title: Drug Treatment of Idiopathic Pulmonary Fibrosis: Systematic Review and Network Meta-Analysis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a form of chronic progressive fibrosing interstitial lung disease of unknown origin. Recently, nintedanib and pirfenidone demonstrated efficacy in slowing disease progression and were approved by the US Food and Drug Administration. Although numerous treatments have been evaluated in IPF, none have shown significant decreases in mortality. The objective of this study was to identify all pharmacologic treatments evaluated for IPF and analyze their efficacy via Bayesian network meta-analysis and pairwise indirect treatment comparisons. This review did not evaluate the effect of steroid therapy.
  
  
  METHODS
  We searched MEDLINE, Embase, and the Cochrane Library for studies published on or before August 2014. Studies were required to contain a randomized evaluation of nonsteroidal drug therapy for treatment of IPF and be published in English. Key outcomes of interest for this analysis were pulmonary function as measured by FVC as well as all-cause and respiratory-specific death. All outcomes were analyzed via a Bayesian framework.
  
  
  RESULTS
  Our review identified 30 eligible studies that evaluated 16 unique treatments. Under both the fixed-effect and random-effect models for respiratory-specific mortality, no treatments performed better than placebo. For all-cause mortality, pirfenidone and nintedanib had effects approaching significance with credible intervals slightly crossing the null under a fixed-effect model. Notably, for respiratory-specific mortality, all-cause mortality, and decline in percent predicted FVC, nintedanib and pirfenidone were virtually indistinguishable and no clear advantage was detected.
  
  
  CONCLUSIONS
  Although two treatments have been approved for IPF on the basis of reduced decline in pulmonary function, neither one has a clear advantage on mortality outcomes.
authors.affiliation: Pharmaceutical Outcomes Research and Policy Program, University of Washington School of Pharmacy, Seattle, WA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Canestaro
authors.affiliation: GroupHealth Cooperative, Seattle, WA.
authors.forename: Sara H
authors.initials: SH
authors.lastname: Forrester
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Center for Interstitial Lung Disease, University of Washington School of Medicine, Seattle, WA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Center for Interstitial Lung Disease, University of Washington School of Medicine, Seattle, WA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Ho
authors.affiliation: Pharmaceutical Outcomes Research and Policy Program, University of Washington School of Pharmacy, Seattle, WA. Electronic address: bdevine@uw.edu.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Devine
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D001499:Bayes Theorem; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D000068800:Etanercept / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy*; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D010666:Phenylpropionates / Q000627:therapeutic use; D011724:Pyridazines / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D014797:Vital Capacity; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007166:Immunosuppressive Agents; D007211:Indoles; D010666:Phenylpropionates; D011724:Pyridazines; D011728:Pyridones; D011743:Pyrimidines; D011994:Recombinant Proteins; D013449:Sulfonamides; C554125:interferon gamma-1b; D014859:Warfarin; D007371:Interferon-gamma; D000068877:Imatinib Mesylate; C093844:pirfenidone; C530716:nintedanib; C467894:ambrisentan; D001379:Azathioprine; D000068800:Etanercept; D000077300:Bosentan; D000111:Acetylcysteine; C533860:macitentan
keywords: epidemiology (pulmonary); evidence-based medicine; idiopathic pulmonary fibrosis; meta-analysis