You are here

Article Text

Article menu
Download PDFPDF
Recommendation
2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19
  1. Alessia Alunno1,
  2. Aurélie Najm2,
  3. Pedro M Machado3,4,5,
  4. Heidi Bertheussen6,
  5. Gerd-Rüdiger R Burmester7,
  6. Francesco Carubbi1,
  7. Gabriele De Marco8,
  8. Roberto Giacomelli9,
  9. Olivier Hermine10,11,
  10. John D Isaacs12,
  11. Isabelle Koné-Paut13,14,
  12. César Magro-Checa15,
  13. Iain B McInnes2,
  14. Pier Luigi Meroni16,
  15. Luca Quartuccio17,
  16. A V Ramanan18,19,
  17. Manuel Ramos-Casals20,
  18. Javier Rodríguez Carrio21,
  19. Hendrik Schulze-Koops22,
  20. Tanja A Stamm23,
  21. Sander W Tas24,
  22. Benjamin Terrier25,
  23. Dennis G McGonagle8,
  24. Xavier Mariette26,27
  1. 1 Internal Medicine and Nephrology Unit, Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy
  2. 2 Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
  3. 3 Centre for Rheumatology and Department of Neuromuscular Diseases, University College London, London, UK
  4. 4 National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC), University College London Hospitals NHS Foundation Trust, London, UK
  5. 5 Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK
  6. 6 Patient Research Partner, EULAR, Oslo, Norway
  7. 7 Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Freie Universität und Humboldt-Universität Berlin, Berlin, Germany
  8. 8 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & The NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK
  9. 9 Rheumatology and Clinical Immunology Unit, University of Rome "Campus Biomedico" School of Medicine, Rome, Italy
  10. 10 Department of Hematology, Hôpital Necker, Assistance Publique - Hôpitaux de Paris, Paris, France
  11. 11 Institut Imagine, Université de Paris, INSERM UMR1183, Paris, France
  12. 12 Translational and Clinical Research Institute, Newcastle University and Musculoskeletal Unit, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  13. 13 Department of Paediatric Rheumatology, Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), Bicêtre University Hospital, AP-HP, Le Kremlin-Bicetre, France
  14. 14 University of Paris Sud Saclay, Paris, France
  15. 15 Department of Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, Netherlands
  16. 16 Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano IRCCS, Milano, Italy
  17. 17 Department of Medicine, Rheumatology Clinic, University of Udine, ASUFC Udine, Udine, Italy
  18. 18 University Hospitals Bristol NHS Foundations Trust, Bristol, UK
  19. 19 Translational Health Sciences, University of Bristol, Bristol, UK
  20. 20 Department of Autoimmune Diseases, ICMiD, Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic, Barcelona, Spain
  21. 21 Department of Functional Biology, Immunology Area, Faculty of Medicine, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), University of Oviedo, Oviedo, Spain
  22. 22 Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Ludwig-Maximilians University Munich, Munich, Germany
  23. 23 Section for Outcomes Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna and Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Wien, Austria
  24. 24 Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and immunology Center, Amsterdam University Medical Centres, AMC/University of Amsterdam, Amsterdam, Netherlands
  25. 25 Department of Internal Medicine, Cochin University Hospital, Paris, France; National Referral Centre for Systemic and Autoimmune Diseases, University Paris Descartes, Sorbonne Paris Cité, Paris, France
  26. 26 Department of Rheumatology, INSERM UMR1184, Le Kremlin Bicêtre, France
  27. 27 Department of Rheumatology, Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, INSERM UMR1184, Le Kremlin Bicêtre, France
  1. Correspondence to Professor Xavier Mariette, Department of Rheumatology, INSERM UMR1184, Le Kremlin Bicêtre, France; xavier.mariette{at}aphp.fr

Abstract

Objectives To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19.

Methods According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting.

Results We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy

Conclusions Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.

  • Covid-19
  • biological therapy
  • glucocorticoids

Data availability statement

Data sharing not applicable as no datasets generated and/or analysed for this study. All data relevant to the study are included in the article or uploaded as online supplemental information.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

https://doi.org/10.1136/annrheumdis-2021-221366

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    Data sharing not applicable as no datasets generated and/or analysed for this study. All data relevant to the study are included in the article or uploaded as online supplemental information.

    View Full Text

    Footnotes

    • DGM and XM are joint senior authors.

    • AA and AN are joint first authors.

    • Handling editor David S Pisetsky

    • Twitter @pedrommcmachado, @ProfJohnIsaacs

    • Contributors All authors contributed and finally approved the current manuscript. AA and AN share first Authorship. DGM and XM share last Authorship.

    • Funding This work was funded by European Alliance of Associations in Rheumatology (EULAR) (CLI122). PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the (UK) National Health Service, NIHR or the Department of Health. JDI is a NIHR Senior Investigator and his work is supported by the NIHR Newcastle Biomedical Research Centre in Ageing and Long-Term Conditions, and the Research Into Inflammatory Arthritis Centre vs Arthritis. AVR is a member of the paediatric steering committee of RECOVERY, the steering committee of COVINTOC study and the steering committee of baricitinib in COVID-19.

    • Competing interests AA, AN, HB, FC, GDM, RG, CM-C and JRC have nothing to declare. PMM has received consulting and/or speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript. G-RRB has received consulting and/or speaker’s fees from Abbvie, Gilead, Lilly, Roche, Sanofi, Pfizer all unrelated to this manuscript. IK-P has received consulting and/or speaker’s fees from Novartis, SOBI, Amgen, CHUGAI, Pfizer, LFB, Novimmune, Abbvie and PAtent for AIDAI score AVR has received speaker fees/Honoraria from Abbvie, Lilly, Roche, UCB, SOBI and Novartis all unrelated to this manuscript. DGM has received consulting and/or speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this manuscript. XM has received consulting and/or speaker’s fees from BMS, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Novartis, Pfizer, Servier and UCB, all unrelated to this manuscript.

    • Patient and public involvement statement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.