Patients with rheumatoid arthritis who were using rituximab at the time of COVID-19 onset had a fourfold higher risk of being hospitalized, needing mechanical ventilation, or dying, compared with patients taking a tumor necrosis factor inhibitor (TNFi), according to a report given at the annual European Congress of Rheumatology.
Dr. Jeffrey A. Sparks
The use of Janus kinase inhibitors (JAKi) also was associated with a twofold higher risk for these COVID-19 outcomes, said Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in presenting the analysis from the COVID-19 Global Rheumatology Alliance (GRA) Physician Registry.
“The strong association of rituximab and JAK inhibitor use with poor COVID-19 outcomes highlights the prioritization of risk mitigation strategies for these patients,” Dr. Sparks said at the meeting.
The full findings have now been published in Annals of the Rheumatic Diseases.
JAKi association questioned
These findings provide “an important understanding for the risk of our patients in times before vaccination,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich, who chaired the session in which the study was presented.
Dr. Hendrik Schulze-Koops
However, “recently, baricitinib was licensed to prevent particular aspects of severe COVID. What’s the explanation for this discrepancy?” he asked.
“Certainly, the JAK inhibitor finding deserves further study,” Dr. Sparks acknowledged, adding that the data were analyzed by class rather than for individual drugs.
“One possible explanation could be when JAK inhibitors are used,” he suggested. “It might be different for patients who [have been] just infected – that might have different biologic effects – as opposed to choosing to treat patients right when there’s a hyperinflammatory cascade, or there’s oxygen need.”
Regarding the JAK inhibitor finding, Ronald van Vollenhoven, MD, PhD, of the University of Amsterdam, pointed out during the online Q&A that “JAKi have a very short half-life compared to biologics.”
Dr. Ronald van Vollenhoven
Dr. van Vollenhoven asked: “Could the practice of stopping these drugs upon COVID infection have a negative impact on the course?” To which Dr. Sparks responded: “The different half-life of drugs would be a promising avenue to look at, to see whether increases in disease activity might have imparted some of the effects we saw.”
Performing the analysis
As of April 12, 2021, the GRA Physician Registry contained the records of more than 15,000 patients. Dr. Sparks, collaborator Zachary Wallace, MD, of Massachusetts General Hospital, Boston, and associates limited their analysis to 2,869 patients with RA who had been treated with either a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) at the time they were diagnosed with COVID-19.
“We wanted to limit it to a single disease and also limit it to drugs that are considered for that disease,” Dr. Sparks explained in an interview.
“Because patients with rheumatoid arthritis are often treated sequentially, we wanted to further limit the analysis to patients who were on advanced therapies so that they were at a similar disease state, and also had the opportunity to receive advanced therapies.”
This approach hopefully minimizes the possibility of confounding by indication, Dr. Sparks said.
Most of the patients included in the analysis had received a TNFi (n = 1,388), and they were used as the control arm of the analysis. Outcomes associated with treatment with the other b/tsDMARDs, which included abatacept (n = 237), rituximab (n = 364), interleukin-6 inhibitors (IL-6i; n = 317), and JAKi (n = 563), were then compared with TNFi.
Baseline characteristics of patients were broadly similar across the groups. The mean age was 56.7 years and 80.8% of the study population was female. There were a few expected differences among users of rituximab versus TNFi, notably a higher percentage of patients with interstitial lung disease (11% vs. 1.4% of TNFi users) or cancer (7.4% vs. 0.9%) among patients treated with rituximab since it is commonly used in these patients, Dr. Sparks said.
“We did perform a sensitivity analysis where we restricted the population to not having ILD or cancer and we actually found really similar findings,” he added.