infections (Boffa and colleagues. CNS Drugs 2020;34:425-432). The B cell (antibody) response is not affected (Longbrake and colleagues. Mult Scler 2021;27:883-894).
In general, the injectable and oral therapies are not associated with a profound or sustained impact on the immune response. So the recommendation is to continue with the usual dose schedule throughout the pandemic and before/after vaccination. None of these treatments would be expected to significantly affect a person’s response to COVID-19 vaccination.
2. Treatments that block immune cells from causing damage: So-called “barrier drugs” do not affect activation of the immune response. Rather, they block activated immune cells from entering the central nervous system (CNS, the brain and spinal cord), which prevents damage to tissues in the CNS. The main example is Tysabri. Since the immune counts are not diminished, the regular schedule of monthly Tysabri infusions can be maintained during the pandemic and before/after vaccination. Some doctors may opt for less frequent dosing (e.g. 1 infusion every 5-8 weeks), which may provide a number of benefits in the post-vaccination period.
One class of DMTs traps activated T cells in the lymph nodes, which prevents them from circulating in the body to cause harm. So they are technically “barrier drugs” (blocking T cells from entering the blood stream), although they can also be seen as treatments that reduce the number of T cells (by trapping rather than killing them) that are available to fight infections. Drugs in this category include Gilenya, Zeposia and Mayzent. These medications can be associated with a higher risk of some infections, such as herpes zoster (shingles) (Lasa and colleagues. Drug Saf 2021;44:645-660). The vaccine response also appears to be impaired to some degree (Kappos and colleagues. Neurology 2015;84:872-879), including the response to COVID vaccination (Achiron and colleagues. Ther Adv Neurol Disord 2021;14:17562864211012835). The recommendation is to delay the start of treatment until a month after vaccination, although people already on treatment are being advised to get vaccinated whenever they can.
3. Treatments that eliminate T and B cells: Two DMTs specifically target immune cells to a greater (Lemtrada) or lesser (Mavenclad) degree and people are advised to delay starting treatment until after they have been vaccinated. An advantage with both is that the treatment period is very short – 1 week for Lemtrada and 2 weeks (separated by a month) for Mavenclad. After that, no more medication is needed for the rest of the year. This means that even though both medications impair the immune response for a few months after the last dose, there are long periods (about 6-9 months) when the immune response has recovered sufficiently to fight off infection. This off-drug period is the best time to schedule your vaccinations.
4. Treatments that eliminate B cells: Two MS medications, Ocrevus and Kesimpta, specifically eliminate B cells. Several studies have reported that people with MS have a higher risk of developing severe COVID if they are taking Ocrevus. People are generally advised to delay starting treatment with one of these medications until 2-4 weeks after they have been vaccinated. If you are already on Ocrevus, the ideal is to be vaccinated at least 4-6 months after the last dose, although this may be difficult to schedule. For Kesimpta, which is administered as a monthly injection, the ideal scheduling to accommodate vaccination is not known.
The most up-to-date information about DMTs and vaccination is provided by the MS International Federation; their website was last updated in June 2021 (www.msif.org/news/2020/02/10/the-coronavirus-and-ms-what-you-need-to-know/). The MSIF recommends vaccination for everyone with MS. However, the MSIF cautions that there is some evidence that people taking certain DMTs (Gilenya, Mayzent, Zeposia, Ocrevus and Kesimpta) may mount less of an immune response to COVID vaccination. That means you may not be fully protected against infection even after you have been vaccinated, so it may be advisable to keep taking precautions against COVID-19 even after you have had your two shots.
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