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

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• 作者：Yoshio Taguchi^a ; ^{ytaguchi@tenriyorozu.jp" class="auth_mail" title="E-mail the corresponding author} ; Masahito Ebina^b ; ^{ebinam@hosp.tohoku-pharm.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Seishu Hashimoto^a ; ^{hassy@tenriyorozu.jp" class="auth_mail" title="E-mail the corresponding author} ; Takashi Ogura^c ; ^{Ogura@kanagawa-junko.jp" class="auth_mail" title="E-mail the corresponding author} ; Arata Azuma^d ; ^{azuma_arata@yahoo.co.jp" class="auth_mail" title="E-mail the corresponding author} ; Hiroyuki Taniguchi^e ; ^{hiro-tosei-lung@kkd.biglobe.ne.jp" class="auth_mail" title="E-mail the corresponding author} ; Yasuhiro Kondoh^e ; ^{konyasu2003@yahoo.co.jp" class="auth_mail" title="E-mail the corresponding author} ; Moritaka Suga^f ; ^{suga-taka-0825@rose.odn.ne.jp" class="auth_mail" title="E-mail the corresponding author} ; Hiroki Takahashi^g ; ^{htaka@sapmed.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Koichiro Nakata^h ; ^{nakata@nakata-clinic.jp" class="auth_mail" title="E-mail the corresponding author} ; Yukihiko Sugiyamaⁱ ; ^{sugiyuki@jichi.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Shoji Kudoh^j ; ^{skudou@jatahq.org" class="auth_mail" title="E-mail the corresponding author} ; Toshihiro Nukiwa^j ; ^{toshinkw47@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Pirfenidone Clinical Study Group in Japan
• 关键词：6MET ; 6-minute steady state exercise test ; ANCOVA ; analysis of covariance ; ATS ; American Thoracic Society ; ERS ; European Respiratory Society ; DLco ; diffusion capacity for carbon monoxide ; FVC ; forced vital capacity ; IPF ; idiopathic pulmonary fibrosis ; MMRM ; mixed model repeated measures ; PaO2 ; arterial oxygen partial pressure ; PFS ; progression-free survival ; SpO2 ; oxygen saturation by pulse oximetry ; VC ; vital capacity
• 刊名：Respiratory Investigation
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：53
• 期：6
• 页码：279-287
• 全文大小：938 K

文摘

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.

<h4 id="absSec_2">Methodsh4>

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.

<h4 id="absSec_3">Resultsh4>

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.

<h4 id="absSec_4">Conclusionh4>

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.