Interventions for ILDs

Early treatment is essential in IPF, SSc-ILD and non-IPF progressive fibrosing ILDs to help improve outcomes for the patient1–5

ILD patients with the HRCT scans in their hands.

The progressive fibrosing phenotype is characterized by increased extent of fibrosis, worsening respiratory symptoms and lung function decline.6–9

IPF DOES NOT WAIT

IPF is considered as the most typical progressive fibrosing ILD.8 When a patient with IPF is left without appropriate treatment, they will continue to lose lung function and remain at risk of an acute exacerbation of IPF.10–13

Icon of down arrow representing progressive nature of IPF disease.

There is no time to watch and wait in IPF1,13

A 5%–10% reduction in FVC over 6 months significantly increases a patient’s risk of death14,15

A reduction in FVC of ≥10% predicted over 24 weeks significantly increases an IPF patient’s risk of death in the following 24 weeks16

However, absence of decline in FVC does not mean absence of underlying progression in IPF.16–18 The appearance of FVC stability at baseline does not indicate a stable state of IPF.16–18

EARLY TREATMENT IS ESSENTIAL IN IPF AND COULD POSITIVELY IMPACT PROGRESSION AND IMPROVE OUTCOMES FOR THE PATIENT1-3

Antifibrotic treatment started immediately after diagnosis3 could help slow progression when there is the most left to preserve.1,13,19

Clock icon.

There is no guarantee a well-preserved FVC at baseline will be maintained, so treatment should start immediately after diagnosis to help preserve as much lung function as possible16,18

Medication icon.

Antifibrotic treatment started immediately after diagnosis can significantly reduce decline in FVC for the following 12 months20

Emphasize treatment goals to patients with IPF, such as preserving lung function and improving survival, to help them make an informed decision to initiate treatment.21*

Educating patients with IPF on how dose adjustment can manage possible side effects of antifibrotic treatment can also help reassure them about starting treatment and help prolong their treatment benefits.18

Antifibrotic treatment should be prescribed for all eligible patients upon a confirmed IPF diagnosis, regardless of IPF severity1–3,13

What are the significant real-world survival benefits for patients with IPF treated with antifibrotics?*

Real-world data shows significant improvement in survival of IPF patients taking antifibrotic treatment vs. those not taking antifibrotic treatment.22,23

European IPF registry: significant improvement in survival of antifibrotic-treated patients with IPF vs. untreated patients22†

European IPF registry shows significant improvement in survival of IPF taking antifibrotics vs. without treatment

*  Kaplan-Meier curves for cumulative survival, based on definite outcome data (survival status definitely known as per end of 2016) and on last visit data.22
†  A statistically significant difference in survival was encountered between patients receiving antifibrotic treatment and those not receiving antifibrotics, with significance level p=0.001.22

 

Australian IPF registry: significant improvement* in survival of antifibrotic-treated patients with IPF vs. untreated patients23†

Australian IPF registry shows significant improvement in survival of IPF taking antifibrotics vs. without treatment

*  HR 0.38, 95% CI 0.24-0.59, p<0.001.
†  Patients receiving lung transplant were censored in analysis. Kaplan-Meier and univariate Cox analysis were performed to calculate mortality per year.23

 

Finnish IPF registry: significant improvement in survival of patients with IPF treated with antifibrotics for >6 months vs. untreated patients24*†

Finnish IPF registry shows significant improvement in survival of IPF taking antifibrotics for >6 months vs. without treatment

*  From the Finnish IPF registry (2011–2015) (n=453) coordinated by Jaana Kaunisto.
†  Transplant-free survival was measured from diagnosis until death or to the date of transplantation. Survival was evaluated using the Kaplan-Meier method and differences in survival curves were evaluated using the log-rank test. The associations of variables with survival were analysed using univariate Cox regression analysis.

 

INSIGHTS-IPF registry: significant improvement* in survival of antifibrotic-treated patients with IPF vs. untreated patients25†

INSIGHTS-IPF registry shows significant improvement in survival of IPF taking antifibrotics vs. without treatment

*  HR 0.63, 95% CI 0.45–0.87, p=0.005.
†  From the INSIGHTS-IPF registry as presented by Prof. Jürgen Behr.

 

Consistent real-world evidence shows antifibrotic treatment significantly improves survival in patients with IPF22–25

MANAGEMENT OF NON-IPF ILDs

Treatment of non-IPF chronic fibrosing ILDs with a progressive phenotype should not wait5,7,26,27

Consensus recommendations for diagnosis and management of non-IPF chronic fibrosing ILDs with a progressive phenotype28

Diagnosis / management of fibrosing ILDs leading to development of progressive fibrosing phenotype

*  Standard of care based on specific ILD.
†  The definition of ILD progression is described in: George PM, et al. Lancet Respir Med. 2020;8:925–934.
‡  Subject to approval in each country.
Adapted from: George PM, et al. Lancet Respir Med. 2020;8:925–954.

Potential measures that may help prevent acute exacerbation of ILD with a progressive fibrosing phenotype include:29

  • Influenza and pneumococcal vaccination

  • Hand washing and avoidance of contact with sick people

  • Avoidance of airborne irritants and pollutants

  • Strategies to minimize mechanical ventilator-induced lung injury

Discover the impact of acute exacerbation of ILD

FOR MANAGEMENT OF SPECIFIC ILDs, THERE ARE TREATMENT RECOMMENDATIONS FOR BOTH PHARMACOLOGIC AND NON-PHARMACOLOGIC APPROACHES

HYPERSENSITIVITY PNEUMONITIS (HP) MANAGEMENT RECOMMENDATIONS:

  • Identification and removal of the antigen responsible for the hypersensitive response should always be the first step in HP management30

  • Among patients with HP, determining the inciting antigen is important for patient counseling and management31

  • Pharmacologic therapy may be appropriate, but it is important to reassess treatment response at 3 months, because patients with HP in whom lung function has not stabilized at this stage are at increased risk of death28,30

  • When a certain pharmacologic therapy lasts more than 3–6 months without success, alternative therapies should be considered30

IDIOPATHIC NON-SPECIFIC INTERSTITIAL PNEUMONIA (iNSIP) MANAGEMENT RECOMMENDATIONS:

  • Similar to your patients with HP, pharmacologic therapy may be appropriate, but it is important to reassess treatment response at 3 months, because patients with NSIP in whom lung function has not stabilized at this stage are at increased risk of death28

  • Supportive care for patients with iNSIP includes oxygen therapy and pulmonary rehabilitation3

  • Lung transplantation should be recommended in patients with progressive iNSIP32

SARCOIDOSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE MANAGEMENT RECOMMENDATIONS:

  • Treatment should be administered to patients with the following criteria:33

  • Worsening symptoms

  • Limited activity

  • Markedly abnormal or declining lung function

  • Worrisome X-ray changes

UNCLASSIFIABLE INTERSTITIAL LUNG DISEASE (uILD) MANAGEMENT CONSIDERATIONS:

Non-pharmacologic therapies for fibrotic ILDs that should be routinely considered include:34

  • Smoking cessation

  • Avoidance of potential harmful exposures

  • Pneumococcal and influenza vaccinations

  • Pulmonary rehabilitation

  • Long-term oxygen therapy

  • Comorbidity management

Choices for pharmacotherapy should be considered on a case-by-case basis34

SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSc-ILD) MANAGEMENT CONSIDERATIONS:

  • Treatment initiation in patients with SSc-ILD should aim for prevention of progression to avoid irreversible lung damage4,35,36

  • The current practice of treating patients with SSc-ILD once worsening has occurred is sub-optimal4

  • This may lead to missed opportunities to treat patients whose disease is progressing, as these patients might be stable during further follow-up

RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (RA-ILD) MANAGEMENT CONSIDERATIONS:

Progression and severity of ILD are the main factors to consider in making treatment decisions37

Treatment may be considered:

  • Irrespective of whether HRCT pattern is UIP or NSIP

  • If ILD is clinically significant (symptoms, severity)

  • If ILD is progressive

What other management considerations should you consider?

Footnotes
  • * Treatment initiation subject to available local country approved treatment.

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  2. 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.

  3. Robalo-Cordeiro C, Campos P, Carvalho L, et al. Idiopathic pulmonary fibrosis in the era of antifibrotic therapy: Searching for new opportunities grounded in evidence. Rev Port Pneumol. 2017;23(5):287–293.

  4. 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.

  5. 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.

  6. Flaherty KR, 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 Respir Res. 2017;4(1):e000212.

  7. 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.

  8. Cottin V, Wollin L, Fischer A, et al. Fibrosing interstitial lung diseases: knowns and unknowns. Eur Respir Rev. 2019b;28(151):pii:180100.

  9. Kolb M, Vašáková M. The natural history of progressive fibrosing interstitial lung diseases. Respir Res. 2019;20(1).

  10. Ryerson C, Cottin V, Brown K, Collard H. Acute exacerbation of idiopathic pulmonary fibrosis: shifting the paradigm. Eur Respir J. 2015;46(2):512–520.

  11. van Manen MJ, Geelhoed JJ, Tak NC, Wijsenbeek MS. Optimizing quality of life in patients with idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2017;11(3):157–169.

  12. Hambly N, Cox G, Kolb M. Acute exacerbations of idiopathic pulmonary fibrosis: tough to define; tougher to manage. Eur Respir J. 2017;49(5):1700811.

  13. Torrisi SE, Pavone M, Vancheri A, Vancheri C. When to start and when to stop antifibrotic therapies. Eur Respir Rev. 2017;26(145):170053.

  14. Cosgrove GP, Bianchi P, Danese S, Lederer DJ. Barriers to timely diagnosis of interstitial lung disease in the real world: the INTENSITY survey. BMC Pulm Med. 2018;18(1):9.

  15. Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431–440.

  16. Richeldi L, Crestani B, Azuma A, et al. Outcomes following decline in forced vital capacity in patients with idiopathic pulmonary fibrosis: Results from the INPULSIS and INPULSIS-ON trials of nintedanib. Resp Med. 2019;156:20-25.

  17. Maher TM, Stowasser S, Nishioka Y, et al. Biomarkers of extracellular matrix turnover in patients with idiopathic pulmonary fibrosis given nintedanib (INMARK study): a randomised, placebo-controlled study. Lancet Respir Med. 2019;S2213-2600(19)30255-3.

  18. Maher TM, Strek ME. Antifibrotic therapy for idiopathic pulmonary fibrosis: time to treat. Respir Res. 2019;20:205.

  19. Kolb M, Richeldi L, Behr J, et al. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. Thorax. 2017;72:340–346.

  20. Poletti V, Vancheri C, Albera C. Clinical course of IPF in Italian patients during 12 months of observation: results from the FIBRONET observational study. Poster presented at the European Respiratory Society International Congress, 28 September – 2 October, 2019, Madrid, Spain.

  21. Moua T, Ryu JH. Obstacles to early treatment of idiopathic pulmonary fibrosis: current perspectives. Ther Clin Risk Manag. 2019;15:73–81.

  22. Guenther A, Krauss E, Tello S, et al. The European IPF registry (eurIPFreg): baseline characteristics and survival of patients with idiopathic pulmonary fibrosis. Respir Res. 2018;19(1):141.

  23. Jo HE, Glaspole I, Grainge C, et al. Baseline characteristics of idiopathic pulmonary fibrosis: analysis from the Australian Idiopathic Pulmonary Fibrosis Registry. Eur Respir J. 2017;49:1601592.

  24. Kaunisto J, Salomaa E, Hodgson U. Demographics and survival of patients with idiopathic pulmonary fibrosis in the Finnish IPF registry. ERJ Open Res. 2019;5:00170-2018.

  25. Behr J, Prasse A, Wirtz H, et al. Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: long-term results of the INSIGHTS-IPF registry. Eur Respir J. 2020; in press (https://doi.org/10.1183/13993003.02279-2019).

  26. Geerts S, Wuyts W, De Langhe E, et al. Connective tissue disease associated interstitial pneumonia: a challenge for both rheumatologists and pulmonologists. Sarcoidosis Vasc Diffuse Lung Dis. 2017;34(4):326–335.

  27. Wells AU, Denton CP. Interstitial lung disease in connective tissue disease— mechanisms and management. Nat Rev Rheumatol. 2014;10(12):728–739.

  28. George PM, Spagnolo P, Kreuter M, et al. Progressive fibrosing interstitial lung disease: clinical uncertainties, consensus recommendations, and research priorities. Lancet Respir Med. 2020;8:925–954.

  29. Kolb M, Bondue B, Pesci A, et al. Acute exacerbations of progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150):pii:180071.

  30. Varone F, Iovene B, Sgalla G, et al. Fibrotic Hypersensitivity Pneumonitis: Diagnosis and Management. Lung. 2020;https://doi.org/10.1007/s00408-020-00360-3.

  31. Fernandez Perez ER, Swigris JJ, Forssen AV, et al. Identifying an Inciting Antigen Is Associated With Improved Survival in Patients With Chronic Hypersensitivity Pneumonitis. Chest. 2013;144:1644–1651.

  32. Tomassetti S, et al. Semin Respir Crit Care Med. 2016;37:378–394.

  33. Ianuzzi MC, Sah BP. Sarcoidosis. Merck Manual Professional Version website. Available at: https://www.merckmanuals.com/professional/pulmonary-disorders/sarcoidosis/sarcoidosis. August 2017. Accessed: November 2020.

  34. Guler SA, Ryerson CJ. Unclassifiable interstitial lung disease: from phenotyping to possible treatments. Curr Opin Pulm Med. 2018;24:461–468.

  35. Hoffmann-Vold AM, Allanore Y, Alves M, et al. Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database. Ann Rheum Dis. 2020a;217455.

  36. 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. The Lancet Rheumatology. 2020b;2: e71–e83.

  37. 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. doi: 10.3390/jcm9041082.

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  39. Ryerson CJ, Cayou C, Topp F, et al. Pulmonary rehabilitation improves long-term outcomes in interstitial lung disease: a prospective cohort study. Respir Med. 2014;108(1):203-210.

  40. Kreuter M, Bendstrup E, Russell A, et al. Palliative care in interstitial lung disease: living well. Lancet Respir Med. 2017;5(12):968-980.

  41. Maher TM, Wuyts W. Management of Fibrosing Interstitial Lung Diseases. Adv Ther. 2019;doi:10.1007/s12325-019-00992-9. [Epub ahead of print].

  42. Sgalla G, Cerri S, Ferrari R, et al. Mindfulness-based stress reduction in patients with interstitial lung diseases: a pilot, single-centre observational study on safety and efficacy. BMJ Open Respir Res. 2015;2(1):e000065.

  43. Wijsenbeek M, Cottin V. Spectrum of Fibrotic Lung Diseases. N Engl J Med. 2020;383:958–968.

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