ABSTRACT
Introduction: Multiple sclerosis (MS), an immune-mediated neurodegenerative disorder, is commonly treated with diseasemodifying therapies (DMTs). DMTs affect the immune system, and some are associated with an increased risk of infections, potentially rendering MS patients vulnerable during the COVID- 19 pandemic. Objectives/aims: To determine the proportion of MS patients followed at Karolinska University Hospital (KS) that tested positive with COVID-19 between September 1st 2019, and September 1st 2021, determining proportion of MS patients that tested positive with COVID-19 depending on MS treatment, and estimating risk of contracting COVID-19 and risk of severe COVID-19 illness (hospitalization), depending on MS treatment. Method(s): A retrospective chart review was performed of all living MS-patients included in the Swedish MS registry and cared for at KS. Clinicodemographic, DMT and COVID-19 variables were recorded. DMTs were pooled into first-line (teriflunomide, interferons, glatiramer, fingolimod, siponimod and dimethylfumarate) and second-line (natalizumab, cladribine, ocrelizumab and haematopoietic stem cell transplantation) treatments. Rituximab was analysed seperately. Risk of contracting COVID-19 and risk of severe illness (hospitalization) was analysed with Chi-squared test. P-values of <0.05 were considered significant. P-values were adjusted according to Holm. Statistical analyses were performed using R version 4.1.1. Result(s): Of 1120 patients, 177 COVID-19 infections were identified (15.8%). Among treatments, rituximab accounted for the greatest proportion of infections (n=74, 41.8%), followed by no treatment (n=39, 22%) and dimethylfumarate (n=22, 12.4%). Compared to no treatment, rituximab (RR=3,36;95% CI 2.34- 4.83, p=0.001,padj = 0.001), pooled first-line treatments (RR=3.55;95% CI 2.43-5.20,p=<0.001,padj=<0.001) and second-line treatments (RR=2.65;95% CI 1.43-4.88,p=0.002,padj=0.013) were associated with increased risk of contracting COVID-19. Rituximab was also associated with an increased risk of hospitalization (RR=2.29;95% CI 1.03-5.13,p=0.037,padj= 0.112), although non-significant after adjustment. Conclusion(s): This project confirms reports of an increased susceptibility for COVID-19 while treated with common DMTs, as well as an increased risk of hospitalization while treated with rituximab. However, some results are not significant after adjustment and should be interpreted with caution.
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.