RESUMO
BackgroundCD20 depletion is a highly-effective treatment for relapsing multiple sclerosis that maintains B cells at low levels through six monthly dosing of 600mg ocrelizumab. This dosing schedule is associated with inhibition of seroconversion following SARS-CoV-2 vaccination, in contrast to the high levels of seroconversion following treatment with alemtuzumab and cladribine tablets. A number of emerging reports suggest that repopulation of 1-3% B cells facilitates seroconversion after CD20-depletion. The frequency of this occurring following repeated ocrelizumab treatment, after other DMT, and after treatment cessation is largely unknown. MethodsRelapse data, lymphocyte and CD19 B cell numbers were extracted from phase II ocrelizumab extension study (NCT00676715) data supplied by the manufacturer via the Vivli Inc, trial data-request portal. Repopulation data of oral cladribine from the phase III CLARITY study (NCT00213135) was supplied by the European Medicines Agency; and the alemtuzumab phase III CARE-MS I (NCT00530348) and CARE-MS II (NCT00548405) trial data were supplied by the manufacturer via the clinicalstudydatarequest.com portal. ResultsOnly 3-5% of people with MS exhibit 1% B cells at 6 months after the last infusion following 3-4 cycles of ocrelizumab, compared to 50-55% at 9 months, and 85-90% at 12 months. During this time relapses occurred at consistent disease breakthrough rates compared to people during standard therapy. In contrast most people (90-100%) exhibited more than 1% B cells during treatment with either cladribine or alemtuzumab. ConclusionsFew people repopulate peripheral B cells with standard ocrelizumab dosing, however an extending the dosing interval by 3-6 months may allow many more people to potentially seroconvert in the relative absence of excess relapse-activity. Most people demonstrate B cell repletion within 3 months of the last treatment of alemtuzumab and cladribine. This may help protect against severe COVID-19.
RESUMO
ObjectiveTo investigate the effect of disease modifying therapies on serological response to SARS-CoV2 vaccines in people with multiple sclerosis Methods473 people with multiple sclerosis from 5 centres provided one or more dried blood spot samples and questionnaires about COVID-19. Information about disease and drug history was extracted from their medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2 receptor binding domain. Seropositivity was expressed according to validated cut-off indices. Antibody titers were partitioned into tertiles using data from people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (Univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of factors including vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response. ResultsCompared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, p<0.001) and fingolimod (odds ratio 0.41; 95% confidence interval 0.01-0.12) were associated with lower seroconversion following SARS-CoV2 vaccine. All other drug groups did not differ significantly from the untreated cohort. Time since last anti-CD20 treatment and total time on treatment were significantly related with response to vaccination. Vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. InterpretationSome disease modifying therapies carry a risk of attenuated response to SARS-CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group.
