Efficacy and safety of pirfenidone for idiopathic pulmonary fibrosis

Figures & data

Figure 1 Pirfenidone (5-methyl-1-phenyl-1H-pyridin-2-one).

Figure 2 Potential mechanisms for the suppression of fibrogenesis by pirfenidone.

Notes: Pirfenidone potentially inhibits the production of pro-fibrotic cytokines, inflammatory cytokines, collagen-specific chaperone HSP-47, and reactive oxygen species, and stimulates the production of IFN-γ and IL-10. It has, however, little suppressive activity for immunity, which is strongly suppressed by corticosteroids.
Abbreviations: ECM, extracellular matrix; FGF, fibroblast growth factor; HSP, heat shock protein; IFN, interferon; IL, interleukin; MCP, monocyte chemoattractant protein; NOX, NADPH oxidase isoform; PDGF, platelet-derived growth factor; ROS, reactive oxygen species; TGF, transforming growth factor; TNF, tumor necrosis factor.

Figure 3 Change in vital capacity at 52 weeks (a primary endpoint) (A) and serial changes in VC in (1,800 mg/day pirfenidone (-) and placebo group (---) over a 52-week period) (B), in a Phase III study of IPF patients in Japan *P<0.05 compared with placebo group.

Notes: From Taniguchi et al.⁴¹ Reproduced with permission of the European Respiratory Society. Eur Respir J April 2010 35:821-829; published ahead of print December 8, 2009, doi:10.1183/09031936.00005209.
Abbreviations: IPF, idiopathic pulmonary fibrosis; VC, vital capacity.

Figure 4 Pirfenidone increased PFS in 1,800 mg/day and 1,200 mg/day pirfenidone groups as compared to the placebo group in a Phase III study of IPF patients in Japan.

Notes: From Taniguchi et al.⁴¹ Reproduced with permission of the European Respiratory Society. Eur Respir J April 2010 35:821–829; published ahead of print December 8, 2009, doi:10.1183/09031936.00005209.
Abbreviations: IPF, idiopathic pulmonary fibrosis; PFS, progression-free survival.

Figure 5 Forest plot of pirfenidone (A) or interferon-γ-1b (B) versus placebo in improving PFS in IPF.

Notes: Reproduced from Spagnolo et al.⁴⁴ Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Abbreviations: CI, confidence interval; HR, hazard ratio; IPF, idiopathic pulmonary fibrosis; PFS, progression-free survival.

Table 1 Incidence of major adverse events in Phase III clinical trial of pirfenidone in Japan

Adverse event	Pirfenidone		Placebo
	1,800 mg/day	1,200 mg/day
Photosensitivity	51.4	52.7	22.4
Anorexia	16.5	10.9	2.8
Abdominal discomfort	2.8	7.3	0.0
Dizziness	7.3	0.0	0.9
γ-GTP elevation	22.9	21.8	9.3
WBC decrease	3.7	5.5	0.0

Notes: Data are presented as %. From Taniguchi et al.⁴¹ Reproduced with permission of the European Respiratory Society. EurRespir J April 2010 35:821–829; published ahead of print December 8, 2009, doi:10.1183/09031936.00005209.

Abbreviations: γ-GTP, γ-glutamyltranspeptidase; WBC, white blood cell.

Table 2 Adverse events of pirfenidone in 76 IPF patients in clinical practice

Event	n (%)	Grade
		1	2	3	4–5
Adverse events	64 (84.2)
Photosensitivity	14 (18.4)	9	5	0	0
Anorexia	32 (42.1)	23	7	2	0
Nausea	9 (11.8)	7	2	0	0
Gastric stress	9 (11.8)	9	0	0	0
Fatigue	11 (14.5)	6	5	0	0
Drowsiness	5 (6.6)	5	0	0	0
Rash	5 (6.6)	5	0	0	0
Hepatic dysfunction
γ-GTP elevation	17 (22.4)	13	4	0	0
AST elevation	13 (17.1)	12	0	1	0
ALT elevation	14 (18.4)	13	0	1	0
Others	4 (5.3)	4	0	0	0

Abbreviations: γ-GTP, γ-glutamyl transpeptidase; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

TaniguchiHEbinaMKondohYPirfenidone in idiopathic pulmonary fibrosis: a Phase III clinical trial in JapanEur Respir J201035482182919996196

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SpagnoloPDel GiovaneCLuppiFNon-steroid agents for idiopathic pulmonary fibrosisCochrane Database Syst Rev201089CD00313420824834

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