ABSTRACT
Introduction: People with multiple sclerosis (PwMS) treated with anti-CD20 therapies and fingolimod are less likely to successfully produce a humoral response to COVID-19 vaccines 1 and 2. Objective(s): To measure the humoral and/or cellular response to COVID-19 booster vaccinations in a cohort of PwMS who were previously seronegative after their initial COVID vaccine course. Aim(s): To determine whether there is a benefit of COVID-19 booster vaccinations for people with MS who are known to have had an attenuated response to initial vaccines. Method(s): We studied a cohort of PwMS all of whom were seronegative for anti-SARS-CoV-2 spike protein IgG after the 1st and 2nd COVID-19 vaccines, including PwMS treated with ocrelizumab (n=53), fingolimod (n=15), other DMTs (n=9) and no DMT (n=2). Dried blood spot +/- whole blood samples were obtained from participants at 2-8 weeks after their 3rd (n=79) and 4th (n=40) COVID-19 vaccines. Samples were used to measure anti-SARS-CoV-2 spike protein IgG (ELISA) and T-cell response (IFN-g release assay measured on whole blood). Result(s): Overall 27/79 (34%) who were seronegative after COVID vaccine 2 seroconverted after vaccine 3. Seroconversion rates were 17% for PwMS treated with ocrelizumab, 47% for fingolimod and 100% for other DMTs. A further 2/30 (7%) of those who remained seronegative after vaccine 3 seroconverted after vaccine 4. Anti-SARS-CoV-2 T-cell responses were measurable in 26/40 (65%) after vaccine 3 and 13/19 (68%) after vaccine 4 but were conspicuously absent in people treated with fingolimod. Overall, 75% of participants showed either humoral or cellular response after receiving 4 COVID vaccinations. PwMS with laboratory evidence of prior COVID-19 infection had higher measurable T-cell responses. Conclusion(s): Booster vaccinations for COVID-19 are associated with incremental benefits in measurable immunity in those with attenuated responses to the initial vaccine course. Overall, three quarters of those who were seronegative after COVID vaccines 1 & 2 had a measurable immune response after COVID vaccine 4. This data supports the use of booster vaccinations in pwMS at risk of attenuated vaccine response.
ABSTRACT
Introduction: Annualized relapse rate (ARR) is routinely used as the primary outcome measure in MS clinical trials and is important in service planning. Most disease modifying therapies (DMTs) are prescribed in people with relapsing remitting MS (RRMS) and the ARR of secondary progressive MS (SPMS) and RRMS has not been accurately described in a modern clinical cohort. Recent treatment advances have led to more people with MS being effectively managed with early intensive medications, reducing the frequency of reported relapse rates in RRMS. Aims: To facilitate MS service planning and improve the feasibility estimations for clinical trials in MS. Objectives: To establish a current estimated ARR observed in a contemporary MS clinic in the UK. Methods: A retrospective cohort study examined all relapses recorded in a university hospital serving the local MS population. A random sample of 812 MS Nottingham patients from our database were reviewed for reported relapses from April 1 to June 30, 2020 and the same period in 2019, to account for potential reporting bias during the COVID-19 pandemic. The MS clinical database, nurse and admin registries, medical and telephone records for those individuals were reviewed at the end of 2020 for possible relapses during the study periods. Results: Among MS patients followed up in clinic, 60% had RRMS, 23% SPMS, 14% PPMS and 4% CIS. We identified 30 clinician confirmed relapses during the study period equating to an ARR of 0.15 for all MS patients treated and untreated. 70% of RRMS and 18% of SPMS were on DMTs. The ARR in RRMS and SPMS were the same (0.15). Validating this with pre-pandemic 2019 records found similar results. Conclusions: This contemporary UK-based study reports halving of the ARR previously reported in 2 similar studies in the UK 8 years ago. While relapse prevention has been achieved in RRMS, there appears to be significant unappreciated relapses occurring in the SPMS (pre-siponimod) cohort.