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February 26, 2021
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EULAR: Immunomodulatory therapy may be effective for COVID-19 subsets

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Patients with COVID-19 who require supplemental oxygen, or noninvasive or mechanical ventilation, should receive systemic glucocorticoids as they can decrease mortality, according to EULAR “points to consider.”

Published in the Annals of the Rheumatic Diseases, the points also recommend providers consider a combination of remdesivir (Veklury, Gilead Sciences) and baricitinib (Olumiant, Eli Lilly & Co.) in patients with COVID-19 requiring noninvasive ventilation or high-flow oxygen, as they can decrease time to recovery and speed up clinical improvement.

Source: Adobe Stock.
Patients with COVID-19 who require supplemental oxygen, or noninvasive or mechanical ventilation, should receive systemic glucocorticoids as they can decrease mortality, according to EULAR “points to consider.”
Source: Adobe Stock

“Since rheumatologists are at the vanguard of immunomodulatory therapy utilization, they are well placed to provide insights in their usage, safety profile and timing towards potential mitigation of the severe inflammatory reactions associated with SARS-CoV-2 infection,” Alessia Alunno, MD, PhD, of the University of Perugia, in Italy, and colleagues wrote. “Although an extremely large volume of publication is already available, most of the research is descriptive and definitive randomized controlled trials (RCTs) remains scarce.”

“In this rapidly evolving landscape, and with the need to optimally define therapeutics solutions, it is considerably important to provide the medical and scientific community with guidance using the best available evidence,” they added. “This is especially the case since antiviral agents have thus far failed to show a significant improvement of survival in COVID-19.”

To develop and elaborate points to consider on COVID-19 pathophysiology and immunomodulatory therapies, all from a rheumatology perspective, EULAR organized an international, 24-member task force that included rheumatologists, translational immunologists, hematologists, pediatric rheumatologist, a methodologist, one health professional and one patient representative. This task force met for four virtual meetings in July and November 2020.

Members conducted a systematic literature review of individual studies on COVID-19 pathophysiology and its management with immunomodulatory therapies, with a cutoff date of Dec. 15, 2020. The final overarching principles and points to consider were drafted and formalized through a series of formal voting, and ultimately ratified by the EULAR Executive Committee.

In all, the task force developed and approved two overarching principles, highlighting the heterogeneous nature of COVID-19, and 14 points to consider, which are split between the disease’s pathophysiology and management with immunomodulators. The two overarching principles are:

COVID-19’s phenotype is heterogenous and ranges from asymptomatic to lethal disease due to multiorgan damage; and

COVID-19 may require different treatment strategies, including antiviral, oxygen, anticoagulation and/or immunomodulatory treatment at different stages of the disease.

The first six points to consider relate to the pathophysiology of the disease, including immune response, endothelial dysfunction and biomarkers. Points seven through 14 focus on management with immunomodulatory therapy.

According to the task force, there is evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. However, no other immunomodulator demonstrated efficacy on mortality to date. In addition, there was no evidence to support the use of any immunomodulatory therapy in non-hospitalized patients, nor in patients who are hospitalized but do not require oxygen. Immunomodulatory treatment was not associated with higher infection rates, the member found.

“These EULAR [points to consider (PtCs)] provide relevant guidance on the pathophysiology of SARS-COV-2 infection, especially immunomodulatory therapy utilization from the rheumatology perspective,” Alunno and colleagues wrote.

“Indeed, the pathophysiology with an initial viral alveolitis and subsequent immunothrombosis and available evidence points towards a central role for immunomodulatory therapy, especially glucocorticoids, in improving disease survival in severe COVID-19,” they added. “These first EULAR PtCs are intended to evolve and should be updated in response to the rapid increase of knowledge about the disease and the forthcoming vaccines.”