Impact of Multiple Sclerosis Disease-Modifying Therapies on Effectiveness of SARS-Cov-2 Vaccines: A Longitudinal Total Population Study of National Health Service (NHS) England
Afagh Garjani1,2, Sameer Patel3, Graham R Law4, Dhiren Bharkhada5, Waqar Rashid6, Alasdair Coles7, Nikos Evangelou1,2
1Clinical Neurology, Nottingham University Hospitals NHS Trust, 2Mental Health and Clinical Neurosciences Academic Unit, School of Medicine, University of Nottingham, 3Direct Commissioning, National Health Services Arden and Greater East Midlands Commissioning Support Unit, 4School of Health and Social Care, University of Lincoln, 5National Health Services England and National Health Services Improvement Midlands, 6Neurology Department, St George's University Hospitals NHS Foundation Trust, 7Department of Clinical Neuroscience, University of Cambridge
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.