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Improved Survival of IPF patients Treated With Antifibrotic Drugs Compared With Untreated Patients

  • IDIOPATHIC PULMONARY FIBROSIS
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Abstract

Purpose

Pirfenidone and nintedanib unequivocally inhibit FVC decline, but have been inconsistently linked to reduced mortality in phase III studies. On the contrary, real-world data show a survival benefit of antifibrotic drugs. However, it is unknown what this benefit is across different Gender, Age, and Physiology (GAP) stages.

Research Questions

Is there a difference in transplant-free (TPF) survival of IPF patients receiving antifibrotic drugs (IPFAF) compared with an untreated cohort (IPFnon−AF)? Is this different for patients with GAP stage I, II, or III.

Methods

This is a single-center observational cohort study using prospectively included patients diagnosed with IPF between 2008–2018. Primary outcomes were TPF survival difference and 1-, 2-, and 3-year cumulative mortality for IPFAF and IPFnon−AF. This was repeated after stratification for GAP stage.

Results

In total, 457 patients were included. The median transplant-free survival was 3.4 years in IPFAF (n = 313) and 2.2 years in IPFnon−AF (n = 144, p = 0.005). For GAP stage II, a median survival of 3.1 and 1.7 years was noted for IPFAF (n = 143) and IPFnon−AF (n = 59, p < 0.001), respectively. A significantly lower 1-, 2-, and 3- year cumulative mortality was found for IPFAF with GAP stage II (1 yr: 7.0% vs 35.6%, 2 yr: 26.6% vs 55.9%, and 3 yr: 46.9% vs 69.5%). The 1-year cumulative mortality of IPFAF with GAP III was also significantly lower (19.0% vs 65.0%).

Conclusion

This large real-world study showed a survival benefit in IPFAF compared with IPFnon−AF. This especially holds true for patients with GAP stage II and III.

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Abbreviations

AF:

Antifibrotic treatment

DLCOc:

Diffusing capacity for carbon monoxide corrected for hemoglobin

FPF:

Familial pulmonary fibrosis

FVC:

Forced vital capacity

GAP:

Gender, age, physiology model

HRCT:

High-resolution computed tomography

IPF:

Idiopathic pulmonary fibrosis

IPFAF :

IPF patients treated with pirfenidone and/or nintedanib

IPFnon − AF :

IPF patients not treated with antifibrotic drugs

Ltx:

Lung transplantation

MDD:

Multi-disciplinary discussion

PANTHER-IPF:

Prednisone, azathioprine, and N-acetylcysteine: a study that evaluates response in IPF

PF:

Pulmonary fibrosis

PFT:

Pulmonary function test

TPF:

Transplant-free

UIP:

Usual interstitial pneumonia

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Acknowledgements

The authors would like to thanks the included patients and research assistants K. Verhoeven, A. Verkleij-van Laarhoven, and A. Wind.

Funding

This study was funded by a ZonMw TopZorg grant (Grant Numbers: 842002001 and 842002003) and a TZO grant (Grant Number: 10070012010004).

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Authors and Affiliations

  1. Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St Antonius Hospital, Koekoekslaan 1, Nieuwegein, 3435CM, The Netherlands

    Mark G. J. P. Platenburg, Coline H. M. van Moorsel, Ivo A. Wiertz, Joanne J. van der Vis, Adriane D. M. Vorselaars, Marcel Veltkamp & Jan C. Grutters

  2. Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands

    Coline H. M. van Moorsel, Adriane D. M. Vorselaars, Marcel Veltkamp & Jan C. Grutters

  3. Department of Clinical Chemistry, St Antonius Hospital, Nieuwegein, The Netherlands

    Joanne J. van der Vis

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Contributions

MGJPP: Collected the data, performed the statistical analysis, drafted the manuscript and rewrote the manuscript after peer review (guarantor of the paper). CHMVM: Played a major role in the conception of this study and peer reviewed the article. IW: Peer reviewed the article. ADMV: Peer reviewed the article. MV: Peer reviewed the article. JCG: Played a major role in the conception of this study and peer reviewed the article.

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Correspondence to Mark G. J. P. Platenburg.

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Platenburg, M.G.J.P., van Moorsel, C.H.M., Wiertz, I.A. et al. Improved Survival of IPF patients Treated With Antifibrotic Drugs Compared With Untreated Patients. Lung 201, 335–343 (2023). https://doi.org/10.1007/s00408-023-00628-4

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