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.
ABSTRACT
COVID-19 is a concern in people with multiple sclerosis (MS), mostly because of their long-term physical disabilities and immunomodulatory disease-modifying therapies (DMTs). In this community-based pro-spective longitudinal study, we have been monitoring a cohort of people with MS via the web-based platform of the UK MS Register since the start of the COVID-19 outbreak. We report our findings from 17/03/2020 to 15/01/ 2021. Out of 7344 participants, 883 (12%) have reported a selfdiagnosis of COVID-19 of whom 211 had a confirmed clinical or laboratory-based (n=114) diagnosis. No individual DMT increased the likelihood of contracting COVID-19 (with any of the diagnoses as the outcome). Gender (male: female, adjusted OR: 95% CI [0.94: 0.68'1.3]), web-based Expanded Disability Status Scale score (webEDSS;one-point increase, 0.92: 0.84'1.01), and MS duration (one-year increase, 1: 0.98'1.02) were not associated with contracting COVID-19. Younger age (one-year decrease, 1.04: 1.03'1.06), ethnicities other than white (1.95: 1.13'3.34), and relapsing-remitting MS (versus progressive, 1.72: 2.56'1.16) increased the likelihood of contracting COVID-19. Within a median (interquartile range) of 26 (0'72) days follow-up of participants with COVID-19 (n=532), 69% reported full recovery. A higher webEDSS (one-point increase, 0.84: 0.74'0.96) lowered the likelihood of full recovery. Overall, MS-specific factors do not predispose people with MS to contracting COVID-19, but physical disability can delay recovery.
ABSTRACT
Introduction: The COVID-19 pandemic potentially affected decisions around prescribing MS disease modifying therapies (DMTs) due to concerns about the safety of their use and disruptions to healthcare services. Objectives: To depict prescribing trends of MS DMTs during the COVID-19 outbreak in England and compare it to DMT use in other countries. Aims: To understand the effect of the pandemic on prescribing MS DMTs in England compared to other countries. Methods: National Health Service (NHS) England and NHS Improvement data on all issued MS DMT prescriptions during (1/03/2020 to 31/12/2020) and before (1/05/2019 to 29/02/2020) the outbreak was analysed. Interrupted time series analysis was used to depict the effect of the outbreak in England on prescribing trends of total and individual DMTs which will be presented as diagrams. Results: The outbreak had not affected the stationary trend of total DMT prescriptions;median (interquartile range) number of prescriptions per month was 20789 (2489) before and 21102 (1824) during the outbreak. COVID-19 significantly accelerated the pre-pandemic decline of alemtuzumab prescriptions, which dropped from 219 (85) to 63 (31) per month and remained low. The upward trend of cladribine and ocrelizumab prescriptions before the outbreak was interrupted by the first wave with their nadir during the first peak (April-May 2020). The monthly prescriptions of cladribine and ocrelizumab were 249 (47) and 641 (297) before the outbreak and dropped to 18 and 191 in May 2020, respectively. During the first 10 months of the pandemic, there was a 16% reduction in the number of MS patients treated with their firstever DMT from 3847 before to 3241 during the outbreak. These changes were mostly due to significant reductions in prescription of alemtuzumab, cladribine, and ocrelizumab especially during the peaks of the first and second (November 2020) waves of the outbreak which were not compensated by other DMTs. There was an increase in monthly natalizumab prescriptions as first-ever treatment from 32 (18) before to 61 (24) during the outbreak. Conclusion: These changes reflect recommendations of published guidelines on MS DMT use. Comparison of prescribing trends of MS DMTs in England with those from other countries highlights the interplay of different factors in altering DMT prescription practices. These observations have implications in population- based studies involving MS disease activity including the period of the COVID-19 pandemic.
ABSTRACT
Introduction: Ocrelizumab is licenced for a fixed treatment interval of six-monthly infusions to treat multiple sclerosis (MS). Disruption in clinical services, triggered by the COVID-19 pandemic, has led to extended intervals between treatments for some patients. Increasing evidence suggests that extended interval dosing of another anti-CD20 medicine, rituximab, maintains its efficacy while reducing the risks of immunosuppression. Objectives: To assess for evidence of clinical or radiological MS disease activity with extended interval dosing of ocrelizumab. To assess the rates of developing low immunoglobulin levels and timing of CD19+ B-cell count repopulation in a real-world clinical population. Methods: We audited the clinical, radiological and immunological data of 301 patients given ocrelizumab by our clinical services. Baseline demographics included age, sex, previous disease modifying treatment (DMT), phase of MS, and Expanded Disability Status Scale (EDSS). Dates of ocrelizumab administration were recorded. Disease activity was defined as on treatment EDSS progression, radiological activity or clinical relapse. All monitoring of CD19+ cell counts and immunoglobulin levels were recorded. Results: 301 participants were included in the analysis, among whom 62% were women, the mean age was 43 years and the median baseline EDSS was 3 (IQR 1-6). Half had previously used other DMTs and six (2%) had low immunoglobulin levels at baseline. They received 966 treatment cycles, of which 70 were administered with a treatment interval of 7-8 months, 45 with an interval of 8-9 months and 14 with an interval of more than nine months. In total, 131 (44%) participants had extended interval dosing. Disease activity included 33 (11%) with EDSS progression, 16 (5%) with new MRI lesions and 4 (1%) participants had clinical relapses. The odds ratio for rates of disease activity comparing extended to standard interval dosing was 0.97. Low immunoglobulin levels developed in 22 (7%). The longest recorded suppression of CD19+ B-cells was 405 days. We will present our mixed effects linear regression model of the factors that influence CD19+ count repopulation. Conclusions: This real-world data of extended interval dosing of ocrelizumab indicates no detrimental effect on short-term treatment efficacy. Our CD19+ dataset, could inform the design of a prospective trial of individualised retreatment intervals in ocrelizumab.