COVID and MS – an update
A virtual congress for MS research, the Americas Committee for Treatment and Research in MS (ACTRIMS Forum), has just concluded and provided some updated information on the COVID-19 pandemic for people with multiple sclerosis.
A U.S. survey found that 88% of doctors and nurses feel they have a high or moderate risk of contracting COVID-19, compared to 59% of people with MS (Ben-Zacharia and colleagues. ACTRIMS 2021; P051). This likely reflects that healthcare workers must remain on the front lines whereas people with MS can often shelter at home. Extra precautions are especially recommended for older people with MS, those with disabilities and people with other medical conditions, such as chronic respiratory disease, heart and lung disease, and obesity. A total of 88% of people surveyed said they would line up for a vaccination when one becomes available.
The latest data suggest that people with MS do not have a higher risk of contracting COVID-19 than the general population, which may be due in part to the precautions taken. The North American CoViMS Registry of MS patients now lists over two thousand people who have developed COVID-19 (Salter and colleagues. ACTRIMS 2021; CE1.1). Overall, 11% have required hospitalization, 4.2% have required ICU admission and 3.0% have died. This death rate is similar to what has been seen in the general population. The death rate is 0% in people under age 35, 1.0% for people aged 35-44 years, 4.4% for those aged 55-64 years, 10.6% for those aged 65-74 years, and 21.1% for those older than age 75. For people who are not ambulatory (i.e. confined to a wheelchair or bed), the mortality rate is 17.8%. So people who are older and/or living with disabilities have a high risk of complications and death from COVID-19.
Some precautions are also needed for people taking an MS medication that suppresses the immune response, such as Ocrevus, Lemtrada, Mavenclad, Gilenya, Mayzent, Zeposia and Kesimpta. The current thinking is that treating your MS is more important than COVID concerns, so people are not being advised to stop taking their medication.
One concern, however, is Ocrevus. According to the most recent published report, there have been 307 cases of COVID-19 recorded in the safety database (Hughes and colleagues. Mult Scler Relat Disord 2021;49:102725). While almost one-half of the cases were mild, about one-third needed to be hospitalized, 22% developed severe or critical COVID disease and 5.5% of people died. So people taking Ocrevus appear to have a higher risk of a poor COVID outcome. Part of this phenomenon can be attributed to the patient population that is prescribed Ocrevus – often older, sicker people with progressive MS who are living with disabilities (Ocrevus is the only medication approved for primary-progressive MS). However, the results do suggest that people taking Ocrevus need to take extra precautions to protect themselves against infection.
The impact of a treatment on the immune system is also a consideration as COVID vaccination becomes available. The Canadian Network of MS Clinics recently updated its recommendations for people with MS (https://cnmsc.ca/). The group advises all people with MS to get vaccinated. Since some MS medications are known to reduce the immune response to vaccination, it will be especially important to receive the two doses that are required. (A one-dose vaccine is not yet available in Canada.) Two of the vaccines (Pfizer-BioNTech and Moderna) do not contain live virus so they cannot cause COVID-19 and should not worsen MS symptoms. The most recently-approved AstraZeneca vaccine does use a live virus (not the CoV-2 virus that causes COVID-19), which raises some concerns since other viruses (e.g. as influenza) can worsen MS. There is no information on the safety of the AstraZeneca virus in people with MS and no recommendations have been issued yet. But it may be that the Pfizer and Moderna vaccines would be better options for people with MS.
The current Canadian Network recommendations apply only to the Pfizer and Moderna vaccines. Most MS medications do not significantly affect the immune response, so it is safe to start or continue on these treatments during the pandemic. This applies to Copaxone (and generics), interferons (Avonex, Plegridy, Rebif, Betaseron/Extavia), Aubagio, Tecfidera and Tysabri.
No dosing changes are recommended for people taking Gilenya, Mayzent or Zeposia, in part because abruptly stopping a drug like Gilenya can cause an MS flare-up. It should be noted that this class of agents does lower the likelihood of response to vaccination (Metze and colleagues. CNS Neurosci Ther 2019;25:245-254. Kappos and colleagues. Neurology 2015;84:872-879. Olberg and colleagues. Eur J Neurol 2018;25:527-534). So these drugs may reduce “vaccine efficacy”. In the Moderna trial, only 5% of COVID cases occurred in people receiving vaccine compared to a placebo so the vaccine efficacy was 95% (Polack and colleagues. N Engl J Med 2020; epublished December 10, 2020). This 95% rate may be lower in people on treatment, but their immune response may still be sufficient to prevent severe COVID, which is probably more important.
For people on Mavenclad (taken two weeks per year) or Lemtrada (taken one week per year), it is best to allow the immune response to recover somewhat before getting vaccinated. In both cases, the recommendation is to wait about 6 months after your last dose before getting vaccinated. This means that there is a 6-month window before the next dose when the vaccine response will be optimal. Your doctor will advise you about the timing of your next dose to accommodate vaccination – a task that would be considerably easier if there were a reliable vaccine rollout schedule.
A treatment delay may also be advised for people taking Ocrevus or Kesimpta. Ocrevus is given once every 6 months and it is recommended to wait 4-6 months after the last dose before getting vaccinated. The vaccine response is known to be substantially impaired after 3 months (Bar-Or and colleagues. Neurology 2020;95:e1999-e2008) and likely for much longer, but it is believed that the response to vaccination will be sufficient (Bar-Or A. ACTRIMS 2021; CE1.2). As for Kesimpta, it is dosed once a month, so the recommendation is to skip a dose, get vaccinated, and resume treatment one month after the second vaccination shot. The second vaccine dose is supposed to be 21-28 days later (up to 12 weeks later for the AstraZeneca vaccine) so that would entail skipping a second dose of Kesimpta. However, the vaccine rollout has seen long delays for the second dose. In this scenario, it not clear if it is best to stay off therapy until you get the booster shot, or resume treatment in the interim and skip a second dose in the month when the booster shot is scheduled.
In all of these scenarios, your doctor or MS nurse will advise you on the best course of action based on your treatment, the severity of your MS and your personal circumstances. In the meantime, it is recommended to continue your MS medication as directed by your doctor until told otherwise.
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