Baricitinib vs tocilizumab treatment for hospitalized adult patients with severe COVID-19 and associated cytokine storm: a prospective, investigational, real-world study.

OBJECTIVES: Our aim was to compare outcomes of hospitalized adults with severe COVID-19 and cytokine storm treated with tocilizumab or baricitinib. METHODS: A prospective, investigational, real-world study was performed from April 2020 to April 2021 at our center. COVID-19 severity was classified by World Health Organization criteria, and cytokine storm was documented along predefined criteria. Eligible patients were enrolled at diagnosis if they fulfilled a priori inclusion criteria and received standard-of-care plus tocilizumab or baricitinib for >48 hours. Patients were followed per protocol for 28 days post-diagnosis. The primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation and major infectious complications. RESULTS: Of 463 patients, 102/463 (22.1%) received tocilizumab, and 361/463 (77.9%) baricitinib. Baseline characteristics were balanced. At 28 days, there was no difference in all-cause mortality (22/102, 21.6% vs 64/361, 17.7%; P-value = 0.38). Requirement for invasive mechanical ventilation was more frequent after tocilizumab (52/102, 50.9% vs 96/361, 26.6%; P <0.01), rate of major infectious complications was similar (32/102, 31.4% vs 96/361, 26.6%; P-value = 0.34). In logistic regression, the immunomodulatory drug was not retained as a predictor of all-cause mortality. Kaplan-Meier analysis revealed statistically similar survival distributions. CONCLUSION: All-cause mortality was similar between adults treated with baricitinib or tocilizumab for severe COVID-19 with cytokine storm.

Baricitinib versus tocilizumab treatment for hospitalized adult patients with severe COVID-19 and associated cytokine storm: A prospective, investigational, real-world study

Objectives Our aim was to compare outcomes of hospitalized adults with severe COVID-19 and cytokine storm, treated with tocilizumab or baricitinib. Methods A prospective, investigational, real-world study was performed between April 2020–April 2021 at our centre. COVID-19 severity was classified by World Health Organization criteria, cytokine storm was documented along pre-defined criteria. Eligible patients were enrolled at diagnosis if they fulfilled a priori inclusion criteria and received standard-of-care plus tocilizumab or baricitinib for >48 hours. Patients were followed per protocol for 28 days post-diagnosis. Primary outcome was all-cause mortality, secondary outcomes were invasive mechanical ventilation and major infectious complications. Results From 463 patients, 102/463 (22.1%) received tocilizumab, 361/463 (77.9%) baricitinib. Baseline characteristics were balanced. At 28 days, there was no difference in all-cause mortality (22/102, 21.6% vs. 64/361, 17.7%;p=0.38). Requirement for invasive mechanical ventilation was more frequent after tocilizumab (52/102, 50.9% vs. 96/361, 26.6%;p<0.01), rate of major infectious complications was similar (32/102, 31.4% vs. 96/361, 26.6%;p=0.34). In logistic regression, immunomodulatory drug was not retained as a predictor of all-cause mortality. Kaplan–Meier analysis revealed statistically similar survival distributions. Conclusions All-cause mortality was similar between adults treated with baricitinib or tocilizumab for severe COVID-19 with cytokine storm.

Favipiravir treatment does not influence disease progression among adult patients hospitalized with moderate-to-severe COVID-19: a prospective, sequential cohort study from Hungary.

Data suggests that favipiravir (FVP) could be used against SARS-CoV-2. Our aim was to investigate the role of FVP in COVID-19 treatment. A prospective sequential cohort study was performed among adults hospitalized at our center between March and August 2020 with moderate-to-severe, PCR-confirmed COVID-19. For diagnosis and severity, ECDC and WHO definitions were utilized. Patients were screened for inclusion by a priori criteria and included in the FVP cohort if standard-of-care (SOC) + FVP or the non-FVP cohort if SOC ± other antivirals without FVP were administered for > 48 h from diagnosis. Treatment allocation was done per national guidelines, based on severity and drug availability. Primary endpoint was disease progression, a composite of 14-day all-cause death, need for mechanical ventilation, or immunomodulatory therapy. The impact of FVP exposure on disease progression was analyzed by binomial logistic regression. In all, 150 patients were included, 75 in each cohort. Disease progression (17/75, 22.7% vs. 10/75, 13.3%, p = 0.13), 14-day all-cause death (9/75, 12.0% vs. 10/75, 13.3%, p = 0.8), and need for mechanical ventilation (8/75, 10.7% vs. 4/75, 5.3%, p = 0.22) were similar, while immunomodulatory therapies were required more frequently among patients receiving FVP (10/75, 13.3% vs. 1/75, 1.3%, p < 0.01). The use of favipiravir was not retained as a protective factor against disease progression in multivatiate analysis. Time to antiviral therapy from PCR positivity, disease severity, need for oxygen supportation, and ICU admittance rates did not differ statistically between cohorts. In this study, favipiravir did not seem to positively affect disease progression.

Laboratory parameters predicting mortality of adult in-patients with COVID-19 associated cytokine release syndrome treated with high-dose tocilizumab.

Large randomized clinical trials in severe Coronavirus Disease 2019 (COVID-19) patients have proven efficacy of intravenous tocilizumab. Our aim was to describe the laboratory parameters predicting in-hospital mortality of patients with tocilizumab administration in COVID-19 associated cytokine release syndrome (CRS).We evaluated high-dose (8 mg/kg) intravenous tocilizumab administration in severe and critically ill COVID-19 adult patients fulfilling predefined strict CRS criteria. A single-centre, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between April 1 and December 31, 2020. The primary endpoint was 28-day all-cause mortality. The changes in laboratory parameters from baseline on day 7 and 14 after administration of tocilizumab were analysed.In total, 1801 patients were admitted to our centre during the study period. One hundred and six patients received tocilizumab, and among them 62 (58.5%) required intensive care unit admittance while 25 (23.6%) deceased. At day 7 after tocilizumab administration, inflammatory markers (CRP, IL-6, ferritin) and lactate dehydrogenase (LDH) values were significantly lower among survivors. Subsequently, at day 14, differences of IL-6 and LDH levels has become more pronounced between subgroups. Restoration of absolute lymphocyte count (ALC) by day 7 and 14 was insufficient among patients who died.In our cohort, administration of high-dose tocilizumab for COVID-19 patients with CRS demonstrated clinical and sustained biochemical parameter improvement in 76.4%. In this patient population high and increasing LDH, IL-6, and low ALC levels had a predictive role for mortality.