Public Health and Primary CareORIGINAL ARTICLE

The role of tocilizumab therapy in critically ill patients with severe acute respiratory syndrome coronavirus 2

Zaid Saffo, DO; Weixia Guo, MD, MSc; Kylie Springer, MS; Kathleen Maksimowicz-McKinnon, DO; Vivek Kak, MD; John E. McKinnon, MD, MSc; and Pallavi Bhargava, MD
Notes and Affiliations
Notes and Affiliations

Received: November 10, 2020

Accepted: March 29, 2021

Published: July 9, 2021

  • Zaid Saffo, DO, 

    Division of Rheumatology, Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA

  • Weixia Guo, MD, MSc, 

    Division of Rheumatology, Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA

  • Kylie Springer, MS, 

    Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA

  • Kathleen Maksimowicz-McKinnon, DO, 

    Division of Rheumatology, Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA

  • Vivek Kak, MD, 

    Division of Infectious Disease, Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA

  • John E. McKinnon, MD, MSc, 

    Division of Infectious Disease, Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA

  • Pallavi Bhargava, MD, 

    Division of Infectious Disease, Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA

Abstract

Context: Tocilizumab (TCZ), an interleukin-6 (IL-6) receptor antagonist, has been approved for use in rheumatoid arthritis and cytokine storm syndrome (CSS) associated with chimeric antigen receptor T cells treatment. Although TCZ is currently utilized in the treatment of critically ill coronavirus 2019 (COVID-19) patients, data on survival impact is minimal.

Objectives: To assess the mortality rate of patients presenting with COVID-19 who received TCZ for suspected CSS.

Methods: This retrospective cohort study was conducted at Henry Ford Health System between March 10, 2020 and May 18, 2020. Data collection began in May 2020 and was completed in June 2020. Patients included in the study required hospital admission and had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction on nasopharyngeal swab. Eligibility criteria to receive TCZ, per hospital protocol, included any of the following: persistent fever, defined as 38.0 °C for at least 6 hours; a diagnosis of the acute respiratory distress syndrome (ARDS); serum ferritin ≥1,000 (ng/mL) or doubling within 24 hours; D-Dimer ≥ 5 (mg/L); serum lactate dehydrogenase ≥500 (IU/L); or interlukin-6 level ≥5 times the upper limit of normal. Dosing was initially determined by weight, then changed to a fixed 400 mg per hospital protocol. A comparator cohort was created from patients with COVID-19 and ARDS who did not receive TCZ. Patient survival was analyzed using the Kaplan–Meier method and compared by log rank test. A multivariable cox regression was applied to evaluate the association between TCZ and mortality.

Results: One hundred and thirty patients were evaluated in the study, 54 (41.5%) of whom received TCZ. Patients who received TCZ were younger (mean age, 63.8 vs. 69.4 years; p=0.0083) and had higher body mass indices (mean, 33.9 vs. 30.4; p=0.005). Of the comorbid conditions evaluated, heart disease was more common in the comparator group than the TCZ group (27 patients [35.5%] vs. 10 patients [18.5%]; p=0.034). A Kaplan–Meier survival curve demonstrated no difference in survival between TCZ and comparator patients (log rank p=0.495). In the multivariable Cox regression model for mortality at 30 days, treatment with TCZ was not associated with decreased mortality (hazard ratio, 1.1; 95% confidence interval, 0.53–2.3; p=0.77). Lower mean C-reactive protein (CRP) levels were demonstrated within 48 hours of disposition in the TCZ group (mean TCZ, 4.9 vs. mean comparator, 13.0; p=<0.0001).

Conclusions: In this cohort study, no difference in survival was observed in critically ill patients treated with TCZ.

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