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30-03-2021 | Rheumatology | News | Article

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Rituximab use may be a risk factor for severe COVID-19

Claire Barnard

medwireNews: People with rheumatic and musculoskeletal diseases (RMDs) treated with rituximab may have a higher risk for developing severe COVID-19 than those given other treatments, researchers report.

Jérôme Avouac (Hôpital Cochin, Paris, France) and colleagues analyzed data from 1090 patients with RMDs and highly suspected or confirmed SARS-CoV-2 infection who were included in the French RMD COVID-19 cohort between April and November 2020. A total of 63 patients were treated with rituximab, primarily for rheumatoid arthritis (49%), antineutrophil cytoplasmic antibody-associated vasculitis (17%), or systemic sclerosis (11%), while the remaining 1027 patients were on other RMD therapies, most commonly methotrexate, corticosteroids, or tumor necrosis factor inhibitors.

As reported in The Lancet Rheumatology, 35% of rituximab-treated patients developed severe COVID-19, resulting in intensive care unit admission or death, compared with 11% of those in the no rituximab group. These findings translated into a significant odds ratio of 3.26 after adjustment for factors including age, sex, comorbidities, and corticosteroid treatment using the inverse probability of treatment weighting propensity score method.

Avouac and colleagues say that these findings remained consistent in a secondary analysis in which the 63 rituximab-treated patients were matched to 250 non-rituximab-treated patients using a propensity score matching method. The association also persisted when the control group was restricted to the 495 patients with diseases for which rituximab is a recognized therapy.

Importantly, among rituximab-treated patients, those with severe COVID-19 had a more recent rituximab infusion than those with mild or moderate COVID-19, say the researchers. The median time between the last infusion of rituximab and onset of COVID-19 symptoms was approximately 30 days for those with severe disease, compared with around 100 days and 120 days for those with mild or moderate disease, respectively.

Taken together, these findings suggest “direct drug accountability” for the association between rituximab and severe COVID-19, write Avouac and team.

“Rituximab will have to be prescribed with particular caution for patients with inflammatory rheumatic and musculoskeletal diseases, especially if they have other comorbidities that render them at risk of severe COVID-19 outcomes,” they add.

The researchers note that mortality rates were numerically higher in the rituximab than the no rituximab group (21 vs 7%), but the between-group difference did not reach statistical significance after adjustment for confounding factors.

Discussing the study results in an accompanying comment, Maxime Dougados, also from Hôpital Cochin, says that “if possible, it is recommended to discontinue rituximab infusions in patients whose rheumatic disease is in remission or to offer a therapeutic alternative if the risk of COVID-19 persists.”

He notes, however, that “[t]he problem is more delicate in patients with systemic autoimmune diseases controlled only by rituximab,” and suggests it could be possible “to administer rituximab without the pre-administration of corticosteroids, especially since corticosteroid therapy is associated with an increased risk of severe COVID-19.”

He adds: “Another possibility is to consider reducing the dose of rituximab either by increasing the interval between infusions or by reducing the dose of each infusion.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

30 March 2021: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00059-X
Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00077-1

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