The European Alliance of Associations for Rheumatology (EULAR) recently updated the points-to-consider on the use of immunomodulatory therapies in patients with moderate to severe COVID-19. The full guidance was published in Annals of the Rheumatic Diseases.1
The treatments for SARS-CoV-2 infection are rapidly evolving, posing a challenge for health care professionals and the scientific community. Evidence on the best practices for the clinical management of patients with COVID-19 have been released weekly, thus requiring a need to update policies in this field.
The EULAR taskforce, along with other scientific societies, developed guidance in 2020 for the treatment of COVID-19.2 The objective of the current report was to update the EULAR points-to-consider on the use of immunomodulatory therapies in COVID-19.
The multidisciplinary taskforce that developed the first version reconvened to establish a team, which included 2 fellow clinicians and a methodologist, to conduct an updated systematic literature review of studies on the management of SARS-CoV-2 infections using immunomodulatory therapies. Studies published between December 11, 2020, and June 30, 2021, were included in the analysis. Studies on the management of SARS-CoV-2 infections with anti-SARS-CoV-2 monoclonal antibodies were also included. Based on the results of the systematic literature review, the 12 points-to-consider were updated and discussed against existing ones. Statements were accepted if more than 75%, 65%, and 50% of the taskforce fellows approved the updates in the first (informal), second, and third rounds, respectively. The level of evidence was established, followed by an anonymous remote polling using a 0 to 10 level of agreement.
The 2 overarching principles remained unchanged compared with the first version in 2020:
- The heterogeneity of SARS-CoV-2 infection ranges from asymptomatic to lethal disease due to multiorgan damage.
- Based on the stages of the SARS-CoV-2 infection, treatment approaches may vary, including antiviral therapy, oxygen therapy, anticoagulation, and/or immunomodulatory treatments.
Table 1: Updated points-to-consider on the use of immunomodulatory therapies in COVID-19
|Current Version (2021)||Updates to 2020 Version|
|No evidence supports the use of immunomodulatory medications in nonhospitalized patients with SARS-CoV-2 infection.||Unchanged|
|No evidence supports the use of immunomodulatory medications in hospitalized patients with SARS-CoV-2 infection who do not require oxygen therapy.||Unchanged|
|Hydroxychloroquine should not be administered at any stage of SARS-CoV-2 infection. No evidence supports additional benefit to standard-of-care therapy, and in combination with azithromycin; it may worsen the prognosis in patients with severe infection.||Unchanged|
|Systemic glucocorticoids should be used in patients requiring supplemental oxygen and noninvasive/mechanical ventilation to reduce mortality risks. However, evidence indicates some concerns with the use of dexamethasone.||Unchanged|
|To reduce disease progression and mortality, a combination of glucocorticoids and tocilizumab should be considered in patients requiring supplemental oxygen and noninvasive/mechanical ventilation. More data supporting the efficacy of other IL-6R inhibitors are required.||Modified from: Routine use of tocilizumab in patients requiring oxygen therapy, noninvasive or invasive ventilation, is not yet formally recommended due to the evolving RCT landscape.|
|No robust evidence supports the use of anakinra at any stage of the infection.||Modified from: No robust evidence supports the use of anakinra or canakinumab at any stage of the infection.|
|No robust evidence supports the use of low-dose colchicine at any stage of the infection.||New|
|A combination of glucocorticoids and baricitinib or tofacitinib could be considered in patients requiring oxygen therapy, noninvasive ventilation, or high-flow oxygen, as it may reduce disease progression and mortality risks.||Modified from: Combination of remdesivir and baricitinib could be considered in patients requiring noninvasive ventilation or high-flow oxygen, as it may reduce recovery time and improve clinical outcomes.|
|Based on the evolving RCT landscape, the use of GM-CSF inhibitors (mavrilimumab, otilimab, and lenzilumab) in COVID-19 is recommended against.||New|
|There is robust evidence against the use of convalescent plasma in patients without hypogammaglobulinemia and with symptom-onset of >5 days.||New|
|Monoclonal antibodies to antispike protein must be considered in patients with risk for severe COVID-19 and symptom-onset of <5 days or still seronegative.||New|
|There is insufficient evidence supporting the use of other immunomodulatory medications, including interferon alpha, interferon beta, interferon kappa, interferon lambda, leflunomide, non-SARS CoV-2 IVIg, eculizumab, and cyclosporine in patients with COVID-19.||Modified from: There is insufficient evidence supporting the use of other immunomodulatory medications, including ruxolitinib, intravenous Ig, convalescent plasma therapy (except patients who are Ig-deficient), interferon kappa, interferon beta, leflunomide, colchicine, sarilumab, lenzilumab, eculizumab, cyclosporine, interferon alpha, and canakinumab in patients with COVID-19.|
GM-CSF, Granulocyte-Macrophage Colony-Stimulating Factor; IL-6R, interleukin 6 receptor; RCT, randomized controlled trial; Ig, immunoglobulin.
The authors concluded, “The update of these EULAR [points-to-consider] provide relevant and updated guidance on immunomodulatory therapy utilization from the rheumatology perspective and opens the way to a new paradigm: the treatment of immunopathology associated with severe and critical acute infections may benefit from immunomodulatory treatments usually given for autoimmune and inflammatory diseases.”
Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
1. Alunno A, Najm A, Machado PM, et al. 2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19. Ann Rheum Dis. Published online October 7, 2021. doi:10.1136/annrheumdis-2021-221366
2. Alunno A, Najm A, Machado PM, et al. EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19. Ann Rheum Dis. 2021;80:698-706.