Tags

Type your tag names separated by a space and hit enter

Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia.
Clin Infect Dis. 2020 12 15; 71(12):3168-3173.CI

Abstract

BACKGROUND

Preliminary data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is approved by the Food and Drug Administration for treatment of cytokine storm associated with chimeric antigen receptor T-cell therapy. Here we examined compassionate use of tocilizumab in patients with SARS-CoV-2 pneumonia.

METHODS

We report on a single-center study of tocilizumab in hospitalized patients with SARS-CoV-2 pneumonia. All patients had confirmed SARS-CoV-2 pneumonia and oxygen saturations <90% on oxygen support with most intubated. We examined clinical and laboratory parameters including oxygen and vasopressor requirements, cytokine profiles, and C-reactive protein (CRP) levels pre- and post-tocilizumab treatment.

RESULTS

Twenty-seven SARS-CoV-2 pneumonia patients received one 400 mg dose of tocilizumab. Interleukin (IL)-6 was the predominant cytokine detected at tocilizumab treatment. Significant reductions in temperature and CRP were seen post-tocilizumab. However, 4 patients did not show rapid CRP declines, of whom 3 had poorer outcomes. Oxygen and vasopressor requirements diminished over the first week post-tocilizumab. Twenty-two patients required mechanical ventilation; at last follow-up, 16 were extubated. Adverse events and serious adverse events were minimal, but 2 deaths (7.4%) occurred that were felt unrelated to tocilizumab.

CONCLUSIONS

Compared to published reports on the morbidity and mortality associated with SARS-CoV-2, tocilizumab appears to offer benefits in reducing inflammation, oxygen requirements, vasopressor support, and mortality. The rationale for tocilizumab treatment is supported by detection of IL-6 in pathogenic levels in all patients. Additional doses of tocilizumab may be needed for those showing slow declines in CRP. Proof of efficacy awaits randomized, placebo-controlled clinical trials.

Authors+Show Affiliations

Department of Medicine, Division of Nephrology, Transplant Immunology Laboratory, Transplant Immunotherapy Program, Los Angeles, California, USA.Division of Infectious Diseases, Los Angeles, California, USA.Department of Pharmacy Services, Los Angeles, California, USA.Department of Pharmacy Services, Los Angeles, California, USA.Division of Infectious Diseases, Los Angeles, California, USA.Department of Pharmacy Services, Los Angeles, California, USA.Division of Infectious Diseases, Los Angeles, California, USA.Division of Infectious Diseases, Los Angeles, California, USA.Division of Infectious Diseases, Los Angeles, California, USA.Division of Infectious Diseases, Los Angeles, California, USA.Division of Infectious Diseases, Los Angeles, California, USA.Department of Pharmacy Services, Los Angeles, California, USA.Department of Medicine, Division of Nephrology, Transplant Immunology Laboratory, Transplant Immunotherapy Program, Los Angeles, California, USA.Department of Medicine, Division of Nephrology, Transplant Immunology Laboratory, Transplant Immunotherapy Program, Los Angeles, California, USA.Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.Department of Medicine, Division of Nephrology, Transplant Immunology Laboratory, Transplant Immunotherapy Program, Los Angeles, California, USA.Department of Medicine, Division of Nephrology, Transplant Immunology Laboratory, Transplant Immunotherapy Program, Los Angeles, California, USA.Department of Medicine, Division of Nephrology, Transplant Immunology Laboratory, Transplant Immunotherapy Program, Los Angeles, California, USA.Department of Medicine, Division of Nephrology, Transplant Immunology Laboratory, Transplant Immunotherapy Program, Los Angeles, California, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32575124

Citation

Jordan, Stanley C., et al. "Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 71, no. 12, 2020, pp. 3168-3173.
Jordan SC, Zakowski P, Tran HP, et al. Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia. Clin Infect Dis. 2020;71(12):3168-3173.
Jordan, S. C., Zakowski, P., Tran, H. P., Smith, E. A., Gaultier, C., Marks, G., Zabner, R., Lowenstein, H., Oft, J., Bluen, B., Le, C., Shane, R., Ammerman, N., Vo, A., Chen, P., Kumar, S., Toyoda, M., Ge, S., & Huang, E. (2020). Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 71(12), 3168-3173. https://doi.org/10.1093/cid/ciaa812
Jordan SC, et al. Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia. Clin Infect Dis. 2020 12 15;71(12):3168-3173. PubMed PMID: 32575124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia. AU - Jordan,Stanley C, AU - Zakowski,Phillip, AU - Tran,Hai P, AU - Smith,Ethan A, AU - Gaultier,Cyril, AU - Marks,Gregory, AU - Zabner,Rachel, AU - Lowenstein,Hayden, AU - Oft,Jillian, AU - Bluen,Benjamin, AU - Le,Catherine, AU - Shane,Rita, AU - Ammerman,Noriko, AU - Vo,Ashley, AU - Chen,Peter, AU - Kumar,Sanjeev, AU - Toyoda,Mieko, AU - Ge,Shili, AU - Huang,Edmund, PY - 2020/04/23/received PY - 2020/06/15/accepted PY - 2020/6/24/pubmed PY - 2021/1/28/medline PY - 2020/6/24/entrez KW - COVID-19 KW - SARS-CoV2 KW - acute respiratory distress syndrome KW - interleukin 6 SP - 3168 EP - 3173 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin Infect Dis VL - 71 IS - 12 N2 - BACKGROUND: Preliminary data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is approved by the Food and Drug Administration for treatment of cytokine storm associated with chimeric antigen receptor T-cell therapy. Here we examined compassionate use of tocilizumab in patients with SARS-CoV-2 pneumonia. METHODS: We report on a single-center study of tocilizumab in hospitalized patients with SARS-CoV-2 pneumonia. All patients had confirmed SARS-CoV-2 pneumonia and oxygen saturations <90% on oxygen support with most intubated. We examined clinical and laboratory parameters including oxygen and vasopressor requirements, cytokine profiles, and C-reactive protein (CRP) levels pre- and post-tocilizumab treatment. RESULTS: Twenty-seven SARS-CoV-2 pneumonia patients received one 400 mg dose of tocilizumab. Interleukin (IL)-6 was the predominant cytokine detected at tocilizumab treatment. Significant reductions in temperature and CRP were seen post-tocilizumab. However, 4 patients did not show rapid CRP declines, of whom 3 had poorer outcomes. Oxygen and vasopressor requirements diminished over the first week post-tocilizumab. Twenty-two patients required mechanical ventilation; at last follow-up, 16 were extubated. Adverse events and serious adverse events were minimal, but 2 deaths (7.4%) occurred that were felt unrelated to tocilizumab. CONCLUSIONS: Compared to published reports on the morbidity and mortality associated with SARS-CoV-2, tocilizumab appears to offer benefits in reducing inflammation, oxygen requirements, vasopressor support, and mortality. The rationale for tocilizumab treatment is supported by detection of IL-6 in pathogenic levels in all patients. Additional doses of tocilizumab may be needed for those showing slow declines in CRP. Proof of efficacy awaits randomized, placebo-controlled clinical trials. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/32575124/Compassionate_Use_of_Tocilizumab_for_Treatment_of_SARS_CoV_2_Pneumonia_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciaa812 DB - PRIME DP - Unbound Medicine ER -