Baricitinib improves respiratory function in patients treated with corticosteroids for SARS-CoV-2 pneumonia: an observational cohort study

Abstract

Objectives: The Janus kinase (JAK) inhibitor baricitinib may block viral entry into pneumocytes and prevent cytokine storm in patients with SARS-CoV-2 pneumonia. We aimed to assess whether baricitinib improved pulmonary function in patients treated with high-dose corticosteroids for moderate to severe SARS-CoV-2 pneumonia.

Methods: This observational study enrolled patients with moderate to severe SARS-CoV-2 pneumonia [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) <200 mmHg] who received lopinavir/ritonavir and HCQ plus either corticosteroids (CS group, n = 50) or corticosteroids and baricitinib (BCT-CS group, n = 62). The primary end point was the change in oxygen saturation as measured by pulse oximetry (SpO2)/FiO2 from hospitalization to discharge. Secondary end points included the proportion of patients requiring supplemental oxygen at discharge and 1 month later. Statistics were adjusted by the inverse propensity score weighting (IPSW).

Results: A greater improvement in SpO2/FiO2 from hospitalization to discharge was observed in the BCT-CS vs CS group (mean differences adjusted for IPSW, 49; 95% CI: 22, 77; P < 0.001). A higher proportion of patients required supplemental oxygen both at discharge (62.0% vs 25.8%; reduction of the risk by 82%, OR adjusted for IPSW, 0.18; 95% CI: 0.08, 0.43; P < 0.001) and 1 month later (28.0% vs 12.9%, reduction of the risk by 69%, OR adjusted for IPSW, 0.31; 95% CI: 0.11, 0.86; P = 0.024) in the CS vs BCT-CS group.

Conclusions: . In patients with moderate to severe SARS-CoV-2 pneumonia a combination of baricitinib with corticosteroids was associated with greater improvement in pulmonary function when compared with corticosteroids alone.

Trial registration: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, ENCEPP (EUPAS34966, http://www.encepp.eu/encepp/viewResource.htm? id = 34967).

Keywords: COVID-19; SARS-CoV-2; baricitinib; corticosteroids.

Fig. 1

Flow chart of patients included in the study ^*SpO₂ ≤ 92% breathing room air. ^**Chronic heart failure, chronic obstructive pulmonary disease (COPD) on oxygen therapy, obstructive sleep apnoea syndrome with continuous positive airway pressure, advanced chronic kidney disease, active malignancies. Standard therapy: lopinavir/ritonavir and HCQ. FiO₂: fraction of inspired oxygen; PaO₂: arterial oxygen partial pressure; SpO₂: oxygen saturation as measured by pulse oximetry.

Fig. 2

Boxplot of SpO₂/FiO₂ from hospitalization to discharge by treatment group FiO₂: fraction of inspired oxygen; SpO₂: oxygen saturation as measured by pulse oximetry.

Fig. 3

Decrease in D-dimer was more pronounced with baricitinib and corticosteroids vs corticosteroids alone