key: cord-0888791-t6j7d4p4
authors: Dougados, Maxime
title: Managing patients with rheumatic diseases treated with rituximab during the COVID-19 pandemic
date: 2021-03-25
journal: Lancet Rheumatol
DOI: 10.1016/s2665-9913(21)00077-1
sha: cb192d6d75b41d7e88c91ac14b944591bf1f23d8
doc_id: 888791
cord_uid: t6j7d4p4

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From the start of the COVID-19 pandemic, patients treated with rituximab approached their rheumatology team in large numbers to ask their opinion on the risk of COVID-19, and whether they should continue with rituximab treatment or not. Later in the pandemic, the relevance of vaccination against COVID-19 also became a concern.

Preliminary answers to these questions appeared in a fragmented way as initial reports of isolated observations in patients receiving rituximab emerged. 1 Very rapid establishment of registries to examine COVID-19 outcomes in patients with rheumatic and musculoskeletal diseases, such as the COVID-19 Global Rheumatology Alliance 2 and the French RMD COVID-19 cohort, 3 made it possible to refine our responses to these questions.

In The Lancet Rheumatology, Jérôme Avouac and colleagues report the results from the French RMD COVID-19 cohort, which included more than 1000 patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. 4 The authors had previously identified several factors associated with severe COVID-19 (defined as that requiring admission to an intensive care unit or leading to death), including corticosteroids at a dose of at least 10 mg per day and treatment with rituximab. 3 The authors went on to analyse in depth the association between rituximab treatment and the risk of severe COVID-19, and found that the risk does exist. Severe disease was observed more frequently in patients treated with rituximab (effect size 3·26, 95% CI 1·66-6·40) and time between last infusion of rituximab and first symptoms of COVID-19 was shorter in patients who developed severe COVID-19 than in those with moderate or mild forms.

These data are very relevant to our daily clinical practice, but raise many questions. Of course, 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. Offering a therapeutic alternative is all the more justified because so far there does not seem to be increased risk of severe COVID-19 in patients taking other biologics or Janus kinase inhibitors. 2 The problem is more delicate in patients with systemic autoimmune diseases controlled only by rituximab. In these patients, it could be suggested to administer rituximab without the pre-administration of corticosteroids, especially since corticosteroid therapy is associated with an increased risk of severe COVID-19. 2,3 Moreover, it has been shown that this pre-administration was useful in avoiding anaphylactic reactions to the infusion, especially during the first cycle of rituximab treatment, but less useful during the following cycles. 5 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.

There is also an absence of data concerning vaccination against COVID-19. The data reported by Avouac and colleagues are an argument in favour of prioritising the vaccination of patients treated with rituximab. In view of the mechanism of action of currently approved or future COVID-19 vaccines, it is anticipated that these vaccinations will not be more toxic in patients receiving rituximab than in the general population. The question is that of the effectiveness of vaccination in these patients. By analogy to what has been observed with vaccination against influenza, 6 we can suspect that the immunological response to COVID-19 vaccination will not be optimal with regard to its efficiency in patients taking rituximab. Currently, it is nevertheless recommended to offer this vaccination to these patients as soon as possible and, if possible, after a substantial period from the last infusion of rituximab (ie at least 4-6 months after the last infusion and 4-6 weeks before the next infusion). In France, in view of the data from the French RMD COVID-19 cohort, patients taking rituximab are considered by the French authorities to be a priority for vaccination, whatever the age of the patient. There is also the possibility of treating patients taking rituximab with the spike protein inhibitor bamlanivimab in the case of confirmed COVID-19. 7 However, it should be acknowledged that these recommendations are based on the opinion of experts and need to be confirmed or invalidated, and fine tuned by evidence from prospective studies. Dr P. Marazzi/SPL

INSERM (U1153): Clinical Epidemiology and Biostatistics

Increased risk for severe COVID-19 in patients with inflammatory rheumatic diseases treated with rituximab

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study

Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis

Rituximab impairs immunoglobulin (Ig) M and IgG (subclass) responses after influenza vaccination in rheumatoid arthritis patients

SARS-CoV-2 neutralizing antibody ly-CoV555 in outpatients with Covid-19