April 13, 2022 | News | MS ResearchMS Treatments

Latest news on high-efficacy therapies for MS

Some concerns have been raised during the pandemic about the safety of high-efficacy disease-modifying therapies (DMTs) used to treat multiple sclerosis. The issue is that these medications, which alter the immune response, may make someone more susceptible to COVID-19 or may make COVID vaccination less effective. This was one of the topics addressed at the American Academy of Neurology (AAN) annual meeting, which was recently held in Seattle. [See also the previous report from this meeting, Update on oral and injectable therapies for MS, MSology, April 7, 2022.)

Hundreds of studies have now reported on the COVID vaccine response for people on MS drugs. A synthesis of these reports involving 1,239 people with MS was provided by researchers at Emory University in Atlanta (Gombolay and colleagues. AAN 2022; S5.007). A protective vaccine response was seen in 100% of people taking Tysabri and Lemtrada. A high proportion of people also responded well during treatment with Mavenclad (93%). About 70% responded to the vaccine during treatment with Gilenya, Mayzent, Zeposia or Ponvory. Only 39% of people taking Ocrevus had a response to vaccination.

A further concern is that people taking Ocrevus may not generate an adequate vaccine response even after a third (booster) dose (Repovic P. AAN 2022; P14.005). The study found that among 19 people who got a booster shot, only two mounted an adequate immune response to the vaccine. This suggests that people who keep taking Ocrevus will continue to have a higher risk of catching COVID even if they have multiple vaccinations and boosters.

People on other therapies, such as Tysabri and Tecfidera, appear to have a good response to the second vaccine dose (Repovic and colleagues. AAN 2022; S14.006). This shows the importance of completing the vaccine regimen. However, vaccine immunity appeared to wane about two months after the second dose, which is why a third booster shot has been recommended. The study did not look at how long protection lasts after a third shot or whether a fourth dose is advisable. (MSology will report on second boosters in a future issue.)

Few medications have been shown to be effective in people who develop secondary-progressive MS (SPMS), although the FDA may still approve them for use (despite an absence of studies). In Canada, Ocrevus is approved for use in relapsing-remitting MS and early primary-progressive MS; in the U.S. it is approved for relapsing MS, which can include early SPMS). A new study, called CONSONANCE, is now looking at the effectiveness of Ocrevus specifically in people with SPMS and PPMS (Comi and colleagues. AAN 2022). After one year, about 25% had worsening disability, which appears to be a slightly poorer result compared to what was seen in the PPMS trial of Ocrevus (Montalban and colleagues. N Engl J Med 2017;376:209-220). However, comparisons are difficult because how they measured disability differs in the two studies. CONSONANCE is ongoing and more will be known over the next few years.

The pandemic has seen an increase in the use of Tysabri, in part because this treatment has little impact on the vaccine response. The limiting factor, however, is that Tysabri is associated with a risk of PML (progressive multifocal leukoencephalopathy), a potentially fatal brain infection. One way to address the problem is to reduce the dose of Tysabri; this can be achieved by less frequent infusions (every 5 or 6 weeks instead of the usual 4 weeks). The NOVA study found that in most people, Tysabri is just as effective if it is taken every six weeks (Foley and colleagues. AAN 2022; S14.005). About 10% of people had worsening disability (compared to 8% with the usual dose), and about 2.8% had a relapse with the lower dose (vs. 2.1% with the usual dose). A separate analysis reported that less frequent dosing lowered the risk of PML (Zhovtis Ryerson and colleagues. AAN 2022; S13.010). A less frequent dosing regimen would also mean less hassle and expense for people due to fewer trips to the infusion centre.

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