Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD.
Ontology highlight
ABSTRACT:
SUBMITTER: Shumar JN
PROVIDER: S-EPMC8197477 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD.
Shumar John N JN Chandel Abhimanyu A King Christopher S CS
Journal of clinical medicine 20210525 11
Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the ...[more]
Similar Datasets
Project description:ObjectivesProgressive fibrosing interstitial lung disease (PF-ILD) is characterised by increased pulmonary fibrosis, lung function decline, acute exacerbations, decreased quality of life and increased mortality. Nintedanib may slow down disease progression, but long-term outcomes are unknown. We aimed to assess the cost-effectiveness of nintedanib in comparison to placebo, both on top of usual care in patients with PF-ILD.MethodsAn individual PF-ILD patient simulation model was created, using data and extrapolations from the nintedanib and placebo arms of the INBUILD trial. Clinical outcomes (mortality, exacerbations, lung transplants), economic outcomes (direct and indirect costs) and the cost-effectiveness of nintedanib over a 10-year time horizon were forecasted using the Netherlands as a case example. Disease progression was driven by lung function decline, with forced vital capacity (FVC) health states ranging from < 40 to ≥ 110 FVC of % predicted. Sensitivity and scenario analyses were performed to assess the impact of parameter assumptions on the cost-effectiveness and to test model robustness.ResultsOver a 10-year follow-up, nintedanib gained an average of 1.31 discounted life years and an average of 0.87 discounted quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of €60,690 per QALY. Sensitivity analyses showed cost variations had a minor impact on the ICER. Results were mainly driven by mortality probabilities and disease-related utilities. Scenario analyses indicated most sensitivity to the time horizon and lung transplantation costs.ConclusionLong-term treatment with nintedanib could result in considerable health gains for patients with PF-ILD and can be considered cost-effective under the common willingness-to-pay threshold.
| S-EPMC9440187 | biostudies-literature
Project description:BackgroundIn the INBUILD trial in patients with chronic fibrosing interstitial lung diseases (ILDs) and a progressive phenotype, nintedanib reduced the rate of ILD progression with adverse events that were manageable for most patients. We investigated the potential impact of immunomodulatory therapies on the efficacy and safety of nintedanib.MethodsSubjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had shown progression of ILD within the prior 24 months despite management in clinical practice, were randomized to receive nintedanib or placebo. Certain immunomodulatory therapies were restricted for the first 6 months. We analyzed post-hoc the rate of decline in forced vital capacity (FVC) over 52 weeks in subgroups by glucocorticoid use at baseline and in analyses excluding subjects or FVC measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies.ResultsOf 663 subjects, 361 (54.4%) were taking glucocorticoids at baseline (353 at a dose of ≤ 20 mg/day). In the placebo group, the adjusted rate of decline in FVC (mL/year) over 52 weeks was numerically greater in subjects taking than not taking glucocorticoids at baseline (- 206.4 [SE 20.2] vs - 165.8 [21.9]). The difference between the nintedanib and placebo groups was 133.3 (95% CI 76.6, 190.0) mL/year in subjects taking glucocorticoids at baseline and 76.1 (15.0, 137.2) mL/year in subjects who were not (interaction P = 0.18). The effect of nintedanib on reducing the rate of FVC decline in analyses excluding subjects or measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies was similar to the primary analysis. The adverse event profile of nintedanib was similar between subjects who did and did not use prohibited or restricted therapies at baseline or during treatment with trial drug.ConclusionsIn patients with progressive fibrosing ILDs, the effect of nintedanib on reducing FVC decline was not influenced by the use of immunomodulatory therapies. Nintedanib can be used in combination with immunomodulatory therapies in patients with progressive fibrosing ILDs. Trial registration ClinicalTrials.gov, NCT02999178. Registered 21 December 2016, https://clinicaltrials.gov/ct2/show/NCT02999178.
| S-EPMC7962343 | biostudies-literature
Project description:BackgroundInterstitial lung diseases (ILDs) include a variety of parenchymal lung diseases. The most common types of ILDs are idiopathic pulmonary fibrosis (IPF), autoimmune ILDs and hypersensitivity pneumonitis (HP). There is limited real world data on care patterns of patients with chronic fibrosing ILDs with a progressive phenotype other than IPF. Therefore, the aim of this study is to describe care patterns in these patients.MethodsThis retrospective cohort study used claims data from 2015 to 2019 from the Optum Research Database. The study population included adults (≥ 18 years old) with at least two diagnosis codes for fibrosing ILD during the identification period (1OCT2016 to 31DEC2018). A claim-based algorithm for disease progression was used to identify patients likely to have a progressive fibrotic phenotype using progression proxies during the identification period. Index date was the first day of progression proxy identification after fibrosing ILD diagnosis. Patients were required to have continuous enrollment for 12 months before (baseline) and after (follow-up) index date. Patients with an IPF diagnosis were excluded. Descriptive statistics were used to describe the patient population and care patterns.Results11,204 patients were included in the study. Mean age of the patient population was 72.7 years, and 54.5% were female. Unclassified ILDs (48.0%), HP (25.2%) and autoimmune ILDs (16.0%) were the most common ILD types. Other respiratory conditions were prevalent among patients including chronic obstructive pulmonary disease (COPD) (58.9%), obstructive sleep apnea (OSA) (25.0%) and pulmonary hypertension (9.8%). During baseline, 65.3% of all patients had at least one pulmonology visit, this proportion was higher during follow-up, at 70.6%. Baseline and follow-up use for HRCT were 39.9% and 48.8%, and for pulmonary function tests were 43.7% and 48.5% respectively. Use of adrenal corticosteroids was higher during follow-up than during baseline (62.5% vs. 58.0%). Anti-inflammatory and immunosuppressive medication classes were filled by a higher percentage of patients during follow-up than during baseline.ConclusionsComprehensive testing is essential for diagnosis of a progressive phenotype condition, but diagnostic tests were underutilized. Patients with this condition frequently were prescribed anti-inflammatory and immunosuppressive medications.
| S-EPMC9034591 | biostudies-literature
Project description:ObjectiveTo analyze the efficacy and safety of nintedanib in patients with fibrosing autoimmune disease-related interstitial lung diseases (ILDs) with a progressive phenotype.MethodsThe INBUILD trial enrolled patients with a fibrosing ILD other than idiopathic pulmonary fibrosis, with diffuse fibrosing lung disease of >10% extent on high-resolution computed tomography, forced vital capacity percent predicted (FVC%) ≥45%, and diffusing capacity of the lungs for carbon monoxide percent predicted ≥30% to <80%. Patients fulfilled protocol-defined criteria for progression of ILD within the 24 months before screening, despite management deemed appropriate in clinical practice. Subjects were randomized to receive nintedanib or placebo. We assessed the rate of decline in FVC (ml/year) and adverse events (AEs) over 52 weeks in the subgroup with autoimmune disease-related ILDs.ResultsAmong 170 patients with autoimmune disease-related ILDs, the rate of decline in FVC over 52 weeks was -75.9 ml/year with nintedanib versus -178.6 ml/year with placebo (difference 102.7 ml/year [95% confidence interval 23.2, 182.2]; nominal P = 0.012). No heterogeneity was detected in the effect of nintedanib versus placebo across subgroups based on ILD diagnosis (P = 0.91). The most frequent AE was diarrhea, reported in 63.4% and 27.3% of subjects in the nintedanib and placebo groups, respectively. AEs led to permanent discontinuation of trial drug in 17.1% and 10.2% of subjects in the nintedanib and placebo groups, respectively.ConclusionIn the INBUILD trial, nintedanib slowed the rate of decline in FVC in patients with progressive fibrosing autoimmune disease-related ILDs, with AEs that were manageable for most patients.
| S-EPMC9321107 | biostudies-literature
Project description:600 patients aged ≥18 years will be randomised in a 1:1 ratio to nintedanib or placebo. Patients with diagnosis of IPF will be excluded. The study population will be enriched with two-thirds having a usual interstitial pneumonia-like pattern on HRCT. The primary endpoint is the annual rate of decline in forced vital capacity over 52 weeks. The main secondary endpoints are the absolute change from baseline in King's Brief Interstitial Lung Disease Questionnaire total score, time to first acute interstitial lung disease exacerbation or death and time to all-cause mortality over 52 weeks.Ethics and disseminationThe trial is conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Tripartite Guideline for Good Clinical Practice (GCP) and Japanese GCP regulations.Trial registration numberNCT02999178.
| S-EPMC5604725 | biostudies-literature
Project description:BackgroundIn the INBUILD trial in patients with progressive fibrosing interstitial lung diseases (ILDs), nintedanib reduced the rate of decline in forced vital capacity compared with placebo, with side-effects that were manageable for most patients. We used data from the INBUILD trial to characterize further the safety and tolerability of nintedanib.MethodsPatients with fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF), who had experienced progression of ILD within the 24 months before screening despite management deemed appropriate in clinical practice, were randomized to receive nintedanib 150 mg twice daily or placebo. To manage adverse events, treatment could be interrupted or the dose reduced to 100 mg twice daily. We assessed adverse events and dose adjustments over the whole trial.ResultsA total of 332 patients received nintedanib and 331 received placebo. Median exposure to trial drug was 17.4 months in both treatment groups. Adverse events led to treatment discontinuation in 22.0% of patients treated with nintedanib and 14.5% of patients who received placebo. The most frequent adverse event was diarrhea, reported in 72.3% of patients in the nintedanib group and 25.7% of patients in the placebo group. Diarrhea led to treatment discontinuation in 6.3% of patients in the nintedanib group and 0.3% of the placebo group. In the nintedanib and placebo groups, respectively, 48.2% and 15.7% of patients had ≥ 1 dose reduction and/or treatment interruption. Serious adverse events were reported in 44.3% of patients in the nintedanib group and 49.5% of patients in the placebo group. The adverse event profile of nintedanib was generally consistent across subgroups based on age, sex, race and weight, but nausea, vomiting and dose reductions were more common among female than male patients.ConclusionsThe adverse event profile of nintedanib in patients with progressive fibrosing ILDs other than IPF is consistent with its established safety and tolerability profile in patients with IPF and characterized mainly by gastrointestinal events, particularly diarrhea. Management of adverse events using symptomatic therapies and dose adjustment is important to minimize the impact of adverse events and help patients remain on therapy. Trial registration Registered 21 December 2016, https://clinicaltrials.gov/ct2/show/NCT02999178 A video abstract summarizing the key results presented in this manuscript is available at: https://www.globalmedcomms.com/respiratory/cottin/INBUILDsafety .
| S-EPMC8991727 | biostudies-literature
Project description:BackgroundAlthough transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real-world utility in the therapeutic decision-making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents.MethodsWe analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC-based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing.ResultsIn our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed-effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC-based UIP "Score ≥ 2" were significantly steeper than those of patients with "Score ≤ 1." During follow-up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure.ConclusionsTBLC-based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti-inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians.
| S-EPMC11251805 | biostudies-literature
Project description:BackgroundProposed criteria for progressive fibrosing interstitial lung disease (PF-ILD) have been linked to increased mortality risk, but lung function trajectory after satisfying individual criteria remains unknown. Because survival is rarely employed as the primary end-point in therapeutic trials, identifying PF-ILD criteria that best predict subsequent change in forced vital capacity (FVC) could improve clinical trial design.MethodsA retrospective, multicentre longitudinal cohort analysis was performed in consecutive patients with fibrotic connective tissue disease-associated ILD (CTD-ILD), chronic hypersensitivity pneumonitis and idiopathic interstitial pneumonia at three US centres (test cohort) and one UK centre (validation cohort). 1-year change in FVC after satisfying proposed PF-ILD criteria was estimated using joint modelling. Subgroup analyses were performed to determine whether results varied across key subgroups.Results1227 patients were included, with CTD-ILD predominating. Six out of nine PF-ILD criteria were associated with differential 1-year change in FVC, with radiological progression of fibrosis, alone and in combination with other features, associated with the largest subsequent decline in FVC. Findings varied significantly by ILD subtype, with CTD-ILD demonstrating little change in FVC after satisfying most PF-ILD criteria, while other ILDs showed significantly larger changes. Findings did not vary after stratification by radiological pattern or exposure to immunosuppressant therapy. Near-term change in FVC after satisfying proposed PF-ILD criteria was heterogeneous depending on the criterion assessed and was strongly influenced by ILD subtype.ConclusionsThese findings may inform future clinical trial design and suggest ILD subtype should be taken into consideration when applying PF-ILD criteria.
| S-EPMC10039317 | biostudies-literature
Project description:Acute exacerbation of interstitial lung disease (ILD) is associated with a poor prognosis and high mortality. Numerous studies have documented acute exacerbation in idiopathic pulmonary fibrosis (IPF), but less is known about these events in other ILDs that may present a progressive-fibrosing phenotype. We propose defining acute exacerbation as an acute, clinically significant respiratory deterioration, typically less than 1 month in duration, together with computerised tomography imaging showing new bilateral glass opacity and/or consolidation superimposed on a background pattern consistent with fibrosing ILDs. Drawing on observations in IPF, it is suspected that epithelial injury or proliferation and autoimmunity are risk factors for acute exacerbation in ILDs that may present a progressive-fibrosing phenotype, but further studies are required. Current acute exacerbation management strategies are based on recommendations in IPF, but no randomised controlled trials of acute exacerbation management have been performed. Although there are no formal strategies to prevent the development of acute exacerbation, possible approaches include antifibrotic drugs (such as nintedanib and pirfenidone), and minimising exposure to infection, airborne irritants and pollutants. This review discusses the current knowledge of acute exacerbation of ILDs that may present a progressive-fibrosing phenotype and acknowledges limitations of the data available.
| S-EPMC9488799 | biostudies-literature
Project description:Despite conventional treatment, a proportion of interstitial lung disease (ILD) patients develop a progressive phenotype known as "fibrosing ILD with a progressive phenotype" (PF-ILD), characterized by worsening respiratory symptoms, decline in lung function, and early mortality. This review describes the epidemiology, and the humanistic and economic burden of PF-ILDs other than idiopathic pulmonary fibrosis (non-IPF PF-ILD). A structured review of the literature was conducted, using predefined search strategies in Ovid MEDLINE and EMBASE, and supplemented with gray literature searches. The search identified 3,002 unique articles and an additional 3 sources were included from the gray literature; 21 publications were included. The estimated prevalence of non-IPF PF-ILD ranges from 6.9 to 70.3/100,000 persons and the estimated incidence from 2.1 to 32.6/100,000 person-years. Limited evidence demonstrates that PF-ILD has a significant impact on patients' quality of life, affecting their daily lives, psychological well-being, careers, and relationships. PF-ILD is also associated with significant economic burden, demonstrating higher healthcare resource use and direct costs compared with the non-progressive phenotype, and indirect costs, which include job losses. This review indicates that PF-ILD places a considerable humanistic burden on both patients and caregivers, and a substantial economic burden on healthcare systems, patients, and society.
| S-EPMC8843847 | biostudies-literature