Abstract
Objectives Some disease-modifying therapies (DMTs) have been associated with COVID-19 severity in people with MS. Comprehensive exploration of these relationships in large international samples is needed.
Methods Clinician-reported demographic/clinical data from 27 countries were aggregated into a dataset of 5,648 patients with suspected/confirmed COVID-19. COVID-19 severity outcomes (hospitalisation, admission to ICU, requiring artificial ventilation, death) assessed using multilevel mixed-effect ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were compared to glatiramer acetate, dimethyl fumarate, pooled other DMTs, and natalizumab.
Results Of 5,648 patients (83.4% confirmed COVID-19) were included. Compared to glatiramer acetate, ocrelizumab and rituximab were associated with higher probability of hospitalisation (4%(95%CI=1–7) & 7%(95%CI=4–11)), ICU/artificial ventilation (2%(95%CI=0–4) & 4%(95%CI=2–6)), and death (1%(95%CI=0–2) & 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 three respective levels of COVID-19 severity than glatiramer acetate. Compared to pooled other DMTs and to natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. Evaluation of interferon associations with COVID-19 severity found these only apparent in comparison with the untreated but not vs individual or pooled other DMTs. All associations persisted/enhanced on restriction to confirmed COVID-19.
Conclusions Analysing the largest international real-world dataset of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab) are associated with more severe course of COVID-19, while interferon-based DMTs have no intrinsic protective benefit from other treatment.
