Propuesta de uso de anakinra en el distrés respiratorio agudo secundario a COVID-19

Jiménez, A. Muñoz; Rubio‐Romero, Esteban; J, Fuente

doi:10.1016/j.reuma.2020.04.009

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…It was repurposed for COVID-19 treatment as IL-1 is one of the cytokines involved in the development of the cytokine storm. 122 Polymorphisms in genes related with pharmacokinetics seem irrelevant. However, the IL-1α G4845T (rs17651) T allele was significantly related to responsiveness to anakinra; the variant was reported to alter IL-1α production.…”

Section: Anakinramentioning

confidence: 99%

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Important Pharmacogenetic Information for Drugs Prescribed During the SARS‐CoV‐2 Infection (COVID‐19)

Zubiaur

Koller

Saiz‐Rodríguez

et al. 2020

Clinical Translational Sci

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In December 2019, the severe acute respiratory syndrome virus‐2 pandemic began, causing the coronavirus disease 2019. A vast variety of drugs is being used off‐label as potential therapies. Many of the repurposed drugs have clinical pharmacogenetic guidelines available with therapeutic recommendations when prescribed as indicated on the drug label. The aim of this review is to provide a comprehensive summary of pharmacogenetic biomarkers available for these drugs, which may help to prescribe them more safely.

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Section: Anakinramentioning

confidence: 99%

“…Anakinra does not suffer CYP450 metabolism and undergoes extensive kidney elimination. It was repurposed for COVID‐19 treatment as IL‐1 is one of the cytokines involved in the development of the cytokine storm 122 . Polymorphisms in genes related with pharmacokinetics seem irrelevant.…”

Section: Anakinramentioning

confidence: 99%

Important Pharmacogenetic Information for Drugs Prescribed During the SARS‐CoV‐2 Infection (COVID‐19)

Zubiaur

Koller

Saiz‐Rodríguez

et al. 2020

Clinical Translational Sci

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“…However, in our experience, many patients do not meet the diagnostic criteria because they do not score high enough in certain items like immune-suppression, organomegaly, or ferritin over 6000 ng/mL. Nevertheless, a marked increase in ferritin level seems to be a good marker of macrophage activation [ 20 ], and may help in the early identification of a COVID-19 patient developing CSS [ 21 ], in order to initiate immunomodulator therapy before clinical worsening ensues. In line with a previous study [ 22 ], at our center, we set the threshold of ferritin >1000 ng/mL for initiating treatment.…”

Section: Discussionmentioning

confidence: 99%

“…ANK blocks IL-1 activity by competitive inhibition of the type 1 cell surface receptor (IL-1 R1) present in the majority of cell types. ANK subcutaneous bioavailability reaches 95% in adults, and the highest blood concentration is achieved between 3 and 7 h after administration (1–2 mg/kg/day), with a half-life of 4–6 h [ 20 ]. This relatively short half-live provides safety in case discontinuation is needed, should adverse effects appear.…”

Section: Discussionmentioning

confidence: 99%

High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients

Enrique

López-Veloso

de-la-Torre-Ferrera

et al. 2020

Journal of Autoimmunity

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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.

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COVID-19-Pneumonie

Pfeifer

Hamer

2020

Internist

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Die „coronavirus disease 2019“ (COVID-19) stellt weiterhin eine große Bedrohung von globalem Ausmaß dar. Auch wenn inzwischen eine Reihe von Organmanifestationen beschrieben ist, steht im Infektionsverlauf weiterhin das respiratorische System im Vordergrund. Es kann zur Entwicklung einer schweren Pneumonie kommen, die in der Regel prognostisch bestimmend ist. Im Folgenden werden die aktuell bekannten Besonderheiten der pulmonalen Manifestation aus pathophysiologischer, klinischer und radiologischer Sicht beschrieben. Bezüglich der Pathophysiologie wird auf den komplexen Charakter der akuten Lungenerkrankung mit schwerer Schädigung des Alveolarepithels und pulmonal-vaskulären Endothels mit der Folge einer schweren respiratorischen Insuffizienz bei einem Teil der Patienten eingegangen. Die Unterschiede zum „klassischen“ „acute respiratory distress syndrome“ mit ihren erheblichen Auswirkungen auf die Therapie von COVID-19 werden herausgearbeitet. Nach einer kurzen Beschreibung der Polymerase-Kettenreaktion(PCR)-gestützten Erregeridentifikation und Angaben zu typischen Laborbefunden wird die bildgebende Darstellung der COVID-19-Pneumonie genauer beschrieben (typische Befunde, Differenzialdiagnosen, Klassifizierung der Wahrscheinlichkeit einer COVID-19-Pneumonie). Daran schließt sich eine Beschreibung der Klinik mit ihren drei Phasen an. Bezüglich der Therapie werden zunächst supportive und intensivmedizinische Ansätze unter Berücksichtigung von O 2 -Gabe, antibiotischer Therapie sowie (nicht-)invasiver Beatmung diskutiert. Der Beitrag schließt mit einer Zusammenfassung der Erkenntnisse zu medikamentösen Therapien – einerseits zur Thromboseprophylaxe, andererseits zur spezifischen antiviralen und immunmodulatorischen Therapie (Remdesivir, Tocilizumab, Anakinra, Dexamethason).

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Propuesta de uso de anakinra en el distrés respiratorio agudo secundario a COVID-19

Cited by 6 publications

References 14 publications

Important Pharmacogenetic Information for Drugs Prescribed During the SARS‐CoV‐2 Infection (COVID‐19)

Important Pharmacogenetic Information for Drugs Prescribed During the SARS‐CoV‐2 Infection (COVID‐19)

High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients

COVID-19-Pneumonie

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