[저자] Jesús Rodríguez-Baño, Jerónimo Pachón, Jordi Carratalà, Pablo Ryan, Inmaculada Jarrín, María Yllescas, José Ramón Arribas, Juan Berenguer, SAM-COVID Study Group, Fundación SEIMC-GESIDA, Hospital Universitario La Paz, Hospital Universitario Gregorio Marañón, Hospital Infanta Leonor, Complejo Hospitalario Virgen de la Salud, Hospital Universitario Rafael Méndez, Hospital Universitario de Cruces, Hospital de Melilla, Hospital San Eloy de Barakaldo, Hospital Universitario Central de Asturias, Hospital Universitario Puerto Real, Hospital do Salnés, Hospital del Mar, Hospital Virgen de la Arrixaca, Hospital Clínico San Cecilio, Parc Sanitari Sant Joan de Déu, Hospital Josep Trueta, Hospital Dos De Maig - Consorci Sanitari Integral, Hospital Clínico Universitario de Valencia, Complejo Asistencial de Ávila, Hospital Universitario Marqués de Valdecilla, Hospital de Barcelona SCIAS, Hospital Álvaro Cunqueiro, Hospital Universitario Severo Ochoa, Hospital CIMA-Sanitas, Hospital La Inmaculada, Hospital de Guadalajara, Hospital Universitario Infanta Sofia, Hospital Comarcal de Blanes, Hospital Universitario de Gran Canaria Dr Negrín, Hospital Son Espases, Complejo Hospitalario Universitario A Coruña, Hospital Costa del Sol, Hospital Clínico Universitario Lozano Blesa, Hospital Mutua de Terrassa, Hospital Universitario Virgen Macarena, Hospital Universitari de Bellvitge, Hospital Universitario y Politécnico La Fe, Hospital de Sabadell (Parc Tauli), Hospital Fundación Jiménez Díaz, Hospital Clínico Universitario de Valladolid, Hospital Son Llatzer, Hospital Universitario de Álava, Complejo Hospitalario Universitario Santa Lucía, Hospital General Universitario Reina Sofía, Complejo Hospitalario Universitario de Ferrol, Hospital Universitario los Arcos del Mar Menor, Hospital Universitario de Jerez, Hospital de Donostia, Hospital Juan Ramón Jiménez, Hospital Vega Baja, Hospital Puerta de Hierro, Hospital Universitario de Getafe, Hospital General de la Palma, Fundación Hospital de Calahorra, Hospital Alto Deba, Hospital Universitario de Jaén, Hospital de Palamós, Hospital Universitario de Valme, Hospital Universitario Virgen del Rocío, Hospital Universitario Ramón y Cajal, Hospital Universitario San Pedro, Hospital Regional de Málaga
[Category] MERS, 진단, 치료법,
[Article Type] Multicenter Study
[Source] PMC
Abstract
Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters.
Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs).
Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001).
Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation.
Keywords: COVID-19; Cohort study; Corticosteroids; Hyperinflammatory state; Mortality; Tocilizumab.
All Keywords
【저자키워드】 COVID-19, Corticosteroids, Mortality, Tocilizumab, cohort study, hyperinflammatory state, 【초록키워드】 Corticosteroid, Treatment, coronavirus disease, Tocilizumab, hospital, randomized trial, intubation, risk, combination therapy, outcome, Probability, Patient, death, Laboratory parameters, Logistic regression, Follow-up, Other, association, Propensity score, primary endpoint, Analysis, dose, Cox regression, Odds ratio, COVID-19 patient, not significant, 95%CI, hazard ratio, laboratory data, confounders, pulse, variable, Spanish, untreated patients, occurred, provided, was performed, calculated, were used, patients treated, patients with COVID-19, pDC, the primary endpoint, 【제목키워드】 Corticosteroid, Corticosteroids, Tocilizumab, multicentre, COVID-19 patient, Hyperinflammatory,
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{{ 목적: }} 이 연구의 목적은 임상 및 실험실 매개변수에 따라 과염증 상태의 코로나바이러스 19(COVID-19) 환자에서 토실리주맙 또는 코르티코스테로이드 간의 연관성과 삽관 또는 사망 위험을 추정하는 것이었습니다.
{{ 방법: }} 코호트 연구는 778명의 COVID-19 환자를 포함하여 60개의 스페인 병원에서 수행되었으며 임상 및 실험실 데이터는 과염증 상태를 나타냅니다. 치료는 주로 토실리주맙, 중간 고용량의 코르티코스테로이드(IHDC), 펄스 용량의 코르티코스테로이드(PDC), 병용 요법 또는 무치료로 이루어졌습니다. 1차 결과는 삽관 또는 사망이었습니다. 후속 조치는 21일이었다. Cox 회귀(필요한 경우 로지스틱 회귀)를 사용한 성향 점수 조정 추정치를 계산했습니다. 성향 점수는 교란 요인, 일치 변수 및 치료 가중치 역 확률(IPTW)로 사용되었습니다.
{{ 결과: }} 토실리주맙, IHDC, PDC 및 병용 요법으로 각각 치료받은 환자 88명, 117명, 78명, 151명을 치료하지 않은 환자 344명과 비교했습니다. 1차 평가변수는 각각 10(11.4%), 27(23.1%), 12(15.4%), 40(25.6%), 69(21.1%)였다. 1차 평가변수에 대한 IPTW 기반 위험 비율(병용 요법에 대한 승산비)은 토실리주맙의 경우 0.32(95%CI 0.22-0.47; p < 0.001), IHDC의 경우 0.82(0.71-1.30; p 0.82), IHDC의 경우 0.61(0.43-0.43) PDC의 경우 0.86; p 0.006), 병용 요법의 경우 1.17(0.86-1.58; p 0.30). 성향 점수의 다른 적용은 유사한 결과를 제공했지만 PDC에 대해서는 유의하지 않았습니다. 토실리주맙은 또한 IPTW 분석에서 단독으로 더 낮은 사망 위험과 관련이 있었습니다(0.07; 0.02-0.17; p < 0.001).
{{ 결론: }} 토실리주맙은 과염증 상태가 있는 COVID-19 환자에게 유용할 수 있으며 이 상황에서 무작위 시험에 우선순위를 두어야 합니다.
{{ 키워드: }} 코로나19; 코호트 연구; 코르티코스테로이드; 과염증 상태; 인류; 토실리주맙.