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Rituximab or JAK inhibitors increase the risk of severe COVID-19

Presented by
Dr Jeffrey Sparks, Brigham and Women’s Hospital, MA, USA
EULAR 2021
The risk of severe COVID-19 outcomes in patients with rheumatoid arthritis (RA) is 4 times higher for those using rituximab and 2 times higher for those using a JAK inhibitor compared with patients who use TNF inhibitors. For abatacept and IL-6-inhibiting DMARDs, this association was not found. This was the conclusion of a large study comparing COVID-19 severity in RA patients treated with different classes of DMARDs. These results demonstrated the importance of risk-mitigation strategies in RA patients on rituximab or JAK inhibitors [1].

To examine the effect of baseline use of different DMARD classes on COVID-19 severity in RA, 2,869 patients with resolved COVID-19 were selected from the COVID-19 Global Rheumatology Alliance physician registry. Treatment with rituximab (n=224), JAK inhibitors (n=306), abatacept (n=154), or IL-6 inhibitors (n=180) was compared with TNF inhibitors (reference group, n=809) on an ordinal COVID-19 severity scale (1: not hospitalised; 2: hospitalised without oxygen; 3: hospitalised with oxygen or ventilation; 4: death). Data was analysed via ordinal logistic regression analysis. Dr Jeffrey Sparks (Brigham and Women’s Hospital, MA, USA) shared the results of this study.

Patients treated with rituximab or JAK inhibitors had a 4-fold or 2-fold increased risk of severe COVID-19 outcomes, respectively, compared with the reference group. In 85.4% of the cases, TNF inhibitor users were not hospitalised as a consequence of COVID-19. These percentages were significantly smaller in patients on rituximab (57.7%) or JAK inhibitors (72.6%). Baseline users of abatacept or IL-6 inhibitors were not hospitalised in 76.4% and 85.5% of the cases, respectively. In addition, treatment with rituximab or JAK inhibitors at COVID-19 onset resulted more often in hospitalisation with oxygen or ventilation (rituximab 22.0%; JAK inhibitors 15.3%; TNF inhibitors 7.4%) or death (rituximab 14.8%; JAK inhibitors 7.1%; TNF inhibitors 2.6%) than TNF inhibitor use. The primary multivariable analysis revealed that treatment with rituximab (OR 4.15; 95% CI 3.16–5.44) and JAK inhibitors (OR 2.06; 95% CI 1.60–2.65) was still associated with an increased risk of severe COVID-19 compared with TNF inhibitors after adjusting for covariates such as comorbidities, glucocorticoid use/dose, current disease activity, and concomitant use of hydroxychloroquine or conventional synthetic DMARDs. For treatment with abatacept (OR 1.26; 95% CI 0.88–1.80) and IL-6 inhibitors (OR 0.81; 95% CI 0.56–1.18) this increased risk was not demonstrated. The results were robust across sensitivity analyses.

Dr Sparks suggested that TNF inhibitors may have a potential protective effect on COVID-19 course of disease. This has been reported in a previous study among patients with rheumatic disease [2]. Nonetheless, the results of the current study should be interpreted with caution. Dr Sparks stressed the importance of COVID-19 risk management in RA patients on rituximab or JAK inhibitors, such as prioritising them for vaccination.

  1. Sparks J, et al. Associations of Baseline Use of Biologic or Targeted Synthetic DMARDs with COVID-19 Severity in Rheumatoid Arthritis: Results from the COVID-19 Global Rheumatology Alliance Physician Registry. OP0006, EULAR 2021 Virtual Congress, 2–5 June.

  2. Gianfrancesco M, et. al. Ann Rheum Dis. 2020;79(7):859-66.


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