Updated Results of the COVID-19 in MS Global Data Sharing Initiative

Abstract

Background and ObjectivesCertain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed.MethodsClinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab.ResultsOf 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1–7] and 7% [95% CI 4–11]), ICU/artificial ventilation (2% [95% CI 0–4] and 4% [95% CI 2–6]), and death (1% [95% CI 0–2] and 2% [95% CI 1–4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2–8), 3% (95% CI 1–5), and 1% (95% CI 0–3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19.DiscussionAnalyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.

COVID-19 Infection in Fingolimod- or Siponimod-Treated Patients

“…To date, large ongoing registries of COVID-19 in people living with MS have not shown an increase or decrease in morbidity or mortality with the administration of modulators. 3-8,20 The data presented herein are consistent with the registry observations 23 ; the risk of more severe COVID-19 symptoms in patients receiving fingolimod seems to be similar to that reported in the general population and the MS population with COVID-19. For siponimod, the less number of cases reported coupled with insufficient information precludes meaningful conclusions.…”

“…The disease course of COVID-19 in people living with MS receiving either fingolimod or siponimod seems to be similar to those reported in the general population 15 and in the overall MS population affected with COVID-19. 3-7 The mean age of patients with COVID-19 receiving fingolimod was 44 years and that of patients receiving siponimod was 54 years. The patient demographics were consistent with those included in the respective pivotal phase 3 studies, in which the siponimod patient cohort was generally older (mean age 44 years) with higher levels of disability (mean Expanded Disability Status Scale [EDSS]) score 5.4) as compared with fingolimod cohort (mean age 37 years, mean EDSS score 2.3).…”

“…The impact of COVID-19 on people living with multiple sclerosis (MS), including how disease-modifying therapies (DMT) might influence the risk of symptomatic infection or COVID-19 outcomes, is being assessed through large local registries 3-6 and a global data sharing initiative. 7 Older age and comorbidities, including obesity, progressive forms of MS, and higher degree of disability, seem to be associated with severe COVID-19 outcomes among people living with MS. 4,8…”

N2 Year in Review

“…The COVID-19 in MS Global Data Sharing Initiative in an impressive sample size of 5,648 pwMS with confirmed (83.4%) or suspected COVID-19 corroborated the findings of previous smaller or single-center studies; again, male sex, older age, progressive MS, and higher disability, as well as the use of ocrelizumab and rituximab, were associated with COVID-19 severity. 55 A few studies have dealt with immune responses to SARS-CoV2 in convalescent COVID-19 pwMS. In a retrospective study from Spain in 145 convalescent COVID-19 pwMS, 121 were positive for SARS-CoV2 antibodies, 56 and 25 of 42 patients presented a cellular response (interferon gamma) to SARS-CoV2 up to 13 months after COVID-19 infection.…”

“…The COVID-19 in MS Global Data Sharing Initiative in an impressive sample size of 5,648 pwMS with confirmed (83.4%) or suspected COVID-19 corroborated the findings of previous smaller or single-center studies; again, male sex, older age, progressive MS, and higher disability, as well as the use of ocrelizumab and rituximab, were associated with COVID-19 severity. 55…”