2021 Update to EULAR Points on Immunomodulatory Use in COVID-19 Save

EULAR has updated its recommendations (points to consider - PtC) for rheumatologists managing patients during COVID-19; now with 2 overarching principles and 12 PtC.

These recommendations apply only to moderate to severe and critical COVID patients. They favor steroids or in combination with tocilizumab in COVID-19 cases who are critical or requiring oxygen therapy. Both baricitinib and tofacitinib are also promising in severe and critical COVID-19. And early in the disease, the sue of anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may prove useful in selected subgroups of immunosuppressed patients.

Despite a number of positive trials with colchicine and IL-1 inhibitors, they do not yet favor this PtC as the data is not yet "robust" enough.

Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.

Overarching principles

• The phenotype of SARS-CoV-2 infection is heterogeneous ranging from asymptomatic to lethal disease due to multiorgan damage.
• SARS-CoV-2 infection may need different treatment approaches, including antiviral, oxygen therapy, anticoagulation and/or immunomodulatory treatment at different stages of the disease

Points to consider

1. In non-hospitalised patients with SARS-CoV-2 infection, there is currently no evidence to support the initiation of immunomodulatory therapy 
2. In hospitalised patients with SARS-CoV-2 infection that do not need oxygen therapy, there is currently no evidence to support the initiation of immunomodulatory therapy to treat their COVID-19 
3. Hydroxychloroquine should be avoided for treating any stage of SARS-CoV-2 infection since it does not provide any additional benefit to the standard of care, and could worsen the prognosis in more severe patients particularly if coprescribed with azithromycin
4. In patients with COVID-19 requiring supplemental oxygen, non-invasive or mechanical ventilation, systemic glucocorticoids should be used since they can decrease mortality; most evidence concerns the use of dexamethasone
5. In patients with COVID-19 requiring supplemental oxygen, non-invasive or mechanical ventilation combination of glucocorticoids and tocilizumab should be considered since it reduces disease progression and mortality. (More data needed on other IL-6R inhibitors)
6. In COVID-19 there is no robust evidence to support the use of anakinra or canakinumab at any disease stage
7. In COVID-19 there is no robust evidence to support the use of low-dose colchicine at any disease stage
8. In patients with COVID-19 requiring oxygen therapy, non-invasive ventilation or high-flow oxygen, the combination of glucocorticoids and baricitinib or tofacitinib could be considered since it might decrease disease progression and mortality
9. An evolving RCT landscape cannot yet allow formal recommendation of the use of GM-CSF inhibitors (mavrilimumab, otilimab, lenzilumab) in COVID-19
10. In patients without hypogammaglobulinaemia and with symptom onset >5 days there is robust evidence against the use of convalescent plasma 
11. In patients at risk of severe COVID-19 course, symptom onset <5 days or still seronegative, monoclonal antibodies against SARS-CoV-2 spike protein should be considered
12. In patients with COVID-19 there is currently insufficient evidence to recommend the use of other immunomodulatory drugs, including interferon alpha, interferon beta, interferon kappa, interferon lambda, leflunomide, non-SARS CoV-2 IVIg, eculizumab and cyclosporine