Efficacy and safety of nintedanib for pulmonary fibrosis in severe pneumonia induced by COVID-19: An interventional study

Yutaka Umemura,Yumi Mitsuyama,Kensuke Minami,Takeshi Nishida,Atsushi Watanabe,Naoki Okada,Kazuma Yamakawa,Kotaro Nochioka,Satoshi Fujimi

doi:10.1016/j.ijid.2021.05.055

Abstract

ObjectivesOne of the most significant features of poor prognosis in COVID-19 is pulmonary fibrosis. Nintedanib is a new antifibrotic agent that interferes with processes of pulmonary fibrosis. This study aimed to investigate the efficacy and safety of nintedanib in COVID-19. MethodsThis was an interventional study in which adult patients with COVID-19 requiring mechanical ventilation were consecutively enrolled. The primary endpoint was 28-day mortality after the initiation of mechanical ventilation. The secondary endpoints were length of mechanical ventilation, volume of lung injury, and the incidence of gastrointestinal adverse events and acute liver failure. ResultsThirty patients with COVID-19 underwent nintedanib therapy. We included 30 patients not receiving nintedanib as the historical control group. There were no significant differences in 28-day mortality between the groups (23.3% vs 20%, P = 0.834). Lengths of mechanical ventilation were significantly shorter in the nintedanib group (P = 0.046). Computed tomography volumetry showed that the percentages of high-attenuation areas were significantly lower in the nintedanib group at liberation from mechanical ventilation (38.7% vs 25.7%, P = 0.027). There were no significant differences in the adverse events. ConclusionsThe administration of nintedanib may offer potential benefits for minimizing lung injury in COVID-19.

Highlights

SARS-CoV-2, a novel RNA coronavirus, was identified in early January 2020 as the cause of a severe pneumonia in Wuhan, China
From August to October 2020, 33 consecutive patients were admitted to the intensive care unit (ICU) with the diagnosis of COVID-19 and underwent mechanical ventilation
A number of studies reported that pulmonary fibrosis was occurring as a sequela of acute lung injury induced by COVID-19 (Pan et al, 2020; Schwensen et al, 2020; Tian et al, 2020; Zhou et al, 2020)

Summary

Introduction

SARS-CoV-2, a novel RNA coronavirus, was identified in early January 2020 as the cause of a severe pneumonia in Wuhan, China. After causing the deaths of thousands of patients in China, SARSCoV-2 infection (COVID-19) has rapidly spread worldwide (Zhu et al, 2020). A number of clinical, radiological and histopathological studies have suggested that the progression of pulmonary fibrosis commonly complicating severe COVID-19 patients can potentially worsen survival and functional outcomes (Pan et al, 2020; Schwensen et al, 2020; Tian et al, 2020; Zhou et al, 2020). In this context, several antifibrotic agents are expected to be beneficial treatments to prevent the progression of pulmonary fibrosis in severe COVID-19-induced ARDS

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