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The evolving pharmacotherapy of pulmonary fibrosis.

AbstractINTRODUCTION:
Novel compounds targeting various aspects of fibrogenesis have been developed consequent to the increasing knowledge of the pathogenetic mechanisms of the interstitial lung diseases (ILDs). The authors review the evolution of treatment approaches in the ILDs, informed by recent placebo-controlled trials, and discuss current clinical trials in which emerging pathogenetic mechanisms are targeted as novel therapeutic agents.
AREAS COVERED:
In idiopathic pulmonary fibrosis (IPF), recent randomised, placebo-controlled trials have tested the efficacy of new therapies, and although primary end points have not been met in most, treatment effects have been observed. The demonstration of harmful effects from widely used IPF therapies has been equally important. Pirfenidone and nintedanib are emerging agents that exert pleiotropic effects, reflective of the multiple mechanistic pathways of IPF. Treatment may necessitate a similarly multifaceted approach using combination regimens of antifibrotic and antioxidant agents in order to be effective. In other ILDs, including systemic sclerosis, other connective tissue diseases and pulmonary sarcoidosis, the inflammatory/fibrotic model remains appropriate. Studies in systemic sclerosis have provided 'proof of concept' data for immunosuppressive therapy in the prevention of disease progression but there is a continuing need for controlled clinical trials in the more prevalent ILDs.
EXPERT OPINION:
In IPF, significant treatment effects have been reported with pirfenidone, nintedanib and N-acetylcysteine. Combinations of these pleiotropic agents, along with future monotherapies, in 'oncological regimens' may hold the key to more effective IPF treatment. In disorders other than IPF, there is an ongoing need for the controlled evaluation of traditional anti-inflammatory and immunosuppressive therapies. 'Cohort enrichment' (the selective recruitment of patients most likely to progress) holds the key to the identification of worthwhile treatment benefits.
AuthorsHarpreet K Lota, Athol U Wells
JournalExpert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 14 Issue 1 Pg. 79-89 (Jan 2013) ISSN: 1744-7666 [Electronic] England
PMID23265249 (Publication Type: Journal Article, Review)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Immunosuppressive Agents
  • Indoles
  • Pyridones
  • pirfenidone
  • nintedanib
  • Acetylcysteine
Topics
  • Acetylcysteine (therapeutic use)
  • Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
  • Humans
  • Idiopathic Interstitial Pneumonias (complications, drug therapy)
  • Immunosuppressive Agents (therapeutic use)
  • Indoles (therapeutic use)
  • Lung Diseases, Interstitial (complications, drug therapy)
  • Pulmonary Fibrosis (drug therapy, etiology)
  • Pyridones (therapeutic use)
  • Randomized Controlled Trials as Topic
  • Sarcoidosis, Pulmonary (complications, drug therapy)
  • Scleroderma, Systemic (complications, drug therapy)
  • Treatment Outcome

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