Fibrosing CTD-ILDs with a progressive phenotype
Up to 4 in 10 patients with connective tissue disease-associated interstitial lung diseases (CTD-ILDs) can develop a progressive fibrosing phenotype1–5
PATIENTS WITH CTD-ILDs ARE AT RISK OF DEVELOPING A PROGRESSIVE FIBROSING PHENOTYPE, REGARDLESS OF THE UNDERLYING CTD2,6–8
The progressive fibrosing phenotype is defined by the presence of:6–9
In progressive fibrosing ILD, pulmonary fibrosis continues to develop independent of the originating disease (SSc, RA, primary Sjögren’s syndrome, etc.) or trigger (inflammation, exposure, etc.), along common pathogenic pathways6,9–11
PREVALENCE OF THE PROGRESSIVE FIBROSING PHENOTYPE IN PATIENTS WITH CTD-ILDs
It is estimated that 16%–40% of patients with CTD-ILDs develop a progressive fibrosing phenotype – based on a systematic review of the published literature and a physician survey1–5
Fibrosing ILD |
Proportion of patients with a progressive phenotype, % |
Reference / source |
---|---|---|
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) |
40 |
Zamora-Legoff 2017 |
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) |
32 |
Hoffmann-Vold 2015 |
Polymyositis- and dermatomyositis-associated interstitial lung disease (PM/DM-ILD) |
16 |
Marie 2011 |
Primary Sjögren’s syndrome-associated interstitial lung disease (primary Sjögren’s syndrome-ILD) | 24 |
Wijsensbeek 2019* |
Systemic lupus erythematosus-associated interstitial lung disease (SLE-ILD) |
24 |
Wijsensbeek 2019* |
Mixed connective tissue disease-associated interstitial lung disease (MCTD-ILD) |
24 |
Wijsensbeek 2019* |
* Estimates of the percentage of patients with non-IPF ILD that develop progressive fibrosis based on an online survey of total 486 physicians (243 pulmonologists, 203 rhuematologists and 40 internists) from the United States, Japan, France, Germany, Italy, Spain and the United Kingdom. Sourced percentages (24%) for primary Sjögren’s syndrome-ILD, SLE-ILD and MCTD-ILD were from the same ‘Other CTD-ILDs’ group.
THE BURDEN OF PROGRESSIVE FIBROSING CTD-ILD CAN SUBSTANTIALLY REDUCE A PATIENT'S HEALTH-RELATED QUALITY OF LIFE9
Cough and dyspnea adversely affect the everyday lives of patients with CTD-ILDs15–17
Patients with progressive CTD-ILDs suffer from emotional distress that may include feelings of depression, anxiety and loss of independence18,19
Depression
Powerlessness
Loss of independence
Anxiety
PROGRESSIVE CTD-ILDs HAVE A WIDE RANGE OF POTENTIAL IMPACTS ON PATIENTS7,18
Patients with progressive CTD-ILDs report almost universal symptoms of anxiety and/or depression18
Progressive fibrosing ILD is characterized by progression of pulmonary fibrosis, worsening of symptoms, decline in lung function and deterioration in health-related quality of life7
Factors that reflect progression of ILDs
Adapted from: Kolb M, Vašáková M. Respir Res. 2019;20(1).
Declines in lung function shown by PFTs are associated with increased mortality in patients with CTD-ILDs14,20–22
UNCOVER THE FULL IMPACT OF PROGRESSIVE FIBROSING CTD-ILDs
See the impact of progressive fibrosing ILD across a range of CTD-ILDs
Patients with interstitial lung diseases face an unpredictable journey. There are over 200 types of ILDs, of which Idiopathic pulmonary fibrosis, or IPF, is the most common fibrosing type. Around 1 in 5 patients with differing ILD diagnoses may develop a ‘progressive fibrosing phenotype’. Progressive fibrosing ILDs are believed to progress via common pathobiological fibrotic pathways, independent of the original trigger. These progressive fibrosing ILDs are characterised by self-sustaining, diffuse and irreversible fibrosis, worsening respiratory symptoms and declining lung function. The progressive and permanent fibrotic lung damage can place an overwhelming burden on patient’s quality of life and is associated with high mortality. No treatments are currently approved for progressive fibrosing ILDs, other than IPF. Thus, there is a high unmet need for effective treatments that slow the disease progression in these patients. Boehringer Ingelheim has a strong commitment to scientific research. The INBUILD® clinical trial is the first and largest phase III global trial to include patients across the broad spectrum of ILDs that develop the ‘progressive fibrosing phenotype’, into a single trial. So together, we hope to help patients with progressive fibrosing ILDs find new ways forward.
The first step to slowing progressive CTD-ILDs is identification of ILD
The first step to slowing progressive CTD-ILDs is identification of ILD
Inflammation and fibrosis in CTD-ILDs
Investigating fibrotic CTD-ILDs with HRCT imaging
Footnotes
CTD, connective tissue disease; CTD-ILD, connective tissue disease-associated interstitial lung disease; DLCO, diffusing capacity of the lung for carbon monoxide; DM-ILD, dermatomyositis-associated interstitial lung disease; FVC, forced vital capacity; HRCT, high-resolution computed tomography; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; MCTD-ILD, mixed connective tissue disease-associated interstitial lung disease; PFT, pulmonary function test; PM-ILD, polymyositis-associated interstitial lung disease; RA-ILD, rheumatoid arthritis-associated interstitial lung disease; SLE-ILD, systemic lupus erythematosus associated interstitial lung disease; SSc-ILD, systemic sclerosis-associated interstitial lung disease.
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Wijsenbeek MS, Kreuter M, Olson A, et al. Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management. Curr Med Res Opin. 2019:1–10.
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Zamora-Legoff JA, Krause ML, Crowson CS, et al. Progressive decline of lung function in rheumatoid arthritis associated interstitial lung disease. Arthritis Rheumatol. 2017;69(3):542–549.
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Hoffmann-Vold A, Aaløkken TM, Lund MB, et al. Predictive Value of Serial High-Resolution Computed Tomography Analyses and Concurrent Lung Function Tests in Systemic Sclerosis. Arthritis Rheumatol. 2015;67:2205–2212.
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Marie I, Hatron PY, Dominique S, et al. Short-Term and Long-Term Outcomes of Interstitial Lung Disease in Polymyositis and Dermatomyositis. Arthritis Rheum. 2011;63:3439–3447.
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Cottin V, Hirani N, Hotchkin D, et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150):180076.
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Kolb M, Vašáková M. The natural history of progressive fibrosing interstitial lung diseases. Respir Res. 2019;20(1).
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Flaherty KR, Brown KK, Wells AU, et al. Design of the PF-ILD trial: A double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Resp Res. 2017;4(1):e000212.
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Wijsenbeek M, Kreuter M, Fischer A, et al. Non-IPF Progressive Fibrosing Interstitial Lung Disease (PF-ILD): The Patient Journey. Am J Respir Crit Care Med. 2018;197:A1678.
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Hoffmann-Vold AM, Maher TM, Philpot EE, et al. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. Lancet Rheum. 2020;2 e71–e83.
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Guler, S.A., Winstone, T.A., Murphy, D., et al. Does systemic sclerosis–associated interstitial lung disease burn out? Specific phenotypes of disease progression. Annals ATS. 2018;15;1427–1433.
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Saketkoo LA, MMittoo S, Huscher D, et al. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials. Thorax. 2014;69(5):428–436.
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Saketkoo LA, Scholand MB, Lammi MR, et al. Patient-reported outcome measures in systemic sclerosis–related interstitial lung disease for clinical practice and clinical trials. Scleroderma Relat Disord. 2020;5(2 Suppl):48–60.
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