Patients with different ILDs can develop a common chronic progressive fibrotic phenotype that drives decline1-3
Chronic progressive fibrotic ILD – many journeys, one
destination
Despite the individual pathologies and clinical pathways that characterise different interstitial lung diseases (ILDs), many patients converge on a common phenotypic expression, described as chronic progressive fibrotic ILD.1-3 For these patients chronic progressive fibrotic ILD has become the primary driver of disease progression and clinical decline, irrespective of the originating pathology or stimulus. Idiopathic pulmonary fibrosis (IPF) is the archetypal chronic progressive fibrotic ILD and the most well-defined clinical expression of the underlying fibrotic mechanism that remodels lung parenchyma. While all IPF patients develop chronic progressive fibrotic ILD, the prevalence in non-IPF ILD patients varies.5 An estimated 13-40% of patients with non-IPF ILDs are at risk of developing a chronic progressive fibrotic phenotype.5,6
The clinical characteristics of the chronic progressive fibrotic phenotype were documented in the landmark INBUILD® study, which looked into the treatment of chronic progressive fibrotic ILD patients with OFEV® (nintedanib). In the study, patients were screened for the extent of their fibrosis and markers of progression. The INBUILD® study offers unique insights into the identification, management and treatment needs of this vulnerable patient population.1
INBUILD® study - ILD progression criteria1
Fibrosis: Physician-diagnosed fibrotic ILD, other than IPF, with greater than 10% fibrosis on high-resolution computed tomography (HRCT).
Progression: Patients met one or more of the following criteria in the 24 months before screening, despite treatment:
Explore chronic progressive fibrotic ILDs
Idiopathic pulmonary fibrosis (IPF)8
Prevalence: 8.2 per 100,000*7 55% of IIPs8
Incidence: 3-9 cases per 100,000 patient-years†9
Cause: unknown aetiology10
More common in men10,11
More common in smokers10,11
Older age at onset: 60-70 years10,11
Mucus clearance and inflammaton12
Characterised by: a radiological/pathological pattern known as usual interstitial pneumonia (UIP) and diagnosis requires the exclusion of known causes of ILD.10 Common symptoms are dyspnoea and dry cough10,13 with possible digital clubbing and bibasilar inspiratory crackles3,10,12-16
Chronic progressive fibrotic phenotype: 100% of patients have fibrotic disease5
Clinical course: progressive fibrotic, fatal lung disease with a prognosis of 2-5 years10,17
*Based on a review of 848 cases from physicians and a social security database in a county in Paris.
†Based on a systematic review of population-based studies that included data from 1968 to 2012.
Prognostic learnings from IPF
While the likelihood of developing the chronic progressive fibrotic phenotype varies between different ILDs and between patients within each ILD, the overall rate of decline in chronic progressive fibrotic ILD patients has been found to be similar to IPF. This was observed in the landmark INBUILD® and INPULSIS® studies, each looking at forced vital capacity (FVC) decline over 52 weeks treatment of chronic progressive fibrotic ILD and IPF patients with OFEV® (nintedanib), respectively.1,2
Patients in the placebo arm of each study experienced rates of lung function loss (measured by decline in FVC) which were comparable. In INPULSIS®, 8.4% of lung capacity (−223.5 ml, n=423) was lost in a year to fibrotic lung scarring in IPF, while 8.1% (−187.8 ml, n=331) was lost in a year to chronic progressive fibrotic ILD in INBUILD®, which excluded IPF patients from the study.1,2
A further retrospective, observational study showed similar results. Out of 2,368 ILD patients studied across nine referral centres in England, 619 were diagnosed and managed as IPF. Of the remaining 1,749 patients, 14.5% (253 patients) met the INBUILD® study criteria for chronic progressive fibrotic ILD despite receiving standard therapy. The incidence ranged from 8.9% to 23.6% across the different centres. For these chronic progressive fibrotic ILD patients, the study also showed that the probability of survival was no different to those with IPF (hazard ratio, 1.06; 95% confidence interval, 0.84–1.35; p=0.6).1,60
Patients with chronic progressive fibrotic ILD share a similar prognosis to IPF
Exacerbations are a further source of dangerously elevated risk during which fibrotic damage can be prolific. Their severity switches patients onto a path of greatly accelerated decline, and they pose a serious risk to survival.61,62 Approximately 14% of IPF patients will experience an exacerbation each year.62 If a patient experiences an exacerbation, their life expectancy reduces from 3 years to a median of less than 3 months.63 Half of patients hospitalised for acute exacerbations die in hospital.62,63
Impact of exacerbations on disease progression in IPF61
In patients with chronic progressive fibrotic ILD, acute exacerbations are rare but devastating events. They are difficult to assess and categorise, but significantly impact patient prognosis.10,62,64 Minimising the risk of exacerbations should be a key goal of managing chronic progressive fibrotic ILD and any signs of rapid unexplained respiratory decline should be treated with suspicion.
When to suspect chronic progressive fibrotic ILD?
Fibrotic changes in lung parenchyma may be detected using high-resolution computed tomography (HRCT) scan and can present as recognisable patterns such as usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP).10 If the HRCT scan is inconclusive after multidisciplinary team (MDT) discussion then further tests, such as a biopsy or extended auto antibody panel, may be conducted. Due to the irreversible loss of lung function, a suspicion of chronic progressive fibrotic ILD is enough to warrant referral and, where appropriate, access to anti-fibrotic treatment to slow progression.
The selection criteria for the recent INBUILD® study provided a succinct framework for identifying patients with chronic progressive fibrotic ILD. The criteria balanced the need for radiological evidence of fibrosis with the risks posed to patients experiencing rapidly declining lung function. Despite the exclusion of IPF patients from the study, half of the patients in INBUILD® had a greater than 10% decline in predicted FVC in the 24 months before the study.1
How can you extend anti-fibrotic benefits in IPF to more patients with chronic progressive fibrotic ILD?
How does the pathophysiology of fibrosis lead to chronic progressive fibrotic ILD?
Adverse events should be reported.
UK: Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Boehringer Ingelheim Drug Safety on 0800 328 1627 (freephone) or by email to PV_local_uk_ireland@boehringer-ingelheim.com.
IE: Reporting forms and information can be found at www.hpra.ie/homepage/about-us/report-an-issue. Adverse events should also be reported to Boehringer Ingelheim Drug Safety on 01 291 3960 or by email to PV_local_uk_ireland@boehringer-ingelheim.com.
OFEV® is indicated in adults for the treatment of idiopathic pulmonary fibrosis (IPF) and for the treatment of other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype. The recommended dose is one 150 mg capsule taken twice daily.65
