Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab

Gremese, Elisa; Larosa, Luigi; Pirronti, Tommaso; Cauda, Roberto; Bellieni, Andrea; Brandi, Vincenzo; Calabrese, Angelo; Calvello, Maria Rosaria; Ciccullo, Arturo; Cingolani, Antonella; Cipriani, Maria Camilla; Corbo, Giuseppe Maria; Falsiroli, Cinzia; Fantoni, Massimo; Intini, Enrica; Landi, Giovanni; Leone, Paolo Maria; Liperoti, Rosa; Montorsi, Francesco; Martis, Ilaria; Montemurro, Giuliano; Murri, Rita; Pais, Cristina; Pasciuto, G.; A, Potenza; Salini, Sara; Simonetti, Joseph A.; Taddei, Eleonora; Tosato, Matteo; Tummolo, A. M.; Varone, Francesco; Ventura, Giulio; Santoni, Matteo

doi:10.1007/s15010-020-01476-7

Cited by 28 publications

(27 citation statements)

References 16 publications

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“…In effect, baricitinib specifically prevents the expression of proinflammatory cytokines, including IL-6 by inhibiting JAK. Interestingly, among the six highly potent inhibitors of AAK1, baricitinib is one of them which works by binding with the cyclin G-associated kinase that disrupts endocytosis, competently leading to a reduction in viral load [ 11 , 12 ]. Nowadays, baricitinib at a 4 mg once daily oral dose has been highlighted as a promising investigational anti-inflammatory (IL-6 inhibitor) drug therapy in patients with COVID-19 pneumonia [ 4 , 11 , 12 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, among the six highly potent inhibitors of AAK1, baricitinib is one of them which works by binding with the cyclin G-associated kinase that disrupts endocytosis, competently leading to a reduction in viral load [ 11 , 12 ]. Nowadays, baricitinib at a 4 mg once daily oral dose has been highlighted as a promising investigational anti-inflammatory (IL-6 inhibitor) drug therapy in patients with COVID-19 pneumonia [ 4 , 11 , 12 , 14 ]. The pharmacokinetics, pharmacodynamics, and safety data of baricitinib at a 4 mg daily dose in COVID-19 are still under investigation and to date, no standard dosing of baricitinib in COVID-19 has yet been established worldwide [ 11 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nowadays, baricitinib at a 4 mg once daily oral dose has been highlighted as a promising investigational anti-inflammatory (IL-6 inhibitor) drug therapy in patients with COVID-19 pneumonia [ 4 , 11 , 12 , 14 ]. The pharmacokinetics, pharmacodynamics, and safety data of baricitinib at a 4 mg daily dose in COVID-19 are still under investigation and to date, no standard dosing of baricitinib in COVID-19 has yet been established worldwide [ 11 , 12 , 13 , 14 , 15 ]. The objective of this study was to compare the clinical outcomes of patients with moderate-to-severe COVID-19 pneumonia treated with baricitinib at a 4 mg once daily oral dose with or without a high oral loading dose.…”

Section: Introductionmentioning

confidence: 99%

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Additional baricitinib loading dose improves clinical outcome in COVID-19

et al. 2020

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Pneumonia associated with coronavirus disease 2019 (COVID-19) has been accounted for high mortality rate in severe COVID-19 worldwide, and additional serious scarcity of standard and effective anti-inflammatory drug in COVID-19 pneumonia management is a big challenge. Baricitinib, a Janus kinase (JAK) inhibitor, is a promising drug in COVID-19 pneumonia. This study aims to compare the clinical outcome of moderate-to-severe COVID-19 pneumonia treated with baricitinib with or without a loading dose. This prospective case-control study enrolled 37 adult patients where 17 patients (control) received baricitinib at 4 mg oral daily dose and 20 patients (case) received an additional single 8 mg oral loading dose. The median day to gain blood oxygen saturation level ≥95% (in room air) and return in normal breathing function were lower in case group than the control group. The requirement of intensive care unit and mechanical ventilation support was higher in the control group than in the case group [29.4% (N = 17)/10% (N = 20), P < 0.05; 11.8% (N = 17)/5% (N = 20), P > 0.05), respectively]. Thus, an additional loading dose of baricitinib revealed better clinical outcome of patients with COVID-19 pneumonia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Additional baricitinib loading dose improves clinical outcome in COVID-19

et al. 2020

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“…Their anti-inflammatory effect may be beneficial in reducing cytokine release in severe patients or detrimental by delaying the interferon response [ 318 , 325 ]. Results of case report and small cohort studies seem encouraging with an improvement of moderate to severe cases and need to be pursued [ 329 , 330 , 331 ].…”

Section: Immunotherapymentioning

confidence: 99%

Deciphering SARS-CoV-2 Virologic and Immunologic Features

Lebeau

Vagner

Frumence

et al. 2020

IJMS

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Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 and its associated pathology, COVID-19, have been of particular concerns these last months due to the worldwide burden they represent. The number of cases requiring intensive care being the critical point in this epidemic, a better understanding of the pathophysiology leading to these severe cases is urgently needed. Tissue lesions can be caused by the pathogen or can be driven by an overwhelmed immune response. Focusing on SARS-CoV-2, we and others have observed that this virus can trigger indeed an immune response that can be dysregulated in severe patients and leading to further injury to multiple organs. The purpose of the review is to bring to light the current knowledge about SARS-CoV-2 virologic and immunologic features. Thus, we address virus biology, life cycle, tropism for many organs and how ultimately it will affect several host biological and physiological functions, notably the immune response. Given that therapeutic avenues are now highly warranted, we also discuss the immunotherapies available to manage the infection and the clinical outcomes.

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“…Since the start of the coronavirus disease 2019 (COVID- 19) pandemic, there has been an increasing need for treatments that can reduce the morbidity, mortality, and length of stay of patients both in the intensive care unit (ICU) and hospital in general [1]. With so many unknown variables involved, it is very unpredictable what further complications are expected, including the management of patients with immunomodula-tory treatments and steroids [2][3][4]. The difficulty, in this case, increased due to the subsequent bacteremia and fungemia that were caused by rare pathogens.…”

Section: Introductionmentioning

confidence: 99%

A COVID-19 Case Complicated by Candida dubliniensis and Klebsiella pneumoniae-Carbapenem-Resistant Enterobacteriaceae

et al. 2020

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There has been increasing evidence of co-infections with coronavirus disease 2019 (COVID-19) pneumonia, which increases the severity of the disease. Organisms such as Klebsiella pneumoniae and Streptococcus pneumoniae have been previously isolated. We present a case of a COVID-19 patient treated with baricitinib and dexamethasone who later developed Klebsiella pneumoniae-carbapenem-resistant Enterobacteriaceae (CRE) and Candida dubliniensis bloodstream infections, treated with meropenem/vaborbactam and micafungin, respectively. These infections are exceedingly rare and are mostly reported in immunosuppressed patients. The finding of these bloodstream infections raises concerns on the cause of immunosuppression in this patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) treated with baricitinib and dexamethasone. There has been no report so far of COVID-19 associated with these co-infections.

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Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab

Cited by 28 publications

References 16 publications

Additional baricitinib loading dose improves clinical outcome in COVID-19

Additional baricitinib loading dose improves clinical outcome in COVID-19

Deciphering SARS-CoV-2 Virologic and Immunologic Features

A COVID-19 Case Complicated by Candida dubliniensis and Klebsiella pneumoniae-Carbapenem-Resistant Enterobacteriaceae

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