People with rheumatoid arthritis treated with rituximab or JAK-inhibitors had worse outcomes when infected with COVID-19 when compared with those on TNF inhibitors, analysis of a large global registry suggests.

The study looking at differences in outcomes from COVID-19 infection in patients who were taking biologic or targeted synthetic disease modifying antirheumatic drugs (DMARDs) highlights the need for “risk mitigation” in those on rituximab or JAK-inhibitors, the researchers concluded.

Writing in the Annals of Rheumatic Diseases, the international team said that in response to the paper from the COVID-19 Global Rheumatology Alliance, doctors may want to consider other interventions such as monoclonal antibody treatment in these patients if exposed to COVID-19 or in the early phases of infection.

Using data on 2869 patients added to the registry between 24 March 2020 and 12 April 2021 who were taking biologic or targeted synthetic DMARDs, the researchers found that overall 4.8% were hospitalised without oxygenation, 11.1% were hospitalised with oxygen or ventilation requirement, and 5.5% died.

Among 364 rituximab users 80 (22.0%) needed hospitalisation with oxygen or ventilation and 54 (14.8%) died compared with 103 (7.4%) and 36 (2.6%) patients taking TNF inhibitors.

For those using JAK-inhibitors 86 of 563 (15.3%) were hospitalised with oxygen or ventilation and 40 (7.1%) died.

By contrast, only 9 (2.8%) patients on interleukin-6 inhibitors died, they reported and no associations were found between IL6-inhibitors or abatacept and COVID outcomes.

In all, those taking rituximab were four times more likely to have worse COVID-19 severity and those taking JAK inhibitors were twice as likely.

The rituximab finding confirms prior studies that have suggested an association between baseline use of B-cell depleting therapies and worse COVID-19 outcomes in people with rheumatic diseases, the researchers said.

And they pointed out the findings are of particular interest given recent clinical trials and observational studies suggesting that IL-6i and JAK inhibitors may improve outcomes for patients in the general population with COVID-19.

Study author Dr Pedro Machado, an Associate Professor and Consultant in Rheumatology and Neuromuscular Diseases at University College London told the limbic that the association of rituximab with increased odds for worse COVID-19 outcomes compared with TNFi users in people with rheumatoid arthritis is an important finding.

“Rituximab binds to CD20 on the surface of B-cells, effectively depleting this cell type, and interferes with antibody development. Therefore, B-cell depletion could potentially compromise antiviral immunity, including the development of SARS-CoV-2 antibodies.”

He added: “An important study limitation is the fact that the exact timing of infection following rituximab infusion was unknown, although all patients were clinically judged by their rheumatologist to have been exposed to the immunological effects of the drug at the time of COVID-19 diagnosis.”