Mortality Rates Among Hospitalized Patients With COVID-19 Infection Treated With Tocilizumab and Corticosteroids

Abstract

IMPORTANCE A World Health Organization (WHO) meta-analysis found that tocilizumab was associated with reduced mortality in hospitalized patients with COVID-19. However, uncertainty remains concerning the magnitude of tocilizumab's benefits and whether its association with mortality benefit is similar across respiratory subgroups. OBJECTIVE To use bayesian methods to assess the magnitude of mortality benefit associated with tocilizumab and the differences between respiratory support subgroups in hospitalized patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSA bayesian hierarchical reanalysis of the WHO metaanalysis of tocilizumab studies published in 2020 and 2021 was performed. Main results were estimated using weakly informative priors to exert little influence on the observed data. The robustness of these results was evaluated using vague and informative priors. The studies featured in the meta-analysis were randomized clinical tocilizumab trials of hospitalized patients with COVID-19. Only patients receiving corticosteroids were included. INTERVENTIONSUsual care plus tocilizumab in comparison with usual care or placebo. MAIN OUTCOMES AND MEASURESAll-cause mortality at 28 days after randomization. RESULTS Among the 5339 patients included in this analysis, most were men, with mean ages between 56 and 66 years. There were 2117 patients receiving simple oxygen only, 2505 receiving noninvasive ventilation (NIV), and 717 receiving invasive mechanical ventilation (IMV) in 15 studies from multiple countries and continents. Assuming weakly informative priors, the overall odds ratios (ORs) for survival were 0.70 (95% credible interval [CrI], 0.50-0.91) for patients receiving simple oxygen only, 0.81 (95% CrI, 0.63-1.03) for patients receiving NIV, and 0.89 (95% CrI, 0.61-1.22) for patients receiving IMV, respectively. The posterior probabilities of any benefit (OR <1) were notably different between patients receiving simple oxygen only (98.9%), NIV (95.5%), and IMV (75.4%).The posterior probabilities of a clinically meaningful association (absolute mortality risk difference >1%) were greater than 95% in patients receiving simple oxygen only and greater than 90% in patients receiving NIV. In contrast, the posterior probability of this clinically meaningful association was only approximately 67% in patients receiving IMV. The probabilities of tocilizumab superiority in the simple oxygen only subgroup compared with the NIV and IMV subgroups were 85% and 90%, respectively. Predictive intervals highlighted that only 72.1% of future tocilizumab IMV studies would show benefit. The conclusions did not change with different prior distributions. (continued) Key Points Question Can bayesian methods clarify the uncertainty around tocilizumab's association with mortality benefit in subgroups of hospitalized patients with COVID-19 receiving corticosteroids? Findings In this bayesian reanalysis of a previous meta-analysis of 15 randomized clinical trials comprising 5339 hospitalized patients with COVID-19 treated with tocilizum...

Application of Machine Learning in Hospitalized Patients with Severe COVID-19 Treated with Tocilizumab

“…Our findings confirm that both baseline status at the start of tocilizumab treatment requiring IMV and hyperferritinemia are associated with poor outcome and add insight into predictors of tocilizumab failure in patients with SARS-CoV2 and SRF. This is in line with the Bayesian reanalysis of a previous meta-analysis of 15 studies of hospitalized patients with COVID-19 treated with tocilizumab and corticosteroids [ 53 ]. This study showed that simple oxygen therapy and non-invasive ventilation (NIV) was associated with a clinically significant mortality benefit of tocilizumab but not in patients with IMV.…”

Biologic disease-modifying antirheumatic drugs to treat multisystem inflammatory syndrome in children

“…The bDMARD tocilizumab, which blocks IL-6 signaling, garnered a lot of attention early during the COVID-19 pandemic, as IL-6 was noted to be elevated in the serum of severe COVID-19 patients [53]. Early reports suggested tociliuzumab treatment helped severe COVID-19 patients, and meta-analyses have demonstrated some benefit to those with severe COVID-19 pneumonia [54,55]. As soon as MIS-C was recognized as a SARS-CoV-2-associated illness, tocilizumab was also explored as a therapeutic option for children with refractory MIS-C [11 ▪▪ ,12].…”

Effect of intraoperative PEEP with recruitment maneuvers on the occurrence of postoperative pulmonary complications during general anesthesia––protocol for Bayesian analysis of three randomized clinical trials of intraoperative ventilation

“…Bayesian analysis has also been used to elucidate the effect of interventions in specific subgroups, 10 to evaluate the effect of selection bias 33 and in metaanalysis. 34 This current analysis has several limitations which need to be addressed. First, some differences between studies concerning how PEEP and RM were used and titrated cannot be unraveled, although we will use a previously harmonized individual patient database.…”