Baricitinib in hospitalised patients with COVID-19: A meta-analysis of randomised controlled trials

Selvaraj, Vijairam; Finn, Arkadiy; Lal, Amos; Khan, Mohammad Saud; Dapaah-Afriyie, Kwame; Carino, Gerardo

doi:10.1016/j.eclinm.2022.101489

Cited by 70 publications

(56 citation statements)

References 31 publications

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“…Despite initially discouraging findings [ 63 ], a meta-analysis of 19 RCTs reported a 17% reduction in the odds for in-hospital mortality with the IL-6 antagonist tocilizumab compared to usual care or placebo [ 64 ]. When compared to usual care, the addition of baracitinib, a janus kinase inhibitor, also resulted in shorter recovery time [ 65 ], reduced mortality [ 66 ], and lower frequency of adverse events [ 67 ]; furthermore, in a meta-analysis of four RCTs, baracitinib was associated with a 31% reduction in the odds for in-hospital death [ 68 ]. Guided by soluble urokinase plasminogen receptor plasma levels, treatment with IL-1 alpha and IL-1 beta antagonists also resulted in a 64% reduction in clinically worsened status at day 28, less organ dysfunction at day 7, and lower in-hospital mortality [ 69 ].…”

Section: Pharmacologic Interventionsmentioning

confidence: 99%

COVID-19-Related ARDS: Key Mechanistic Features and Treatments

Selickman

Vrettou

Mentzelopoulos

et al. 2022

JCM

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Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome historically characterized by the presence of severe hypoxemia, high-permeability pulmonary edema manifesting as diffuse alveolar infiltrate on chest radiograph, and reduced compliance of the integrated respiratory system as a result of widespread compressive atelectasis and fluid-filled alveoli. Coronavirus disease 19 (COVID-19)-associated ARDS (C-ARDS) is a novel etiology caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may present with distinct clinical features as a result of the viral pathobiology unique to SARS-CoV-2. In particular, severe injury to the pulmonary vascular endothelium, accompanied by the presence of diffuse microthrombi in the pulmonary microcirculation, can lead to a clinical presentation in which the severity of impaired gas exchange becomes uncoupled from lung capacity and respiratory mechanics. The purpose of this review is to highlight the key mechanistic features of C-ARDS and to discuss the implications these features have on its treatment. In some patients with C-ARDS, rigid adherence to guidelines derived from clinical trials in the pre-COVID era may not be appropriate.

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Section: Pharmacologic Interventionsmentioning

confidence: 99%

COVID-19-Related ARDS: Key Mechanistic Features and Treatments

Selickman

Vrettou

Mentzelopoulos

et al. 2022

JCM

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“…Die Wirkstoffgruppe der Januskinase-Inhibitoren wurden bislang aufgrund ihrer immunmodulierenden Wirkung bei Autoimmun-Erkrankungen, insbesondere bei schwerer aktiver Rheumatoider Arthritis (RA), eingesetzt. Die Behandlung mit dem Januskinase-Inhibitor Baricitinib zusätzlich zur Standardbehandlung mit Dexamethason war in Studien ebenfalls mit einer geringeren Sterblichkeit bei hospitalisierten Erwachsenen mit COVID-19 verbunden 13 . Baricitinib sollte daher bei Patienten mit COVID-19-Pneumonie und Low-Flow-/High-Flow-Sauerstofftherapie oder nicht invasiver Beatmung unter Beachtung der Kontraindikationen eingesetzt werden.…”

Section: Medikamentöse Therapieunclassified

Medikamentöse Therapiemaßnahmen bei akuter SARS-CoV-2-Infektion: wer, wann und was?

Sensen¹,

Wichmann²,

Kluge³

2022

Dtsch Med Wochenschr

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Mittlerweile gibt es eine Vielzahl von medikamentösen Therapieoptionen zur Behandlung einer akuten SARS-CoV-2-Infektion. Die aktualisierte S3-Leitlinie „Empfehlungen zur stationären Therapie von Patienten mit COVID-19“ gibt dazu klare Empfehlungen. Welche Therapie für welchen Patienten und in welcher Krankheitsphase am besten geeignet ist, muss individuell anhand der Risikofaktoren, der Komorbiditäten und der Kontraindikationen entschieden werden. Hierüber geben wir in diesem Beitrag einen Überblick.

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“…The optimal approach to the treatment of COVID-19 is continually evolving. In a single-center study from Wuhan, China, which included 15 patients with COVID-19 pneumonia at risk for CRS, treatment with tocilizumab (a recombinant humanized anti-human IL-6 receptor monoclonal antibody) appeared to have a clinical benefit [19,20]. The accumulating evidence suggests medications targeting dysregulated inflammation comprises a promising therapeutic strategy among critically ill COVID-19 patients.…”

Section: Immunomodulators and Raising Concerns For Infectionmentioning

confidence: 99%

Nosocomial Infections in COVID-19 Patients Treated with Immunomodulators: A Narrative Review

Chidambaram¹,

Narayan²,

Mishra³

et al. 2022

Front. Biosci. (Schol Ed)

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Nosocomial infections pose an imminent challenge to hospitalized Coronavirus disease-19 (COVID-19) patients due to complex interplay of dysregulated immune response combined with immunomodulator therapy. In the pre-pandemic era, immunomodulatory therapy has shown benefit in certain autoimmune conditions with untamed inflammatory response. Efforts to recapitulate these immunomodulatory effects in COVID-19 patients has gained impetus and were followed by NIH COVID-19 expert panel recommendations. The current NIH guideline recommends interleukin-6 inhibitors (tocilizumab and sarilumab) and Janus kinase inhibitors (baricitinib and tofacitinib). Several landmark research trials like COVAVTA, EMPACTA, REMDACTA, STOP-COVID and COV BARRIER have detailed the various effects associated with administration of immunomodulators. The historical evidence of increased infection among patients receiving immunomodulators for autoimmune conditions, raised concerns regarding administration of immunomodulators in COVID-19 patients. The aim of this review article is to provide a comprehensive update on the currently available literature surrounding this issue. We reviewed 40 studies out of which 37 investigated IL-6 inhibitors and 3 investigated JAK inhibitors. Among the studies reviewed, the reported rates of nosocomial infections among the COVID-19 patients treated with immunomodulators were similar to patients receiving standard of care for COVID-19. However, these studies were not powered to assess the side effect profile of these medications. Immunomodulators, by dampening the pyrogenic response and inflammatory markers may delay detection of infections among the patients. This underscores the importance of long-term surveillance which are necessary to discover the potential risks associated with these agents.

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Baricitinib in hospitalised patients with COVID-19: A meta-analysis of randomised controlled trials

Cited by 70 publications

References 31 publications

COVID-19-Related ARDS: Key Mechanistic Features and Treatments

COVID-19-Related ARDS: Key Mechanistic Features and Treatments

Medikamentöse Therapiemaßnahmen bei akuter SARS-CoV-2-Infektion: wer, wann und was?

Nosocomial Infections in COVID-19 Patients Treated with Immunomodulators: A Narrative Review

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