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High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients.
J Autoimmun. 2020 Aug 20 [Online ahead of print]JA

Abstract

OBJECTIVE

Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients.

METHODS

Retrospective cohort study of COVID-19 patients developing ARDS (PaO2/FiO2 <300) and exhibiting signs of hyperinflammation (ferritin >1000 ng/mL and/or d-dimers > 1.5 μg/mL, plus IL-6 < 40 mg/mL) that received ANK. For comparison, a propensity score matched historical cohort of patients treated with IL-6 inhibitor Tocilizumab (TCZ) was used. Patients had previously received combinations of azithromycin, hydroxy-chloroquine, and methyl-prednisolone. Laboratory findings, respiratory function and adverse effects were monitored. Resolution of ARDS within the first 7 days of treatment was considered a favorable outcome.

RESULTS

Subcutaneous ANK (100 mg every 6 h) was given to 9 COVID-19 ARDS CSS patients (77.8% males). Median age was 62 years (range, 42 to 87). A TCZ cohort of 18 patients was selected by propensity score matching and treated with intravenous single dose of 600 mg for patients weighing >75 Kg, or 400 mg if < 75 Kg. Prior to treatment, median PaO2/FiO2 ratio of the ANK and TCZ cohorts were 193 and 249, respectively (p = 0.131). After 7 days of treatment, PaO2/FiO2 ratio improved in both groups to 279 (104-335) and 331 (140-476, p = 0.099) respectively. On day 7, there was significant reduction of ferritin (p = 0.046), CRP (p = 0.043), and IL-6 (p = 0.043) levels in the ANK cohort but only of CRP (p = 0.001) in the TCZ group. Favorable outcome was achieved in 55.6% and 88.9% of the ANK and TCZ cohorts, respectively (p = 0.281). Two patients that failed to respond to TCZ improved after ANK treatment. Aminotransferase levels significantly increased between day 1 and day 7 (p = 0.004) in the TCZ group. Mortality was the same in both groups (11%). There were not any opportunistic infection in the groups nor other adverse effects attributable to treatment.

CONCLUSION

Overall, 55.6% of COVID-19 ARDS CSS patients treated with ANK exhibited favorable outcome, not inferior to a TCZ treated matched cohort. ANK may be a potential alternative to TCZ for patients with elevated aminotransferases, and may be useful in non-responders to TCZ.

Authors+Show Affiliations

Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Burgos University Hospital, Spain. Electronic address: eiglesiasjulian@gmail.com.Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Burgos University Hospital, Spain.Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Burgos University Hospital, Spain.Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Burgos University Hospital, Spain.Department of Neurosurgery, Burgos University Hospital, Spain.Department of Rheumatology, Burgos University Hospital, Spain.Department of Pharmacy, Burgos University Hospital, Spain.Department of Intensive Care Medicine, Burgos University Hospital, Spain.Department of Rheumatology, Burgos University Hospital, Spain.Department of Pneumology, Burgos University Hospital, Spain.Department of Pneumology, Burgos University Hospital, Spain.Department of Anesthesiology, Burgos University Hospital, Spain.Department of Pharmacy, Burgos University Hospital, Spain.Department of Internal Medicine, Burgos University Hospital, Spain.Infectious Diseases Unit, Department of Internal Medicine, Burgos University Hospital, Spain.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32843231

Citation

Iglesias-Julián, Enrique, et al. "High Dose Subcutaneous Anakinra to Treat Acute Respiratory Distress Syndrome Secondary to Cytokine Storm Syndrome Among Severely Ill COVID-19 Patients." Journal of Autoimmunity, 2020, p. 102537.
Iglesias-Julián E, López-Veloso M, de-la-Torre-Ferrera N, et al. High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients. J Autoimmun. 2020.
Iglesias-Julián, E., López-Veloso, M., de-la-Torre-Ferrera, N., Barraza-Vengoechea, J. C., Delgado-López, P. D., Colazo-Burlato, M., Ubeira-Iglesias, M., Montero-Baladía, M., Lorenzo-Martín, A., Minguito-de-la-Iglesia, J., García-Muñoz, J. P., Sanllorente-Sebastián, R., Vicente-González, B., Alemán-Alemán, A., & Buzón-Martín, L. (2020). High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients. Journal of Autoimmunity, 102537. https://doi.org/10.1016/j.jaut.2020.102537
Iglesias-Julián E, et al. High Dose Subcutaneous Anakinra to Treat Acute Respiratory Distress Syndrome Secondary to Cytokine Storm Syndrome Among Severely Ill COVID-19 Patients. J Autoimmun. 2020 Aug 20;102537. PubMed PMID: 32843231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients. AU - Iglesias-Julián,Enrique, AU - López-Veloso,María, AU - de-la-Torre-Ferrera,Noelia, AU - Barraza-Vengoechea,Julio Cesar, AU - Delgado-López,Pedro David, AU - Colazo-Burlato,María, AU - Ubeira-Iglesias,Marta, AU - Montero-Baladía,Miguel, AU - Lorenzo-Martín,Andrés, AU - Minguito-de-la-Iglesia,Javier, AU - García-Muñoz,Juan Pablo, AU - Sanllorente-Sebastián,Rodrigo, AU - Vicente-González,Blanca, AU - Alemán-Alemán,Ana, AU - Buzón-Martín,Luis, Y1 - 2020/08/20/ PY - 2020/05/29/received PY - 2020/08/04/revised PY - 2020/08/07/accepted PY - 2020/8/28/pubmed PY - 2020/8/28/medline PY - 2020/8/27/entrez KW - Acute respiratory distress syndrome KW - Anakinra KW - COVID-19 KW - Cytokine storm syndrome KW - IL-1 KW - SARS-CoV2 KW - Tocilizumab SP - 102537 EP - 102537 JF - Journal of autoimmunity JO - J. Autoimmun. N2 - OBJECTIVE: Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients. METHODS: Retrospective cohort study of COVID-19 patients developing ARDS (PaO2/FiO2 <300) and exhibiting signs of hyperinflammation (ferritin >1000 ng/mL and/or d-dimers > 1.5 μg/mL, plus IL-6 < 40 mg/mL) that received ANK. For comparison, a propensity score matched historical cohort of patients treated with IL-6 inhibitor Tocilizumab (TCZ) was used. Patients had previously received combinations of azithromycin, hydroxy-chloroquine, and methyl-prednisolone. Laboratory findings, respiratory function and adverse effects were monitored. Resolution of ARDS within the first 7 days of treatment was considered a favorable outcome. RESULTS: Subcutaneous ANK (100 mg every 6 h) was given to 9 COVID-19 ARDS CSS patients (77.8% males). Median age was 62 years (range, 42 to 87). A TCZ cohort of 18 patients was selected by propensity score matching and treated with intravenous single dose of 600 mg for patients weighing >75 Kg, or 400 mg if < 75 Kg. Prior to treatment, median PaO2/FiO2 ratio of the ANK and TCZ cohorts were 193 and 249, respectively (p = 0.131). After 7 days of treatment, PaO2/FiO2 ratio improved in both groups to 279 (104-335) and 331 (140-476, p = 0.099) respectively. On day 7, there was significant reduction of ferritin (p = 0.046), CRP (p = 0.043), and IL-6 (p = 0.043) levels in the ANK cohort but only of CRP (p = 0.001) in the TCZ group. Favorable outcome was achieved in 55.6% and 88.9% of the ANK and TCZ cohorts, respectively (p = 0.281). Two patients that failed to respond to TCZ improved after ANK treatment. Aminotransferase levels significantly increased between day 1 and day 7 (p = 0.004) in the TCZ group. Mortality was the same in both groups (11%). There were not any opportunistic infection in the groups nor other adverse effects attributable to treatment. CONCLUSION: Overall, 55.6% of COVID-19 ARDS CSS patients treated with ANK exhibited favorable outcome, not inferior to a TCZ treated matched cohort. ANK may be a potential alternative to TCZ for patients with elevated aminotransferases, and may be useful in non-responders to TCZ. SN - 1095-9157 UR - https://www.unboundmedicine.com/medline/citation/32843231/High_dose_subcutaneous_Anakinra_to_treat_acute_respiratory_distress_syndrome_secondary_to_cytokine_storm_syndrome_among_severely_ill_COVID_19_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0896-8411(20)30163-3 DB - PRIME DP - Unbound Medicine ER -