Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. 2021

Shruti Gupta, and Wei Wang, and Salim S Hayek, and Lili Chan, and Kusum S Mathews, and Michal L Melamed, and Samantha K Brenner, and Amanda Leonberg-Yoo, and Edward J Schenck, and Jared Radbel, and Jochen Reiser, and Anip Bansal, and Anand Srivastava, and Yan Zhou, and Diana Finkel, and Adam Green, and Mary Mallappallil, and Anthony J Faugno, and Jingjing Zhang, and Juan Carlos Q Velez, and Shahzad Shaefi, and Chirag R Parikh, and David M Charytan, and Ambarish M Athavale, and Allon N Friedman, and Roberta E Redfern, and Samuel A P Short, and Simon Correa, and Kapil K Pokharel, and Andrew J Admon, and John P Donnelly, and Hayley B Gershengorn, and David J Douin, and Matthew W Semler, and Miguel A Hernán, and David E Leaf, and
Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. To test whether tocilizumab decreases mortality in this population. The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Treatment with tocilizumab in the first 2 days of ICU admission. Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.

UI MeSH Term Description Entries
D007362 Intensive Care Units Hospital units providing continuous surveillance and care to acutely ill patients. ICU Intensive Care Units,Intensive Care Unit,Unit, Intensive Care
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009026 Mortality All deaths reported in a given population. CFR Case Fatality Rate,Crude Death Rate,Crude Mortality Rate,Death Rate,Age Specific Death Rate,Age-Specific Death Rate,Case Fatality Rate,Decline, Mortality,Determinants, Mortality,Differential Mortality,Excess Mortality,Mortality Decline,Mortality Determinants,Mortality Rate,Mortality, Differential,Mortality, Excess,Age-Specific Death Rates,Case Fatality Rates,Crude Death Rates,Crude Mortality Rates,Death Rate, Age-Specific,Death Rate, Crude,Death Rates,Determinant, Mortality,Differential Mortalities,Excess Mortalities,Mortalities,Mortality Declines,Mortality Determinant,Mortality Rate, Crude,Mortality Rates,Rate, Age-Specific Death,Rate, Case Fatality,Rate, Crude Death,Rate, Crude Mortality,Rate, Death,Rate, Mortality,Rates, Case Fatality
D012121 Respiration, Artificial Any method of artificial breathing that employs mechanical or non-mechanical means to force the air into and out of the lungs. Artificial respiration or ventilation is used in individuals who have stopped breathing or have RESPIRATORY INSUFFICIENCY to increase their intake of oxygen (O2) and excretion of carbon dioxide (CO2). Ventilation, Mechanical,Mechanical Ventilation,Artificial Respiration,Artificial Respirations,Mechanical Ventilations,Respirations, Artificial,Ventilations, Mechanical
D012131 Respiratory Insufficiency Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed) Acute Hypercapnic Respiratory Failure,Acute Hypoxemic Respiratory Failure,Hypercapnic Acute Respiratory Failure,Hypercapnic Respiratory Failure,Hypoxemic Acute Respiratory Failure,Hypoxemic Respiratory Failure,Respiratory Depression,Respiratory Failure,Ventilatory Depression,Depressions, Ventilatory,Failure, Hypercapnic Respiratory,Failure, Hypoxemic Respiratory,Failure, Respiratory,Hypercapnic Respiratory Failures,Hypoxemic Respiratory Failures,Respiratory Failure, Hypercapnic,Respiratory Failure, Hypoxemic,Respiratory Failures
D005260 Female Females
D006760 Hospitalization The confinement of a patient in a hospital. Hospitalizations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000086382 COVID-19 A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent. 2019 Novel Coronavirus Disease,2019 Novel Coronavirus Infection,2019-nCoV Disease,2019-nCoV Infection,COVID-19 Pandemic,COVID-19 Pandemics,COVID-19 Virus Disease,COVID-19 Virus Infection,Coronavirus Disease 2019,Coronavirus Disease-19,SARS Coronavirus 2 Infection,SARS-CoV-2 Infection,Severe Acute Respiratory Syndrome Coronavirus 2 Infection,COVID19,2019 nCoV Disease,2019 nCoV Infection,2019-nCoV Diseases,2019-nCoV Infections,COVID 19,COVID 19 Pandemic,COVID 19 Virus Disease,COVID 19 Virus Infection,COVID-19 Virus Diseases,COVID-19 Virus Infections,Coronavirus Disease 19,Disease 2019, Coronavirus,Disease, 2019-nCoV,Disease, COVID-19 Virus,Infection, 2019-nCoV,Infection, COVID-19 Virus,Infection, SARS-CoV-2,Pandemic, COVID-19,SARS CoV 2 Infection,SARS-CoV-2 Infections,Virus Disease, COVID-19,Virus Infection, COVID-19

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