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Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

ABSTRACT: Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

SUBMITTER: Mert A

PROVIDER: S-EPMC8436189 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTocilizumab was approved for chimeric antigen receptor T-cell therapy induced cytokine release syndrome and it may provide clinical benefit for selected COVID-19 patients.MethodsIn this retrospective cohort study, we analyzed hypoxic COVID-19 patients who were consecutively admitted between March 13, 2020 and April 19, 2020. Patients with lung infiltrates and elevated inflammatory markers received a single dose of tocilizumab if no contraindication was present. Systemic steroid, hydroxychloroquine, and azithromycin were concomitantly used for majority of the patients.FindingsOf the 51 patients included for analysis, 28 (55%) received tocilizumab and 23 (45%) did not receive tocilizumab. Tocilizumab cohort required more invasive ventilation (68% vs. 22%) at baseline and during entire hospitalization (75% vs. 48%). The median time to clinical improvement in tocilizumab vs. no tocilizumab cohorts was 8 days (Interquartile range [IQR]: 6·25 - 9·75 days) vs. 13 days (IQR: 9·75 - 15·25 days) among patients who required mechanical ventilation at any time (Hazard ratio for clinical improvement: 1·83, 95% confidence interval [CI]: 0·57 - 5·84) and 6·5 days vs. 7 days among all patients (Hazard ratio for clinical improvement: 1·14, 95% CI: 0·55 - 2·38), respectively. The median duration of vasopressor support and invasive mechanical ventilation were 2 days (IQR: 1·75 - 4·25 days) vs. 5 days (IQR: 4 - 8 days), p = 0.039, and 7 days (IQR: 4 - 14 days) vs. 10 days (IQR: 5 - 15 days) in tocilizumab vs. no tocilizumab cohorts, p = 0.11, respectively. Similar rates of hospital-acquired infections occurred in both cohorts (18% in tocilizumab and 22% in no tocilizumab cohort).InterpretationIn patients with severe COVID-19, tocilizumab was associated with significantly shorter duration of vasopressor support. Although not statistically significant, tocilizumab also resulted in shorter median time to clinical improvement and shorter duration of invasive ventilation. These findings require validation from ongoing clinical trials of Tocilizumab in COVID-19 patients.

Project description:Background:No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment. Methods:This retrospective, observational cohort study included adults (?18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. Findings:Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p<0·0001) patients treated with tocilizumab (six [7%] treated intravenously and seven [8%] treated subcutaneously). After adjustment for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0·61, 95% CI 0·40-0·92; p=0·020). 24 (13%) of 179 patients treated with tocilizumab were diagnosed with new infections, versus 14 (4%) of 365 patients treated with standard of care alone (p<0·0001). Interpretation:Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia. Funding:None.

Project description:BackgroundThe effectiveness of the best combination between different antiviral and anti-inflammatory drugs stills an interest in the treatment of COVID19 infection.Patients and methodsA prospective randomized cohort study comprised 108 adult patients with confirmed PCR COVID 19 infection with systemic hyper inflammation state, divided into two groups according to the treatment regimen, 56 in the tocilizumab- hydroxychloroquine (TCZ-HCQ) treatment, and 52 in the tocilizumab-remdesivir (TCZ-RMV) treatment. The first group received a combination of I.V. TCZ (400-800 mg every 24 h for only two doses) and HCQ (400 mg twice in the first day then 200 mg twice for 5 days) while the second group of patients received I.V. RMV of 200 mg on day 1 followed by 100 mg once daily infused over 60 min for 5 days with the same TCZ regimen used in the first group. All clinical parameters and laboratory investigations were assessed before and after treatment.ResultsThe CRP was significantly decreased while PaO2/FiO2 (P/F) ratio post-treatment was significantly improved in both treatment groups. TCZ-HCQ group showed a significant decrease in the ferritin, LDH, and D. Dimer levels. The median days of hospitalization with interquartile range (IQR) were 10 (6-16) and 8 (5-12) for TCZ-HCQ and TCZ-RMV groups, respectively. The numbers of mechanically ventilated patients were 25 and 43 for TCZ-HCQ and TCZ-RMV groups, respectively. Therapeutic failure was about 26.8% in the TCZ-HCQ group and 30.8% in the TCZ-RMV group but there was no significant difference between both groups. Some complications were recognized only in TCZ-RMV following treatment including secondary bacterial infections (42.3%), myocarditis (15.4%), and finally pulmonary embolism (7.7%).ConclusionEfficacy of both TCZ-RMV and TCZ-HCQ combinations are observed in the treatment of severe COVID-19 patients; however the increased need for ICU or mechanical ventilation in the TCZ-RMV arm contributed to the appearance of cardiac and thrombotic events. The study was registered at the Clinical Trials registry (ClinicalTrials.gov; NCT04779047).

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Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

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