Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis
“…Furthermore, it should be considered that many of these biomarkers, and especially those most strictly related to cytokine storm, could also be valuable tools to monitor therapeutic responses (i.e., CRP and IL6 after 7 days of hospitalization) and promising direct (i.e., IL6) or indirect (i.e., D-dimer) pharmacological targets in selected patients. Lastly, it is noteworthy that the continuous biotechnological progresses in the field of COVID-19 biomarkers discovery have also led to new and promising findings in terms of possible therapeutic approaches, as demonstrated by the anti-inflammatory and anti-viral activity of heparin [ 198 , 199 , 200 ], by the ability of IL6 and other IL- and cytokine-signaling inhibitors to improve the disease course [ 101 , 102 , 109 , 110 , 201 , 202 , 203 , 204 , 205 ] and by the promising antiviral effects of the already existing Gas6/TAM axis inhibitors [ 131 , 150 , 151 ]. Moreover, several studies are currently focused on both drug repurposing and new drug development, thus representing new potential options to directly or indirectly target several key mediators of COVID-19 pathogenesis [ 203 , 206 , 207 , 208 ].…”
Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormously increased during the pandemic. Nevertheless, because of the great heterogeneity of disease manifestations, a precise patient stratification at admission is still difficult, thus rendering a rational allocation of limited medical resources as well as a tailored therapeutic approach challenging. To date, many hematologic biomarkers have been validated to support the early triage of SARS-CoV-2-positive patients and to monitor their disease progression. Among them, some indices have proven to be not only predictive parameters, but also direct or indirect pharmacological targets, thus allowing for a more tailored approach to single-patient symptoms, especially in those with severe progressive disease. While many blood test-derived parameters quickly entered routine clinical practice, other circulating biomarkers have been proposed by several researchers who have investigated their reliability in specific patient cohorts. Despite their usefulness in specific contexts as well as their potential interest as therapeutic targets, such experimental markers have not been implemented in routine clinical practice, mainly due to their higher costs and low availability in general hospital settings. This narrative review will present an overview of the most commonly adopted biomarkers in clinical practice and of the most promising ones emerging from specific population studies. Considering that each of the validated markers reflects a specific aspect of COVID-19 evolution, embedding new highly informative markers into routine clinical testing could help not only in early patient stratification, but also in guiding a timely and tailored method of therapeutic intervention.
“…Furthermore, it should be considered that many of these biomarkers, and especially those most strictly related to cytokine storm, could also be valuable tools to monitor therapeutic responses (i.e., CRP and IL6 after 7 days of hospitalization) and promising direct (i.e., IL6) or indirect (i.e., D-dimer) pharmacological targets in selected patients. Lastly, it is noteworthy that the continuous biotechnological progresses in the field of COVID-19 biomarkers discovery have also led to new and promising findings in terms of possible therapeutic approaches, as demonstrated by the anti-inflammatory and anti-viral activity of heparin [ 198 , 199 , 200 ], by the ability of IL6 and other IL- and cytokine-signaling inhibitors to improve the disease course [ 101 , 102 , 109 , 110 , 201 , 202 , 203 , 204 , 205 ] and by the promising antiviral effects of the already existing Gas6/TAM axis inhibitors [ 131 , 150 , 151 ]. Moreover, several studies are currently focused on both drug repurposing and new drug development, thus representing new potential options to directly or indirectly target several key mediators of COVID-19 pathogenesis [ 203 , 206 , 207 , 208 ].…”
Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormously increased during the pandemic. Nevertheless, because of the great heterogeneity of disease manifestations, a precise patient stratification at admission is still difficult, thus rendering a rational allocation of limited medical resources as well as a tailored therapeutic approach challenging. To date, many hematologic biomarkers have been validated to support the early triage of SARS-CoV-2-positive patients and to monitor their disease progression. Among them, some indices have proven to be not only predictive parameters, but also direct or indirect pharmacological targets, thus allowing for a more tailored approach to single-patient symptoms, especially in those with severe progressive disease. While many blood test-derived parameters quickly entered routine clinical practice, other circulating biomarkers have been proposed by several researchers who have investigated their reliability in specific patient cohorts. Despite their usefulness in specific contexts as well as their potential interest as therapeutic targets, such experimental markers have not been implemented in routine clinical practice, mainly due to their higher costs and low availability in general hospital settings. This narrative review will present an overview of the most commonly adopted biomarkers in clinical practice and of the most promising ones emerging from specific population studies. Considering that each of the validated markers reflects a specific aspect of COVID-19 evolution, embedding new highly informative markers into routine clinical testing could help not only in early patient stratification, but also in guiding a timely and tailored method of therapeutic intervention.
“…L’inclusion d’études avant l’examen par les pairs [ [86] , [87] , [98] , [99] ], l’asymétrie des graphiques en entonnoir [ [80] , [86] , [93] , [96] ], le poids d’un petit nombre d’essais dans l’analyse globale [ [93] , [95] , [100] ] sont d’autres limites fréquemment citées dans ces travaux méta-analytiques. Points forts à retenir : La plupart des études randomisées s’intéressant au Sarilumab, ne mettent pas en évidence de bénéfice de ce traitement en termes de mortalité ou d’amélioration clinique ; De nombreuses études soulignent l’absence de bénéfice probable du Tocilizumab dans les formes peu graves et son intérêt potentiel dans les formes sévères ; Les études RECOVERY et REMAP-CAP ont mis en évidences une réduction de la mortalité après utilisation des inhibiteurs du récepteur de l’IL-6 ; L’étude TOCIBRAS contrebalance les résultats des études précédentes avec une mortalité plus importante après utilisation du Tocilizumab ; L’ambivalence des résultats de toutes ces études randomisées peut s’expliquer par différentes limites existantes, comme l’hétérogénéité des patients, les traitements confondants concomitants, l’absence d’aveugle, les critères de jugements composites ; Les travaux récents ont fait l’objet de plusieurs méta-analyses récentes dont les résultats restent hétérogènes.…”
Section: Essais Cliniquesunclassified
“…Dans l’étude RECOVERY, l’administration de Baricitinib était associée à une réduction significative de la mortalité à 28 jours (12 % vs 14 % ; RR : 0,87 [0,77–0,98] ; p = 0,026). Une récente méta-analyse démontre la non-infériorité du Baricitinib par rapport au Tocilizumab chez les patients traités recevant une corticothérapie systémique [ 98 ]. Une autre méta-analyse, incluant les résultats de RECOVERY, suggère une réduction de 20 % de la mortalité [ 123 ].…”
Section: Dans Quelles Conditions Doit-on Utiliser Le Tocilizumab ?unclassified
“…In the absence of a robust body of evidence from trials reporting on direct comparisons, in this issue of Clinical Microbiology and Infection Albuquerque and colleagues propose a Bayesian meta-regression to indirectly assess the efficacy of sarilumab and baricitinib in comparison to tocilizumab. [ 9 ] Authors initially conducted several pairwise Bayesian meta-analyses studying the effects of tocilizumab, sarilumab, and baricitinib verses an inactive comparison (i.e., placebo or standard of care) when added to corticosteroid therapy for COVID-19 on 28-day mortality. The meta-regression, based on multiple levels of assumptions, aimed to determine probabilities of noninferiority of sarilumab and baricitinib to the reference of tocilizumab.…”
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