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Review
. 2024 Jan-Dec:18:17534666241266343.
doi: 10.1177/17534666241266343.

Key learnings from the INBUILD trial in patients with progressive pulmonary fibrosis

Isabel Mira-Avendano  1 , Mitchell Kaye  2
Affiliations
Review

Key learnings from the INBUILD trial in patients with progressive pulmonary fibrosis

Isabel Mira-Avendano et al. Ther Adv Respir Dis. 2024 Jan-Dec.

Abstract

In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option.

Keywords: clinical trial; disease progression; drug tolerance; interstitial; lung disease; pulmonary fibrosis.

Plain language summary

What did we find out from the INBUILD trial about progressive lung fibrosis?Lung fibrosis is a rare disease in which the lung tissue becomes scarred and hardened. This makes it more difficult for the lungs to inflate and for the lungs to exchange oxygen with the blood. In some patients, lung fibrosis gets worse over time. This is known as progressive lung fibrosis. In the INBUILD trial, researchers looked at the effects of a drug called nintedanib in patients with progressive lung fibrosis. In this trial, 663 patients were randomly allocated to receive either nintedanib or a placebo and then followed for approximately 19 months. The patients and the researchers did not know which patients were taking the active drug (nintedanib) and which patients were taking placebo. The results showed that the criteria used to find patients with progressive lung fibrosis to take part in the trial successfully identified patients whose disease would continue to worsen. These criteria were based on a decline in the volume (size) of the lungs, worsening symptoms such as shortness of breath, and worsening of changes seen on a scan of the chest. The trial results also showed that nintedanib slowed down loss of lung function and had a similar benefit in patients with different severities of disease at the start of the trial. The most common side-effects of nintedanib were gastrointestinal problems, particularly diarrhea, but most patients given nintedanib were able to cope with these side-effects without needing to stop treatment. Large trials like the INBUILD trial are important for helping us understand how diseases progress and in which patients particular drugs should be used.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
ILD diagnoses in the INBUILD trial. Source: Wells et al. Copyright (2020), with permission from Elsevier. Included other autoimmune lLDs (e.g. Sjögren’s syndrome-associated ILD, systemic lupus erythematosus-associated ILD), and other llPs (e.g. pleuroparenchymal fibroelastosis, cryptogenic organizing pneumonia, desquamative interstitial pneumonia). IIP, idiopathic interstitial pneumonia; ILDs, interstitial lung diseases; MCTD, mixed connective tissue disease; RA, rheumatoid arthritis; SSc, systemic sclerosis.
Figure 2.
Figure 2.
Course of FVC decline in the INPULSIS trials in patients with IPF and the INBUILD trial in patients with progressive fibrosing ILDs other than IPF. Source: Brown et al. Reproduced with permission of the © ERS 2023. IPF, idiopathic pulmonary fibrosis; ILDs, interstitial lung diseases.
Figure 3.
Figure 3.
Consistent effect of nintedanib on reducing the rate of decline in FVC across subgroups by ILD diagnosis in the INBUILD trial. Source: Wells et al. Copyright (2020), with permission from Elsevier. Treatment-by-subgroup-by-time interaction p = 0.41. *Included rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD, mixed connective tissue disease-associated ILD, plus autoimmune disease-related ILDs in the “other fibrosing ILDs” category of the case report form. †Included sarcoidosis, exposure-related ILDs, and other terms in the “other fibrosing ILDs” category of the case report form. FVC, forced vital capacity; ILD, interstitial lung disease.
Figure 4.
Figure 4.
Most frequent adverse events reported in the INBUILD trial. Data are based on adverse events reported between the first trial drug intake and 28 days after the last trial drug intake. The median exposure to the trial drug was 17.4 months in both groups. Adverse events were coded based on single preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) version 22.0, except for abdominal pain, which was based on a group of MedDRA-preferred terms. Adverse events with a rate >10 events per 100 patient-years in either treatment group are shown. *Based on MedDRA preferred term interstitial lung disease. ALT, alanine aminotransferase; AST, aspartate aminotransferase.
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References

    1. Flaherty KR, Wells AU, Cottin V, et al.. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med 2019; 381(18): 1718–1727. - PubMed
    1. Raghu G, Remy-Jardin M, Richeldi L, et al.. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2022; 205(9): e18–e47. - PMC - PubMed
    1. Pugashetti JV, Adegunsoye A, Wu Z, et al.. Validation of proposed criteria for progressive pulmonary fibrosis. Am J Respir Crit Care Med 2023; 207(1): 69–76. - PMC - PubMed
    1. Wells AU, Flaherty KR, Brown KK, et al.. 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. Lancet Respir Med 2020; 8(5): 453–460. - PubMed
    1. George PM, Spagnolo P, Kreuter M, et al.. Progressive fibrosing interstitial lung disease: clinical uncertainties, consensus recommendations, and research priorities. Lancet Respir Med 2020; 8(9): 925–934. - PubMed

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