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. 2023 Mar 11;10(4):ofad133.
doi: 10.1093/ofid/ofad133. eCollection 2023 Apr.

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

Marta Trigo-Rodríguez  1 , Sheila Cárcel  2 , Ana Navas  3 , Reinaldo Espíndola-Gómez  1 , José Carlos Garrido-Gracia  4 , María Ángeles Esteban Moreno  5 , Rafael León-López  2 , Pedro María Martínez Pérez-Crespo  1 , Eduardo Aguilar Alonso  6 , David Vinuesa  7 , Alberto Romero-Palacios  8 , Inés Pérez-Camacho  9 , Belén Gutiérrez-Gutiérrez  10 , Francisco Javier Martínez-Marcos  11 , Concepción Fernández-Roldán  12 , Eva León  1 , Alexandra Aceituno Caño  5 , Juan E Corzo-Delgado  1 , Elena Perez-Nadales  13   14   15   16 , Cristina Riazzo  17 , Carmen de la Fuente  2 , Aurora Jurado  3 , Julián Torre-Cisneros  18 , Nicolás Merchante  1
Affiliations

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

Marta Trigo-Rodríguez et al. Open Forum Infect Dis. .

Abstract

Background: The 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.

Methods: The 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.

Results: One 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.

Conclusions: IP-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.

Keywords: COVID-19; IL-6; IP-10; SARS-CoV-2; sarilumab; tocilizumab.

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Conflict of interest statement

Potential conflict of interest. All authors report no potential conflicts.

Figures

Figure 1.
Figure 1.
Kaplan-Meier survival curves according to the cutoff value of IL-8 levels (A), IL-10 levels (B), MCP-1 levels (C), and IP-10 levels (D) in the overall population. Abbreviations: IL, interleukin; IP, interferon-inducible protein; MCP, monocyte chemoattractant protein.
Figure 2.
Figure 2.
Kaplan-Meier survival curves according to treatment group in patients with low IL-10 (A), MCP-1 (C), or IP-10 (E) levels and patients with high IL-10 (B), MCP-1 (D), or IP-10 (F) levels. Abbreviations: IL, interleukin; IP, interferon-inducible protein; MCP, monocyte chemoattractant protein.
See this image and copyright information in PMC

References

    1. Del Valle DM, Kim-Schulze S, Huang H-H, et al. . An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 2020; 26:1636–43. - PMC - PubMed
    1. Dorward DA, Russell CD, Um IH, et al. . Tissue-specific immunopathology in fatal COVID-19. Am J Respir Crit Care Med 2021; 203:192–201. - PMC - PubMed
    1. Jørgensen MJ, Holter JC, Christensen EE, et al. . Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19. Sci Rep 2020; 10:21697. - PMC - PubMed
    1. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Domingo P, Mur I, et al. . Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: a meta-analysis. JAMA 2021; 326:499–518. - PMC - PubMed
    1. Merchante N, Cárcel S, Carlos Garrido-Gracia J, et al. . Early use of sarilumab in patients hospitalized with COVID-19 pneumonia and features of systemic inflammation: the SARICOR randomized clinical trial. Antimicrob Agents Chemother 2022; 66:e0210721. - PMC - PubMed