tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2023 Mar 11;10(4)
fad133.
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[SUP] 1 [/SUP], Sheila Cárcel[SUP] 2 [/SUP], Ana Navas[SUP] 3 [/SUP], Reinaldo Espíndola-Gómez[SUP] 1 [/SUP], José Carlos Garrido-Gracia[SUP] 4 [/SUP], María Ángeles Esteban Moreno[SUP] 5 [/SUP], Rafael León-López[SUP] 2 [/SUP], Pedro María Martínez Pérez-Crespo[SUP] 1 [/SUP], Eduardo Aguilar Alonso[SUP] 6 [/SUP], David Vinuesa[SUP] 7 [/SUP], Alberto Romero-Palacios[SUP] 8 [/SUP], Inés Pérez-Camacho[SUP] 9 [/SUP], Belén Gutiérrez-Gutiérrez[SUP] 10 [/SUP], Francisco Javier Martínez-Marcos[SUP] 11 [/SUP], Concepción Fernández-Roldán[SUP] 12 [/SUP], Eva León[SUP] 1 [/SUP], Alexandra Aceituno Caño[SUP] 5 [/SUP], Juan E Corzo-Delgado[SUP] 1 [/SUP], Elena Perez-Nadales[SUP] 13 14 15 16 [/SUP], Cristina Riazzo[SUP] 17 [/SUP], Carmen de la Fuente[SUP] 2 [/SUP], Aurora Jurado[SUP] 3 [/SUP], Julián Torre-Cisneros[SUP] 18 [/SUP], Nicolás Merchante[SUP] 1 [/SUP]
Affiliations
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.
. 2023 Mar 11;10(4)
fad133.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[SUP] 1 [/SUP], Sheila Cárcel[SUP] 2 [/SUP], Ana Navas[SUP] 3 [/SUP], Reinaldo Espíndola-Gómez[SUP] 1 [/SUP], José Carlos Garrido-Gracia[SUP] 4 [/SUP], María Ángeles Esteban Moreno[SUP] 5 [/SUP], Rafael León-López[SUP] 2 [/SUP], Pedro María Martínez Pérez-Crespo[SUP] 1 [/SUP], Eduardo Aguilar Alonso[SUP] 6 [/SUP], David Vinuesa[SUP] 7 [/SUP], Alberto Romero-Palacios[SUP] 8 [/SUP], Inés Pérez-Camacho[SUP] 9 [/SUP], Belén Gutiérrez-Gutiérrez[SUP] 10 [/SUP], Francisco Javier Martínez-Marcos[SUP] 11 [/SUP], Concepción Fernández-Roldán[SUP] 12 [/SUP], Eva León[SUP] 1 [/SUP], Alexandra Aceituno Caño[SUP] 5 [/SUP], Juan E Corzo-Delgado[SUP] 1 [/SUP], Elena Perez-Nadales[SUP] 13 14 15 16 [/SUP], Cristina Riazzo[SUP] 17 [/SUP], Carmen de la Fuente[SUP] 2 [/SUP], Aurora Jurado[SUP] 3 [/SUP], Julián Torre-Cisneros[SUP] 18 [/SUP], Nicolás Merchante[SUP] 1 [/SUP]
Affiliations
- PMID: 37035487
- PMCID: PMC10077828
- DOI: 10.1093/ofid/ofad133
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.