COVID vs. MS treatments

The ongoing COVID-19 pandemic has illustrated the challenges of treating a condition such as multiple sclerosis when there is a high background rate of infections in society.

In MS, the immune system is dysregulated so that immune cells (T and B cells) attack the body’s own tissues. That has led to two key approaches to treatment: eliminate the offending immune cells with immune-suppressing drugs; or block the immune cells from entering the central nervous system (CNS) and causing damage.

The first approach is used by medications such as Ocrevus, Lemtrada and Mavenclad. Unfortunately, knocking out the immune response impairs the body’s defences against infection. Lemtrada and Mavenclad only do this intermittently so there is only a defined period of time when the defences are down. However, when immune suppression is ongoing, as with Ocrevus, the body remains susceptible to infections. This higher risk of infections may be of minimal concern when infection rates are low but assumes greater significance during a pandemic – when a person is likely to come in contract with someone who is sick.

This immune impairment is why people taking Ocrevus have a higher risk of contracting COVID-19, and a higher risk of developing more severe COVID, compared to people on other MS medications (Sormani M. ECTRIMS 2021. Simpson-Yap and colleagues. ECTRIMS 2021;098).

The other problem with this approach is that targeting immune cells will also impair the body’s ability to respond to a vaccine. So during this time of COVID vaccination, people taking Ocrevus get less protection from vaccination – even if they get a booster (third) shot. For example, a recent study reported that getting a third dose of vaccine did not actually provide much of a boost in protecting against COVID (Bajwa and colleagues. medRxiv preprint, January 28, 2022).

The second strategy is to block immune cells from entering the CNS. This is the approach used by Tysabri, and a group of medications called the S1P drugs (e.g. Gilenya, Zeposia, Mayzent, Ponvory). However, the S1P drugs are not true “barrier drugs”. They trap T cells (and B cells to a lesser degree) in the lymph nodes so they can’t enter the brain; they are tucked away where they can’t do any harm. But any immune cells that continue to circulate in the blood stream are not actively blocked from entering the brain (Kowarik and colleagues. Neurotherapeutics 2021;18:364-377). So Gilenya and its sister drugs essentially act as immune-suppressing drugs, which means they can also impair the response to vaccination. Recent studies have reported that people taking Gilenya continue to be at risk of severe COVID despite getting vaccinated (Meyer-Arndt and colleagues. medRxiv preprint, February 7, 2022).

Tysabri differs in this regard because it was specially designed to block immune cells from entering the CNS. Immune cells normally float along in the blood stream. If they want to get into the CNS, they use so-called adhesion molecules to attach themselves to the inner lining of a blood vessel so they can squeeze through the gaps between cells. What Tysabri does is block these adhesion molecules, in effect making the immune cells less ‘sticky’. Immune cells bounce off the barrier rather than get inside. This Tysabri effect occurs where blood vessels are in contact with the brain (called the blood-brain barrier), which is where inflammatory lesions often start in the brain. It also occurs where blood vessels are in contact with the structure that produces cerebrospinal fluid (called the choroid plexus); this so-called the blood-CSF barrier is the entry point for a type of B cell that is particularly damaging in MS (Haas and colleagues. Front Immunol 2021;11:618544). So Tysabri guards the gates and stops immune cells from invading the brain.

Both of these approaches – suppressing the immune response and enhancing the barrier defences – have been shown to be highly effective in controlling MS. However, when doctors assess which treatment approach is a better option, that calculation has changed during the pandemic. While Ocrevus and Tysabri are similarly effective, the pandemic is now a consideration. Tysabri does not knock out the normal immune response (in fact the number of immune cells increases in the blood stream), so it does not affect a person’s ability to fight COVID. Tysabri also does not impair the body’s ability to mount a long-term immune response to COVID vaccines (Altieri and colleagues. Neurol Sci 2022; epublished February 16, 2022).

That is why we have seen some changes in how MS medications are used during the pandemic. A survey by the U.S. National MS Society found that about 83% of neurologists had changed the way they prescribe. A majority were prescribing less Ocrevus, Lemtrada, Mavenclad and Gilenya. Many were prescribing more Tysabri, interferons and Aubagio (Morrison and colleagues. Mult Scler Relat Disord 2021;51:102913).

These changes in prescribing may shift back once the pandemic is over. However, one of the lessons during the pandemic is that chronic suppression of the immune response can create problems. This may become part of the treatment conversation – especially if people are required to get annual COVID booster shots in the years ahead.

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