Physicians and patients alike question the impact and efficacy of vaccinations among individuals with multiple sclerosis (MS), especially in the context of the ongoing COVID-19 pandemic. “In an ever-changing world where a pandemic will likely be present for the foreseeable future, it is critical to assess the impact of common [nonlive] vaccinations in those taking disease-modifying therapies,“ stated Maria Rivas, MD, Chief Medical Officer, EMD Serono. New evidence presented at ACTRIMS Forum 2021 suggested that patients with relapsing MS who are being treated with MAVENCLAD® (cladribine) tablets mounted protective antibody responses with common vaccines.

MAVENCLAD, approved by the US Food and Drug Administration in March 2019, is the only short-course oral therapy for relapsing remitting MS and active secondary progressive MS. Two studies, the MAGNIFY-MS study and the CLOCK-MS substudy, showed sustained or elevated antibody levels independent of lymphocyte counts in patients with MS treated with MAVENCLAD.

MAGNIFY-MS, a retrospective study, indicated that patients with MS may mount a protective antibody response for a minimum of 6 months after seasonal influenza and varicella zoster vaccines, independent of timing of the vaccine relative to MAVENCLAD dosing. Comparatively, the CLOCK-MS vaccine substudy suggested protective influenza antibody levels at 4 weeks following vaccination in patients with MS taking this therapy.


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We interviewed Klaus Schmierer, MBBS, Professor of Neurology at Queen Mary University of London and The Royal London Hospital, to learn more about the potential antibody response in this population, and the clinical implications related to the current COVID-19 pandemic.

“Understanding vaccine efficacy in MS patients,” he stated, “is particularly important in the face of the current pandemic and the growing availability of COVID-19 vaccines.”

Could you summarize your research?

The data shared during ACTRIMS suggest people with relapsing multiple sclerosis (pwRMS) receiving MAVENCLAD are able to mount an effective response to seasonal influenza and varicella zoster vaccination. In the MAGNIFY-MS study, those who were vaccinated against varicella zoster virus (VZV; n=3) before, or seasonal influenza (n=12) after, a first course of MAVENCLAD retained effective antibody titers against those viruses. In 9 [out of 12 patients] receiving seasonal influenza vaccination, antibody titers even increased by a factor of 2 to 4, for at least 6 months. These increased antibody titers appeared independent of the timing of vaccination and were observed in some pwRMS whose lymphocyte count was below the lower limit of normal (as a result of MAVENCLAD treatment).

Additionally, in a [substudy] of the CLOCK-MS study, those who were vaccinated against seasonal influenza after having at least 1 dose of MAVENCLAD (n=3) also had protective antibody titers 4 weeks after vaccination. In this small substudy, 2 individuals had vaccination and antibody response despite experiencing lymphopenia following MAVENCLAD treatment 2 to 4 months prior to vaccination.

What are the relevant clinical implications for your studies’ findings?

These data provide preliminary evidence that treatment with MAVENCLAD does not affect antibody levels, suggesting that pwRMS taking MAVENCLAD remain able to mount and maintain effective vaccine responses. For pwRMS starting MAVENCLAD treatment, this suggests anti-SARS-CoV-2 antibody levels are unlikely to be affected by the treatment, and they should safely receive the vaccination approximately 1 month before starting MAVENCLAD. For those already receiving MAVENCLAD treatment, the new data provide reassurance they will be able to produce an effective immune response against SARS-CoV-2 following vaccination.

What do your findings suggest about associations between MAVENCLAD, MS pathology, and protective antibody responses? 

Bearing in mind the preliminary nature of these data based on a limited sample, the findings nevertheless provide reassurance there is only limited overlap between the cell populations modulated by MAVENCLAD, underpinning its effect in pwRMS, and the cell populations driving immune responses against viral pathogens.

What implications does your research have regarding the current COVID-19 pandemic and COVID-19 vaccines?

Understanding vaccine efficacy in [patients with MS] is obviously particularly important in the current fight against COVID-19 and the growing availability of effective vaccines. Given immunity against SARS-CoV-2 is not only antibody but also T cell dependent, it is worth remembering [that] MAVENCLAD depletes CD8+ T cells by only about 20% to 30%, again suggesting little interference with the effective immune response.

What have findings suggested regarding MAVENCLAD’s mechanisms of action in MS?

Although we already had a good conceptual and evidence-based understanding of how MAVENCLAD works in pwRMS, we now have evidence [that] vaccine responses appear to be rather unaltered by the treatment. MAVENCLAD exerts cytotoxic effects on B cell and – to a lesser degree – T cell subsets through semiselective apoptosis, thereby effectively interrupting the cascade of damaging immune events central to MS.

What remaining research is needed in this area?

Larger case numbers and data on specific immune responses to SARS-CoV-2 vaccination will be important to better understand the favorable safety profile of MAVENCLAD during the pandemic.

How would findings affect current practice among physicians treating patients with MS?

For people starting MAVENCLAD, this suggests anti-SARS-CoV-2 antibody levels are unlikely to be affected by the treatment, and they should safely receive the vaccination approximately 1 month before starting MAVENCLAD. For individuals already receiving MAVENCLAD, the new data provide reassurance they will be able to produce an effective immune response against SARS-CoV-2 following vaccination. In light of the new data, it appears justified to consider reducing the 3-month gap between completing a course of MAVENCLAD and vaccination to 4 to 6 weeks.

Reference

New data presented at ACTRIMS Forum 2021 indicate MAVENCLAD®-treated RMS patients mount protective antibody response to common 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.