TY - JOUR
T1 - EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19
AU - Alunno, Alessia
AU - Najm, Aurélie
AU - Machado, Pedro M.
AU - Bertheussen, Heidi
AU - Burmester, Gerd R.
AU - Carubbi, Francesco
AU - de Marco, Gabriele
AU - Giacomelli, Roberto
AU - Hermine, Olivier
AU - Isaacs, John D.
AU - Koné-Paut, Isabelle
AU - Magro-Checa, C. sar
AU - Mcinnes, Iain
AU - Meroni, Pier Luigi
AU - Quartuccio, Luca
AU - Ramanan, Athimalaipet V.
AU - Ramos-Casals, Manuel
AU - Rodríguez Carrio, Javier
AU - Schulze-Koops, Hendrik
AU - Stamm, Tanja A.
AU - Tas, Sander W.
AU - Terrier, Benjamin
AU - Mcgonagle, Dennis G.
AU - Mariette, Xavier
N1 - Funding Information: Funding This work was funded by European League Against Rheumatism (CLI122). PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). 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 versus 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. Publisher Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Objectives: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. Methods: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. Results: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. Conclusions: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19.
AB - Objectives: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. Methods: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. Results: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. Conclusions: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19.
KW - immune system diseases
KW - inflammation
KW - therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85100543424&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/annrheumdis-2020-219724
DO - https://doi.org/10.1136/annrheumdis-2020-219724
M3 - Article
C2 - 33547062
SN - 0003-4967
VL - 80
SP - 698
EP - 706
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 6
M1 - 219724
ER -