Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial-Reference-Cited by-同舟云学术

Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial

Published:2023-03-11 Issue:4 Volume:10 Page:
ISSN:2328-8957
Container-title:Open Forum Infectious Diseases
language:en
Short-container-title:

Author:

Trigo-Rodríguez Marta¹^ORCID,Cárcel Sheila²,Navas Ana³,Espíndola-Gómez Reinaldo¹,Garrido-Gracia José Carlos⁴^ORCID,Esteban Moreno María Ángeles⁵^ORCID,León-López Rafael²,Pérez-Crespo Pedro María Martínez¹^ORCID,Alonso Eduardo Aguilar⁶^ORCID,Vinuesa David⁷^ORCID,Romero-Palacios Alberto⁸^ORCID,Pérez-Camacho Inés⁹^ORCID,Gutiérrez-Gutiérrez Belén¹⁰^ORCID,Martínez-Marcos Francisco Javier¹¹,Fernández-Roldán Concepción¹²^ORCID,León Eva¹,Caño Alexandra Aceituno⁵,Corzo-Delgado Juan E¹,Perez-Nadales Elena¹³¹⁴¹⁵¹⁶^ORCID,Riazzo Cristina¹⁷^ORCID,de la Fuente Carmen²,Jurado Aurora³^ORCID,Torre-Cisneros Julián¹⁸^ORCID,Merchante Nicolás¹^ORCID

Affiliation:

1. Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Universidad de Sevilla, Instituto de Investigaciones Biomédicas de Sevilla, IBIS (Universidad de Sevilla, Junta de Andalucía, CSIC) , Sevilla , Spain

2. Unidad de Gestión Clínica de Cuidados Intensivos, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba (UCO) , Córdoba , Spain

3. Unidad de Inmunología y Alergia, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO) , Córdoba , Spain

4. Unidad de Ensayos Clínicos, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba (UCO) , Córdoba , Spain

5. Servicio de Medicina Interna, Hospital Universitario Torrecárdenas , Almería , Spain

6. Servicio de Medicina Intensiva, Hospital Infanta Margarita , Córdoba , Spain

7. Unidad de Gestión Clínica de Enfermedades Infecciosas, Hospital Universitario Clínico San Cecilio , Granada , Spain

8. Unidad de Enfermedades Infecciosas, Hospital Universitario Puerto Real, Instituto de Investigacion Biomédica de Cádiz (INiBICA) , Cádiz , Spain

9. Servicio de Enfermedades Infecciosas, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA) , Málaga , Spain

10. Unidad de Gestión Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, Instituto de Biomedicina de Sevilla (IBIS) , Seville , Spain

11. Unidad de Enfermedades Infecciosas, Hospital Universitario Juan Ramón Jiménez , Huelva , Spain

12. Unidad de Enfermedades Infecciosas, Hospital Universitario Virgen de las Nieves , Granada , Spain

13. CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII) , Madrid , Spain

14. Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III (ISCIII) , Madrid , Spain

15. Grupo de Enfermedades Infecciosas, Instituto de Investigaciones Biomédicas de Córdoba, Hospital Universitario Reina Sofía, Universidad de Córdoba (IMIBIC/HURS/UCO) , Córdoba , España

16. Departamento de Química Agrícola, Edafología y Microbiología, Universidad de Córdoba , Córdoba , Spain

17. Servicio de Microbiología, Hospital Universitario Reina Sofía-IMIBIC , Córdoba , Spain

18. Servicio de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO) , Córdoba , Spain

Abstract

AbstractBackgroundThe Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention.MethodsThe SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020–March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein–1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated.ResultsOne hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04–0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences.ConclusionsIP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.

Funder

Consejeria de Salud y Familias

General Sub-Directorate of Networks

Ministry of Science and Innovation

Spanish Network for Research in Infectious Diseases

European Regional Development Fund,

Spanish Clinical Research

ISCIII

Center of Biomedical Investigation Network for Infectious Diseases

Publisher

Oxford University Press (OUP)

Subject