ABSTRACT
Background: The immune response to COVID-19 vaccines varies between people with multiple sclerosis (pwMS) receiving different disease-modifying therapies (DMTs). Objective(s): To assess the clinical effectiveness of COVID-19 vaccines in preventing infections and their severe outcomes among pwMS receiving DMTs. Method(s): National Health Service England and United Kingdom Health and Security Agency datasets were used to analyse data on all COVID-19 tests, outcomes, and vaccines among the total population of pwMS receiving DMTs in England. Publicly available data were used for the general population. Monthly COVID- 19 incidence was compared between pwMS receiving DMTs and the general population. COVID-19 related hospitalisation and in-hospital mortality following full vaccination, with at least two doses, were compared between pwMS receiving different DMTs. These results are from March 2020 to December 2021 and will be updated. Result(s): A mean (standard deviation) of 44,170 (4,951) pwMS taking DMTs per month were included. Monthly COVID-19 incidence among pwMS receiving all DMTs, except for fingolimod and ocrelizumab, followed the pattern among the general population, before and after mass vaccination. COVID-19 incidence in pwMS on fingolimod and ocrelizumab compared to the general population increased despite mass vaccination (incidence rate ratio [95% confidence interval]: from 0.50 [0.37-0.66] to 0.91 [0.80-1.03] for fingolimod, and from 1.01 [0.79-1.26] to 1.57 [1.44-1.72] for ocrelizumab, in January 2021 [when vaccination started] to December 2021 [when over 80% of the populations were vaccinated]). COVID-19 related hospitalisation (per 10,000 people) was higher among vaccinated pwMS on fingolimod (94) and ocrelizumab (140) than other DMTs (ranging from 0 to 37). COVID-19 related in-hospital mortality (per 1,000 people) was 0.3 for fingolimod, 2 for ocrelizumab, and 0-1.2 for other DMTs. Conclusion(s): PwMS taking ocrelizumab and fingolimod are at increased risk of contracting COVID-19 and hospitalisation due to COVID-19 compared to the general population and other DMTs using current vaccination protocols.
ABSTRACT
Objective: To compare the risk of SARS-CoV-2 infection before and after mass vaccination among patients with multiple sclerosis (pwMS) taking different disease-modifying therapies (DMTs) compared to the general population (GP). Background: Real-world data in the GP show that SARS-CoV-2 vaccines are effective in preventing infections, but it is still unclear whether vaccination offers the same level of protection for pwMS taking immunomodulatory DMTs. Design/Methods: National Health Service (NHS) England and NHS Improvement (NHSE/I) hold prescribing data on all MS DMTs in England. Public Health England (PHE) collected data on all SARS-CoV-2 tests in England. Datasets of NHE/I and PHE were merged to estimate the monthly rates of SARS-CoV-2 infections in the entire population of pwMS taking DMTs in England. Publicly available data were used for the same analysis in the GP. The relative risk (RR) of infection in pwMS taking DMTs compared to the GP was calculated during two waves of the pandemic: before (November 2020-January 2021) and after (July-September 2021) mass vaccination. Results: All 42,402 pwMS taking DMTs in England were included. A total of 28,113 (66.3%) patients were tested for SARS-CoV-2 out of whom 4,104 (14.6%) tested positive. Pre-vaccination, the RR (95%CI) of infection was beta-interferon: 0.75(0.65-0.87), cladribine: 0.93(0.75-1.14), dimethyl fumarate: 1.15(1.05-1.25), fingolimod: 0.88(0.76-1.02), glatiramer acetate: 1.05(0.93-1.19), natalizumab: 1.08(0.96-1.21), ocrelizumab: 1.20(1.07-1.34), teriflunomide 0.79(0.63-0.99). Post-vaccination, it was beta-interferon: 0.73(0.63-0.85), cladribine: 1.21(1.02-1.45), dimethyl fumarate: 1.34(1.24-1.45), fingolimod: 1.63(1.47-1.82), glatiramer acetate: 0.85(0.74-0.98), natalizumab: 1.22(1.10-1.36), ocrelizumab: 2.18(2-2.36), teriflunomide: 1.04 (0.85-1.27). Conclusions: The risk of SARS-CoV-2 infection in patients taking ocrelizumab and fingolimod substantially increased compared to the general population following vaccination which agrees with the suppressed humoral immune response observed with these DMTs. The changes associated with other DMTs are less clear. Further analysis of data collected longitudinally over a longer period will reveal their impact on the effectiveness of SARS-CoV-2 vaccines.