Development and validation of a prediction model for tocilizumab failure in hospitalized patients with SARS-CoV-2 infection

Abstract

Background The aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients’ profile. Methods Patients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day 6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort. Results 266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively. Conclusions Our score could assist clinicians in identifying, early after tocilizumab administration, patients who are likely to progress to mechanical ventilation or death, so that they could be selected for eventual rescue therapies.

Predictors of poor outcome in tocilizumab treated patients with Sars-CoV-2 related severe respiratory failure: A multicentre real world study

“…The Authors combined these variables in the CERRAHPASA-PREDICT score, whose positive and negative predictive values were 94.5% and 92.9%, respectively [29] . In another study enrolling two-hundreds and sixty-six COVID-19 patients treated with Tocilizumab, Mussini C et al identified sex, day-4, P/F after Tocilizumab administration, platelets count and CRP as independent risk factors for treatment failure and associated with 28-day mortality and mechanical ventilation [30] . In their study 28-day mortality was 10%, while 15% of patients underwent mechanical ventilation.…”

“…In their study 28-day mortality was 10%, while 15% of patients underwent mechanical ventilation. Combining these variables, the Authors proposed a predictive score with an area under the receiving operating curve of 0.80 [30] . In one hundred and twenty COVID-19 patients treated with Tocilizumab, Sarabia de Ardanaz L et al found that patients who died had significantly higher values of lactate dehydrogenase, CRP, troponin I, lower levels of platelets and lymphocytes and lower P/F [31] .…”

Predictors of the Outcomes Following the Tocilizumab Treatment for Severe COVID-19

“…Mussini et al also tried to identify and model the predictors for tocilizumab failure. Their model reached a cross-validation-corrected AUC of 0.87 for a composite outcome measure of being on mechanical ventilation or mortality on the 28th day following the initiation of treatment, including gender, CRP, baseline platelet count, and PFR on the fourth day following tocilizumab administration [ 23 ]. However, the standard of care in their study cohort was hydroxychloroquine, lopinavir, and anticoagulation, which does not reflect current practice.…”

Decreased mortality and increased side effects in COVID-19 patients treated with IL-6 receptor antagonists: systematic review and meta-analysis

“…Careful patient selection and timing for IL-6 (receptor) antagonist treatment in COVID-19 patients is crucial 15 – 17 , especially considering the increased risk of side effects—neutropenia, impaired liver function and secondary infections—when IL-6 (receptor) antagonists were used. Our analyses suggested that Il-6 (receptor) antagonist treatment is beneficial in reducing mortality for patients with a high baseline risk of mortality, while it may be harmful for patients with a low baseline risk of mortality.…”