Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience
Wiktor Schmidt, Katarzyna Pawlak-Buś, Barbara Jóźwiak, Piotr Leszczyński
Journal of Clinical Medicine, doi:10.3390/jcm12062429
Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among clinical, laboratory, and radiological variables. We conducted a prospective, observational study with 120 patients with severe COVID-19 not improving despite dexamethasone (DEX) treatment. We used parametric and non-parametric statistics, univariate logistic regression, receiver operating characteristic (ROC) curves, and nonlinear factors tertile analysis. In total, 86 (71.7%) patients achieved the primary outcome of a good clinical response to TCZ. We identified forty-nine predictive factors with potential utility in patient selection and treatment monitoring. The strongest included time from symptom onset between 9 and 12 days, less than 70% of estimated radiological lung involvement, and lower activity of lactate dehydrogenase. Additional predictors were associated with respiratory function, vitamin D concentration, comorbidities, and inflammatory/organ damage biomarkers. Adverse events analysis proved the safety of such a regimen. Our study confirmed that using TCZ early in the hyperinflammatory phase, before severe respiratory failure development, is most beneficial. Considering the described predictive factors, employing simple and widely available laboratory, radiological, and clinical tools can optimize patient selection for immunomodulatory treatment with TCZ.
Supplementary Materials: The following supporting information can be downloaded at: https://www. mdpi.com/article/10.3390/jcm12062429/s1, Table S1 . Definitions of additional outcomes of the study. Table S2 . Full demographic and initial clinical characteristics of study group, presented as n (%), mean (±SD) or median (Q1-Q3). Table S3 . Extended clinical characteristics of study groups, presented as median (Q1-Q3). p values were derived with Mann-Whitney U test. Table S4 . Extended laboratory characteristics of studied groups and outcomes, presented as median (Q1-Q3). p values were derived with Mann-Whitney U test. Table S5 . Outcomes and their prevalence upon administration and occurrence after treatment with tocilizumab in studied groups. Author Contributions: P.L. and K.P.-B. supervised the whole project. All authors participated in the conception and design of the study. P.L. conceived the analysis and W.S. designed it. Collection of data was performed by B.J. and W.S. Data were analyzed by W.S. and interpreted by W.S. and P.L. W.S. and B.J. were responsible for drafting the article, whereas K.P.-B. and P.L. gave critical revisions. All authors collectively gave final approval of the version of the article to be published. All authors have read and agreed to the published version of the manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
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'abstract': '<jats:p>Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; '
'thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good '
'clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among '
'clinical, laboratory, and radiological variables. We conducted a prospective, observational '
'study with 120 patients with severe COVID-19 not improving despite dexamethasone (DEX) '
'treatment. We used parametric and non-parametric statistics, univariate logistic regression, '
'receiver operating characteristic (ROC) curves, and nonlinear factors tertile analysis. In '
'total, 86 (71.7%) patients achieved the primary outcome of a good clinical response to TCZ. '
'We identified forty-nine predictive factors with potential utility in patient selection and '
'treatment monitoring. The strongest included time from symptom onset between 9 and 12 days, '
'less than 70% of estimated radiological lung involvement, and lower activity of lactate '
'dehydrogenase. Additional predictors were associated with respiratory function, vitamin D '
'concentration, comorbidities, and inflammatory/organ damage biomarkers. Adverse events '
'analysis proved the safety of such a regimen. Our study confirmed that using TCZ early in the '
'hyperinflammatory phase, before severe respiratory failure development, is most beneficial. '
'Considering the described predictive factors, employing simple and widely available '
'laboratory, radiological, and clinical tools can optimize patient selection for '
'immunomodulatory treatment with TCZ.</jats:p>',
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