ABSTRACT
Background: People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). Objective(s): To assess characteristics of COVID-19 severity in an international sample of people with MS, including hospitalisation, ICU admission, requiring artificial ventilation, and death. Method(s): Data from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/ confirmed COVID-19 using multilevel mixed-effects logistic regression. Result(s): 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19. Older age, progressive MS-phenotype, and higher disability associated with worse COVID-19 outcomes. Ocrelizumab and rituximab associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38;aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36;aOR=4.32, 95%CI=2.27-8.23) vs pooled-other-DMTs but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Similar associations seen compared to dimethyl fumarate and to natalizumab. No associations observed between DMTs and death. Conclusion(s): Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab and ocrelizumab with worse COVID-19, suggesting their use may be a risk factor for more severe COVID-19.
ABSTRACT
Background: As the COVID-19 pandemic continues, evidencebased clinical guidance for managing the care of people with multiple sclerosis (MS) is an ongoing concern. In recent months, data from cohorts of people with MS has indicated that certain demographic and clinical characteristics, including use of some disease- modifying therapies (DMTs), leads to worse outcomes from SARS-CoV-2 infection. The COVID-19 in MS global data sharing initiative, which now includes over 4,500 confirmed COVID- 19 cases in people with MS, gives the opportunity to corroborate previous findings with greater certainty. Methods: Clinician-reported data from 32 countries were aggregated into a dataset of 5,543 patients who had suspected or confirmed COVID-19. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes. These outcomes (hospitalisation, admission to ICU, requiring artificial ventilation, and death) were assessed in patients with suspected/ confirmed COVID-19 using multilevel mixed-effects logistic regression. All models were corrected for age, sex, EDSS, and MS type. DMTs were individually compared to glatiramer acetate (GA), as well as to pooled other DMTs and natalizumab. Results: Of 5,543 patients in the clinician-reported dataset, 909 with suspected and 4,634 with confirmed COVID-19 were included in the analysis. Previous demographic findings were confirmed: male sex, older age, progressive MS, and higher disability were associated with worse outcomes from SARS-CoV-2 infection. Use of anti-CD20 DMTs (ocrelizumab and rituximab) was associated with worse COVID-19 outcomes. Compared to GA, ocrelizumab and rituximab were associated with increased risk of hospitalisation (aOR=1.61(95%CI=1.06-2.43);aOR=2.42(95%CI=1.54-3.81) and ICU admission (aOR=3.13(95%CI=1.22-8.00);aOR=4.46 (95%CI=1.64-12.09)). Rituximab was associated with increased risk of artificial ventilation (aOR=3.57(95%CI=1.38-9.20));ocrelizumab showed a positive trend (aOR=1.86(95%CI=0.76-4.55). Rituximab showed a positive trend with increased risk of death (aOR=2.74(95%CI=0.68-11.09). Associations persisted on restriction to confirmed COVID-19 cases. Conclusions: Analysing the largest international real world dataset of people with MS who have suspected or confirmed COVID- 19 confirms previous findings that male sex, older age, progressive MS, higher disability, the use of anti-CD20 medication (ocrelizumab and rituximab) are associated with worse COVID-19 outcomes.
ABSTRACT
Introduction: This study group has previously demonstrated a significantly increased risk of hospitalisation for COVID-19 amongst rituximab-treated patients in Sweden. Objective: The primary objective of this study was to analyse the association between multiple sclerosis (MS) disease modifying therapy (DMT) exposure and hospitalisation in patients infected with COVID-19. Methods: Nationwide registry-based cohort study. Associations between MS DMT exposure and COVID-19 hospitalisation were analysed using univariable and multivariable clustered propensity score weighted logistic regression, where the models were clustered on the individual patients to control for patients contributing multiple COVID-19 episodes. Results: As of 4th June 2021, a total of 950 reported COVID-19 cases had been recorded in MS patients in the Swedish MS registry. Of these, 697 (73.4%) had confirmed COVID-19. The mean (SD) age at infection was 44.4 years (11.2). Of the 697 confirmed infections 117 (16.8%) required hospitalisation. A total of 73 of the 308 confirmed COVID-19 patients on rituximab at baseline (23.7%) required hospitalisation, compared to a rate of 11.3% for all other DMTs combined. Rituximab in confirmed COVID-19 patients was associated with 3.10 times the odds of hospitalisation relative to any other DMT combined (adjusted Odds Ratio 3.10;95% CI 1.68-5.74), controlling for age, sex, EDSS and MS course and duration of treatment at baseline. There was no difference in the rate of hospitalisation between any of the non-rituximab DMTs when compared to one another. Amongst rituximab treated patients only, the duration of rituximab at baseline was not associated with a changed risk of hospitalisation. Conclusions: Rituximab treatment, known to increase the risk of severe infections in general, also confers such a risk for MS patients with COVID-19, in comparison with other MS DMTs.