The Effect of Nintedanib in Post-COVID-19 Lung Fibrosis: An Observational Study

Abstract

Background. Lung fibrosis is a sequela of COVID-19 among patients with severe pneumonia. Idiopathic pulmonary fibrosis and lung fibrosis due to COVID-19 may share many similar features. There are limited data on effects of antifibrotic treatment of infection-related lung fibrosis. This study aimed to evaluate the effect of nintedanib on patients’ post-COVID-19 lung fibrosis. Methods. A retrospective, matched case-control study was performed on hospitalized patients with COVID-19 pneumonia. Patients who received nintedanib treatment for COVID-19 pulmonary fibrosis (nintedanib group) were compared to patients with standard treatment (control group). The primary outcome was oxygen improvement. The secondary outcomes were chest X-ray improvement, SpO2/FiO2 ratio improvement, mortality rates at 60 days, and adverse events. Results. A total of 42 patients with COVID-19 pneumonia were included (21 in each group). Mean age was 64.43 ± 14.59 years, and 54.8% were men. At baseline, SpO2/FiO2 ratio before treatment was 200.57 ± 105.77 in the nintedanib group and 326.90 ± 137.10 in the control group ( P = 0.002 ). Oxygen improvement and chest X-ray improvement were found in 71.4% and 71.4% in the nintedanib group and in 66.7% and 66.7% in the control group ( P = 0.739 ). The nintedanib group had more improvement in SpO2/FiO2 ratio than in the control group (144.38 ± 118.05 vs 55.67 ± 75.09, P = 0.006 ). The 60-day mortality rates of the nintedanib and the control groups were 38.1% vs 23.8%, P = 0.317 . Hepatitis and loss of appetite were common adverse events (9.5% and 9.5%), while the incidence of diarrhea was 4.8%. Conclusions. Nintedanib as add-on treatment in post-COVID-19 lung fibrosis did not improve oxygenation, chest X-ray findings, or the 60-day mortality. However, this antifibrotic drug improved SpO2/FiO2 ratio in our patients. Further randomized controlled trials are needed to determine the efficacy of nintedanib for treatment of patients with post-COVID-19 lung fibrosis. Trial Registration. This study was registered in TCTR20220426001.

Characteristics and Determinants of Pulmonary Long COVID

“…41 If true, pulmonary fibrosis therapeutics like Nintedanib and Pirfenidone, which have been sparingly used in post-COVID associated fibrosis, may be uniquely suited for the subset of pulmonary Long COVID patients with diffusion impaired restriction. 42,43,46 This report provides novel definition of a distinct endotype of Long COVID and emphasizes the need to stratify patients for targeted therapeutic and clinical management.…”

Effects of pharmacotherapy on post-COVID-19 pulmonary fibrosis: Systemic review

“…It demonstrated absence of differences between the study and control groups in terms of oxygen improvement and chest X-ray improvement. The nintedanib group had more improvement in SpO2/FiO2 ratio than the control group (144.38 ± 118.05 vs 55.67 ± 75.09, p= 0.006), but higher 60-day mortality rate (38.1% vs 23.8%, p = 0.317) [24]. Second was a multicenter, retrospective survey study of subjects administered pirfenidone or nintedanib for post-COVID-19 interstitial lung abnormalities.…”

Integrative single‐cell transcriptome analysis provides new insights into post‐COVID‐19 pulmonary fibrosis and potential therapeutic targets

“…We explored the potential of these drugs as therapeutic interventions against PCPF. Nintedanib, 18,19 pirfenidone, 20 and sorafenib 21 were administered to a rat model of TGF‐β1‐induced pulmonary fibrosis, and a bulk RNA‐seq analysis was conducted on the lung tissue samples 22 . We compared the transcriptomic profiles of the lung tissues of untreated rats (Negative control), those with TGF‐β1‐induced pulmonary fibrosis (Fibrosis group), those with TGF‐β1‐induced pulmonary fibrosis, and nintedanib treatment (Nintedanib group), those with TGF‐β1‐induced pulmonary fibrosis and pirfenidone treatment (Pirfenidone group), and those with TGF‐β1‐induced pulmonary fibrosis and sorafenib treatment (Sorafenib group).…”

“…We explored the potential of these drugs as therapeutic interventions against PCPF. Nintedanib, 18,19 pirfenidone, 20 and sorafenib 21 were administered to a rat model of TGF-β1-induced pulmonary fibrosis, and a bulk RNA-seq analysis was conducted on the lung tissue samples. 22 We compared the transcrip- A principal component analysis (PCA) showed that the Nintedanib group presented with a gene expression profile comparable to that of the TGFβ1-induced fibrosis group.…”