Background Contradicting assumptions have been made about the effectiveness of SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) receiving immunomodulatory disease-modifying therapies (DMTs) based on the quantification of humoral and cellular immune responses. This study aimed to understand changes in the risk of SARS-CoV-2 infection among the total population of patients receiving MS DMTs in England following mass vaccination. Methods This is a retrospective analysis of national data collected prospectively and longitudinally. National Health Service (NHS) England and NHS Improvement (NHSE/I) hold prescribing data on all commissioned MS DMTs in England. United Kingdom Health Security Agency (UKHSA) has been collecting data on all registered SARS-CoV-2 test results, including polymerase chain reaction and rapid antigen tests. All patients receiving MS DMTs were identified using NHSE/I datasets. All patients receiving MS DMTs with SARS-CoV-2 infection (i.e., positive test) from March 2020 to August 2021 were identified by merging NHSE/I and UKHSA datasets. Similar data for the general population were captured using publicly available datasets of the United Kingdom government. The incidence rate ratios (IRR) of SARS-CoV-2 infection among patients receiving MS DMTs compared to the general population during the pre-vaccination (November 2020 to January 2021) and post-vaccination (June to August 2021) periods were calculated. Results A mean (standard deviation) of 41,208 (4,301) patients received an MS DMT in England during each month from March 2020 to August 2021. The IRR (95% confidence interval) of infection in patients taking ocrelizumab versus the general population increased from 1.13 (0.97-1.31) during the pre-vaccination period to 1.79 (1.57-2.03) during the post-vaccination period. For patients on fingolimod, it increased from 0.87 (0.73-1.02) to 1.40 (1.20-1.63) during the same periods. There were no significant changes for patients on other MS DMTs. Conclusion SARS-CoV-2 vaccines offer less protection against infection to patients taking ocrelizumab or fingolimod, who have an impaired immune response to vaccines, than the general population. These findings will have implications for vaccination policies.

This study aimed to understand changes in the risk of SARS-CoV-2 infection among all people with multiple sclerosis (MS) receiving immunomodulatory disease-modifying therapies (DMTs) in England, compared to the general population, following mass vaccination. Longitudinal data collected by the National Health Service (NHS) England on all MS DMT prescriptions and the UK Health Security Agency on all registered SARS-CoV-2 test results were analysed. The incidence rate ratio of SARS-CoV-2 infection among people with MS taking DMTs compared to the general population was calculated before (November 2020-January 2021) and after (July-August 2021) mass vaccination. Risk of SARS-CoV-2 infection among people on ocrelizumab or fingolimod compared to the general population increased following liberalisation of COVID-19 restrictions (during March-July 2021) despite mass vaccination. No changes were found with other DMTs. These findings converge with the impaired immune response to vaccines observed with ocrelizumab and fingolimod.

Studies have measured the immunological response to COVID-19 vaccines among multiple sclerosis (MS) patients receiving disease-modifying therapies (DMTs), but its clinical relevance is unclear. We aim to understand how MS DMTs affect the clinical effectiveness of COVID-19 vaccines.We analysed data of all MS patients receiving DMTs in England from December-2020 to January-2022. We calculated post-vaccination (≥14 days following second dose) incidence of infection (positive COVID-19 test) and COVID-19 related hospitalisation (within 0-28 days of a positive test and >1 day). We used merged datasets of the NHS England and NHS Improvement and the UK Health Security Agency.A total of 38,039 MS patients on DMTs (90%) had at least two COVID-19 vaccines. Post-vaccination incidence of infection was 24% (859/3624) for ocrelizumab, 22% (819/3797) for fingolimod, and ranged from 11% to 16% for other DMTs. Hospitalisation rate among infected patients was 7% (n=61) for ocreli- zumab, 4% (n=33) for fingolimod, and ranged from 1% to 4% for other DMTs.Patients on ocrelizumab have higher rates of COVID-19 related infection and hospitalisation compared to other DMTs using current vaccination protocols. Patients on fingolimod also have higher rates of post- vaccination infection but their hospitalisation rate is similar to other DMTs. Further analysis including demo- graphics, booster vaccines, unvaccinated, and mortality is ongoing to be presented at the meeting.