Bexotegrast in people with idiopathic pulmonary fibrosis (IPF): a plain language summary of publication of the INTEGRIS-IPF study.

This plain language summary shares results from a clinical study called INTEGRIS-IPF that was published in the in 2024. This study looked at a medicine called (beck-so-teh-grast) as a possible treatment for (i-dee-uh-pa-thick pul-muh-ner-ee fie-bro-sis; IPF). is an investigational medicine, which means that it is being studied and has not yet been approved by the US Food and Drug Administration (FDA), for people with IPF to take as a treatment.

Inhaled Nitric Oxide in Fibrotic Lung Disease: A Randomized, Double-Blind, Placebo-controlled Trial.

Inhaled nitric oxide (iNO) has been shown to result in benefits in moderate to vigorous physical activity (MVPA) in patients with fibrotic interstitial lung disease (f-ILD) receiving supplemental oxygen in two independent trials. This phase III randomized, double-blind, placebo-controlled study sought to validate the benefit of ambulatory iNO in patients with f-ILD requiring supplemental oxygen. Patients with f-ILD receiving supplemental long-term oxygen were randomized in a 1:1 fashion to iNO at 45 μg/kg ideal body weight per hour or placebo for 16 weeks.

Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial.

Idiopathic pulmonary fibrosis (IPF) is a rare and progressive disease that causes progressive cough, exertional dyspnea, impaired quality of life, and death. Bexotegrast (PLN-74809) is an oral, once-daily, investigational drug in development for the treatment of IPF. This Phase-2a multicenter, clinical trial randomized participants with IPF to receive, orally and once daily, bexotegrast at 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib), in an approximately 3:1 ratio in each bexotegrast dose cohort, for at least 12 weeks.

Phase 2, Double-Blind, Placebo-controlled Trial of a c-Jun N-Terminal Kinase Inhibitor in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a fatal and progressive disease with limited treatment options. We sought to assess the efficacy and safety of CC-90001, an oral inhibitor of c-Jun N-terminal kinase 1, in patients with idiopathic pulmonary fibrosis. In a Phase 2, randomized (1:1:1), double-blind, placebo-controlled study (ClinicalTrials.

Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency.

Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints.

Visual and morphometric description of feral horse hooves from Sable Island National Park Reserve.

Objective: To visually evaluate and morphometrically describe a sample of abnormal hooves from Sable Island horses that died between 2007 and 2013.

Animal: Equine.

Procedure: An opportunistic sample of 356 abnormal hooves from horses inhabiting Sable Island National Park Reserve (Canada) was collected postmortem between 2007 and 2013 from 101 Sable Island horses.

Characteristics of patients with pulmonary arterial hypertension from an innovative, comprehensive real-world patient data repository.

Pulmonary arterial hypertension (PAH) is a rare, life-limiting disease. PAH registries provide real-world data that complement clinical trial data and inform treatment decisions. The TRIO comprehensive, integrated patient data repository (TRIO CIPDR), is an innovative US repository capturing data on contemporary patients diagnosed with pulmonary hypertension and receiving US Food and Drug Administration-approved PAH therapies.

Efficacy and Safety of Pirfenidone in Advanced Versus Non-Advanced Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Six Clinical Studies.

Introduction: In the European Union (EU), the indication for the antifibrotic pirfenidone prior to April 2023 did not include patients with advanced idiopathic pulmonary fibrosis (IPF). This analysis compared the efficacy and safety of pirfenidone in advanced IPF versus non-advanced IPF.

Methods: Data were included from the following studies of pirfenidone: ASCEND (NCT01366209); CAPACITY (004 [NCT00287716] and 006 [NCT00287729]); RECAP (NCT00662038; advanced IPF defined as percent predicted forced vital capacity [%FVC] < 50% and/or percent predicted carbon monoxide diffusing capacity [%DLco] < 35% at baseline); PASSPORT (NCT02699879; advanced IPF defined as baseline %FVC < 50%); and SP-IPF (NCT02951429; patients with advanced IPF [defined as %DLco ≤ 40% at screening] at risk of group 3 pulmonary hypertension).

Low Gut Microbial Diversity Augments Estrogen-Driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease.

Although profibrotic cytokines, such as IL-17A and TGF-β1, have been implicated in the pathogenesis of interstitial lung disease (ILD), the interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as the phosphorylation of STAT3, have not been defined. Here, through chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells, we show that regions within the STAT3 locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung.

Low Gut Microbial Diversity Augments Estrogen-driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease.

Although profibrotic cytokines such as IL-17A and TGF-β1 have been implicated in interstitial lung disease (ILD) pathogenesis, interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as phosphorylation of STAT3, have not been defined. Here we show by chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells that regions within the locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung.

PCSK6 and Survival in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. A better understanding of the molecular drivers of IPF progression is needed. To identify and validate molecular determinants of IPF survival.

The Association between Exposures and Disease Characteristics in Familial Pulmonary Fibrosis.

Heterogeneous characteristics are observed in familial pulmonary fibrosis (FPF), suggesting that nongenetic factors contribute to disease manifestations. To determine the relationship between environmental exposures and disease characteristics of FPF, including the morphological characteristics on chest computed tomography (CT) scan, and timing of FPF symptom onset, lung transplantation, or death. Subjects with FPF with an exposure questionnaire and chest CT were selected from a prospective cohort at Vanderbilt.

Study design and rationale for the TETON phase 3, randomised, controlled clinical trials of inhaled treprostinil in the treatment of idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF) greatly impacts quality of life and eventually leads to premature death from respiratory failure. Inhaled treprostinil was associated with improvements in forced vital capacity (FVC) and reduced exacerbations of underlying lung disease in post hoc analyses from a phase 3 study in patients with precapillary pulmonary hypertension due to interstitial lung disease. These results, combined with preclinical evidence of treprostinil's antifibrotic activity, support its investigation in the treatment of IPF.

The Antifibrotic Effects of Inhaled Treprostinil: An Emerging Option for ILD.

Interstitial lung diseases (ILD) encompasses a heterogeneous group of parenchymal lung diseases characterized by variable amounts of inflammation and fibrosis. The targeting of fibroblasts and myofibroblasts with antifibrotic treatments is a potential therapeutic target for these potentially fatal diseases. Treprostinil is unique among the prostacyclin mimetics in that it has distinct actions at additional prostaglandin receptors.

A Phase IIb Randomized Clinical Study of an Anti-αβ Monoclonal Antibody in Idiopathic Pulmonary Fibrosis.

Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. To evaluate the efficacy and safety of BG00011, an anti-αβ IgG1 monoclonal antibody, in the treatment of patients with IPF. In a phase IIb randomized, double-blind, placebo-controlled trial, patients with IPF (FVC ⩾50% predicted, on or off background therapy) were randomized 1:1 to once-weekly subcutaneous BG00011 56 mg or placebo.

Multidisciplinary clinical guidance on trastuzumab deruxtecan (T-DXd)-related interstitial lung disease/pneumonitis-Focus on proactive monitoring, diagnosis, and management.

Trastuzumab deruxtecan (T-DXd; DS-8201) is an antibody-drug conjugate targeting human epidermal growth factor receptor 2. Interstitial lung disease (ILD)/pneumonitis is an adverse event associated with T-DXd; in most cases, it is low grade (grade ≤ 2) and can be treated effectively but may develop to be fatal in some instances. It is important to increase patient and provider understanding of T-DXd-related ILD/pneumonitis to improve patient outcomes.

Screening Strategies for Pulmonary Hypertension in Patients With Interstitial Lung Disease: A Multidisciplinary Delphi Study.

Background: Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD) and is associated with worse outcomes and increased mortality. Evaluation of PH is recommended in lung transplant candidates, but there are currently no standardized screening approaches. Trials have identified therapies that are effective in this setting, providing another rationale to routinely screen patients with ILD for PH.

Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD).

Introduction: Idiopathic pulmonary fibrosis (IPF) and non-IPF, progressive fibrotic interstitial lung diseases (PF-ILD), are associated with a progressive loss of lung function and a poor prognosis. Treatment with antifibrotic agents can slow, but not halt, disease progression, and treatment discontinuation because of adverse events is common. Fibrotic diseases such as these can be mediated by lysophosphatidic acid (LPA), which signals via six LPA receptors (LPA).

Management of Progressive Fibrosing Interstitial Lung Diseases (PF-ILD).

Progressive fibrosing interstitial lung diseases (PF-ILD) consist of a diverse group of interstitial lung diseases (ILD) characterized by a similar clinical phenotype of accelerated respiratory failure, frequent disease exacerbation and earlier mortality. Regardless of underlying disease process, PF-ILD progresses through similar mechanisms of self-sustained dysregulated cell repair, fibroblast proliferation and alveolar dysfunction that can be therapeutically targeted. Antifibrotic therapy with nintedanib or pirfenidone slow lung function decline and are the backbone of treatment for IPF with an expanded indication of PF-ILD for nintedanib.

A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen.

Patients with fibrotic interstitial lung disease often progress to the point of requiring supplemental oxygen. This is invariably accompanied by an impaired quality of life and limitations on activities of daily living. This study aimed to assess the improvement in physical activity in patients with interstitial lung disease requiring supplemental oxygen treated with pulsed inhaled nitric oxide via INOpulse (Bellerophon Therapeutics).

Idiopathic pulmonary fibrosis: Physician and patient perspectives on the pathway to care from symptom recognition to diagnosis and disease burden.

Background And Objective: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that requires ongoing care and is associated with considerable socioeconomic burden. We evaluated the IPF care pathway from symptom recognition to treatment. We describe the impact of IPF on healthcare resource use (HCRU), quality of life (QoL) and work impairment, and report differences in patient and physician perspectives using real-world data from France, Germany, Japan and the United States.

Effects of nintedanib by inclusion criteria for progression of interstitial lung disease.

Background: The INBUILD trial investigated nintedanib placebo in patients with progressive fibrosing interstitial lung diseases (ILDs). We investigated the decline in forced vital capacity (FVC) in subgroups based on the inclusion criteria for ILD progression.

Methods: Subjects had a fibrosing ILD other than idiopathic pulmonary fibrosis and met the following criteria for ILD progression within the 24 months before screening despite management deemed appropriate in clinical practice: Group A, relative decline in FVC ≥10% predicted; Group B, relative decline in FVC ≥5-<10% predicted with worsened respiratory symptoms and/or increased extent of fibrosis on high-resolution computed tomography (HRCT); Group C, worsened respiratory symptoms and increased extent of fibrosis on HRCT only.

A Phase I Randomized, Controlled, Clinical Trial of Valganciclovir in Idiopathic Pulmonary Fibrosis.

Human herpesviruses Epstein-Barr virus and cytomegalovirus are frequently detectable in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and could contribute to disease pathogenesis. With the goal of inhibiting herpesvirus replication, we tested the safety and tolerability of adding valganciclovir to standard IPF therapy (pirfenidone). We performed a single-center, Phase I, double-blind, randomized, placebo-controlled trial comparing valganciclovir 900 mg daily with placebo in patients with IPF with serologic evidence of prior Epstein-Barr virus and/or cytomegalovirus infection who were tolerating full-dose pirfenidone (2,403 mg/d).