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Original research
Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis
  1. Tyler Pitre1,
  2. Jasmine Mah2,
  3. Wryan Helmeczi3,
  4. Muhammad Faran Khalid4,
  5. Sonya Cui4,
  6. Melanie Zhang4,
  7. Renata Husnudinov4,
  8. Johnny Su1,
  9. Laura Banfield5,
  10. Brent Guy4,
  11. Jade Coyne4,
  12. Ciaran Scallan1,6,
  13. Martin RJ Kolb1,6,
  14. Aaron Jones7,
  15. Dena Zeraatkar7,8
  1. 1 Division of Internal Medicine, McMaster University, Hamilton, Ontario, Canada
  2. 2 Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  3. 3 Division of Internal Medicine, University of Ottawa, Ottawa, Ontario, Canada
  4. 4 Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
  5. 5 Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
  6. 6 Division of Respirology, St. Joseph's Hospital, Hamilton, Ontario, Canada
  7. 7 Health Evidence Impact and Research, McMaster University, Hamilton, Ontario, Canada
  8. 8 Bioinformatics, Harvard Medical School, Cambridge, Massachusetts, USA
  1. Correspondence to Dr Dena Zeraatkar, Havard Medical School, Harvard University, Cambridge, Massachusetts, USA; Dena_Zeraatkar{at}


Background Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments.

Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework.

Results We identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (–88.35 to 411.12)), pirfenidone (2.47% (–0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty).

Conclusion and relevance Future guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.

  • idiopathic pulmonary fibrosis
  • interstitial fibrosis
  • rare lung diseases

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • AJ and DZ are joint senior authors.

  • Twitter @tylerpitre6, @faranKhalidPK, @denazera

  • Contributors TP is the main author and the study guarantor. He came up with the study design, developed the methods, recruited the team and led the analytics. He helped write, edit and approve the protocol. He wrote the first draft of the manuscript. JM helped design the methods, she developed the search strategy in conjunction with an academic librarian and trained the data collectors on risk of bias assessment. She helped write, edit and approve the protocol. SC, MZ, RH, MFK, WH and JS screened abstracts, full-text screening and performed data collection. They also performed the risk of bias assessment. All of these tasks were adjudicated and reviewed by TP and JM. LB provided expertise in search strategy and data collection. BG, JC and CS are respirologists who consulted on development of treatment nodes, copy edited and helped review and write the manuscript.MK helped supervise, provide guidance in writing the manuscript and expert advice in idiopathic pulmonary fibrosis. DZ co-supervised the study, consulted in applying risk of bias tools and GRADE, as well as methodology. AJ co-supervised the study. He is the analytic lead and consulting on methodology. All authors reviewed and approved the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MK discloses research funding for preclinical work from Boehringer Ingelheim and Pieris. He received research funding for clinical projects from Roche. He has received consulting fees from Boehringer Ingelheim, Roche, Horizon, Cipla, Abbvie, Bellerophon, Algernon and CSL Behring. He has received payments or honoraria for lectures, presentations, speaker bruins, manuscript writings or educational events from Novartis, Boehringer Ingelheim and Roche. He has received payments for expert testimony from Roche. He participates on the data safety monitoring board or advisory board for Covance and United Therapeutics. He is the chief editor for the European Respiratory Journal and received a Chief Editor allowance. No other authors have conflicts of interest to disclose. CS discloses research funding from the Canadian Pulmonary Fibrosis Foundation and Boehringer Ingelheim. He has also received payments for presentations and advisory work from Boehringer Ingelheim.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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