Year in Review – Treating MS during COVID – Part 2

We continue our look back at the Year of the Pandemic by reviewing some of the research highlights of 2020 regarding the use of higher-efficacy medications for MS. (Click here to read Part 1, What did COVID teach us about MS therapies?).

The emphasis in recent years has been to use increasingly potent disease-modifying therapies to treat MS in the hope that shutting down inflammation more effectively will be better at reducing the amount of MS disability in the years ahead. To offset that potential benefit is the slightly higher rate of infections seen with more potent medications. The pandemic upset that weighing of benefits and risks. How much more important is the risk of infection when there is an epidemic of infections in the community?

MS experts quickly cobbled together some recommendations on treatments during COVID that necessarily were based more on common sense than actual data. ( The lack of information was addressed by large, international databases, which were set up to record COVID infections in people with MS. Their preliminary findings became available in September.

Perhaps the most important result was that people with MS who develop COVID do not appear to do any worse than anyone else. But the same COVID risks apply: Older people and those with disability or other medical conditions (e.g. kidney or heart disease) are at risk of COVID-related complications (Salter and colleagues. ECTRIMS 2020; LB1242). Another important finding was that people who got COVID while on an MS medication generally did better than people who were not treating their MS – which shows the importance of remaining well and controlling MS.

The two key issues that emerged regarding the use of higher-efficacy therapies during the pandemic were the risk of infections and the implications for vaccination as the newly-approved COVID vaccine is distributed. The following is a summary of what was learned this year.

Tysabri: This treatment became one of the preferred higher-efficacy therapies because it has a lesser impact on the immune response (Zheng and colleagues. CNS Drugs 2020;34:879-896). It does not significantly impair the vaccine response (Kaufman and colleagues. J Neurol Sci 2014;341:22-27), which means that there will not be much of a delay between stopping treatment and getting a COVID vaccine. There is a risk of an MS flare-up when stopping, which might be lessened with a less frequent dose regimen (e.g. every 5 or 6 weeks) (van Kempen and colleagues. Neurology 2020;95:e745-e754).

Gilenya, Mayzent and Zeposia: This class of drugs reduces the number of immune cells, which increases the risk of infections (Luna and colleagues. JAMA Neurol 2020;77:184-191). The effect on immune cells also impairs the effectiveness of vaccines but the response will likely be sufficient in many cases (Kappos et al. Neurology 2015;84:872-879). Treatment would likely need to be stopped for a few months before getting the COVID vaccine.

Mavenclad: The remaining three medications in this list are cell-depleting, that is they reduce the number of immune cells as their mode of action. This depletion is less severe and less prolonged with Mavenclad. Immune cells reach their lowest point in the three months after the last dose (the drug is taken for two weeks a year). So it’s prudent to take some precautions against infections during that time period. A COVID vaccine could probably be administered during that off-drug period, although it should be noted that no vaccine studies have been published yet for Mavenclad.

Lemtrada: This medication has profound effects on the immune response and may not be the best option during the pandemic because of the infection risk and the delay to vaccination. Part of the immune response recovers quickly after the last infusion (the drug is administered for one treatment week per year), but some precautions against infections are advised for the six-month period after dosing. One report found that the vaccine response was sufficient if the person was inoculated at least six months after the last dose, although many people in that study waited 18 months or more (McCarthy and colleagues. Neurology 2020;10.1212).

Ocrevus: This medication is the most popular of the cell-depleting therapies. It has profound and sustained effects on the immune response and has been shown to be associated with a higher risk of poor outcomes with COVID (Simpson-Yap and colleagues. ECTRIMS 2020; SS02.04). So it’s important to take precautions during treatment to avoid infections.

There were two very timely bits of research published this year about Ocrevus. One issue with Ocrevus is the long time you need to spend in the infusion centre to receive the medication – about five or six hours for each six-monthly visit. A new study found that a more rapid infusion might shave off an hour or two from the visit – welcome news during a time of social distancing (Hartung and colleagues. Mult Scler Relat Disord 2020;46:102492). Secondly, a vaccine study was published during the summer which showed that there was a reduced response to vaccination (Bar-Or and colleagues. Neurology 2020;95:e1999-e2008). This means that people would probably need to be off treatment for six months before getting the COVID vaccine; in some cases, the time off therapy might have to be considerably longer. A further problem is what to do after vaccination. There is one case report of a person losing their vaccine response after taking Ocrevus (Rapisarda and colleagues. Clin Immunol 2020; epublished August 8, 2020). If this happened with the COVID vaccine, it would mean you would need to go back into the queue to get vaccinated again.

At the close of 2020, the general sentiment was that even during the pandemic, the top health priority must remain MS – controlling the disease process is more urgent than possibly contracting COVID. For some this will entail a higher-potency medication and the usual precautions – handwashing, maintaining physical distancing, wearing a mask in public and avoiding large gatherings of people.

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