Nintedanib in patients with progressive fibrosing interstitial lung diseases—subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial

Abstract

Background The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis. Methods The INBUILD trial was a randomised, double-blind, placebo-controlled, parallel group trial done at 153 sites in 15 countries. Participants had an investigator-diagnosed fibrosing ILD other than IPF, with chest imaging features of fibrosis of more than 10% extent on high resolution CT (HRCT), forced vital capacity (FVC) of 45% or more predicted, and diffusing capacity of the lung for carbon monoxide (DLco) of at least 30% and less than 80% predicted. Participants fulfilled protocol-defined criteria for ILD progression in the 24 months before screening, despite management considered appropriate in clinical practice for the individual ILD. Participants were randomly assigned 1:1 by means of a pseudorandom number generator to receive nintedanib 150 mg twice daily or placebo for at least 52 weeks. Participants, investigators, and other personnel involved in the trial and analysis were masked to treatment assignment until after database lock. In this subgroup analysis, we assessed the rate of decline in FVC (mL/year) over 52 weeks in patients who received at least one dose of nintedanib or placebo in five prespecified subgroups based on the ILD diagnoses documented by the investigators: hypersensitivity pneumonitis, autoimmune ILDs, idiopathic non-specific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. The trial has been completed and is registered with ClinicalTrials.gov, number NCT02999178.

Clinical diagnosis of patients subjected to surgical lung biopsy with a probable usual interstitial pneumonia pattern on high-resolution computed tomography

“…The INBUILD trial was a randomized, double-blind, multicentre, parallel group trial performed in 663 patients with a progressive brosing ILD other than IPF. (37,38) Chronic hypersensitivity pneumonitis was diagnosed in 173 patients (26%). Participants were randomly assigned to receive 150 mg nintedanib twice daily or placebo for at least 52 weeks.…”

“…In patients with a UIP-like brotic pattern, the adjusted rate of decline in the FVC over the 52-week period was more conspicuous. (38) These studies raise the question of whether the diagnosis of ILD brosing really matters. In FHP, if the antigen is not identi ed, the prognosis is worse.…”

Real-world Experience of Nintedanib Therapy in Idiopathic-inflammatory-myopathy-related Interstitial Lung Disease: Efficacy and Tolerability

“…In in SENSCIS trial, nintedanib was identi ed to decrease FVC decline in Ssc-ILD, nevertheless, its effect on RP-ILD was not probed into [18]. The recently completed INBUILD trial demonstrated the consistent effect of nintedanib on reducing FVC decline in different ILD subgroups, irrespective of the underlying ILD diagnosis [20]. In our study, nintedanib was found to reduce the incidence of the fatal RP-ILD in IIM-ILD patients, which for the rst time initially demonstrated the therapeutic value of nintedanib in IIM-ILD regardless of the retrospective nature and lack of follow-up lung function testing.…”

“…Preceding researches in animal models with manifestations of brosing ILDs like idiopathic pulmonary brosis (IPF), systemic-sclerosis-related ILD (Ssc-ILD), rheumatoid-arthritis-related ILD (RA-ILD), hypersensitivity pneumonitis and silicosis have uncovered that nintedanib has anti-brotic effect regardless of the trigger for the ILD pathology [15]. And the therapeutic value of nintedanib has been demonstrated in different subgroups of ILD via TOMORROW, INPULSIS-1, INPULSIS-2, SENSCIS and INBUILD trials as well as several real-world analyses [16][17][18][19][20]. However, the effect and safety of nintedanib in IIM-ILD remain an enigma to researchers and physicians.…”

Urgent avenues in the treatment of COVID-19: Targeting downstream inflammation to prevent catastrophic syndrome

“…More recently, it has been suggested that pulmonary fibrosis in SARS-CoV is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signalling [20]. Inhibiting EGFR signalling, by the use of tyrosine kinase inhibitors like nintedanib, a drug licensed for idiopathic lung fibrosis, seems promising for interstitial lung disease in systemic sclerosis [21], and might also be useful for COVID-19.…”