Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: Extended analysis of phase III trial in Japan.

Abstract

BACKGROUND:

A phase III clinical trial of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) in Japan has revealed that pirfenidone attenuated the decline in vital capacity (VC) and improved progression-free survival (PFS). We conducted an extended analysis of the pirfenidone trial to investigate its efficacy with respect to IPF severity in the trial population.

METHODS:

Patients in the phase III trial were stratified by baseline pulmonary functions including %VC predicted, %diffusion capacity for carbon monoxide predicted, and oxygen saturation by pulse oximetry on exertion and were categorized into mild, moderate, and severe groups of functional impairment. The efficacy of pirfenidone for VC and PFS over 52 weeks was compared among the three sub-populations.

RESULTS:

Of 264 patients, 102 (39%), 90 (34%), and 72 patients (27%) were classified as having mild, moderate, and severe grades of functional impairment, respectively. This classification was associated with arterial oxygen partial pressure at rest and degree of dyspnea at baseline. While pirfenidone attenuated VC decline at all grades of severity, covariance analysis revealed pirfenidone to have better efficacy in the sub-population with mild-grade IPF. Mixed model repeated measures analysis confirmed that pirfenidone markedly attenuated VC decline in patients with mild-grade IPF compared to its effects in patients with moderate or severe IPF. Pirfenidone also improved PFS markedly in patients with mild-grade IPF.

CONCLUSION:

This extended analysis suggested that pirfenidone exerted better therapeutic effects in patients with milder IPF. Further analysis with a larger population is needed to confirm these results.

• Authors: Yoshio Taguchi, Masahito Ebina, Seishu Hashimoto, Takashi Ogura, Arata Azuma, Hiroyuki Taniguchi, Yasuhiro Kondoh, Moritaka Suga, Hiroki Takahashi, Koichiro Nakata, Yukihiko Sugiyama, Shoji Kudoh, Toshihiro Nukiwa, Pirfenidone Clinical Study Group in Japan
• Journal: Respiratory investigation (Respir Investig) Vol. 53 Issue 6 Pg. 279-87 (Nov 2015) ISSN: 2212-5353 [Electronic] Netherlands
• PMID: 26521105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier B.V.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Pyridones
• pirfenidone

Topics

• Adult
• Aged
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Clinical Trials, Phase III as Topic
• Female
• Humans
• Idiopathic Pulmonary Fibrosis (drug therapy, mortality, physiopathology)
• Male
• Middle Aged
• Oxygen Consumption
• Pyridones (therapeutic use)
• Retrospective Studies
• Severity of Illness Index
• Survival Rate
• Treatment Outcome
• Vital Capacity
• Young Adult