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Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration.
Clin Exp Rheumatol. 2020 Jul-Aug; 38(4):742-747.CE

Abstract

OBJECTIVES

Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 is likely due to a cytokine storm characterised by a major release of pro-inflammatory cytokines, including interleukin-6 (IL-6). Blocking excessive IL-6 production might be the key to the COVID-19-ARDS treatment. Beneficial effects of IL-6 blockade using a humanised anti-IL-6 receptor antibody, tocilizumab (TCZ) were previously reported in patients with COVID-19 related ARDS. The aim of the study was to study the variation over time of several biomarkers, demonstrated to be predictors of poor prognostic, in subjects successfully treated with TCZ for severe COVID-19.

METHODS

Retrospective analysis of a case series of patients with COVID-19-ARDS, evidenced by RT-PCR and lung CT-scan. Patients with increasing O2 requirements, within the window of opportunity for TCZ treatment (Day 7 to Day 17 after onset of symptoms) were treated with TCZ (2 infusions of 8 mg/kg). Demographic, biological and clinical data were collected from the patients' files. Serum levels of CRP, ferritin, fibrinogen, lymphocytes, platelets, creatinine, D-dimer and liver enzymes were assayed at the time of the first TCZ administration, then every two days for 8 days.

RESULTS

40 patients were treated with TCZ. Most of them had several comorbidities, and all had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer, liver enzymes). 30 patients (75%) benefited from TCZ and 10 patients died. In the survivors, following TCZ administration CRP decreased dramatically as early as day 4 (-86.7%, p<0.0001) and returned to normal at day 6. Fibrinogen and lymphocyte count returned to normal values at day 6. Ferritin also decreased significantly. No significant change was observed for D-dimer (p=0.68) and other studied biomarkers (haemoglobin, leucocyte count, AST).

CONCLUSIONS

In patients with COVID-19 acute respiratory distress syndrome, treatment with TCZ resulted in favourable evolution in 75% of the cases. Biomarkers of inflammation (CRP, ferritin, fibrinogen) decreased dramatically as early as the 4th day after TCZ injection. Lymphopenia, a predictor of poor prognostic, was reversed 6 days after TCZ injection.

Authors+Show Affiliations

Department of Rheumatology, Nord Franche-Comté Hospital, Belfort, France. thierry.conrozier@hnfc.fr.Department of Rheumatology, Nord Franche-Comté Hospital, Belfort, France.Department of Rheumatology, Nord Franche-Comté Hospital, Belfort, France.Department of Biology, Nord Franche-Comté Hospital, Belfort, France.Department of Infectious Diseases, Nord Franche-Comté Hospital, Belfort, France.Department of Rheumatology, Nord Franche-Comté Hospital, Belfort, France.Department of Rheumatology, Nord Franche-Comté Hospital, Belfort, France.Department of Infectious Diseases, Nord Franche-Comté Hospital, Belfort, France.Department of Rheumatology, Nord Franche-Comté Hospital, Belfort, France.Department of Infectious Diseases, Nord Franche-Comté Hospital, Belfort, France.Intensive Care Unit, Nord Franche-Comté Hospital, Belfort, France.Intensive Care Unit, Nord Franche-Comté Hospital, Belfort, France.Pharmacy, Nord Franche-Comté Hospital, Belfort, France.Department of Infectious Diseases, Nord Franche-Comté Hospital, Belfort, France.Pharmacy, Nord Franche-Comté Hospital, Belfort, France.Department of Rheumatology, Nord Franche-Comté Hospital, Belfort, France.Department of Biology, Nord Franche-Comté Hospital, Belfort, France.Department of Infectious Diseases, Nord Franche-Comté Hospital, Belfort, France.Department of Infectious Diseases, Nord Franche-Comté Hospital, Belfort, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32573419

Citation

Conrozier, Thierry, et al. "Biomarker Variation in Patients Successfully Treated With Tocilizumab for Severe Coronavirus Disease 2019 (COVID-19): Results of a Multidisciplinary Collaboration." Clinical and Experimental Rheumatology, vol. 38, no. 4, 2020, pp. 742-747.
Conrozier T, Lohse A, Balblanc JC, et al. Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration. Clin Exp Rheumatol. 2020;38(4):742-747.
Conrozier, T., Lohse, A., Balblanc, J. C., Dussert, P., Royer, P. Y., Bossert, M., Bozgan, A. M., Gendrin, V., Charpentier, A., Toko, L., Badie, J., Mezher, C., Roux, M. F., Kadiane-Oussou, N. J., Contreras, R., Kessler, J., Mazurier, I., Klopfenstein, T., & Zayet, S. (2020). Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration. Clinical and Experimental Rheumatology, 38(4), 742-747.
Conrozier T, et al. Biomarker Variation in Patients Successfully Treated With Tocilizumab for Severe Coronavirus Disease 2019 (COVID-19): Results of a Multidisciplinary Collaboration. Clin Exp Rheumatol. 2020 Jul-Aug;38(4):742-747. PubMed PMID: 32573419.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration. AU - Conrozier,Thierry, AU - Lohse,Anne, AU - Balblanc,Jean-Charles, AU - Dussert,Pascale, AU - Royer,Pierre-Yves, AU - Bossert,Marie, AU - Bozgan,Ana-Maria, AU - Gendrin,Vincent, AU - Charpentier,Aline, AU - Toko,Lynda, AU - Badie,Julio, AU - Mezher,Chaouki, AU - Roux,Marie-Françoise, AU - Kadiane-Oussou,Ndri Juliette, AU - Contreras,Rémy, AU - Kessler,Julie, AU - Mazurier,Isabelle, AU - Klopfenstein,Timothée, AU - Zayet,Souheil, Y1 - 2020/06/23/ PY - 2020/05/25/received PY - 2020/05/27/accepted PY - 2020/6/24/pubmed PY - 2020/8/1/medline PY - 2020/6/24/entrez SP - 742 EP - 747 JF - Clinical and experimental rheumatology JO - Clin. Exp. Rheumatol. VL - 38 IS - 4 N2 - OBJECTIVES: Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 is likely due to a cytokine storm characterised by a major release of pro-inflammatory cytokines, including interleukin-6 (IL-6). Blocking excessive IL-6 production might be the key to the COVID-19-ARDS treatment. Beneficial effects of IL-6 blockade using a humanised anti-IL-6 receptor antibody, tocilizumab (TCZ) were previously reported in patients with COVID-19 related ARDS. The aim of the study was to study the variation over time of several biomarkers, demonstrated to be predictors of poor prognostic, in subjects successfully treated with TCZ for severe COVID-19. METHODS: Retrospective analysis of a case series of patients with COVID-19-ARDS, evidenced by RT-PCR and lung CT-scan. Patients with increasing O2 requirements, within the window of opportunity for TCZ treatment (Day 7 to Day 17 after onset of symptoms) were treated with TCZ (2 infusions of 8 mg/kg). Demographic, biological and clinical data were collected from the patients' files. Serum levels of CRP, ferritin, fibrinogen, lymphocytes, platelets, creatinine, D-dimer and liver enzymes were assayed at the time of the first TCZ administration, then every two days for 8 days. RESULTS: 40 patients were treated with TCZ. Most of them had several comorbidities, and all had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer, liver enzymes). 30 patients (75%) benefited from TCZ and 10 patients died. In the survivors, following TCZ administration CRP decreased dramatically as early as day 4 (-86.7%, p<0.0001) and returned to normal at day 6. Fibrinogen and lymphocyte count returned to normal values at day 6. Ferritin also decreased significantly. No significant change was observed for D-dimer (p=0.68) and other studied biomarkers (haemoglobin, leucocyte count, AST). CONCLUSIONS: In patients with COVID-19 acute respiratory distress syndrome, treatment with TCZ resulted in favourable evolution in 75% of the cases. Biomarkers of inflammation (CRP, ferritin, fibrinogen) decreased dramatically as early as the 4th day after TCZ injection. Lymphopenia, a predictor of poor prognostic, was reversed 6 days after TCZ injection. SN - 0392-856X UR - https://www.unboundmedicine.com/medline/citation/32573419/Biomarker_variation_in_patients_successfully_treated_with_tocilizumab_for_severe_coronavirus_disease_2019__COVID_19_:_results_of_a_multidisciplinary_collaboration_ L2 - https://antibodies.cancer.gov/detail/CPTC-IL6-1 DB - PRIME DP - Unbound Medicine ER -