코로나바이러스(COVID-19) 치료제: Dexamethasone(덱사메타손)

RECOVERY trial

Methods

Although the randomization of patients to receive dexamethasone, hydroxychloroquine, lopinavir–ritonavir, azithromycin, convalescent plasma, or tocilizumab has now been stopped, the trial continues randomization to other treatments, including REGN-COV2 (a combination of two monoclonal antibodies directed against the SARS-CoV-2 spike protein), aspirin, colchicine, or usual care alone.

Initially, recruitment was limited to patients who were at least 18 years of age, but the age limit was removed starting on May 9, 2020. Pregnant or breast-feeding women were eligible.

Eligible and consenting patients were assigned in a 2:1 ratio to receive either the usual standard of care alone or the usual standard of care plus oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days (or until hospital discharge if sooner) or to receive one of the other suitable and available treatments that were being evaluated in the trial.

• the usual standard of care alone  
• the usual standard of care plus oral or intravenous dexamethasone
• the usual standard of care plus one of the other suitable and available treatments

 

Results

The Kaplan–Meier curves have not been adjusted for age. The rate ratios have been adjusted for the age of the patients in three categories (<70 years, 70 to 79 years, and ≥80 years). Estimates of the rate ratios and 95% confidence intervals in Panels B, C, and D were derived from a single age-adjusted regression model involving an interaction term between treatment assignment and level of respiratory support at randomization.

 

In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.

 

 

Discussion

glucocorticoid는 SARS, Middle East respiratory syndrome (MERS), severe influenza, and community-acquired pneumonia 등에서 널리 사용되어 왔다. 그러나 이러한 조건에서 glucocorticoid의 사용은 무작위화되고 통제된 시험으로부터의 데이터가 부족하므로 근거가 약하다. 또한 약제 사용의 근거 데이터들 역시 heterogeneity in glucocorticoid doses, medical conditions, and disease severity의 한계를 가진다.

중증의 호흡기계 감염에서 glucocorticoid를 적절한 용량 사용한다면 상당한 이점이 기대되지만 고용량을 사용한다면 오히려 악영향을 끼칠 수 있다.

SARS, MERS, influenza 환자에서 전신 glucocorticoid의 사용은 viral RNA의 clearance를 느리게 하였지만 임상적으로 유의한지는 알 수 없다.

질병 2주차에 viral replication peak를 찍는 SARS와는 달리, SARS-CoV-2는 더 빠른 peak 달성을 보인다.

첫 주에 모집된 Covid-19 환자군에서의 dexamethasone의 mortality benefit이 더 큰 것은 immunopathological elements의 영향을 배제할 수 없다.(The greater mortality benefit of dexamethasone in patients with Covid-19 who are receiving respiratory support and among those recruited after the first week of their illness suggests that at that stage the disease may be dominated by immunopathological elements, with active viral replication playing a secondary role.)

This hypothesis would caution against extrapolation of the effect of dexamethasone in patients with Covid-19 to patients with other viral respiratory diseases with a different natural history.

이번 trial 이전의 Covid-19 가이드라인에서는 glucocorticoid의 사용은 권장되지 않았다. Dexamethasone is on the list of essential medicines of the World Health Organization and is readily available worldwide at low cost. Guidelines issued by the U.K. chief medical officers, the European Medicines Agency, the World Health Organization, and the National Institutes of Health in the United States have been updated to recommend the use of glucocorticoids in patients hospitalized with Covid-19 requiring oxygen with or without ventilatory support.

 

 

reference:

1) RECOVERY Collaborative Group. "Dexamethasone in hospitalized patients with Covid-19." New England Journal of Medicine 384.8 (2021): 693-704.

2) 약학정보원