Funda COŞKUN, Ahmet URSAVAŞ, İsmail HANTA, Can SEVİNÇ, Aykut ÇİLLİ, Ayşe ÖDEMİŞ

Evaluation of efficacy and safety of pirfenidone 200 mg tablets in patients with idiopathic pulmonary fibrosis in a real-life setting

Background/aim: Phase III trials have demonstrated a significant efficacy and an acceptable safety for pirfenidone in patients having mild to moderate idiopathic pulmonary fibrosis (IPF). Real-life data on the use of pirfenidone 200 mg tablets are limited. This study aimed to investigate the efficacy and safety of pirfenidone 200 mg tablets for the treatment of IPF in a real-life setting. Materials and methods: A retrospective, multicenter study conducted in four university hospitals in Turkey between January 2017 and January 2019. Clinical records of patients diagnosed with mild to moderate IPF and receiving pirfenidone (200 mg tablets, total 2400 mg/day) were reviewed retrospectively and consecutively. Pulmonary function measurements including forced vital capacity (FVC%) and diffusing capacity of the lungs for carbon monoxide (DLCO%) were analyzed at baseline and after 6-month of pirfenidone treatment. Descriptive statistics were expressed as mean, standard error or median (minimum-maximum), number and percentage, where appropriate. Results: The study included 82 patients, of whom 87.8% were males (mean age, 66 years). After 6-month of treatment, 7 patients discontinued the treatment. Of the remaining 75 patients, 71 (94.6%) remained stable, 4 (5.4%) had progressive disease as evident by a decline in the FVC% of at least 10% while on treatment, and 45 (61.3%) had improved cough. At least one adverse event (AE) associated with the treatment was observed in 28 (37.3%) patients. Conclusion: Pirfenidone 200 mg was effective and well tolerated and associated with relatively mild and manageable AEs in IPF patients.Key words: Cough, idiopathic pulmonary fibrosis, treatment

PDF

___

1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. American Journal of Respiratory Critical Care Medicine 2011; 183: 788-824. doi: 10.1164/rccm.2009-040GL
2. Fernández Pérez ER, Daniels CE, Schroeder DR, St Sauver J, Hartman TE et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest 2010; 137: 129-137. doi: 10.1378/chest.09-1002
3. Costabel U, Albera C, Bradford WZ, Hormel P, King TE Jr et al. Analysis of lung function and survival in RECAP: An openlabel extension study of pirfenidone in patients with idiopathic pulmonary fibrosis. Sarcoidosis Vascular Diffuse Lung Disease 2014; 31: 198-205. PMID: 25363219
4. Meltzer EB, Noble PW. Idiopathic pulmonary fibrosis. Orphanet Journal of Rare Diseases 2008; 3: 8. doi: 10.1186/1750-1172-3-8
5. Collard HR, King TE Jr, Bartelson BB, Vourlekis JS, Schwarz MI et al. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. American Journal of Respiratory Critical Care Medicine 2003; 168: 538-542. doi: 10.1164/rccm.200211-1311OC
6. Kim DS, Collard HR, King TE Jr. Classification and natural history of the idiopathic interstitial pneumonias. Proceedings of American Thoracic Society 2006; 3: 285-292. doi: 10.1513/ pats.200601-005TK
7. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ ERS/JRS/ALAT clinical practice guideline. American Journal of Respiratory Critical Care Medicine 2018; 198: e44-e68. doi: 10.1164/rccm.201807-1255ST
8. Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Annals of Internal Medicine 2012; 156: 684-691. doi: 10.7326/0003-4819-156-10-201205150-00004
9. Hunninghake GW, Kalica AR. Approaches to the treatment of pulmonary fibrosis. American Journal of Respiratory Critical Care Medicine 1995; 151(3): 915-918. doi: 10.1164/ ajrccm.151.3.7881692
10. Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S et al. Doubleblind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. American Journal of Respiratory Critical Care Medicine 2005; 171: 1040-1047. doi: 10.1164/rccm.200404-571OC
11. Taniguchi H, Ebina M, Kondoh Y, Ogura T, Azuma A et al. Pirfenidone in idiopathic pulmonary fibrosis. European Respiratory Journal 2010; 35: 821-829. doi:10.1183/09031936.00005209
12. Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 2011; 377: 1760-1769. doi: 10.1016/S0140-6736(11)60405-4
13. King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. New England Journal of Medicine 2014; 370: 2083-2092. doi: 10.1056/NEJMoa1402582
14. Nathan SD, Costabel U, Glaspole I, Glassberg MK, Lancaster LH et al. Efficacy of pirfenidone in the context of multiple disease progression events in patients with idiopathic pulmonary fibrosis. Chest 2019; 155: 712-719. doi: 10.1016/j.chest.2018.11.008
15. Bando M, Yamauchi H, Ogura T, Taniguchi H, Watanabe K et al; Japan Pirfenidone Clinical Study Group. Clinical experience of the long-term use of pirfenidone for idiopathic pulmonary fibrosis. Internal Medicine 2016; 55: 443-448. doi: 102169/ internalmedicine.55.5272
16. van Manen MJG, Wijsenbeek MS. Cough, an unresolved problem in interstitial lung diseases. Current Opinion Supportive Palliative Care 2019; 13: 143-151. doi: 10.1097/SPC.0000000000000447
17. van Manen MJG, Birring SS, Vancheri C, Vindigni V, Renzoni E et al. Effect of pirfenidone on cough in patients with idiopathic pulmonary fibrosis. European Respiratory Journal 2017; 50: 1701157. doi: 10.1183/13993003.01157-2017
18. Arai T, Inoue Y, Sasaki Y, Tachibana K, Nakao K et al. Predictors of the clinical effects of pirfenidone on idiopathic pulmonary fibrosis. Respiratory Investigation 2014; 52: 136-143. doi: 10.1016/j.resinv.2013.09.002
19. Hanta I, Cilli A, Sevinc C. The effectiveness, safety, and tolerability of pirfenidone in idiopathic pulmonary fibrosis: A retrospective study. Advances in Therapy 2019; 36: 1126-1131. doi: 10.1007/ s12325-019-00928-3
20. Homma S, Sugino K, Sakamoto S. Usefulness of a disease severity staging classification system for IPF in Japan: 20 years of experience from empirical evidence to randomized control trial enrollment. Respiratory Investigation 2015; 53: 7-12. doi: 10.1016/j.resinv.2014.08.003
21. Taguchi Y, Ebina M, Hashimoto S, Ogura T, Azuma A et al. Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: Extended analysis of phase III trial in Japan. Respiratory Investigation 2015; 53: 279-287. doi: 10.1016/j. resinv.2015.06.002
22. Okuda R, Hagiwara E, Baba T, Kitamura H, Kato T et al. Safety and efficacy of pirfenidone in idiopathic pulmonary fibrosis in clinical practice. Respiratory Medicine 2013; 107: 1431-1437. doi: 10.1016/j.rmed.2013.06.011
23. Lancaster L, Albera C, Bradford WZ, Costabel U, du Bois RM et al. Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials. British Medical Journal Open Respiratory Research 2016; 3: e000105. doi: 10.1136/bmjresp-2015-000105
24. Perelas A, Glennie J, van Kerkhove K, Li M, Scheraga RG et al. Choice of antifibrotic medication and disease severity predict weight loss in idiopathic pulmonary fibrosis. Pulmonary Pharmacology and Therapeutics 2019; 59: 101839. doi: 10.1016/j. pupt.2019.101839
25. Ogawa K, Miyamoto A, Hanada S, Takahashi Y, Murase K et al. The efficacy and safety of long-term pirfenidone therapy in patients with idiopathic pulmonary fibrosis. Internal Medicine 2018; 57: 2813-2818. doi: 10.2169/internalmedicine.0559-17
26. Ogura T, Azuma A, Inoue Y, Taniguchi H, Chida K et al. All-case post-marketing surveillance of 1371 patients treated with pirfenidone for idiopathic pulmonary fibrosis. Respiratory Investigation 2015; 53: 232-241. doi: 10.1016/j. resinv.2015.06.001