Late Breaking Abstract - Exploring Efficacy and Safety of oral Pirfenidone for progressive, non-IPF Lung Fibrosis (RELIEF)

Güenther, Andreas; Prasse, Antje; Kreuter, Michael; Neuser, Petra; Rabe, Klaus F.; Bonella, Francesco; Bonnet, R.; Grohé, Christian; Held, Matthias; Wilkens, Heinrike; Hammerl, Peter; Koschel, Dirk; Blaas, Stefan; Wirtz, Hubert; Ficker, Joachim H.; Neumeister, Wolfgang; Schönfeld, N; Claussen, Martin; Kneidinger, Nikolaus; Frankenberger, Marion; Hummler, Simone; Kahn, Nicolas; Tello, Silke; Freise, Julia; Welte, Tobias; Schade‐Brittinger, Carmen; Behr, Jürgen

doi:10.1183/13993003.congress-2019.rct1879

Cited by 14 publications

(20 citation statements)

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“…The disease behaviour of various ILD subtypes has been studied in many observational cohorts and clinical trials, with many of these studies focusing on patients with a progressive fibrotic phenotype. The eligibility criteria of these studies have provided a starting point for the definition of PF-ILD [14,15,23,24], with the clinical utility of this concept supported by the therapeutic benefits observed in some of these clinical trials [14,15]. Despite these significant advances, there are many uncertainties that still remain in the classification and management of PF-ILD.…”

Section: Discussionmentioning

confidence: 99%

“…Patients in the INBUILD study were not permitted use of immunosuppressive medications, possibly suggesting a study population with less abundant inflammatory features. Several studies of pirfenidone have enrolled patients with a variety of non-IPF PF-ILD subtypes who have worsened despite therapy, including a study in unclassifiable ILD [15], and another study published only in abstract form that included patients with CTD-ILD, fibrotic idiopathic NSIP, fibrotic HP, and ILD associated with asbestosis [23]. In a recent phase 2 study evaluating pirfenidone in unclassifiable ILD, the safety profile of pirfenidone was reassuring with promising, but inconsistent efficacy signals that depended on both the endpoint and the method of statistical analysis.…”

Section: Antifibrotic Therapymentioning

confidence: 99%

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Progression of fibrosing interstitial lung disease

2020

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Fibrotic interstitial lung diseases (ILDs) are often challenging to diagnose and classify, but an accurate diagnosis has significant implications for both treatment and prognosis. A subset of patients with fibrotic ILD experience progressive deterioration in lung function, physical performance, and quality of life. Several risk factors for ILD progression have been reported, such as male sex, older age, lower baseline pulmonary function, and a radiological or pathological pattern of usual interstitial pneumonia. Morphological similarities, common underlying pathobiologic mechanisms, and the consistently progressive worsening of these patients support the concept of a progressive fibrosing (PF)-ILD phenotype that can be applied to a variety of ILD subtypes. The conventional approach has been to use antifibrotic medications in patients with idiopathic pulmonary fibrosis (IPF) and immunosuppressive medications in patients with other fibrotic ILD subtypes; however, recent clinical trials have suggested a favourable treatment response to antifibrotic therapy in a wider variety of fibrotic ILDs. This review summarizes the literature on the evaluation and management of patients with PF-ILD, and discusses questions relevant to applying recent clinicial trial findings to real-world practice.

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Section: Discussionmentioning

confidence: 99%

Section: Antifibrotic Therapymentioning

confidence: 99%

Progression of fibrosing interstitial lung disease

2020

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“…However, a major limitation of this study was its small sample size (collagen-vascular disease-ILD (n=37), fibrotic non-specific interstitial pneumonia (NSIP) (n=27), chronic hypersensitivity pneumonitis (n=57) and asbestos-related lung fibrosis (n=6)), and the full results have not yet been published. 29 The immunosuppressive agents cyclophosphamide (CYC) and mycophenolate mofetil (MMF) have also been evaluated in SSc-ILD. In one study, CYC showed beneficial effects on lung function compared with placebo after 1 year of treatment, although these mostly dissipated after 2 years.…”

Section: Interstitial Lung Diseases and The Current Treatment Landscapementioning

confidence: 99%

Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)

et al. 2020

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Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease (CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. Data from phase II studies also suggest that pirfenidone, which has a different—yet largely unknown—mechanism of action, may also have activity in other fibrosing ILDs with a progressive phenotype, in addition to its known efficacy in IPF. Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population.

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“…Using a similar ‘basket approach’, the RELIEF study, a phase II trial, randomized 127 patients with ILD and a progressive fibrotic phenotype (37 CTD-ILD, 27 fibrotic NSIP, 57 chronic hypersensitivity pneumonia and 6 asbestos-related lung fibrosis) to receive, in addition to conventional anti-inflammatory therapy, placebo or pirfenidone 68 ( Table 1 ). The primary aim of the RELIEF study was to assess the absolute change in percentage predicted FVC over 48 weeks.…”

Section: Antifibrotic Drugs In Ctd-ildsmentioning

confidence: 99%