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Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study.
Ann Rheum Dis. 2020 09; 79(9):1143-1151.AR

Abstract

OBJECTIVES

To prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only.

METHODS

From 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein >100 mg/L; ferritin >900 µg/L; D-dimer >1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2-5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.

RESULTS

At baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.

CONCLUSIONS

A strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.

Authors+Show Affiliations

Rheumatology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands sofiaramiro@gmail.com. Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands.Department of Pulmonology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Rheumatology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Rheumatology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Department of Intensive Care, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Department of Internal Medicine, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Department of Pulmonology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Department of Pulmonology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Department of Pulmonology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Department of Pulmonology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Department of Clinical Chemistry and Hematology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Rheumatology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Department of Clinical Pharmacy, Pharmacology and Toxicology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.Rheumatology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands. Amsterdam Rheumatology Center, AMC, Amsterdam, The Netherlands.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

32719045

Citation

Ramiro, Sofia, et al. "Historically Controlled Comparison of Glucocorticoids With or Without Tocilizumab Versus Supportive Care Only in Patients With COVID-19-associated Cytokine Storm Syndrome: Results of the CHIC Study." Annals of the Rheumatic Diseases, vol. 79, no. 9, 2020, pp. 1143-1151.
Ramiro S, Mostard RLM, Magro-Checa C, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Ann Rheum Dis. 2020;79(9):1143-1151.
Ramiro, S., Mostard, R. L. M., Magro-Checa, C., van Dongen, C. M. P., Dormans, T., Buijs, J., Gronenschild, M., de Kruif, M. D., van Haren, E. H. J., van Kraaij, T., Leers, M. P. G., Peeters, R., Wong, D. R., & Landewé, R. B. M. (2020). Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Annals of the Rheumatic Diseases, 79(9), 1143-1151. https://doi.org/10.1136/annrheumdis-2020-218479
Ramiro S, et al. Historically Controlled Comparison of Glucocorticoids With or Without Tocilizumab Versus Supportive Care Only in Patients With COVID-19-associated Cytokine Storm Syndrome: Results of the CHIC Study. Ann Rheum Dis. 2020;79(9):1143-1151. PubMed PMID: 32719045.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. AU - Ramiro,Sofia, AU - Mostard,Rémy L M, AU - Magro-Checa,César, AU - van Dongen,Christel M P, AU - Dormans,Tom, AU - Buijs,Jacqueline, AU - Gronenschild,Michiel, AU - de Kruif,Martijn D, AU - van Haren,Eric H J, AU - van Kraaij,Tom, AU - Leers,Mathie P G, AU - Peeters,Ralph, AU - Wong,Dennis R, AU - Landewé,Robert B M, Y1 - 2020/07/20/ PY - 2020/07/01/received PY - 2020/07/11/revised PY - 2020/07/13/accepted PY - 2020/7/29/pubmed PY - 2020/9/9/medline PY - 2020/7/29/entrez KW - biological therapy KW - cytokines KW - epidemiology KW - glucocorticoids SP - 1143 EP - 1151 JF - Annals of the rheumatic diseases JO - Ann Rheum Dis VL - 79 IS - 9 N2 - OBJECTIVES: To prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only. METHODS: From 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein >100 mg/L; ferritin >900 µg/L; D-dimer >1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2-5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation. RESULTS: At baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses. CONCLUSIONS: A strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS. SN - 1468-2060 UR - https://www.unboundmedicine.com/medline/citation/32719045/Historically_controlled_comparison_of_glucocorticoids_with_or_without_tocilizumab_versus_supportive_care_only_in_patients_with_COVID_19_associated_cytokine_storm_syndrome:_results_of_the_CHIC_study_ L2 - https://ard.bmj.com/lookup/pmidlookup?view=long&pmid=32719045 DB - PRIME DP - Unbound Medicine ER -