Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
Noa Biran, MD Andrew Ip, PhD Jaeil Ahn, MD Ronaldo C Go, Shuqi Wang, Shivam Mathura, Brittany A Sinclaire, Urszula Bednarz, BS Michael Marafelias, Eric Hansen, David S Siegel, MD Andre H Goy, MD Andrew L Pecora, Ihor S Sawczuk, MD Lauren S Koniaris, Micky Simwenyi, MD, L K Tank MD Daniel W Varga, Lisa K Tank, Aaron A Stein, Valerie Allusson, George S Lin, William F Oser, Roman A Tuma, Joseph Reichman, Louis Brusco Jr, MD Kim L Carpenter, Eric J Costanzo, Vincent Vivona, Stuart L Goldberg
The Lancet Rheumatology, doi:10.1016/s2665-9913(20)30277-0
Background Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19.
Methods We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA). We included patients (aged ≥18 years) with laboratory-confirmed COVID-19 who needed support in the ICU. We obtained data from a prospective observational database and compared outcomes in patients who received tocilizumab with those who did not. We applied a multivariable Cox model with propensity score matching to reduce confounding effects. The primary endpoint was hospital-related mortality. The prospective observational database is registered on ClinicalTrials.gov, NCT04347993.
Findings Between March 1 and April 22, 2020, 764 patients with COVID-19 required support in the ICU, of whom 210 (27%) received tocilizumab. Factors associated with receiving tocilizumab were patients' age, gender, renal function, and treatment location. 630 patients were included in the propensity score-matched population, of whom 210 received tocilizumab and 420 did not receive tocilizumab. 358 (57%) of 630 patients died, 102 (49%) who received tocilizumab and 256 (61%) who did not receive tocilizumab. Overall median survival from time of admission was not reached (95% CI 23 days-not reached) among patients receiving tocilizumab and was 19 days (16-26) for those who did not receive tocilizumab (hazard ratio [HR] 0•71, 95% CI 0•56-0•89; p=0•0027). In the primary multivariable Cox regression analysis with propensity matching, an association was noted between receiving tocilizumab and decreased hospital-related mortality (HR 0•64, 95% CI 0•47-0•87; p=0•0040). Similar associations with tocilizumab were noted among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher. Interpretation In this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited.
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