2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19

Alessia Alunno¹, Aurélie Najm², Pedro M Machado^{3

4

5}, Heidi Bertheussen⁶, Gerd-Rüdiger R Burmester⁷, Francesco Carubbi¹, Gabriele De Marco⁸, Roberto Giacomelli⁹, Olivier Hermine^{10

11}, John D Isaacs¹², Isabelle Koné-Paut^{13

14}, César Magro-Checa¹⁵, Iain B McInnes², Pier Luigi Meroni¹⁶, Luca Quartuccio¹⁷, A V Ramanan^{18

19}, Manuel Ramos-Casals²⁰, Javier Rodríguez Carrio²¹, Hendrik Schulze-Koops²², Tanja A Stamm²³, Sander W Tas²⁴, Benjamin Terrier²⁵, Dennis G McGonagle⁸, Xavier Mariette^{26

27}

Affiliations

¹ Internal Medicine and Nephrology Unit, Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
² Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
³ Centre for Rheumatology and Department of Neuromuscular Diseases, University College London, London, UK.
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 Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK.
⁶ Patient Research Partner, EULAR, Oslo, Norway.
⁷ Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Freie Universität und Humboldt-Universität Berlin, Berlin, Germany.
⁸ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & The NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
⁹ Rheumatology and Clinical Immunology Unit, University of Rome "Campus Biomedico" School of Medicine, Rome, Italy.
¹⁰ Department of Hematology, Hôpital Necker, Assistance Publique - Hôpitaux de Paris, Paris, France.
¹¹ Institut Imagine, Université de Paris, INSERM UMR1183, Paris, France.
¹² Translational and Clinical Research Institute, Newcastle University and Musculoskeletal Unit, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
¹³ Department of Paediatric Rheumatology, Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), Bicêtre University Hospital, AP-HP, Le Kremlin-Bicetre, France.
¹⁴ University of Paris Sud Saclay, Paris, France.
¹⁵ Department of Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, Netherlands.
¹⁶ Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano IRCCS, Milano, Italy.
¹⁷ Department of Medicine, Rheumatology Clinic, University of Udine, ASUFC Udine, Udine, Italy.
¹⁸ University Hospitals Bristol NHS Foundations Trust, Bristol, UK.
¹⁹ Translational Health Sciences, University of Bristol, Bristol, UK.
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 Department of Functional Biology, Immunology Area, Faculty of Medicine, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), University of Oviedo, Oviedo, Spain.
²² Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Ludwig-Maximilians University Munich, Munich, Germany.
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 Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and immunology Center, Amsterdam University Medical Centres, AMC/University of Amsterdam, Amsterdam, Netherlands.
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 Department of Rheumatology, INSERM UMR1184, Le Kremlin Bicêtre, France xavier.mariette@aphp.fr.
²⁷ Department of Rheumatology, Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, INSERM UMR1184, Le Kremlin Bicêtre, France.

PMID: 34620584
DOI: 10.1136/annrheumdis-2021-221366

Free article

Practice Guideline

2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19

Alessia Alunno et al. Ann Rheum Dis. 2022 Jan.

Free article

. 2022 Jan;81(1):34-40.

doi: 10.1136/annrheumdis-2021-221366. Epub 2021 Oct 7.

Authors

Affiliations

¹ Internal Medicine and Nephrology Unit, Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
² Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
³ Centre for Rheumatology and Department of Neuromuscular Diseases, University College London, London, UK.
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 Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK.
⁶ Patient Research Partner, EULAR, Oslo, Norway.
⁷ Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Freie Universität und Humboldt-Universität Berlin, Berlin, Germany.
⁸ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & The NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
⁹ Rheumatology and Clinical Immunology Unit, University of Rome "Campus Biomedico" School of Medicine, Rome, Italy.
¹⁰ Department of Hematology, Hôpital Necker, Assistance Publique - Hôpitaux de Paris, Paris, France.
¹¹ Institut Imagine, Université de Paris, INSERM UMR1183, Paris, France.
¹² Translational and Clinical Research Institute, Newcastle University and Musculoskeletal Unit, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
¹³ Department of Paediatric Rheumatology, Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), Bicêtre University Hospital, AP-HP, Le Kremlin-Bicetre, France.
¹⁴ University of Paris Sud Saclay, Paris, France.
¹⁵ Department of Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, Netherlands.
¹⁶ Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano IRCCS, Milano, Italy.
¹⁷ Department of Medicine, Rheumatology Clinic, University of Udine, ASUFC Udine, Udine, Italy.
¹⁸ University Hospitals Bristol NHS Foundations Trust, Bristol, UK.
¹⁹ Translational Health Sciences, University of Bristol, Bristol, UK.
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 Department of Functional Biology, Immunology Area, Faculty of Medicine, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), University of Oviedo, Oviedo, Spain.
²² Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Ludwig-Maximilians University Munich, Munich, Germany.
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 Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and immunology Center, Amsterdam University Medical Centres, AMC/University of Amsterdam, Amsterdam, Netherlands.
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 Department of Rheumatology, INSERM UMR1184, Le Kremlin Bicêtre, France xavier.mariette@aphp.fr.
²⁷ Department of Rheumatology, Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, INSERM UMR1184, Le Kremlin Bicêtre, France.

PMID: 34620584
DOI: 10.1136/annrheumdis-2021-221366

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.

Keywords: Covid-19; biological therapy; glucocorticoids.

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Conflict of interest statement

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.

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2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19

Affiliations

2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19

Authors

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

Full Text Sources

Medical

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