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Mortality of ILDs

Pulmonary fibrosis is a key driver of early mortality in patients with fibrotic ILDs1–8

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ILDs characterized by pulmonary fibrosis carry the threat of early mortality9–12

5-year mortality rates of non-IPF ILDs7,13–19

5-year mortality rate of non-IPF ILDs

5-year mortality rate for iNSIP sourced from a retrospective study.7 5-year mortality rates for unclassifiable ILD, RA-ILD, SSc-ILD and pSS-ILD sourced as midpoint values from ranges for 5-year mortality rates as follows: unclassifiable ILD 5-year mortality rate 30%–54%.13 RA-ILD 5-year mortality rate 35%–39%.14,15 SSc-ILD 5-year mortality rate 10%–18%.16 pSS-ILD 5-year mortality rate 12%–16%.17–19

PATIENTS WITH NON-IPF ILDs MAY DEVELOP A PROGRESSIVE FIBROSING PHENOTYPE, WHICH CARRIES THE RISK OF EARLY MORTALITY, LIKE IPF20

The progressive fibrosing phenotype is characterized by increased extent of fibrosis, worsening respiratory symptoms and lung function decline9,21–23


Patients diagnosed with IPF, or a non-IPF ILD with progressive pulmonary fibrosis, face a dismal prognosis20,24

Patients diagnosed with IPF have a median survival of 2–5 years24,25

HOW DOES THE PROGNOSIS OF IPF COMPARE TO OTHER DISEASES?

IPF has a worse 5-year survival than many cancers, including breast, prostate, colon, skin cancer, and lymphoma8

Lower 5-year survival rate for IPF compared with many common cancers

Reproduced with permission of the © ERS 2021. European Respiratory Journal 35 (3) 496-504; DOI: 10.1183/09031936.00077309 Published 28 February 2010.

Patients with ILDs, such as RA-ILD, have a high risk of mortality,9–11 but the threat is highest in patients with IPF26

Lower cumulative survival for IPF compared with different HRCT patterns of RA-ILD

Kaplan-Meier curve demonstrating mortality for IPF patients vs. RA-ILD patients subdivided according to Fleischner Society IPF diagnostic guidelines on HRCT pattern.
Reproduced with permission of the © ERS 2021. European Respiratory Journal 53 (1) 1800869; DOI: 10.1183/13993003.00869-2018 Published 3 January 2019.
RA-ILD definite UIP pattern (honeycombing): 48% 3-year and 45% 6-year survival, n=55. Mean survival 3.5 years
RA-ILD probable UIP pattern (no honeycombing): 76% 3-year and 58% 6-year survival, n=56. Mean survival 4.6 years
RA-ILD non-UIP pattern: 92% 3-year and 75% 6-year survival, n=46. Mean survival 5.3 years
IPF: 42% 3-year and 18% 6-year survival, n=284. Mean survival 2.9 years

Compared with fibrotic NSIP, patients with IPF have a worse survival rate27

Lower survival of IPF compared with fibrotic NSIP

Reprinted from Annals of the American Thoracic Society, 171(6), Jegal et al, Physiology Is a Stronger Predictor of Survival than Pathology in Fibrotic Interstitial Pneumonia, 639-644, ©2022.

The 5-year survival rate of patients with fibrotic NSIP (n=41) was 76.2% vs. 43.8% of patients with IPF (n=131) (p=0.007).

6-month changes in FVC and initial DLco, and male sex, are statistically significant predictors of survival in patients with fibrotic NSIP and IPF27

 

Hazard Ratio

95% CI

P Value

Age

1.027

0.992–1.064

0.134

Sex*

2.724

1.277–5.813

0.010

NSIP diagnosis

0.854

0.349–2.093

0.730

Initial FVC, % predicted*

0.987

0.964–1.010

0.262

Initial DLco, % predicted*

0.972

0.949–0.996

0.022

6-month change in FVC*

0.925

0.893–0.958

<0.001

Resting PaO2

0.995

0.961–1.031

0.798

Results of multivariate analysis of prognostic factors of patients with fibrotic NSIP (n=41) and IPF (n=131) after 6 months of follow-up.
*  Analyzed as continuous variables.
Reprinted from Annals of the American Thoracic Society, 171(6), Jegal et al, Physiology Is a Stronger Predictor of Survival than Pathology in Fibrotic Interstitial Pneumonia, 639-644, ©2022.

PATIENTS WITH FIBROTIC ILDs ARE AT RISK OF EARLY MORTALITY20

Icon representing estimated 2,5-4 years survival time for non-IPF progressive fibrosing ILDs.

Patients with non-IPF progressive fibrosing ILD have an estimated survival time of 2.5–4 years20*†

Icon showing that 10-15% patient with RA-ILD are at risk of early mortality.

In patents with RA, ILD triples the risk of death28 and accounts for 10%–20% of deaths29–31

Icon showing that ILD causes around 35% of SSc-related deaths.

ILD is the leading cause of death in SSc, accounting for approximately 35% of SSc-related deaths32–37

Understanding and identifying the risk of mortality in your patients

Footnotes
  • *
    Estimated time between detection of progressive fibrosis and death. 
  • †
    Estimates of patients with non-IPF ILD that develop progressive fibrosis based on an online survey of total 486 physicians (243 pulmonologists, 203 rheumatologists and 40 internists) from the United States, Japan, France, Germany, Italy, Spain and the United Kingdom).20
  • CI, confidence interval; DLCO, diffusing capacity of the lung for carbon; FVC, forced vital capacity; HRCT, high-resolution computed tomography; ILD, interstitial lung disease; iNSIP, idiopathic non-specific interstitial; IPF, idiopathic pulmonary fibrosis; NSIP, non-specific interstitial pneumonia; PaO2, partial pressure of oxygen; pSS-ILD, primary Sjögren's syndrome-associated interstitial lung disease; RA, rheumatoid arthritis; RA-ILD, rheumatoid arthritis-associated interstitial lung disease; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease; UIP, usual interstitial pneumonia.

  1. Fischer A and Distler J. Progressive fibrosing interstitial lung disease associated with systemic autoimmune diseases. Clin Rheumatol. 2019;38(10):2673–2681. 

  2. Mathai SC and Danoff SK. Management of interstitial lung disease associated with connective tissue disease. BMJ. 2016;352:h6819.

  3. Wallace B, Vummidi D, Khanna D. Management of connective tissue diseases associated interstitial lung disease: a review of the published literature. Curr Opin Rheumatol. 2016;28(3):236–245.
  4. Spagnolo P, Cordier JF, Cottin V. Connective tissue diseases, multimorbidity and the ageing lung. Eur Respir J. 2016;47(5):1535–1558.
  5. Vacchi C, Sebastiani M, Cassone G, et al. Therapeutic options for the treatment of interstitial lung disease related to connective tissue diseases. A narrative review. J Clin Med. 2020;9(2):407. doi: 10.3390/jcm9020407. 
  6. Maher TM, Wuyts W. Management of fibrosing interstitial lung diseases. Adv Ther. 2019;36(7):1518–1531.
  7. Park IN, Jegal Y, Kim DS, et al. Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia. Eur Respir J. 2009;33(1):68–76. 
  8. Vancheri C, Failla M, Crimi N, Raghu G. Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology. Eur Respir J. 2010;35(3):496–504. 
  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 ... in patients with progressive fibrosing interstitial lung disease. BMJ Open Resp Res. 2017;4(1):e000212.
  10. Patterson KC, Strek ME. Pulmonary fibrosis in sarcoidosis. Clinical features and outcomes. Ann Am Thorac Soc. 2013;10(4):362-370.
  11. Caban JJ, Yao J, Bagci U, Mollura DJ. Monitoring pulmonary fibrosis by fusing clinical, physiological, and computed tomography features. Conf Proc IEEE Eng Med Biol Soc. 2011;6216-6219.
  12. Wells AU, Brown KK, Flaherty KR, Kolb M, Thannickal VJ, on behalf of the IPF Consensus Working Group. Eur Resp J. 2018;51:1800692.
  13. Guler SA, Ellison K, Algamdi M, et al. Heterogeneity in Unclassifiable Interstitial Lung Disease: A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2018;15:854–863.
  14. Hyldgaard C, Hilberg O, Pedersen AB, et al. A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis. 2017;76(10):1700–1706.
  15. Raimundo K, Solomon JJ, Olson AL, et al. Rheumatoid arthritis – interstitial lung disease in the United States: prevalence, incidence, and healthcare costs and mortality. J Rheumatol. 2019;46(4):360–369. 
  16. Bouros D, Wells AU, Nicholson AG, et al. Histopathologic Subsets of Fibrosing Alveolitis in Patients with Systemic Sclerosis and Their Relationship to Outcome. Am J Respir Crit Care Med. 2002;165:1581–1586.
  17. Palm Ø, Garen T, Enger TV, et al. Clinical pulmonary involvement in primary Sjögren’s syndrome: prevalence, quality of life and mortality—a retrospective study based on registry data. Rheumatology. 2013;52:173-179.
  18. Ito I, Nagai S, Kitaichi M, et al. Pulmonary Manifestations of Primary Sjögren’s Syndrome: A Clinical, Radiologic, and Pathologic Study. Am J Respir Crit Care Med. 2005;171:632–638.
  19. Enomoto Y, Takemura T, Hagiwara E, et al. Prognostic Factors in Interstitial Lung Disease Associated with Primary Sjögren’s Syndrome: A Retrospective Analysis of 33 Pathologically–Proven Cases. PLoS One. 2013;8:e73774.
  20. Wijsenbeek M, Kreuter M, Olson A, et al. Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management. Curr Med Res Opin. 2019;35(11):2015–2024.
  21. Kolb M, Vašáková M. The natural history of progressive fibrosing interstitial lung diseases. Respir Res. 2019;20(1).
  22. 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. 
  23. Cottin V, Wollin L, Fischer A, et al. Fibrosing interstitial lung diseases: knowns and unknowns. Eur Respir Rev. 2019b;28(151):pii:180100.
  24. Molina-Molina M, Aburto M, Acosta O, et al. Importance of early diagnosis and treatment in idiopathic pulmonary fibrosis. Exp Rev Resp Med. 2018;12(7):537–539.
  25. Nathan SD, du Bois RM. Idiopathic pulmonary fibrosis trials: recommendations for the jury. Eur Respir J. 2011;38(5):1002-1004. 
  26. Jacob J, Hirani N, van Moorsel CHM, et al. Predicting outcomes in rheumatoid arthritis related interstitial lung disease. Eur Respir J. 2019;53:1800869.
  27. Jegal Y, Kim DS, Shim TS, et al. Physiology Is a Stronger Predictor of Survival than Pathology in Fibrotic Interstitial Pneumonia. Am J Respir Crit Care Med. 2005;171:639–644.
  28. Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2010;62(6):1583–1591. 
  29. Cassone G, Manfredi A, Vacchi C, et al. Treatment of rheumatoid arthritis-associated interstitial lung disease: lights and shadows. J Clin Med. 2020;9(4):1082.
  30. Olson AL, Swigris JJ, Sprunger DB, et al. Rheumatoid Arthritis–Interstitial Lung Disease–associated Mortality. Am J Respir Crit Care Med. 2011;183:372–378.
  31. Hyldgaard C, Ellingsen T, Hilberg O, et al. Rheumatoid arthritis-associated interstitial lung disease: clinical characteristics and predictors of mortality. Respiration. 2019;98(5):455–460.
  32. Cappelli S, Bellando Randone S, Camiciottoli G, et al. Interstitial lung disease in systemic sclerosis: where do we stand? Eur Respir Rev. 2015;24;411–419. 
  33. Distler O, Assassi S, Cottin V, et al. Predictors of progression in systemic sclerosis patients with interstitial lung disease. Eur Respir J. 2020;55;1902026.
  34. Distler O, Volkmann ER, Hoffmann-Vold AM, et al. Current and future perspectives on management of systemic sclerosis-associated interstitial lung disease. Expert Rev Clin Immunol. 2019;15;1009–1017. 
  35. Tyndall AJ, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010;69(10):1809-1815. doi:10.1136/ ard.2009.114264.
  36. Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis. 2007;66(7):940-944. doi:10.1136/ard.2006.066068. 
  37. Roofeh D, Jaafar S, Vummidi D, et al. Management of systemic sclerosis-associated interstitial lung disease. Curr Opin Rheumatol. 2019;31;241–249. 
  38. Brauner M, et al. Imagerie des pneumopathies infiltrantes diffuses. Press Med. 2010;39:73–84.
  39. Kolb M, Bondue B, Pesci A, et al. Acute exacerbations of progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150):pii:180071. 
  40. Song JW, Hong S-B, Lim C-M, et al. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011;37(2):356–363. 
  41. Song JW, Lee HK, Lee CK, et al. Clinical course and outcome of rheumatoid arthritis-related usual interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis. 2013;30(2):103-112.
  42. Tomiyama F, Watanabe R, Ishii T, et al. High Prevalence of Acute Exacerbation of Interstitial Lung Disease in Japanese Patients with Systemic Sclerosis. Tohoku J. Exp. Med. 2016;239, 297–305.
  43. Okamoto M, Fujimoto K, Sadohara J, et al. A retrospective cohort study of outcome in systemic sclerosis-associated interstitial lung disease. Respiratory Investigation. 2016;54, 445–453. 

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