Baseline rituximab, JAK inhibitor use linked to worse COVID-19 severity in patients with RA
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Baseline rituximab or JAK inhibitor use for rheumatoid arthritis was associated with worse COVID-19 severity, compared with TNF-inhibitor use, according to a speaker at the EULAR 2021 Congress.
The results, presented at the virtual meeting by Jeffrey Sparks, MD, MMSc, of Brigham and Women’s Hospital and Harvard Medical School, in Boston, are based on an analysis of data from the COVID-19 Global Rheumatology Alliance physician registry.
“As we all know, there has been an intense interest throughout the pandemic in repurposing immunomodulators for COVID-19 treatment,” Sparks told attendees during the virtual meeting. “Some targeted DMARDs used in rheumatic diseases may dampen the hyperinflammatory response in COVID-19, perhaps leading to a less severe clinical course. Indeed, an observational study showed lower odds of hospitalization for patients on biologic or targeted synthetic DMARDs compared with no DMARDs. However, some DMARD targets may impair viral immune defenses, leading to more severe course.”
“This has been shown with rituximab, with increased odds of mortality and ICU stay, compared to methotrexate or nonuse, within observational studies,” he added. “However, some of these studies included many rheumatic diseases and often investigated only a single COVID-19 outcome.”
To examine the associations between the use of biologic or targeted synthetic DMARDs at baseline and poor COVID-19 outcomes in patients with RA, Sparks and colleagues analyzed voluntarily reported cases of SARS-CoV-2 from the COVID-19 Global Rheumatology Alliance physician registry from March 12, 2020, to Jan. 6, 2021. Using these data, the researchers identified 1,673 patients with RA who had been using biologic or targeted synthetic DMARDs at the onset of COVID-19. These included 154 using abatacept (Orencia, Bristol Myers Squibb), 224 on rituximab (Rituxan; Genentech, Biogen), 306 on JAK inhibitors, 180 using IL-6 inhibitors and 809 using TNF inhibitors.
“These were collected by class, not by individual drug,” Sparks said. “... TNF inhibitors were the reference group, since it was the most commonly used.”
For their outcome, the researchers used an ordinal scale of 1 to 4, with 1 meaning no hospitalization, 2 meaning hospitalization without oxygen needed, 3 denoting hospitalization with any oxygen need or ventilation, and 4 signifying death. In addition, they used baseline covariates — including age, sex, smoking, obesity, comorbidities, concomitant non-biologic DMARD use, glucocorticoid use and dose, RA disease activity, country and calendar time — to estimate propensity scores for patients’ treatments.
The researchers’ primary analysis included propensity score matching to compare each drug class with TNF inhibitors, as well as ordinal logistic regression to estimate odds ratios for COVID-19 severity outcomes. They also used traditional multivariable ordinal logistic regression, adjusting for covariates without matching, for the sensitivity analysis.
The investigators reported that 34.3% of the included patients were hospitalized and 6.7% died. Among all participants, 25.3% were ever smokers, 11.8% were obese, 27.6% were using glucocorticoids, 59.8% were on concomitant DMARDs, and 21.7% demonstrated moderate-to-high RA disease activity. Additionally, patients taking rituximab were more likely than those who used TNF inhibitors to have interstitial lung disease — 11.6% compared with 1.7% — and a history of cancer — 7.1% compared with 2%. Those taking JAK inhibitors were more likely than TNF inhibitor users to be obese — 17.3% compared with 9%.
After propensity score matching, baseline rituximab use was “strongly associated” with greater odds for developing a worse COVID-19 outcome, compared with TNF inhibitors (OR = 3.8; 95% CI, 2.47-5.85), according to Sparks. Among patients taking rituximab, 18.8% died compared with 3.3% for TNF-inhibitor users. The use of JAK inhibitors was also associated with greater odds for demonstrating a worse COVID-19 severity (OR = 1.52; 95% CI, 1.02, 2.28).
Neither abatacept nor IL-6 inhibitors were associated with COVID-19 severity compared with TNF inhibitors. The results were similar in the sensitivity analysis, as well as after excluding cancer or interstitial lung disease.
“We found that baseline use of rituximab or JAK inhibitors for rheumatoid arthritis was associated with worse COVID-19 severity than TNF-inhibitor use,” Sparks said. “Rituximab had a fourfold increased risk of ordinal COVID-19 severity, and JAK inhibitors had a twofold risk of ordinal COVID-19 severity. We found no consistent associations of abatacept or IL-6 inhibitors with COVID-19 severity, compared with TNF inhibitors. Strong associations of rituximab and JAK-inhibitor use with COVID-19 outcomes highlights the prioritization of risk-mitigation strategies for these patients.”
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