Baricitinib Reduces 30-day Mortality in Older Adults With Moderate-to-severe COVID-19 Pneumonia

Pedro Abizanda MD, PhD; Juan María Calbo Mayo MD; Marta Mas Romero RN; Elisa Belén Cortés Zamora RN; María Teresa Tabernero Sahuquillo BE; Luis Romero Rizos MD, PhD; Pedro Manuel Sánchez-Jurado MD, PhD; Ginés Sánchez-Nievas MD; Carlos Campayo Escolano MD; Alba Ochoa Serrano MD; Victoria Sánchez-Flor Alfaro MD; Rita López Bru MD; Cristina Gómez Ballesteros MD; David Caldevilla Bernardo MD; Francisco Javier Callejas González MD, PhD; Fernando Andrés-Pretel BS; Volker Martin Lauschke PhD; Justin Stebbing MD, PhD

Disclosures

J Am Geriatr Soc. 2021;69(10):2752-2758. 

In This Article

Abstract and Introduction

Abstract

Background: Older adults are at the highest risk of severe disease and death due to COVID-19. Randomized data have shown that baricitinib improves outcomes in these patients, but focused stratified analyses of geriatric cohorts are lacking. Our objective was to analyze the efficacy of baricitinib in older adults with COVID-19 moderate-to-severe pneumonia.

Methods: This is a propensity score [PS]-matched retrospective cohort study. Patients from the COVID-AGE and Alba-Score cohorts, hospitalized for moderate-to-severe COVID-19 pneumonia, were categorized in two age brackets of age <70 years old (86 with baricitinib and 86 PS-matched controls) or ≥70 years old (78 on baricitinib and 78 PS-matched controls). Thirty-day mortality rates were analyzed with Kaplan–Meier and Cox proportional hazard models.

Results: Mean age was 79.1 for those ≥70 years and 58.9 for those <70. Exactly 29.6% were female. Treatment with baricitinib resulted in a significant reduction in death from any cause by 48% in patients aged 70 or older, an 18.5% reduction in 30-day absolute mortality risk (n/N: 16/78 [20.5%] baricitinib, 30/78 [38.5%] in PS-matched controls, p < 0.001) and a lower 30-day adjusted fatality rate (HR 0.21; 95% CI 0.09–0.47; p < 0.001). Beneficial effects on mortality were also observed in the age group <70 (8.1% reduction in 30-day absolute mortality risk; HR 0.14; 95% CI 0.03–0.64; p = 0.011).

Conclusions: Baricitinib is associated with an absolute mortality risk reduction of 18.5% in adults older than 70 years hospitalized with COVID-19 pneumonia.

Introduction

Advanced age is the most important risk factor for adverse outcomes and mortality in COVID-19 patients.[1,2] More than 50% of COVID-19 deaths occur in adults aged 70 years and older, despite the fact that the majority of SARS-CoV-2 infections are found in younger adults.[3] Case fatality rates are up to 22.7% among those aged 70–79 years old and between 22% and 38.1% in persons older than 80 years.[1,2,4–8]

Thus far, remdesivir, dexamethasone, or remdesivir plus baricitinib are the only Food and Drug Administration (FDA) approved drug for COVID-19 for adults.[9] Baricitinib received the Emergency Use Authorization from the FDA on November 19, 2020 in association with remdesivir in patients requiring supplemental oxygen, after revision of the Adaptive COVID-19 Treatment Trial 2 (ACTT-2).[10] More recently, the COV-BARRIER trial showed that baricitinib alone resulted in a significant reduction in death from any cause by 38% by day 28, the greatest risk reduction for any treatment observed thus far, although it did not meet statistical significance on the primary endpoint, progression to the first occurrence of noninvasive (NIMV) or invasive mechanical ventilation (IMV) or death.[11] However, little information is available for its use in older populations.

Baricitinib is a small molecule reversible Janus kinase (JAK) 1 and 2 inhibitor with suggested dual anti-cytokine and anti-viral activity against SARS-CoV-2 infection. It curtails excessive inflammatory signaling and blunts interferon-mediated induction of interferon response genes that include at least in some tissues the viral receptor angiotensin-converting enzyme 2 (ACE2).[12] In addition, baricitinib inhibits numb associated kinases that are directly involved in viral endocytosis.[13]

In our hospital, baricitinib has been largely used in patients with COVID-19 pneumonia, independent of age. Here, we present the results of the first 164 consecutive patients treated with baricitinib (78 with an age ≥70 years and 86 with an age <70 years), and 164 matched controls who did not receive baricitinib.

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