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28th June 2021
The European Alliance of Associations for Rheumatology (EULAR) is the organisation that represents the people with arthritis/rheumatism, health professions in rheumatology and scientific societies of rheumatology of all the European nations. With immune mechanisms clearly involved in the evolution of more severe COVID-19, there is a potentially important role for immunotherapy in those infected with the virus. As a result, EULAR convened a task force to develop overarching principles (OPs) and points to consider (PtC) on the pathophysiology of COVID-19 from a rheumatological perspective through a systematic review of the available evidence. The task force included 24 members from 8 different countries and comprised rheumatologists, translational immunologists, haematologists, paediatric rheumatologists and a patient representative. Based on the evidence from the literature, a series of statements were prepared and circulated to members, discussed and voted on. Initially EULAR sought at least 75% agreement on statement wording from members but where this did not occur, refinements were made and the revised statement re-circulated and the accepted level of acceptance was set at 67% for this second round.
The task force defined two overarching principles. The first was that the phenotype of COVID-19 infection is heterogenous and ranged from asymptomatic to lethal disease as a result of multi-organ failure. The second highlighted the need for different treatment approaches to manage an infection and that these were required at different stages of the disease.
The task force also approved 14 PtC, with a view to offering guidance on the management COVID-19 with immunotherapy. Six of the PtC covered aspects of the pathophysiology of COVID-19 with the remainder discussing the use of immunotherapy. For example, it was recognised that while cellular and humoral immune responses to COVID-19 were highly variable in patients, there was insufficient evidence to associate these differing responses directly with patient outcomes. The first PtC for immunotherapy noted the absence of evidence supporting a role for this treatment modality among non-hospitalised patients, or for the value of initiating such treatment. In contrast, given the evidence on oral corticosteroids, there was a recommendation to use these drugs (in particular dexamethasone and which has the strongest evidence), in patients receiving supplemental oxygen, non-invasive or mechanical ventilation. While the evidence base continued to change rapidly, another PtC was that it was still inappropriate to offer a formal recommendation for the routine use of tocilizumab in hospitalised COVID-19 patients requiring either supplemental oxygen, non-invasive or mechanical ventilation. The final PtC was that there was a lack of evidence to recommend the use of immunomodulators including convalescent plasma, interferon kappa, interferon beta, lenzilumab, cyclosporin or canakinumab.
An important caveat with the EULAR document is that it is not intended to undermine or override local regulations or guidelines produced by bodies such as the World Health Organization. Rather the purpose is to provide recommendations of good practice to help clinicians analyse their own therapeutic strategy and inspire change were appropriate. The authors concluded that given how knowledge around COVID-19 changes quickly, these PtCs will be updated as and when appropriate.
Aluno A et al. EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19. Ann Rheum Dis 2021; 80(6): 698-706