Associations of DMT therapies with COVID-19 severity in multiple sclerosis: an international cohort study

Abstract

Background: MRI scanning tends to reflect the history of acute inflammation rather than the stage of progressive disease, and hence is poorly correlated with EDSS scores. Some variants of visual function testing may be more related to progressive disease. We explore two new forms here. Objective: To examine the diagnostic power of two new forms of rapid objective pupil perimetry in patients with multiple sclerosis (MS). We compared persons with different EDSS scores, and those with and without Optic Neuritis (ON) as a marker for acute inflammation in the visual system. Methods: We tested 44 MS patients, 60.7 ± 10.1 y, and 40 normal controls 60.2 ± 12.5 y (mean ± SD). We used the W12 and W20 test variants of the Konan objectiveFIELD Analyser. These presented 12 or 20 stimuli/eye across ±30 degrees, testing both eyes concurrently in 80 seconds. We calculated Receiver Operator Characteristic %AUCs for the mean of the worst 4 per-region response delay asymmetries for different EDSS groups. Results: %AUCs increased across our 3 EDSS groups: <2.5; 2.5 to <4.5; >=4.5, reaching 94.4 ± 3.16 for EDSS-3. W20 was better for EDSS-1 patients: 81.1 ± 6.69 vs. 75.0 ± 8.33. A sub-analysis compared subjects who had experienced ON (N=30) and those who had not (no-ON, N=14). %AUC for NoON and ON were: W12, 86.9 ± 5.24 vs 86.0 ± 4.46; and W20, 87.2 ± 5.45 vs 86.8 ± 4.36. Conclusion: The relatively large %AUCs for EDSS-1 suggest an ability to monitor early-stage disease. The similarity of ON vs. noON results suggest that the tests are more biased towards disease progression rather than the history of acute inflammation , like our earlier data: Background: People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immu-nosuppressive disease-modifying therapies (DMTs). Objective: To assess characteristics of COVID-19 severity in an international sample of people with MS, including hospitalisation, ICU admission, requiring artificial ventilation , and death. Methods: Data from 12 data-sources in 28 countries were aggre-gated. 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 sus-pected/confirmed COVID-19 using multilevel mixed-effects logistic regression. Results: 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 natali-zumab. No associations observed between DMTs and death. Conclusion: 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. Background: Modifiable lifestyle factors, including diet, have been shown to affect clinical outcomes in multiple sclerosis (MS). Objective: This study assessed the prospective relationships between diet, and disability, fatigue, and depression-risk in people with MS. Methods: Participants from the HOLISM international cohort were assessed over 2.5-years' follow-up. Diet was assessed using the modified Diet Habits Questionnaire (DHQ).