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

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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
Defining characteristics of the progressive fibrosing phenotype

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.

It is important to note, SSc-ILD shows heterogeneous rates of progression but is fundamentally progressive over the long term13,14

How could ILD affect your SSc patients?

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

  • ILD-related cough adversely impacts physical function, social participation, activities of daily living, and sleep quality17

  • Dyspnea impacts the patients’ ability to perform functional activities and life priorities17

How progressive CTD-ILDs can impact patients’ quality of life

Patients with progressive CTD-ILDs suffer from emotional distress that may include feelings of depression, anxiety and loss of independence18,19

Depression

Depression

Powerlessness

Powerlessness

Loss of independence

Loss of independence

Anxiety

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
Characteristics and potential impacts of the progressive fibrosing phenotype

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. 

Decline in lung function predicts mortality in patients with CTD-ILDs14,20–22 – slow ILD progression in patients with a progressive fibrosing ILD before the risk of early mortality is increased9

The first step to slowing progressive CTD-ILDs is identification of ILD
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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  2. 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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  9. 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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