Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study. (October 2020)

• Record Type: Journal Article
• Authors: Biran, Noa; Ip, Andrew; Ahn, Jaeil; Go, Ronaldo C; Wang, Shuqi; Mathura, Shivam; Sinclaire, Brittany A; Bednarz, Urszula; Marafelias, Michael; Hansen, Eric; Siegel, David S; Goy, Andre H; Pecora, Andrew L; Sawczuk, Ihor S; Koniaris, Lauren S; Simwenyi, Micky; Varga, Daniel W; Tank, Lisa K; Stein, Aaron A; Allusson, Valerie; Lin, George S; Oser, William F; Tuma, Roman A; Reichman, Joseph; Brusco, Louis; Carpenter, Kim L; Costanzo, Eric J; Vivona, Vincent; Goldberg, Stuart L
• Is Part Of: Lancet. Volume 2:Number 10(2020)
• Page Start: e603
• Page End: e612
• Publication Date: 2020-10
• Subjects: Rheumatology -- periodicals; 616.72305
• DOI: 10.1016/S2665-9913(20)30277-0
• Languages: English
• ISSNs: 2665-9913

Abstract

Summary: 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. Funding: None.