Rituximab, JAK inhibitors linked to worse COVID-19 severity in RA patients
medwireNews: Study findings from the COVID-19 Global Rheumatology Alliance (C19-GRA) suggest that rheumatoid arthritis (RA) patients taking rituximab or Janus kinase (JAK) inhibitors are more likely to experience poor outcomes following SARS-CoV-2 infection than those taking tumor necrosis factor (TNF) inhibitors.
The study, which was presented at the EULAR 2021 Virtual congress and published in the Annals of the Rheumatic Diseases, included 2869 RA patients (mean age 57 years, 81% women) treated with biologics or targeted synthetic DMARDs at the time of COVID-19 onset who were entered into the C19-GRA registry between March 2020 and April 2021. Approximately half of the patients were taking concomitant conventional DMARDs.
Jeffrey Sparks (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and colleagues used an ordinal scale to categorize patients according to a range of COVID-19 outcomes, finding that the majority (78.6%) did not require hospital admission, while 4.8% were hospitalized without oxygenation, 11.1% required oxygenation or ventilation, and 5.5% died.
Among the 364 patients taking rituximab, 22.0% required hospitalization with oxygenation or ventilation, compared with just 7.4% of the 1388 taking TNF inhibitors, while a respective 14.8% and 2.6% died. These findings translated into a significantly higher risk for worse COVID-19 severity among patients taking rituximab versus TNF inhibitors in a multivariable ordinal logistic regression model, at an odds ratio (OR) of 4.15.
The 563 patients taking JAK inhibitors also had a significantly higher risk for worse COVID-19 severity than those taking TNF inhibitors (OR=2.06). A total of 15.3% of JAK inhibitor-treated individuals were hospitalized with oxygenation or ventilation, while 7.1% died.
Conversely, Sparks and colleagues found no significant association between treatment with abatacept or interleukin-6 inhibitors and COVID-19 severity.
They note that these findings remained consistent in sensitivity analyses excluding patients with interstitial lung disease or cancer (who may be more likely to receive rituximab), and when the analysis was restricted to people from the USA and adjusted additionally for race.
“Our observations, which use the largest sample of individuals with RA and COVID-19 assembled to date, […] confirm findings from prior studies suggesting an association between baseline use of B cell depleting therapies and worse COVID-19 outcomes in people with rheumatic diseases and multiple sclerosis,” write the researchers.
Speaking to medwireNews, study co-lead Zachary Wallace (Harvard Medical School, Boston, Massachusetts, USA) said that there are “two main reasons why [we may be] seeing this association between rituximab and worse outcomes.”
He explained that firstly, “rituximab depletes peripheral B cells, which may interfere with the ability to form [neutralizing antibodies]” that “are thought to be important for gaining initial control of [COVID-19] infection.”
And secondly, “depleting peripheral B cells may also [impact] the T-cell response that a patient would normally have to COVID-19,” because “B and T cells interact with one another,” Wallace continued.
The researchers conclude that RA patients taking rituximab or JAK inhibitors “should be prioritised for [COVID-19] risk mitigation strategies,” including vaccination and social distancing measures.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
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