Rituximab should be 'prescribed with caution' due to possible risk for severe COVID-19
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Rituximab was associated with more severe COVID-19 in patients with inflammatory rheumatic and musculoskeletal diseases, according to data published in The Lancet Rheumatology.
“Various observations suggest that the course of COVID-19 seems less favorable with rituximab than that described with other targeted treatments, with the possibility that severe forms of COVID-19 might be linked to a drug-induced defect in the antiviral humoral response,” Jérôme Avouac, MD, of the University of Paris, and colleagues wrote.
“Conversely, non-serious cases of COVID-19 in patients treated with rituximab have also been reported,” they added. “Thus, it is crucial to further clarify the risk of severe COVID-19 in patients receiving rituximab, and to assess whether rituximab itself adversely affects COVID-19 outcomes or whether other confounding factors have an effect.”
To determine whether rituximab (Rituxan; Genentech, Biogen) is linked to more severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases, Avouac and colleagues studied data from the French RMD COVID-19 cohort. According to the researchers, this cohort includes adult patients with inflammatory rheumatic and musculoskeletal diseases as well as confirmed, or highly suspected, COVID-19. For their study, Avouac and colleagues analyzed data on 1,090 patients, collected between April 15 and Nov. 20, 2020. Among these patients, 63 received rituximab.
The primary endpoint was the severity of COVID-19 in patients who received rituximab, compared with those who did not. The researchers defined severe disease as requiring admission to an intensive care unit or leading to death. Secondary endpoints included examining deaths and duration of hospitalization.
In their analyses, the researchers used the inverse probability of treatment weighting propensity score method to adjust for potential confounding factors, included age, sex, arterial hypertension, diabetes, smoking status, BMI, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying inflammatory disease. They also calculated odds and hazard ratios, as well as confidence intervals, as effect size, by dividing the two population mean differences by their standard deviation.
According to the researchers, 13% of all included patients developed severe COVID-19 and 8% died. After adjusting for potential confounders, severe disease was more frequent (effect size = 3.26; 95% CI, 1.66-6.4), with “markedly longer” hospital stays (effect size = 0.62; 95% CI, 0.46-0.85), in patients who received rituximab, compared with those who did not. In addition, 21% of patients in the rituximab group died, compared with 7% in the non-rituximab group. However, the adjusted risk for death in the rituximab group was not significantly increased (effect size = 1.32; 95% CI, 0.55-3.19).
“The analysis of the French COVID-19 RMD cohort suggests the possibility for differential risk of adverse clinical outcomes among patients with inflammatory rheumatic and musculoskeletal diseases based on the type of biological agents received,” Avouac and colleagues wrote. “In particular, rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases, especially if they have other comorbidities that render them particularly at risk of severe COVID-19 outcomes.”
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