Doctors and patients alike are questioning the effects and effectiveness of vaccinations in people with multiple sclerosis (MS), particularly in the context of the ongoing COVID-19 pandemic. “In an ever-changing world, where a pandemic is likely to occur for the foreseeable future, it is important to assess the impact of Common [nonlive] Vaccinations for patients taking disease-modifying therapies, ”explained Dr. Maria Rivas, Chief Medical Officer of EMD Serono. New findings presented at the ACTRIMS Forum 2021 indicate that patients with relapsing MS treated with MAVENCLAD® (cladribine) tablets had protective antibody responses with common vaccines.
MAVENCLAD, approved by the US Food and Drug Administration in March 2019, is the only short-term oral therapy for the treatment of relapsing remitting MS and active secondary progressive MS. Two studies, the MAVENCLAD-MS study and the CLOCK-MS sub-study, showed persistent or elevated antibody levels regardless of lymphocyte count in patients with MS treated with MAVENCLAD.
MAGNIFY-MS, a retrospective study, showed that patients with MS after seasonal influenza and varicella zoster vaccines can demonstrate a protective antibody response for at least 6 months, regardless of the timing of the vaccine in relation to the MAVENCLAD dosage. In comparison, the CLOCK-MS vaccine sub-study suggested protection against influenza antibodies in patients with MS taking this therapy 4 weeks after vaccination.
We interviewed Klaus Schmierer, MBBS, Professor of Neurology at Queen Mary University in London and the Royal London Hospital, to learn more about the possible antibody response in this population and the clinical implications of the current COVID-19 pandemic.
“Understanding the effectiveness of vaccines in MS patients is particularly important given the current pandemic and the increasing availability of COVID-19 vaccines,” he said.
Can you summarize your research?
Data shared during ACTRIMS suggest that people with recurrent multiple sclerosis (pwRMS) receiving MAVENCLAD are able to have an effective response to seasonal influenza and varicella-zoster vaccinations. In the MAGNIFY-MS study, those vaccinated against varicella zoster virus (VZV; n = 3) before or after initial seasonal influenza (n = 12) after initial treatment with MAVENCLAD retained effective antibody titers against these viruses. In 9 [out of 12 patients] After a seasonal influenza vaccination, the antibody titers even increased by a factor of 2 to 4 for at least 6 months. These increased antibody titers appeared to be independent of the time of vaccination and were observed in some pwRMS whose lymphocyte count was below the lower normal limit (as a result the MAVENCLAD treatment).
Additionally in a [substudy] In the CLOCK-MS study, those vaccinated against seasonal influenza after at least 1 dose of MAVENCLAD (n = 3) also had protective antibody titers 4 weeks after vaccination. In this small sub-study, 2 people had a vaccination and an antibody response 2 to 4 months before vaccination despite lymphopenia after MAVENCLAD treatment.
What are the relevant clinical implications for the results of your studies?
These data provide preliminary evidence that treatment with MAVENCLAD does not affect antibody levels, suggesting that pwRMS taking MAVENCLAD is still able to generate and maintain effective vaccine responses. For pwRMS starting MAVENCLAD treatment, this suggests that anti-SARS-CoV-2 antibody levels are unlikely to be affected by treatment and they should be vaccinated approximately 1 month before starting MAVENCLAD treatment receive. For those already receiving MAVENCLAD treatment, the new data provide assurance that they will be able to produce an effective immune response against SARS-CoV-2 after vaccination.
What do your results suggest associations between MAVENCLAD, MS pathology, and protective antibody responses?
However, given the preliminary nature of these data, which are based on a limited sample, the results provide assurance that there is only limited overlap between the MAVENCLAD-modulated cell populations that underpin its action in pwRMS and the cell populations that support viral immune responses Trigger pathogens.
What is the impact of your research on the current COVID-19 pandemic and COVID-19 vaccines?
Understanding the effectiveness of the vaccine in [patients with MS] is obviously particularly important in the current fight against COVID-19 and the growing availability of effective vaccines. Since immunity to SARS-CoV-2 is not only dependent on antibodies, but also on T cells, it should be remembered [that] MAVENCLAD only consumes CD8 + T cells by around 20% to 30%, which in turn suggests that the effective immune response is hardly disturbed.
What results suggest the mechanisms of action of MAVENCLAD in MS?
Although we already had a good conceptual and evidence-based understanding of how MAVENCLAD works in pwRMS, we now have evidence [that] The vaccine responses seem to be rather unchanged by the treatment. MAVENCLAD exerts cytotoxic effects on B-cell and, to a lesser extent, T-cell subsets through semi-selective apoptosis, effectively disrupting the cascade of harmful immune events central to MS.
What remaining research is needed in this area?
Larger case numbers and data on specific immune responses to the SARS-CoV-2 vaccination are important to better understand the favorable safety profile of MAVENCLAD during the pandemic.
How would the results affect current practice among doctors treating patients with MS?
For people starting MAVENCLAD, this means that anti-SARS-CoV-2 antibody levels are unlikely to be affected by treatment, and they should safely receive vaccination approximately 1 month before starting MAVENCLAD. For people who are already receiving MAVENCLAD, the new data offer the security that they will be able to generate an effective immune response against SARS-CoV-2 after vaccination. Given the new data, it seems warranted to shorten the three-month break between completing a MAVENCLAD course and vaccination to 4 to 6 weeks.
New data presented at the ACTRIMS Forum 2021 indicate that MAVENCLAD®-treated RMS patients show a protective antibody response to a popular vaccine [news release]. EMD Serono; February 25, 2021. http://media.emdserono.com/2021-02-25-New-Data-Presented-at-ACTRIMS-Forum-2021-Indicate-MAVENCLAD-R-treated-RMS-Patients-Mount-Protective -Antibody-Response-to-Common-Vaccines. Accessed February 26, 2021.