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Cited by 535COVID-19 Clinical Research StudiesRespiratory Support and MechanismsSepsis Diagnosis and Treatment

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

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Gupta, Shruti, Wang, Wei, Hayek, Salim S., Chan, Lili, Mathews, Kusum S., Melamed, Michal L., Brenner, Samantha K., Leonberg-Yoo, Amanda +334 more·2021·JAMA Internal Medicine
DOI 10.1001/jamainternmed.2020.6252PMC PMC7577201
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Abstract

Importance: 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. Objective: To test whether tocilizumab decreases mortality in this population. Design, Setting, and Participants: 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. Exposures: Treatment with tocilizumab in the first 2 days of ICU admission. Main Outcomes and Measures: Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results: 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%). Conclusions and Relevance: 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.

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  • For critically ill patients, starting tocilizumab within the first two ICU days was linked to lower in-hospital death risk.

    “In contrast, among critically ill patients, the risk of in-hospital mortality was lower in patients treated with tocilizumab in the first 2 days of ICU admission (Gupta et al., 2021)”

    From COVID-19 and the human innate immune system (2021) · cites this paper as Gupta et al., 2021

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  1. Meng Y, Liao YB, Xu P, Wei WR, Wang J. Statin use and mortality of patients with prostate cancer. Onco Targets Ther. 2016;9:1689-1696.

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Gupta, S., Wang, W., Hayek, S. S., Chan, L., Mathews, K. S., Melamed, M. L., Brenner, S. K., Leonberg-Yoo, A., Schenck, E. J., Radbel, J., Reiser, J., Bansal, A., Srivastava, A., Zhou, Y., Finkel, D., Green, A., Mallappallil, M., Faugno, A. J., Zhang, J., Velez, J. C. Q., Shaefi, S., Parikh, C. R., Charytan, D. M., Athavale, A. M., Friedman, A. N., Redfern, R. E., Short, S. A. P., Correa, S., Pokharel, K. K., Admon, A. J., Donnelly, J. P., Gershengorn, H. B., Douin, D. J., Semler, M. W., Hernán, M. A., Leaf, D. E., STOP-COVID Investigators, Walther, C. P., Anumudu, S. J., Arunthamakun, J., Kopecky, K. F., Milligan, G. P., McCullough, P. A., Nguyen, T.-D., Shaefi, S., Krajewski, M. L., Shankar, S., Pannu, A., Valencia, J. D., Waikar, S. S., Kibbelaar, Z. A., Athavale, A. M., Hart, P., Upadhyay, S., Vohra, I., Oyintayo, A., Green, A., Rachoin, J.-S., Schorr, C. A., Shea, L., Edmonston, D. L., Mosher, C. L., Shehata, A. M., Cohen, Z., Allusson, V., Bambrick-Santoyo, G., Bhatti, N. U. A., Mehta, B., Williams, A., Brenner, S. K., Walters, P., Go, R. C., Rose, K. M., Hernán, M. A., Lisk, R., Zhou, A. M., Kim, E. C., Chan, L., Mathews, K. S., Coca, S. G., Altman, D. R., Saha, A., Soh, H., Wen, H. H., Bose, S., Leven, E. A., Wang, J. G., Mosoyan, G., Nadkarni, G. N., Pattharanitima, P., Gallagher, E. J., Friedman, A. N., Guirguis, J., Kapoor, R., Meshberger, C., Kelly, K. J., Parikh, C. R., Garibaldi, B. T., Corona-Villalobos, C. P., Wen, Y., Menez, S., Malik, R. F., Cervantes, C. E., Gautam, S. C., Mallappallil, M. C., Ouyang, J., John, S., Yap, E., Melaku, Y., Mohamed, I., Bajracharya, S., Puri, I., Thaxton, M., Bhattacharya, J., Wagner, J., Boudourakis, L., Nguyen, H. B., Ahoubim, A., Kashani, K., Tehranian, S., Thomas, L. F., Sirganagari, D. R., Guru, P. K., Zhou, Y., Bergl, P. A., Rodriguez, J., Shah, J. A., Gupta, M. S., Kumar, P. N., Lazarous, D. G., Kassaye, S. G., Melamed, M. L., Johns, T. S., Mocerino, R., Prudhvi, K., Zhu, D., Levy, R. V., Azzi, Y., Fisher, M., Yunes, M., Sedaliu, K., Golestaneh, L., Brogan, M., Kumar, N., Chang, M., Thakkar, J., Raichoudhury, R., Athreya, A., Farag, M., Schenck, E. J., Cho, S. J., Plataki, M., Alvarez-Mulett, S. L., Gomez-Escobar, L. G., Pan, D., Lee, S., Krishnan, J., Whalen, W., Charytan, D., Macina, A., Chaudhry, S., Wu, B., Modersitzki, F., Srivastava, A., Leidner, A. S., Martinez, C., Kruser, J. M., Wunderink, R. G., Hodakowski, A. J., Velez, J. C. Q., Price-Haywood, E. G., Matute-Trochez, L. A., Hasty, A. E., Mohamed, M. M., Avasare, R. S., Zonies, D., Leaf, D. E., Gupta, S., Sise, M. E., Newman, E. T., Omar, S. A., Pokharel, K. K., Sharma, S., Singh, H., Correa, S., Shaukat, T., Kamal, O., Wang, W., Yang, H., Boateng, J. O., Lee, M., Strohbehn, I. A., Li, J., Mueller, A. L., Redfern, R. E., Cairl, N. S., Naimy, G., Abu-Saif, A., Hall, D., Bickley, L., Rowan, C., Madhani-Lovely, F., Peev, V., Reiser, J., Byun, J. J., Vissing, A., Kapania, E. M., Post, Z., Patel, N. P., Hermes, J.-M., Sutherland, A. K., Patrawalla, A., Finkel, D. G., Danek, B. A., Arikapudi, S., Paer, J. M., Cangialosi, P., Liotta, M., Radbel, J., Puri, S., Sunderram, J., Scharf, M. T., Ahmed, A., Berim, I., Vatson, J. S., Anand, S., Levitt, J. E., Garcia, P., Boyle, S. M., Song, R., Arif, A., Zhang, J., Woo, S. H., Deng, X., Katz-Greenberg, G., Senter, K., Sharshir, M. A., Rusnak, V. V., Ali, M. I., Peters, T., Hughes, K., Bansal, A., Podoll, A. S., Chonchol, M., Sharma, S., Burnham, E. L., Douin, D. J., Rashidi, A., Hejal, R., Judd, E., Latta, L., Tolwani, A., Albertson, T. E., Adams, J. Y., Chang, S. Y., Beutler, R. M., Schulze, C. E., Macedo, E., Rhee, H., Liu, K. D., Jotwani, V. K., Koyner, J. L., Shah, C. V., Jaikaransingh, V., Toth-Manikowski, S. M., Joo, M. J., Lash, J. P., Neyra, J. A., Chaaban, N., Elias, M., Ahmad, Y., Iardino, A., Au, E. H., Sharma, J. H., Sosa, M. A., Taldone, S., Contreras, G., Zerda, D. D. L., Fornoni, A., Gershengorn, H. B., Hayek, S. S., Blakely, P., Berlin, H., Azam, T. U., Shadid, H., Pan, M., O’ Hayer, P., Meloche, C., Feroze, R., Padalia, K. J., Bitar, A., Leya, J., Donnelly, J. P., Admon, A. J., Flythe, J. E., Tugman, M. J., Chang, E. H., Brown, B. R., Leonberg-Yoo, A. K., Spiardi, R. C., Miano, T. A., Roche, M. S., Vasquez, C. R., Bansal, A. D., Ernecoff, N. C., Kapoor, S., Verma, S., Chen, H., Kovesdy, C. P., Molnar, M. Z., Azhar, A., Hedayati, S. S., Nadamuni, M. V., Shastri, S., Willett, D. L., Short, S. A. P., Renaghan, A. D., Enfield, K. B., Bhatraju, P. K., Malik, A. B., Semler, M. W., Vijayan, A., Joy, C. M., Li, T., Goldberg, S., Kao, P. F., Schumaker, G. L., Goyal, N., Faugno, A. J., Hsu, C. M., Tariq, A., Meyer, L., Kshirsagar, R. K., Jose, A., Weiner, D. E., Christov, M., Griffiths, J., Gupta, S., Kapoor, A., Wilson, P., Arora, T., & Ugwuowo, U.
Affiliations
  • Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • Department of Medicine, Division of Infectious Diseases, New Jersey Medical School, Rutgers University, Newark
  • Division of Nephrology, Kings County Hospital Center, New York City Health and Hospital Corporation, Brooklyn, New York
  • Division of Nephrology, Department of Medicine, NYU (New York University) Langone Medical Center, New York, New York
  • for the STOP-COVID Investigators
  • University of Colorado Anschutz (US)
  • Brigham and Women's Hospital (US)
ORCID
Venue
JAMA Internal Medicine
Publisher
American Medical Association (AMA)
Published
2021-01-01
Volume
181
Issue
1
Pages
41
ISSN
2168-6106 (ISSN-L)
DOI
10.1001/jamainternmed.2020.6252
PMC
PMC7577201
OpenAlex
W3094209984
Cited by
535
References
41
Citations by year
2026: 11 · 2025: 37 · 2024: 54 · 2023: 64 · 2022: 119 · 2021: 226 · 2020: 23
FWCI
14.17
Type
journal article
Language
en
Open access
Locations
  • JAMA Internal Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • Purdue University Indianapolis (Indiana University) (submittedVersion)
Funders
  • National Institutes of Health (UL1TR001422, UL1TR002389, UL1TR001863)
  • National Institute on Aging (R03AG060179)
  • National Heart, Lung, and Blood Institute (R01HL153384, L30 HL149016, F32HL149337, K23HL143053, R01HL085757, R01HL144566, K23HL130648, K12HL138039, T32HL087738)
  • National Institute on Deafness and Other Communication Disorders (F32DC017342)
  • National Institute of General Medical Sciences (K08GM134220)
  • National Institute of Allergy and Infectious Diseases (R37AI102634)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K23DK120811, K23DK116967, P30DK114857, R01DK125786)
  • National Institute of Environmental Health Sciences (P30ES005022)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
Keywords
COVID-19 pandemic, critically ill patients, mortality, IL-6 receptor, cytokine release syndrome, intensive care unit, 30-day mortality, early treatment, hypoxemia, mechanical ventilation, inverse probability weighting, monoclonal antibody therapy, SARS-CoV-2, cytokine storm, prognostic factors
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Adolescent, Adrenal Cortex Hormones, Adult, Aged, Anticoagulants, Female, Hospitalization, Humans, Intensive Care Units, Male, Middle Aged, Mortality, Respiration, Artificial, Respiratory Insufficiency, Cohort Studies, Proportional Hazards Models, Critical Illness, Prone Position, Hospital Mortality, Receptors, Interleukin-6, Young Adult, Patient Positioning, Antibodies, Monoclonal, Humanized, Early Medical Intervention, Organ Dysfunction Scores

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