Treatment in the COVID era – thinking ahead to the COVID vaccine
All of the disease-modifying therapies (DMT) used to control multiple sclerosis target a person’s immune response. Some therapies modulate the response so it’s less inflammatory, some block immune cells from entering the brain and still others eliminate immune cells so they can’t contribute to inflammation and damage. However, the very same immune response that is potentially harmful in MS is also needed to mount a vaccine response – raising questions about whether a COVID vaccine (when available) will work in people taking an MS medication.
Vaccination introduces a substance (called an antigen) that is intended to elicit an immune response. The goal is to teach the immune system to recognize that foreign antigen so it will be better able to fight off infection. The antigen used is typically a weakened (attenuated) live virus (as in the measles/mumps/rubella vaccine), an inactivated virus (as in the flu vaccine) or a component of the virus (e.g. a virus protein or toxin) that can be distinguished from the body’s own proteins (as in the pneumonia vaccine).
Of the many hundreds of vaccines in development against COVID-19, Canada has pre-purchased six different vaccine candidates that use one of three technologies.
The first type uses virus proteins as the antigen (as with pneumonia and HPV vaccines) and is being developed by two companies, Novavax and Sanofi. The other two types are more experimental. One is a variation of a live-virus vaccine (called a viral vector vaccine) that uses a non-COVID virus that has been manipulated to produce COVID proteins. This type of vaccine is being produced by two drug companies, Astra Zeneca and Janssen. The third type uses genetic material (RNA) from the virus to induce the body’s cells to produce viral antigen. This type of vaccine, which has never been successfully used before, is being produced by the companies Pfizer and Moderna.
Once a virus antigen is injected, the body activates a sequence of immune defences to fight infection. The first is called the innate immune response. This response begins right after the injection itself – the skin at the injection site becomes swollen and red. After recognizing a foreign substance, the innate immune system passes this information along to the acquired immune system – and this is where T cells and B cells get involved. Some T cells attack infected cells directly while others prod B cells into action. Some B cells stimulate T cells and others develop into cells that produce antibodies. After the initial vaccination, some T and B cells become memory cells, which are able to respond quickly if that same antigen is ever encountered again. This later response is what occurs when a person receives a second booster injection.
Vaccines and MS medications
For a vaccine to work, all of the moving parts of an immune response need to work properly, which means that the cells of the innate immune system (e.g. macrophages, neutrophils) and the acquired immune system (e.g. T cells and B cells) must be present in sufficient quantity and with enough activity to protect the body. As a general rule, DMTs have little effect on the innate immune response so that isn’t a major source of concern. However, DMTs can have differing effects on the acquired response (T and B cells) that need to be considered.
Vaccine studies have shown that people taking an injectable DMT (Copaxone or one of the interferons) generally respond well to inoculation. Similarly, the oral medications Aubagio and Tecfidera do not appear to be a problem. There is some blunting of the immune response (Bar-Or and colleagues. Neurol Neuroimmunol Neuroinflamm 2015;2:e70. von Hehn and colleagues. Neurol Neuroimmunol Neuroinflamm 2017;5:e409). But with both of these medications, people will typically mount enough of an immune response to fight off infection.
The situation is a little different with the other two oral DMTs. Gilenya reduces the number of T cells in the blood stream and has been shown to impair the immune response (Kappos and colleagues. Neurology 2015;84:872-879). The response may be enough for some, but others may need another inoculation to achieve a full effect. The usual advice is to stop Gilenya for 2 months so the vaccine will be more likely to be effective. No vaccine studies have been done for Mavenclad, but it’s likely that there would be a reduced vaccine response in the 3-6 months after the last dose. The timing of the drug dosing and vaccination will need to be coordinated.
Tysabri can slightly slow the development of a vaccine response but doesn’t appear to impair immunity to a significant degree (Kaufman and colleagues. J Neurol Sci 2014;341:22-27). Lemtrada causes a profound reduction in T and B cells; B cells return within a few months, so it’s generally advised to wait for at least 6 months after the last dose before getting vaccinated (McCarthy and colleagues. Neurology 2020;10.1212). Since treatment is intermittent (like Mavenclad), the timing of the vaccination will be important.
Vaccination is more of a problem with Ocrevus. This medication causes profound suppression of B cells, and B cell numbers remain low for as long as you stay on treatment. Studies have shown that Ocrevus will reduce the response to a vaccine and to booster shots (Bar-Or and colleagues. Neurology 2020;10.1212). So it’s generally recommended that vaccination be put off until the number of B cells recovers. This means stopping treatment and remaining off therapy for 6-12 months. It remains to be seen if COVID immunity will be lost once Ocrevus is re-started.
The above recommendations are for non-live vaccines. Some of the COVID-19 vaccines are a type of live vaccine, so different rules may apply. In general, live vaccines should not be administered while taking a DMT. If a live vaccine is to be used, Aubagio needs to be actively eliminated from the body, a regimen that takes about two weeks. Tecfidera washes out of the body rapidly but a blood test may be needed to ensure that blood cell counts are in the normal range. T and B cells will also need to be within range for the other DMTs, which will take about 2-3 months for Gilenya, at least 9 months for Mavenclad, over a year for Lemtrada and perhaps 12-18 months for Ocrevus (Comi and colleagues. Mult Scler Relat Disord 2019;29:168-174. Baker and colleagues. Clin Exp Immunol 2020;202:149-161). A blood test beforehand will determine if the immune system has recovered enough for vaccination to be effective. A concern, however, if that MS treatment will need to be stopped during that time, so there is a risk of an MS flare-up while you are waiting to be vaccinated.
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