Efficacy and Safety of Pirfenidone in Treatment of Idiopathic Pulmonary Fibrosis: A Meta-analysis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZhangJiacui ¹ , LiuShurao ² , LiuHua ¹ , CaiXiguang ¹ , SongPan ³ , WuWanzhou ⁴ , SunLina ³ , LuoYunxia ² ,  WeiHaidong ⁵

1. Department of Respiratory Medicine, Gansu Province People's Hospital, Lanzhou, Gansu, 730000, China;
2. ;
3. ;
4. ;
5. ;

Corresponding author：

WeiHaidong, Email: weihaidong123456@163.com

Keywords：

Pirfenidone; Idiopathic pulmonary fibrosis; Meta-analysis

DOI：

10.7507/1671-6205.2015138

Video：

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Objective To evaluate the efficacy and safety of pirfenidone in patients with idiopathic pulmonary fibrosis. Methods PubMed, Cochrane Library, CNKI, CBM, Wanfang, and VIP databases were searched for randomized controlled trials of pirfenidone as interventions for the treatment of idiopathic pulmonary fibrosis. According to the Cochrane system evaluation method, the methodological quality of included studies was evaluated and the effective data were extracted. The meta-analysis was performed with RevMan 5.2 software. Results Six studies were included with 1727 patients in total. Compared with placebo groups, pirfenidon could improve the changing rate of vital capacity at the end of the treatment[WMD=0.06, 95% CI (0.01, 0.12), Z=2.48, P=0.01; heterogeneity inspection χ²=1.03, P=0.31]. Pirfenidon could not improve the changing rate of lowest SpO₂ in 6-minute walking test[WMD=0.82, 95% CI (-1.35, 2.98), Z=0.74, P=0.46; heterogeneity inspection χ²=8.90, P=0.003] and could not reduce the mortality[RR=0.62, 95% CI (0.37, 1.03), Z=1.85, P=0.06; heterogeneity inspection χ²=3.05, P=0.55]. The incidences of photosensitivity, dizziness, nausea, abdominal discomfort, joint pain, fatigue in pirfenidone group were more frequent than those in placebo group. Conclusions Because of lack of enough eligible studies and defects in design and reporting data in the studies, this meta-analysis can not evaluate pirfenidone's long-term efficacy and safety. Hence, the existed clinical evidences can't support pirfenidone to be the treatment of IPF medication.

Citation： ZhangJiacui, LiuShurao, LiuHua, CaiXiguang, SongPan, WuWanzhou, SunLina, LuoYunxia, WeiHaidong. Efficacy and Safety of Pirfenidone in Treatment of Idiopathic Pulmonary Fibrosis: A Meta-analysis. Chinese Journal of Respiratory and Critical Care Medicine, 2015, 14(6): 569-576. doi: 10.7507/1671-6205.2015138 Copy

1.	Raghu G, Collard HR, Egan JJ, et al. An Official ATS/ERS/JRS/ALAT Statement:Idiopathic Pulmonary Fibrosis:Evidence based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med,2011,183:788-824.
2.	Raghu G, Weycker D, Edelsberg J, et al. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med,2006,174:810-816.
3.	King TE Jr, Albera C, Bradford WZ, et al. Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE):a multicentre, randomised, placebo-controlled trial. Lancet,2009,374:222-228.
4.	King TE Jr, Brown KK, Raghu G, et al. BUILD-3:a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med,2011,184:92-99.
5.	Raghu G, Brown KK, Costabel U, et al. Treatment of idiopathic pulmonary fibrosis with etanercept:an exploratory, placebo-controlled trial. Am J Respir Crit Care Med,2008,178:948-955.
6.	Zisman DA, Schwarz M, Anstrom KJ, et al. Idiopathic Pulmonary Fibrosis Clinical Research Network. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med,2010,363:620-628.
7.	Luppi F,pagnolo P,Cerri S, et al. The big clinical trials in idiopathic pulmonary fibrosis. Curr Opin Pulm Med, 2012,18:428-432.
8.	Raqhu G, Johnson WC, Lockhart D, et al. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone:results of a prospective, open-label Phase Ⅱ study. Am J Respir Crit Care Med,1999,159:1061-1069.
9.	Nagai S, Hamada K, Shigematsu M, et al. Open-label compassionate use one year-treatment with pirfenidone to patients with chronic pulmonary fibrosis. Intern Med,2002,41:1118-1123.
10.	Azuma A, Nukiwa T, Tsuboi E, et al. Double-blind, placebo controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med,2005,171:1040-1047.
11.	Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary Fibrosis (CAPACITY):two randomised trials. Lancet,2011,577:1760-1769.
12.	Higgins J, Green S. Cochrane Collaboration:Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011].John Wiley\&Sons Ltd and The Cochrane Collaboration, Chichester, 2011.
13.	Liedman R, Hansson SR, Howe D, et al. Endometrial expression of vasopressin, oxytocin and their receptors in patients with primary dysmenorrheal and healthy volunteers at ovulation. Eur J Obstet Gynecol Reprod Biol,2008,137:189-192.
14.	Higgim JP, Airman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ,201l,343:d5928.
15.	康德英,洪旗,刘关键,等.Meta分析中发表性偏倚的识别与处理.中国循证医学杂志,2003,3:45-48.
16.	Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J,2010,35:821-829.
17.	Gahl WA, Brantly M, Troendle J, et al. Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome. Mol Genet Metab,2002,76:234-242.
18.	O'Brien K, Troendle J, Gochuico BR, et al. Pirfenidone for the treatment of Hermansky-Pudlak syndrome pulmonary fibrosis. Mol Genet Metab,2011,103:128-134.
19.	King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med,2014,370:2083-2092.
20.	Jiang C, Huang H, Liu J, et al. Adverse events of pirfenidone for the treatment of pulmonary fibrosis:a meta-analysis of randomized controlled trials. PLoS One,2012,7:e47024.

1. Raghu G, Collard HR, Egan JJ, et al. An Official ATS/ERS/JRS/ALAT Statement:Idiopathic Pulmonary Fibrosis:Evidence based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med,2011,183:788-824.
2. Raghu G, Weycker D, Edelsberg J, et al. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med,2006,174:810-816.
3. King TE Jr, Albera C, Bradford WZ, et al. Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE):a multicentre, randomised, placebo-controlled trial. Lancet,2009,374:222-228.
4. King TE Jr, Brown KK, Raghu G, et al. BUILD-3:a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med,2011,184:92-99.
5. Raghu G, Brown KK, Costabel U, et al. Treatment of idiopathic pulmonary fibrosis with etanercept:an exploratory, placebo-controlled trial. Am J Respir Crit Care Med,2008,178:948-955.
6. Zisman DA, Schwarz M, Anstrom KJ, et al. Idiopathic Pulmonary Fibrosis Clinical Research Network. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med,2010,363:620-628.
7. Luppi F,pagnolo P,Cerri S, et al. The big clinical trials in idiopathic pulmonary fibrosis. Curr Opin Pulm Med, 2012,18:428-432.
8. Raqhu G, Johnson WC, Lockhart D, et al. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone:results of a prospective, open-label Phase Ⅱ study. Am J Respir Crit Care Med,1999,159:1061-1069.
9. Nagai S, Hamada K, Shigematsu M, et al. Open-label compassionate use one year-treatment with pirfenidone to patients with chronic pulmonary fibrosis. Intern Med,2002,41:1118-1123.
10. Azuma A, Nukiwa T, Tsuboi E, et al. Double-blind, placebo controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med,2005,171:1040-1047.
11. Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary Fibrosis (CAPACITY):two randomised trials. Lancet,2011,577:1760-1769.
12. Higgins J, Green S. Cochrane Collaboration:Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011].John Wiley\&Sons Ltd and The Cochrane Collaboration, Chichester, 2011.
13. Liedman R, Hansson SR, Howe D, et al. Endometrial expression of vasopressin, oxytocin and their receptors in patients with primary dysmenorrheal and healthy volunteers at ovulation. Eur J Obstet Gynecol Reprod Biol,2008,137:189-192.
14. Higgim JP, Airman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ,201l,343:d5928.
15. 康德英,洪旗,刘关键,等.Meta分析中发表性偏倚的识别与处理.中国循证医学杂志,2003,3:45-48.
16. Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J,2010,35:821-829.
17. Gahl WA, Brantly M, Troendle J, et al. Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome. Mol Genet Metab,2002,76:234-242.
18. O'Brien K, Troendle J, Gochuico BR, et al. Pirfenidone for the treatment of Hermansky-Pudlak syndrome pulmonary fibrosis. Mol Genet Metab,2011,103:128-134.
19. King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med,2014,370:2083-2092.
20. Jiang C, Huang H, Liu J, et al. Adverse events of pirfenidone for the treatment of pulmonary fibrosis:a meta-analysis of randomized controlled trials. PLoS One,2012,7:e47024.

Chinese Journal of Respiratory and Critical Care Medicine

Efficacy and Safety of Pirfenidone in Treatment of Idiopathic Pulmonary Fibrosis: A Meta-analysis

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