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  1. R. Felten1,
  2. P. M. Duret2,
  3. E. Bauer3,
  4. M. Ardizzone4,
  5. H. J. Djossou5,
  6. J. H. Salmon6,
  7. C. Fabre7,
  8. J. Walther7,
  9. I. Chary Valckenaere3,
  10. M. Geoffroy6,
  11. L. Messer2,
  12. F. Berenbaum5,
  13. M. Soubrier8,
  14. J. Sellam5,
  15. J. E. Gottenberg1
  16. on behalf of BIOCOV Study Group
  1. 1Hôpitaux Universitaires de Strasbourg, Service de Rhumatologie, Centre National de Référence des Maladies Auto-immunes Systémiques Rares Est Sud-Ouest (RESO), Strasbourg, France
  2. 2Hospices Civils de Colmar, Hôpital Pasteur, Service Rhumatologie, Colmar, France
  3. 3Hôpitaux Universitaires de Nancy, Service de Rhumatologie, Nancy, France
  4. 4Hôpital Emile MULLER de Mulhouse, Service de Rhumatologie, Mulhouse, France
  5. 5Hôpital Saint Antoine, APHP, Service de Rhumatologie, Paris, France
  6. 6Hôpitaux Universitaires Reims, Service de Rhumatologie, Reims, France
  7. 7Hôpitaux Universitaires de Strasbourg, Service de Pharmacie-Stérilisation, Strasbourg, France
  8. 8Hôpitaux Universitaires de Clermont-Ferrand, Service de Rhumatologie, Clermont-Ferrand, France


Background: At a time when vaccines are being prioritized for individuals most at risk, there is currently no clear evidence that risk of SARS-CoV-2 infection is higher for patients with than without inflammatory arthritides (IA). Biologic use was not associated with worse COVID-19 outcomes for yet but the case of rituximab (RTX) remains an issue, given its immunological long term effect, the role of humoral response against SARS-CoV-2 and its indirect effect on T-cell response. A potential association between rituximab and worse COVID-19 outcomes was raised by case reports and retrospective, declarative studies (with few data on the total number of patients exposed).

Objectives: To address differently the issue of the risk of COVID-19 related to RTX and limit biases, we examined the occurrence of severe COVID-19 in all patients receiving intravenous biologic agents at day-hospitals during the pandemic in France.

Methods: From 1st September 2019 to 1st January 2021, we analyzed patients with IA prospectively treated with intravenous biologic agents (RTX, abatacept, infliximab or tocilizumab) in 7 clinical centers in France. We obtained the list of patients receiving intravenous biologic agents in each center from the pharmacist of the hospitals. Therefore, all consecutive patients receiving 1 of the 4 drugs at the time of the study were included in each center. Patients with no follow-up after September 2020 were systematically contacted by phone. The occurrence of a severe COVID -19 (i.e. resulting in death, hospitalization or increase in length of hospitalization related to COVID-19) was the primary outcome criteria.

Results: In total, 1116 patients receiving intravenous biologic agents were included: 449 with infliximab, 392 RTX, 170 tocilizumab and 105 abatacept. From 1st September 2019, the median follow-up time was 15 months (interquartile range 14-16). In total, 10 cases of severe COVID-19 occurred, 9 treated with RTX and 1 with infliximab (supplementary Table 1). Four deaths occurred in our cohort during follow-up but none was related to COVID-19 (1 patient treated by tocilizumab, 1 by RTX and 2 by infliximab). In univariate analysis, the proportion of severe COVID-19 was significantly higher for patients receiving RTX than other biologic agents (9/392 vs 1/724, p=0.0003, OR [95%CI] 17.0 [2.1-134.6]). To take into account potential confounders, we performed multivariate analysis accounting for baseline parameters that differed between RTX and other biologic groups. RTX remained significantly associated with risk of severe COVID-19 (p=0.019) (Table 1).

Conclusion: The present results highly indicate increased risk of severe COVID-19 with RTX. Among patients with inflammatory arthritides, those receiving RTX should be prioritized for vaccination against SARS-CoV-2, sufficiently long before infusion/reinfusion and the immunization checked, or an alternative targeted therapy proposed.

Acknowledgements: We thank Dr. Karine Demesmay and all the pharmacists who helped us for this study.

Disclosure of Interests: Renaud FELTEN Speakers bureau: Abbvie, Biogen, BMS, Lilly, Novartis, Pfizer, Pierre-Marie Duret: None declared, Elodie BAUER: None declared, Marc Ardizzone: None declared, H Julien Djossou: None declared, Jean-Hugues Salmon: None declared, Cassandre Fabre: None declared, Julia Walther: None declared, Isabelle CHARY VALCKENAERE: None declared, marion geoffroy: None declared, Laurent Messer: None declared, Francis Berenbaum: None declared, Martin SOUBRIER: None declared, Jérémie SELLAM Speakers bureau: MSD, Pfizer, Abbvie, Roche, BMS, Lilly, Janssen, Novartis, Galapagos, Sandoz, Fresenius Kabi, Grant/research support from: Roche, MSD, Pfizer, Jacques-Eric Gottenberg: None declared

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