Skip to main content

Main menu

  • Home
  • Current issue
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • COVID-19 submission information
    • Institutional open access agreements
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • COVID-19 submission information
    • Institutional open access agreements
    • Peer reviewer login
  • Alerts
  • Subscriptions

Antifibrotic therapy for fibrotic lung disease beyond idiopathic pulmonary fibrosis

Bridget F. Collins, Ganesh Raghu
European Respiratory Review 2019 28: 190022; DOI: 10.1183/16000617.0022-2019
Bridget F. Collins
Center for Interstitial Lung Diseases, University of Washington Medical Center, Seattle, WA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ganesh Raghu
Center for Interstitial Lung Diseases, University of Washington Medical Center, Seattle, WA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: graghu@uw.edu
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Tables

  • TABLE 1

    Major randomised controlled trials of antifibrotics among patients with idiopathic pulmonary fibrosis (IPF)

    PhasePatientsInterventionDurationPrimary outcome(s)Key secondary outcome(s)
    Nintedanib
     TOMORROW [25]II432Randomised to 1 of 4 doses nintedanib or placebo52 weeksAnnual rate of FVC decline 60 mL·year−1 in nintedanib 150 mg twice daily group versus 190 mL·year−1 in placebo groupLower incidence of AE-IPF, small decrease in SGRQ with nintedanib 150 mg twice daily
     INPULSUS I [7]III515 IPF patientsRandomised 3:2 ratio to nintedanib 150 mg twice daily or placebo52 weeksAnnual rate of decline FVC −114.7 mL nintedanib versus −239.9 mL placebo (p<0.01)No significant difference in time to first AE or proportion with AE
     INPULSIS II [7]III551 IPF patientsRandomised 3:2 ratio to nintedanib 150 mg twice daily or placebo52 weeksAnnual rate of decline FVC −113.6 mL nintedanib versus −207.3 mL placebo (p<0.01)Increase in time to first AE in nintedanib group and lower proportion with AE in nintedanib group; significant small increase in SGRQ in nintedanib group
    Pirfenidone
     CAPACITY I (004) [26]III435 IPF patientsRandomised 2:1:2 pirfenidone 2403 mg·day−1, pirfenidone 1197 mg·day−1 or placebo72 weeksMean decline FVC −8% pirfenidone versus −12.4% placebo (p<0.01)Decreased proportion of patients with ≥10% decline in FVC; prolonged PFS
     CAPACITY II (006) [26]III344 IPF patientsRandomised 1:1 pirfenidone 2403 mg·day−1 or placebo72 weeksMean decline FVC −9% pirfenidone versus −9.6% placebo (p=0.5)Reduced decline in 6MWD
     ASCEND [8]III555 with IPF (surgical biopsy required if possible UIP)Randomised to pirfenidone 801 mg three times daily or placebo52 weeksProportion of patients with ≥10% decline in FVC or death reduced by 47.9% pirfenidone versus placebo (p<0.01)Decreased decline in 6MWD, improved PFS
    Combination nintedanib and pirfenidone
     Safety and pharmacokinetics of nintedanib and pirfenidone in IPF [27]IIn=50: 25 patients on pirfenidone ≥3 months; 25 patients not on antifibroticNintedanib (100 mg twice daily or 150 mg twice daily) or placebo added to pirfenidone14 days (100 mg), 28 days (150 mg)Adverse events: 10 out of 21 patients on combination; 9 out of 17 patients on only nintedanibNintedanib did not affect pharmacokinetics of pirfenidone

    FVC: forced vital capacity; AE: adverse event; SGRQ: St George's Respiratory Questionnaire; PFS: progression-free survival; 6MWD: 6-min walk distance; UIP: usual interstitial pneumonia.

    • TABLE 2

      Ongoing clinical trials of antifibrotic medications in non-idiopathic pulmonary fibrosis (IPF) fibrotic interstitial lung diseases (ILDs)

      NamePhasePatientsInterventionDurationPrimary outcomeKey secondary outcomes
      Nintedanib
       NCT02597933 [91]Safety and Efficacy of 150 mg Nintedanib Twice Daily in Systemic Sclerosis (SENSCIS)IIIn=580, SSc-pulmonary fibrosisNintedanib 150 mg twice daily or placebo added to exisiting treatment (stable dose methotrexate, MMF and/or prednisone ≤10 mg daily)52 weeksAnnual rate of decline FVC (mL)Time to all-cause mortality, absolute change dyspnoea score, Modified Rodan Skin Score, SGRQ, change in FVC % pred, change DLCO
       NCT02999178 [92]Efficacy and Safety of Nintedanib in Patients with Progressive Fibrosing-ILD (INBUILD®)IIIn=663, progressive fibrosing ILD (see text)Nintedanib 150 mg twice daily or placebo52 weeksAnnual rate of decline FVCChange in K-BILD score, time to first AE or death, time to progression (≥10% decrease FVC or death)
       NCT03283007 [93]Nintedanib in Lung Transplant Recipients with BOS Grade 1–2 (INFINITx-BOS)IIIn=80, ≥6 months post-lung transplant with BOSNintedanib 150 mg twice daily or placebo (patients already on azithromycin)6 monthsRate of decline in FEV1 (mL) over 6 monthsChange 6MWD, change SGRQ, change in BOS grade, absolute change oxygen saturation
      Pirfenidone
       NCT02821689 [94]Pirfenidone in Progressive ILD Associated with Clinically Amyopathic DermatomyositisIVn=60, CADM with ILD1800 mg pirfenidone total per day or placebo added on to existing treatment52 weeksOverall survivalChange in HRCT score, change in PFT from baseline
       NCT03221257 [95]Scleroderma Lung Study III – Combining Pirfenidone with Mycophenolate (SLSIII)IIn=150, SSc-pulmonary fibrosisPirfenidone (target dose 801 mg three times daily) or placebo+MMF (target dose of 1500 mg twice daily)18 monthsChange in FVC % predChange DLCO % pred, change modified Rodan Skin Score, SGRQ, dyspnoea assessment score, change from baseline ILD by computer-quantified HRCT
       DRKS00009822 [96]Exploring Efficacy and Safety of Pirfenidone for Progressive, Non-IPF Lung Fibrosis (RELIEF)IICollagen vascular disease-associated fibrosis, fibrotic NSIP, cHP, asbestos-related lung fibrosisPirfenidone (801 mg three times daily) or placebo48 weeksAbsolute change in FVC (%) from baseline to week 48Time to disease worsening, change in DLCO, 6MWD, SGRQ and EQ-5D
       NCT03099187 [97]A Study of Pirfenidone in Patients with Unclassifiable Progressive Fibrosing Interstitial Lung DiseaseIIn=252, nonclassifiable ILD (cannot be classified to a specific category of ILD with moderate or high level of confidence with MDD)Pirfenidone (801 mg three times daily) or placebo (stable dose MMF allowed)24 weeksRate of decline in FVC over 24 weeksChange in FVC (% pred), change in DLCO (% pred), change in FVC of >5%, change in FVC of >10%, change in 6MWD, change in symptom scores (dyspnoea, cough), SGRQ score, AE-IPF, PFS
       NCT03385668 [98]Pilot Study of Pirfenidone in Pulmonary Fibrosis with Anti-myeloperoxidase Antibodies (PIRFENIVAS)II15 patients with+anti-MPO antibody and pulmonary fibrosis (definite or possible UIP or NSIP on HRCT)Pirfenidone (2403 mg total daily dose) (no placebo group)52 weeksAbsolute change FVC % predTreatment emergent adverse events, change FVC % pred, 6MWD, change % DLCO, PFS
       NCT02808871 [99]Phase II Study of Pirfenidone in Patients with RA-ILD (TRAIL1)II270 patients with RA-ILDPirfenidone 801 mg three times daily or placebo52 weeksComposite end-point: ≥10% decline in FVC or deathRelative decline DLCO (≥15%), relative decline in FVC (≥10%), acute exacerbation, dyspnoea scores, SGRQ
       NCT03260556 [100]Pirfenidone for Progressive Fibrotic Sarcoidosis (PirFS)IV60 patients with sarcoidosis and >20% fibrosis on HRCT (stable immunosuppressive medications and/or ≤ 20 mg prednisone/day for 2 months prior allowed)Pirfenidone 801 mg three times daily or placebo24 monthsTime until clinical worseningChange in FVC, change in composite physiologic index
       NCT02958917 [90]Study of Efficacy and Safety of Pirfenidone in Patients with Fibrotic Hypersensitivity PneumonitisN/A40 patients with fibrotic hypersensitivity pneumonitisPirfenidone 801 mg three times daily or placebo52 weeksMean change in FVCPFS, ≥5% mean change FVC, acute exacerbation, 6MWD
       NCT02496182 [89]Pirfenidone in the Chronic Hypersensitivity Pneumonitis Treatment (Picheon)II/IIIn=60, cHPPirfenidone (1800 mg or 1200 mg total daily dose) or placebo in addition to conventional therapy (prednisone and azathioprine)52 weeksChange in FVCInflammation and fibrosis grade on HRCT (Kazerooni scale), 6MWD, SGRQ score
       NCT02262299 [101]European Trial of Pirfenidone in BOS, A European Multi-center Study (EPOS)II/IIIn=80, ≥6 months post-lung transplant with grade 1–3 BOSPirfenidone 801 mg three times daily or placebo (patients already on azithromycin)26 weeksChange in FEV1 (in L) over 26 weeks% change in FEV1, % change FVC, change in % pred DLCO, change 6MWD, change BOS grade, hospitalisation, survival

      SSc: systemic sclerosis; MMF: mycophenolate mofetil; FVC: forced vital capacity; SGRQ: St George's Respiratory Questionnaire; % pred: % predicted; DLCO: diffusing capacity of the lung for carbon monoxide; K-BILD: King's Brief Interstitial Lung Disease questionnaire; AE: adverse event; BOS: bronchiolitis obliterans syndrome; FEV1: forced expiratory volume in 1 s; 6MWD: 6-min walk distance; CADM: clinically amyopathic dermatomyositis; HRCT: high-resolution computed tomography; PFT: pulmonary function test; NSIP: nonspecific interstitial pneumonia; cHP: chronic hypersensitivity pneumonitis; EQ-5D: EuroQuol five-dimensions questionnaire; MDD: multidisciplinary discussion; MPO: myeloperoxidase; UIP: usual interstitial pneumonia; PFS: progression-free survival; RA: rheumatoid arthritis.

      PreviousNext
      Back to top
      View this article with LENS
      Vol 28 Issue 153 Table of Contents
      European Respiratory Review: 28 (153)
      • Table of Contents
      • Index by author
      Email

      Thank you for your interest in spreading the word on European Respiratory Society .

      NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

      Enter multiple addresses on separate lines or separate them with commas.
      Antifibrotic therapy for fibrotic lung disease beyond idiopathic pulmonary fibrosis
      (Your Name) has sent you a message from European Respiratory Society
      (Your Name) thought you would like to see the European Respiratory Society web site.
      CAPTCHA
      This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
      Print
      Citation Tools
      Antifibrotic therapy for fibrotic lung disease beyond idiopathic pulmonary fibrosis
      Bridget F. Collins, Ganesh Raghu
      European Respiratory Review Sep 2019, 28 (153) 190022; DOI: 10.1183/16000617.0022-2019

      Citation Manager Formats

      • BibTeX
      • Bookends
      • EasyBib
      • EndNote (tagged)
      • EndNote 8 (xml)
      • Medlars
      • Mendeley
      • Papers
      • RefWorks Tagged
      • Ref Manager
      • RIS
      • Zotero

      Share
      Antifibrotic therapy for fibrotic lung disease beyond idiopathic pulmonary fibrosis
      Bridget F. Collins, Ganesh Raghu
      European Respiratory Review Sep 2019, 28 (153) 190022; DOI: 10.1183/16000617.0022-2019
      del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
      Full Text (PDF)

      Jump To

      • Article
        • Abstract
        • Abstract
        • Introduction
        • Antifibrotic medications
        • Rationale for antifibrotic medications in non-IPF-PF
        • Understanding end-points in clinical trials for non-IPF-PF
        • Currently available reports and ongoing clinical trials of antifibrotic medications for non-IPF-PF
        • Conclusion
        • Footnotes
        • References
      • Figures & Data
      • Info & Metrics
      • PDF

      Subjects

      • Pulmonary vascular disease
      • Tweet Widget
      • Facebook Like
      • Google Plus One

      More in this TOC Section

      • Role of air pollutants in airway epithelial barrier dysfunction
      • E-cigarettes and nicotine abstinence
      • Lung imaging in cystic fibrosis
      Show more Review

      Related Articles

      Navigate

      • Home
      • Current issue
      • Archive

      About the ERR

      • Journal information
      • Editorial board
      • Reviewers
      • Press
      • Permissions and reprints
      • Advertising
      • Sponsorship

      The European Respiratory Society

      • Society home
      • myERS
      • Privacy policy
      • Accessibility

      ERS publications

      • European Respiratory Journal
      • ERJ Open Research
      • European Respiratory Review
      • Breathe
      • ERS books online
      • ERS Bookshop

      Help

      • Feedback

      For authors

      • Instructions for authors
      • Publication ethics and malpractice
      • Submit a manuscript

      For readers

      • Alerts
      • Subjects
      • RSS

      Subscriptions

      • Accessing the ERS publications

      Contact us

      European Respiratory Society
      442 Glossop Road
      Sheffield S10 2PX
      United Kingdom
      Tel: +44 114 2672860
      Email: journals@ersnet.org

      ISSN

      Print ISSN: 0905-9180
      Online ISSN: 1600-0617

      Copyright © 2023 by the European Respiratory Society