Tocilizumab Versus Baricitinib in Patients Hospitalized With COVID-19 Pneumonia and Hypoxemia: A Multicenter Retrospective Cohort Study.
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ABSTRACT: Design
Retrospective cohort study.Setting
Seven inpatient acute-care hospitals in Wisconsin.Participants
Patients hospitalized with COVID-19, hypoxemia, and Pao2-to-Fio2 ratio less than or equal to 300 mm Hg, who received either tocilizumab or baricitinib.Interventions
Electronic chart review.Measurements and main results
Patients were divided into tocilizumab and baricitinib cohorts based on actual medication received. The primary outcome was hospital discharge alive and free from mechanical ventilation within 60 days, assessed by logistic regression. Three hundred eighty-two patients were included: 194 in the tocilizumab cohort and 188 in the baricitinib cohort. Most baseline characteristics in the two cohorts were similar. All patients received dexamethasone. Two patients were lost to follow-up. In the remaining 380 patients, probability of successful discharge in the two cohorts was quantitatively similar in unadjusted, multivariate-adjusted, and propensity score-matched analyses. Hospital length of stay, rates of thromboembolic events, and rates of hospital-acquired infections were all similar in the two cohorts.Conclusions
In patients hospitalized with COVID-19 pneumonia and hypoxemia who receive dexamethasone, treatment with tocilizumab or baricitinib appears to result in similar outcomes.
SUBMITTER: Roddy J
PROVIDER: S-EPMC9243240 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCoronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear.MethodsWe randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28.ResultsA total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P?=?0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -?5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group.ConclusionsIn hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).
| S-EPMC7781101 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.MethodsIn this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo.ResultsOf the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P = 0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points; 95% CI, -7.6 to 8.2; nominal P = 0.94).ConclusionsIn this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann-La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.).
| S-EPMC7953459 | biostudies-literature
Project description:Introduction and objectivesTocilizumab is an interleukin-6 receptor-blocking agent proposed for the treatment of severe COVID-19; however, limited data are available on their efficacy. The aim of this study was to assess the effect of tocilizumab on the outcomes of patients with COVID-19 pneumonia by using propensity-score-matching (PSM) analysis.MethodsA retrospective observational analysis of hospitalized COVID-19 adult patients admitted to the Vall d'Hebron Hospital was performed between March and April 2020. We used the logistic regression to analyze the effect of tocilizumab on mortality, as main outcome, and PSM analysis to further validate their effect. Secondary outcomes were length-of-stay (LOS) and intensive-care-unit (ICU) stay. Same outcomes were also assessed for early tocilizumab administration, within 72h after admission. Patients were selected by matching their individual propensity for receiving therapy with tocilizumab, conditional on their demographic and clinical variables.ResultsA total of 544 COVID-19 patients were included, 197 (36.2%) were treated with tocilizumab of whom 147 were treated within the first 72h after admission; and 347 were included in the control group. After PSM analyses, the results showed no association between tocilizumab use and overall mortality (OR=1.03, 95%CI: 0.63-1.68). However, shorter ICU-stay in the tocilizumab group was found compared to the control group (Coefficient -4.27 95%CI: -6.63 to -1.92). Similar results were found in the early tocilizumab cohort.ConclusionsThe administration of tocilizumab in patients with moderate to severe COVID-19 did not reduce the risk of mortality in our cohort of patients, regardless of the time of administration.
| S-EPMC8101781 | biostudies-literature
Project description:Tocilizumab, an anti-interleukin-6 receptor, administrated during the right timeframe may be beneficial against coronavirus-disease-2019 (COVID-19) pneumonia. All patients admitted for severe COVID-19 pneumonia (SpO2 ? 96% despite O2-support ? 6 L/min) without invasive mechanical ventilation were included in a retrospective cohort study in a primary care hospital. The treatment effect of a single-dose, 400 mg, of tocilizumab was assessed by comparing those who received tocilizumab to those who did not. Selection bias was mitigated using three statistical methods. Primary outcome measure was a composite of mortality and ventilation at day 28. A total of 246 patients were included (106 were treated with tocilizumab). Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-day follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes than the control group (hazard ratio (HR) = 0.49 (95% confidence interval (95%CI) = 0.3-0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95%CI = 0.135-0.51, p = 0.0001), confirmed by inverse probability score weighting (IPSW) analysis (p < 0.0001). Analyses on mortality only, with 28 days of follow-up, yielded similar results. In this study, tocilizumab 400 mg in a single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.
| S-EPMC7603074 | biostudies-literature
Project description:ObjectiveTo evaluate the effectiveness of Tocilizumab (with or without corticosteroids) in a real-life context among moderate-to-severe COVID-19 patients hospitalized at the Infectious Diseases ward of two hospitals in Lazio region, Italy, during the first wave of SARS-CoV-2 pandemic.MethodWe conducted a retrospective cohort study among moderate-to-severe COVID-19 pneumonia to assess the influence of tocilizumab (with or without corticosteroids) on: 1) primary composite outcome: risk for death/invasive mechanical ventilation/ICU-transfer at 14 days from hospital admission; 2) secondary outcome: COVID-related death only. Both outcomes were also assessed at 28 days and restricted to baseline more severe cases. We also evaluated the safety of tocilizumab.ResultsOverall, 412 patients were recruited, being affected by mild (6.8%), moderate (66.3%) or severe (26.9%) COVID-19 at baseline. The median participant' age was 63 years, 56.5% were men, the sum of comorbidities was 1.34 (±1.44), and the median time from symptom onset to hospital admission was 7 [3-10] days. Patients were subdivided in 4 treatment groups: standard of care (SoC) only (n = 172), SoC plus corticosteroid (n = 65), SoC plus tocilizumab (n = 50), SoC plus tocilizumab and corticosteroid (n = 125). Twenty-six (6.3%) patients underwent intubation, and 37 (9%) COVID-related deaths were recorded. After adjusting for several factors, multivariate analysis showed that tocilizumab (with or without corticosteroids) was associated to improved primary and secondary outcomes at 14 days, and at 28-days only when tocilizumab administered without corticosteroid. Among more severe cases the protective effect of tocilizumab (± corticosteroids) was observed at both time-points. No safety concerns were recorded.ConclusionAlthough contrasting results from randomized clinical trials to date, in our experience tocilizumab was a safe and efficacious therapeutic option for patients with moderate-to-severe COVID-19 pneumonia. Its efficacy was improved by the concomitant administration of corticosteroids in patients affected by severe-COVID-19 pneumonia at baseline.
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Project description:BackgroundThere is currently no single treatment that mitigates all harms caused by severe acute respiratory syndrome coronavirus 2 infection. Tocilizumab, an interleukin-6 antagonist, may have a role as an adjunctive immune-modulating therapy.MethodsThis was an observational retrospective study of hospitalized adult patients with confirmed coronavirus disease 2019 (COVID-19). The intervention group comprised patients who received tocilizumab; the comparator arm was drawn from patients who did not receive tocilizumab. The primary outcome was all-cause mortality censored at 28 days; secondary outcomes were all-cause mortality at discharge, time to clinical improvement, and rates of secondary infections. Marginal structural Cox models via inverse probability treatment weights were applied to estimate the effect of tocilizumab. A time-dependent propensity score-matching method was used to generate a 1:1 match for tocilizumab recipients; infectious diseases experts then manually reviewed these matched charts to identify secondary infections.ResultsThis analysis included 90 tocilizumab recipients and 1669 controls. Under the marginal structural Cox model, tocilizumab was associated with a 62% reduced hazard of death (adjusted hazard ratio [aHR], 0.38; 95% CI, 0.21 to 0.70) and no change in time to clinical improvement (aHR, 1.13; 95% CI, 0.68 to 1.87). The 1:1 matched data set also showed a lower mortality rate (27.8% vs 34.4%) and reduced hazards of death (aHR, 0.47; 95% CI, 0.25 to 0.88). Elevated inflammatory markers were associated with reduced hazards of death among tocilizumab recipients compared with controls. Secondary infection rates were similar between the 2 groups.ConclusionsTocilizumab may provide benefit in a subgroup of patients hospitalized with COVID-19 who have elevated biomarkers of hyperinflammation, without increasing the risk of secondary infection.
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Project description:Introduction: COVID-19 patients with hypotension and hypoxemia had a significantly worse outcome. The purpose of this research was to ascertain the risk factors affecting the prognoses of these patients and to develop appropriate prognostic prediction tools. Methods: From March 1, 2020, to April 16, 2020, a retrospective cohort analysis of COVID-19 patients with hypotension and hypoxemia was performed. The univariate and multivariate analyses were performed to identify the associated risk factors influencing the prognosis of COVID-19 patients with hypotension and hypoxemia, and the selected variables were then utilized to construct and validate the prediction model for these patients. Results: Three hundred and twenty-seven COVID-19 patients with hypotension and hypoxemia who met the inclusion and exclusion criteria were included in this study. Age, temperature, troponin, and blood glucose were related to mortality in COVID-19 patients with hypotension and hypoxemia in both univariate and multivariate analyses. The MFP model (multiple fractional polynomial model), full model, and stepwise model were utilized to build the prediction model, and their AUCs were, respectively, 0.902 (0.868, 0.936), 0.902 (0.868, 0.936), and 0.902 (0.868, 0.936). Because the sample size for this research was limited, we utilized bootstrapping for internal validation. The AUCs of Bootstrap full and Bootstrap stepwise were 0.902 (0.867, 0.936) and 0.902 (0.868, 0.936), respectively. Conclusion: Age, temperature, troponin, and blood glucose levels were associated with mortality in COVID-19 patients with hypotension and hypoxemia. Additionally, the prediction model developed using the variables above showed a high predictive value for predicting the prognosis of these individuals.
| S-EPMC8581201 | biostudies-literature
Project description:BackgroundSeveral anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib.MethodsThe matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020.ResultsRuxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6-14.6%]) vs 13.0% (95% CI [7.5-18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31-1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11-1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8-16 mg dexamethasone).ConclusionsRuxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date.
| S-EPMC8693127 | biostudies-literature
Project description:ObjectivesThe purpose of this study is to evaluate clinical outcomes in patients with critical COVID-19 pneumonia requiring invasive mechanical ventilation who were treated with tocilizumab DESIGN: Single-center retrospective cohort study SETTING: Stony Brook University Hospital, a 600-bed academic tertiary medical center in Suffolk County, New York PARTICIPANTS: Consecutive patients with COVID-19 confirmed by nasopharyngeal polymerase chain reaction (PCR) who were admitted to Stony Brook University Hospital between March 10 and April 2 2020 and required mechanical ventilation in any intensive care unit during their hospitalization EXPOSURE: Treatment with tocilizumab while intubated MAIN OUTCOME: Overall mortality 30 days from the date of intubation RESULTS: Forty-five patients received tocilizumab compared to seventy controls. Baseline demographic characteristics, inflammatory markers, treatment with corticosteroids, and sequential organ failure assessment (SOFA) scores were similar between the two cohorts. Patients who received tocilizumab had significantly lower Charlson co-morbidity index (2.0 vs 3.0,P = 0.01) than controls. There was a trend towards younger mean age in the tocilizumab exposed group (56.2 vs 60.6; P = 0.09). In logistic regression analysis there was no reduction in mortality associated with receipt of tocilizumab (odds ratio (OR) 1.04; 95% CI, 0.27-3.75). There was no observed increased risk of secondary infection in patients given tocilizumab (28.9 vs 25.7; OR 1.17; 95% CI, 0.51-2.71).ConclusionWhen controlling for age, severity of illness, and co-morbidities, tocilizumab was not associated with reduction in mortality in this retrospective cohort study of mechanically ventilated patients with COVID-19 pneumonia. Further studies are needed to determine the role of tocilizumab in the treatment of COVID-19.
| S-EPMC7836535 | biostudies-literature
Project description:BackgroundThe effect of immunomodulatory therapy with tocilizumab for coronavirus disease 2019 (COVID-19) in real-life clinical practice remains controversial.MethodsSingle-center retrospective matched cohort analysis including 47 consecutive patients treated with intravenous tocilizumab for severe COVID-19 pneumonia ("TCZ group"), matched by age, comorbidities, time from symptoms onset and baseline SpO2/FiO2 ratio with 47 patients receiving standard of care alone ("SoC group").ResultsThere were no significant differences between the TCZ and SoC groups in the rate of clinical improvement (hospital discharge and/or a decrease of ≥2 points on a six-point ordinal scale) by day 7 (51.1% [24/47] versus 48.9% [23/47]; P-value=1.000). No differences were observed at day 14 in terms of clinical improvement (72.3% versus 76.6%; P-value=0.791), all-cause mortality (10.6% versus 12.8%; P-value=1.000), and the composite of invasive mechanical ventilation and/or death (25.5% versus 23.4%; P-value=1.000) either. Patients in the TCZ group had a more rapid normalization of C-reactive protein levels.ConclusionsNo apparent benefit was observed in patients with severe COVID-19 treated with tocilizumab as compared to a matched retrospective cohort.
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