lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

IP-10 Predicts Clinical Progression and Response to IL-6 Blockade with Sarilumab in Early COVID-19 Pneumonia. The SARICOR Clinical Trial

28 Pages Posted: 7 Oct 2022

See all articles by Marta Trigo-Rodriguez

Marta Trigo-Rodriguez

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología

Sheila Cárcel

Universidad de Córdoba (UCO) - Unidad de Gestión Clínica de Cuidados Intensivos

Ana Navas

Universidad de Córdoba (UCO) - Unidad de Inmunología y Alergia

Reinaldo Espíndola-Gómez

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología

José Carlos Garrido-Gracia

Universidad de Córdoba (UCO) - Unidad de Ensayos Clínicos

María Ángeles Esteban Moreno

Universidad de Córdoba (UCO) - Unidad de Inmunología y Alergia

Rafael León-López

Universidad de Córdoba (UCO) - Unidad de Gestión Clínica de Cuidados Intensivos

Pedro María Martínez Pérez-Crespo

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología

Eduardo Aguilar Alonso

Hospital Infanta Margarita - Servicio de Medicina Intensiva

David Vinuesa

Hospital Universitario San Cecilio de Granada - Unidad de Gestión Clínica de Enfermedades Infecciosas

Alberto Romero-Palacios

Instituto de Investigacion Biomédica de Cádiz (INiBICA) - Unidad de Enfermedades Infecciosas

Inés Pérez-Camacho

Instituto de Investigacion Biomédica de Cádiz (INiBICA) - Unidad de Enfermedades Infecciosas

Belén Gutiérrez-Gutiérrez

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología

Francisco Javier Martínez-Marcos

Hospital Juan Ramón Jiménez - Unidad de Enfermedades Infecciosas

Concepción Fernández-Roldán

Hospital Universitario Virgen Macarena - Unidad Clínica de Enfermedades Infecciosas

Eva León

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología

Alexandra Aceituno Caño

Torrecárdenas Hospital - Servicio de Medicina Internal

Juan E. Corzo

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología

Carmen de la Fuente

Universidad de Córdoba (UCO) - Unidad de Gestión Clínica de Cuidados Intensivos

Aurora Jurado

Universidad de Córdoba (UCO) - Unidad de Inmunología y Alergia

Julián Torre-Cisneros

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología

Nicolás Merchante

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología

More...

Abstract

Background and objectives: SARICOR clinical trial (CT) showed that patients with COVID19 pneumonia and increased levels of interleukin (IL)-6 might benefit from early blockade of IL6-pathway. However, the benefit from this intervention might not be uniform in all patients. We sought to determine if other biomarkers of immunoactivation, besides IL-6, could identify which subgroup of patients benefit the most of this intervention.

Methodology: The SARICOR CT was a phase II, open-label, randomized, multicentre, controlled CT (July 2020-March 2021) in which patients were randomized to receive standard of care (SOC) (control group); SOC plus single dose of Sarilumab 200 mg (Sarilumab-200 group) or SOC plus single dose of Sarilumab 400 mg (Sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, MCP-1, IP-10) were included in this secondary analysis. Progression to severe respiratory failure requiring high-flow oxygen therapy or mechanical ventilation according to cytokine levels and treatment received was evaluated.  Results: One hundred and one (88%) of 115 patients enrolled in the SARICOR CT had available 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. Thus, in patients with IP-10 < 2500 pg/ml, there were no differences in the probability of presenting the primary outcome between treatment groups. Conversely, patients with IP-10 ≥ 2500 pg/ml treated with Sarilumab-400 had a lower probability of progression (13%) compared to the control group (58%) (HR 0.19; 95% CI: 0.04-0.90; p=0.04).Conclusions: IP-10 predicts clinical progression in patients hospitalized with COVID-19 pneumonia and IL-6 levels > 40 pg/ml. Importantly, IP-10 value < 2500 pg/ml might discriminate those individuals with high IL-6 levels who might not benefit of Sarilumab therapy.

Trial Registration Details: The trial was registered in accessible public databases such as the Spanish Clinical Studies Registry (REec), EUDRACT (2020-001531-27), and ClinicalTrials.gov (NCT04357860).

Funding Information: This study has been supported by the Consejeria de Salud y Familias, Junta de Andalucia, Spain (COVID-19 Research Program. Project code COVID-0013-2020). B.G.G. and J.T.C. are supported by General Sub-Directorate of Networks and Cooperative Research Centers, Ministry of Science and Innovation, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001, RD16/0016/0008]—co-financed by the European Regional Development Fund “A Way to Achieve Europe, Operational Program Smart Growth 2014–2020.” J.C.G. is supported by SCReN (Spanish Clinical Research Network) funded by the ISCIII-Sub-Directorate General for Research Assessment and Promotion through project PT17/0017/0032 and PT20/0039. R.L.L., C.D.L.F., J.T.-C., and B.G.-G. are supported by the Center of Biomedical Investigation Network for Infectious Diseases (CIBERINFEC) funded by ISCIII through projects CB21/13/00049 and CB21/13/ 00012.

Declaration of Interests: The authors have no conflict of interest or financial relationships relevant to the submitted work to disclose.

Ethics Approval Statement: The trial was approved by the Committee for Biomedical Research Ethics of the Reina Sofía University Hospital and was conducted in accordance with the International Conference on Harmonization E6 Guideline for Good Clinical Practice and ethical principles of the Declaration of Helsinki. Authorization was also obtained from the Spanish Agency of Medicines and Medical Products (AEMPS, 20-0262).

Suggested Citation

Trigo-Rodriguez, Marta and Cárcel, Sheila and Navas, Ana and Espíndola-Gómez, Reinaldo and Garrido-Gracia, José Carlos and Moreno, María Ángeles Esteban and León-López, Rafael and Pérez-Crespo, Pedro María Martínez and Aguilar Alonso, Eduardo and Vinuesa, David and Romero-Palacios, Alberto and Pérez-Camacho, Inés and Gutiérrez-Gutiérrez, Belén and Martínez-Marcos, Francisco Javier and Fernández-Roldán, Concepción and León, Eva and Caño, Alexandra Aceituno and Corzo, Juan E. and de la Fuente, Carmen and Jurado, Aurora and Torre-Cisneros, Julián and Merchante, Nicolás, IP-10 Predicts Clinical Progression and Response to IL-6 Blockade with Sarilumab in Early COVID-19 Pneumonia. The SARICOR Clinical Trial. Available at SSRN: https://ssrn.com/abstract=4238635 or http://dx.doi.org/10.2139/ssrn.4238635

Marta Trigo-Rodriguez

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología ( email )

Sheila Cárcel

Universidad de Córdoba (UCO) - Unidad de Gestión Clínica de Cuidados Intensivos ( email )

Ana Navas

Universidad de Córdoba (UCO) - Unidad de Inmunología y Alergia ( email )

Reinaldo Espíndola-Gómez

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología ( email )

José Carlos Garrido-Gracia

Universidad de Córdoba (UCO) - Unidad de Ensayos Clínicos ( email )

María Ángeles Esteban Moreno

Universidad de Córdoba (UCO) - Unidad de Inmunología y Alergia ( email )

Rafael León-López

Universidad de Córdoba (UCO) - Unidad de Gestión Clínica de Cuidados Intensivos ( email )

Pedro María Martínez Pérez-Crespo

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología ( email )

Eduardo Aguilar Alonso

Hospital Infanta Margarita - Servicio de Medicina Intensiva ( email )

David Vinuesa

Hospital Universitario San Cecilio de Granada - Unidad de Gestión Clínica de Enfermedades Infecciosas ( email )

Alberto Romero-Palacios

Instituto de Investigacion Biomédica de Cádiz (INiBICA) - Unidad de Enfermedades Infecciosas ( email )

Inés Pérez-Camacho

Instituto de Investigacion Biomédica de Cádiz (INiBICA) - Unidad de Enfermedades Infecciosas ( email )

Belén Gutiérrez-Gutiérrez

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología ( email )

Francisco Javier Martínez-Marcos

Hospital Juan Ramón Jiménez - Unidad de Enfermedades Infecciosas ( email )

Concepción Fernández-Roldán

Hospital Universitario Virgen Macarena - Unidad Clínica de Enfermedades Infecciosas ( email )

Eva León

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología ( email )

Alexandra Aceituno Caño

Torrecárdenas Hospital - Servicio de Medicina Internal ( email )

Juan E. Corzo

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología ( email )

Carmen De la Fuente

Universidad de Córdoba (UCO) - Unidad de Gestión Clínica de Cuidados Intensivos ( email )

Aurora Jurado

Universidad de Córdoba (UCO) - Unidad de Inmunología y Alergia ( email )

Julián Torre-Cisneros (Contact Author)

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología ( email )

Nicolás Merchante

University of Seville - Unidad de Enfermedades Infecciosas y Microbiología ( email )