Anti-CD20 DMTs associated with worse COVID-19 outcomes

The first results of the COVID-19 in MS Global Data Sharing Initiative suggest anti-CD20 disease-modifying treatment (DMT) is consistently associated with hospitalisation, intensive care admission, and artificial ventilation [1]. These results suggest that anti-CD20 DMT among MS patients at risk for COVID-19 exposure may be a risk factor for more severe COVID-19 disease. Confirmation with Roche's pharmacovigilance program is however needed.

Clinician-reported data from 21 countries all over the world were aggregated into a dataset of 1,540 patients. Of these, 476 (30.9%) with suspected and 776 (50.4%) with confirmed COVID-19 were included in the analysis.

Older age, progressive MS, and higher EDSS were associated with a higher likelihood of hospital admission but being female with a lower likelihood. Progressive MS and higher disability were associated with a higher risk of intensive care unit admission. Mortality risk was elevated in patients with progressive MS, older age, and higher disability.

The adjusted prevalence ratios (aPRs) of hospitalisation (313 events) were established per DMT, with dimethyl fumarate as comparison. Use of anti-CD20 DMT ocrelizumab and rituximab was positively associated with hospital admission (aPRs 1.19 and 1.58), intensive care admission (aPRs 3.53 and 4.12), and the need for artificial ventilation (aPRs 3.17 and 7.27). There was no association between any DMT and death. Risk of all 3 clinical outcomes was higher in anti-CD20 users (n=343) compared with all other DMT users (n=492): hospitalisation aPR 1.49; intensive care admission aPR 2.55; and ventilation aPR 3.05. These risks were also higher compared with natalizumab: hospitalisation aPR 1.99; intensive care admission aPR 2.39; ventilation aPR 2.84. Associations persisted when restricting analysis to confirmed COVID-19 cases only.

There are different possible explanations for the consistently stronger association with COVID-19 severity of rituximab versus ocrelizumab. The most simple and appropriate explanation is the difference in affinities, with rituximab binding the exact same epitope on CD20 but binding more strongly.

An update from Roche's pharmacovigilance program did not confirm the above findings for ocrelizumab. Notwithstanding the limitations of the data sources, the experience of ocrelizumab-treated MS patients with COVID-19 appeared in line with the data reported from the general population and MS datasets [2]. The majority of SARS-CoV-2 infections in MS patients treated with ocrelizumab across Roche clinical trials (n=51; 26 confirmed) and post-marketing spontaneous reports (n=307; 263 confirmed) with reported severity, resulted in mild-to-moderate disease. Case fatality rates in ocrelizumab-treated MS patients were in line with the general population and MS datasets overall. Ocrelizumab-treated patients with risk factors associated with worse COVID-19 outcomes appeared to experience more severe disease, which is also in line with published experience.

1. Simpson-Yap S, et al. First results of the COVID-19 in MS Global Data Sharing Initiative suggest anti-CD20 DMTs are associated with worse COVID-19 outcomes. MSVirtual 2020, Abstract SS02.04.


2. Hughes R, et al. COVID-19 in persons with multiple sclerosis treated with ocrelizumab: pharmacovigilance update. MSVirtual 2020, Abstract SS02.05.

 





Posted on 25 November, 2020