Survival Impact and Safety Comparison of Pirfenidone and Nintedanib for Idiopathic Pulmonary Fibrosis: Meta-analysis
Keywords:
Idiopathic Pulmonary Fibrosis, Nintedanib, Pirfenidone, Anti-fibrotic therapyAbstract
Background and aim: Idiopathic pulmonary fibrosis (IPF) is a severe restrictive lung disease affecting approximately 3 million people worldwide with two approved antifibrotics, nintedanib and pirfenidone, available for use. This review aims to compare their survival impact and safety profile.
Methods: Two databases and two trial registers along with additional sources were searched for cohorts reporting IPF patients of any age or stage, receiving either pirfenidone or nintedanib. The Inverse-Variance and Mantel-Haenszel method along with either a fixed- or random-effects model was used for analysing survival and other dichotomous outcomes, respectively.
Results: 23 cohorts were included. The pooled analysis showed that compared to pirfenidone, nintedanib group had similar survival (HR=1.12; 95%-CI:0.99-1.27; P=0.07), all-cause mortality (OR=1.11; 95%-CI:0.94-1.31; P=0.22), drug switches (OR=1.82; 95%-CI:0.69-4.78; P=0.22), and treatment discontinuations (OR=0.92; 95%-CI:0.60-1.41; P=0.70), higher odds of diarrhoea (OR=12.39; 95%-CI: 5.67-27.07; P<0.00001) and abnormal liver-function tests (OR=2.98; 95%-CI:1.92-4.61; P<0.00001), and lower odds of photosensitivity (OR=0.06; 95%-CI:0.01-0.25; P=0.0001), and skin-rash (OR=0.17; 95%-CI:0.08-0.34; P<0.00001).
Conclusions: While both treatment groups had similar overall survival and all-cause mortality, the safety profiles of nintedanib and pirfenidone differed significantly, with nintedanib being associated with greater odds of liver toxicity and diarrhoea, and pirfenidone with photosensitivity and skin rash, suggesting they could be favoured in slightly distinct population groups. Further research is necessary to refine the current comprehension of these drugs and their optimal utilization in IPF treatment, particularly taking into account factors such as disease stage and sequential therapy
References
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Smith ML. The histologic diagnosis of usual interstitial pneumonia of idiopathic pulmonary fibrosis. Where we are and where we need to go. Mod Pathol. 2022 Jan 1;35:8–14.
Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep;198(5):e44–68.
Duhig EE. Usual interstitial pneumonia: a review of the pathogenesis and discussion of elastin fibres, type II pneumocytes and proposed roles in the pathogenesis. Pathology (Phila). 2022 Aug 1;54(5):517–25.
Honda T, Uehara T, Sano K. Heterogeneous proliferation of type II pneumocytes in usual interstitial pneumonia. Pathology (Phila). 2006 Jan 1;38(5):433–6.
Raghu G, Rochwerg B, Zhang Y, Garcia CAC, Azuma A, Behr J, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015 Jul 15;192(2):e3–19.
Tepede A, Yogaratnam D. Nintedanib for Idiopathic Pulmonary Fibrosis. J Pharm Pract. 2019 Apr;32(2):199–206.
Aimo A, Spitaleri G, Nieri D, Tavanti LM, Meschi C, Panichella G, et al. Pirfenidone for Idiopathic Pulmonary Fibrosis and Beyond. Card Fail Rev. 2022 Apr 14;8:e12.
Conte E, Gili E, Fagone E, Fruciano M, Iemmolo M, Vancheri C. Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts. Eur J Pharm Sci. 2014 Jul 16;58:13–9.
Bocchino M, Bruzzese D, Scioscia G, Capitelli L, Tondo P, Rea G, et al. Disease stage-related survival in idiopathic pulmonary fibrosis patients treated with nintedanib and pirfenidone: An exploratory study. Respir Med Res. 2023;84:101013.
Richeldi L, Bois RM du, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. N Engl J Med. 2014 May 29;370(22):2071–82.
Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. The Lancet. 2011 May 21;377(9779):1760–9.
King TE, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2014 May 29;370(22):2083–92.
Nathan SD, Albera C, Bradford WZ, Costabel U, Glaspole I, Glassberg MK, et al. Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis. Lancet Respir Med. 2017 Jan 1;5(1):33–41.
Richeldi L, Cottin V, du Bois RM, Selman M, Kimura T, Bailes Z, et al. Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials. Respir Med. 2016 Apr 1;113:74–9.
Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2022 May;205(9):e18–47.
Wells G, Shea B, Connell DO, Petersn J, Welch V. Ottawa Hospital Research Institute. [cited 2024 Sep 6]. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
Granholm A, Alhazzani W, Møller MH. Use of the GRADE approach in systematic reviews and guidelines. Br J Anaesth. 2019 Nov;123(5):554–9.
Barratt SL, Mulholland S, Al Jbour K, Steer H, Gutsche M, Foley N, et al. South-West of England’s Experience of the Safety and Tolerability Pirfenidone and Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis (IPF). Front Pharmacol. 2018;9:1480.
Belhassen M, Dalon F, Nolin M, Van Ganse E. Comparative outcomes in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis. Respir Res. 2021;22(1):135.
Cameli P, Refini RM, Bergantini L, d’Alessandro M, Alonzi V, Magnoni C, et al. Long-Term Follow-Up of Patients With Idiopathic Pulmonary Fibrosis Treated With Pirfenidone or Nintedanib: A Real-Life Comparison Study. Front Mol Biosci. 2020;7:581828.
Corral M, DeYoung K, Kong AM. Treatment patterns, healthcare resource utilization, and costs among patients with idiopathic pulmonary fibrosis treated with antifibrotic medications in US-based commercial and Medicare Supplemental claims databases: a retrospective cohort study. BMC Pulm Med. 2020 Jul 11;20(1):188.
Dempsey TM, Sangaralingham LR, Yao X, Sanghavi D, Shah ND, Limper AH. Clinical Effectiveness of Antifibrotic Medications for Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2019;200(2):168–74.
Fournier D, Jouneau S, Bouzillé G, Polard E, Osmont MN, Scailteux LM. Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients. Pulm Pharmacol Ther. 2022;76:102149.
Galli JA, Pandya A, Vega-Olivo M, Dass C, Zhao H, Criner GJ. Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions. Respirol Carlton Vic. 2017;22(6):1171–8.
Holtze CH, Freiheit EA, Limb SL, Stauffer JL, Raimundo K, Pan WT, et al. Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry. Respir Res. 2020;21(1):48.
Honda K, Saraya T, Ishii H. A Real-World Prognosis in Idiopathic Pulmonary Fibrosis: A Special Reference to the Role of Antifibrotic Agents for the Elderly. J Clin Med [Internet]. 2023 [cited 5AD Jan 1];12(10). Available from: https://pubmed.ncbi.nlm.nih.gov/37240670/
Iwasaki K, Wakabayashi H, Saiki A, Ueshiba H, Murakami Y, Matsuzawa Y. Real-World Clinical Efficacy of Antifibrotic Agents for Idiopathic Pulmonary Fibrosis: A Single-Center Retrospective Study in Japan. Drugs - Real World Outcomes. 2024;11(1):43–52.
Khan MA, Ghamdi BA, Alhamadi M, Rajendram R, Alyami S, Al-Gamedi M, et al. A survival analysis of idiopathic pulmonary fibrosis in the context of antifibrotic therapy in Saudi Arabia. Ann Thorac Med. 2023;18(2):79–85.
Khan MA, Sherbini N, Alyami S, Al-Harbi A, Al-Ghamdi M, Alrajhi S, et al. Nintedanib and pirfenidone for idiopathic pulmonary fibrosis in King Abdulaziz Medical City, Riyadh: Real-life data. Ann Thorac Med. 2023;18(1):45–51.
Levra S, Guida G, Sprio AE, Crosa F, Ghio PC, Bertolini F, et al. Long-Term Safety of Antifibrotic Drugs in IPF: A Real-World Experience. Biomedicines [Internet]. 2022 [cited 12AD Jan 1];10(12). Available from: https://pubmed.ncbi.nlm.nih.gov/36551989/
Marijic P, Schwarzkopf L, Schwettmann L, Ruhnke T, Trudzinski F, Kreuter M. Pirfenidone vs. nintedanib in patients with idiopathic pulmonary fibrosis: a retrospective cohort study. Respir Res. 2021;22(1):268.
Noor S, Nawaz S, Chaudhuri N. Real-World Study Analysing Progression and Survival of Patients with Idiopathic Pulmonary Fibrosis with Preserved Lung Function on Antifibrotic Treatment. Adv Ther. 2021;38(1):268–77.
Takehara K, Koga Y, Hachisu Y, Utsugi M, Sawada Y, Saito Y, et al. Differential Discontinuation Profiles between Pirfenidone and Nintedanib in Patients with Idiopathic Pulmonary Fibrosis. Cells [Internet]. 2022 [cited 1AD Jan 1];11(1). Available from: https://pubmed.ncbi.nlm.nih.gov/35011705/
Üzer F, Akanlar S, Çilli A. Real-life data in the treatment and follow-up of idiopathic pulmonary fibrosis: A single-center study. Tuberk Ve Toraks. 2023;71(4):347–55.
Wright WA, Crowley LE, Parekh D, Crawshaw A, Dosanjh DP, Nightingale P, et al. Real-world retrospective observational study exploring the effectiveness and safety of antifibrotics in idiopathic pulmonary fibrosis. BMJ Open Respir Res. 2021 Mar;8(1):e000782.
Romero Ortiz AD, Jiménez-Rodríguez BM, López-Ramírez C, López-Bauzá Á, Pérez-Morales M, Delgado-Torralbo JA, et al. Antifibrotic treatment adherence, efficacy and outcomes for patients with idiopathic pulmonary fibrosis in Spain: a real-world evidence study. BMJ Open Respir Res [Internet]. 2024 [cited 4AD Jan 1];11(1). Available from: https://pubmed.ncbi.nlm.nih.gov/38663886/
Sadon AAEA, Kenawy AS, Abdelsalam AH, Attia HM. Pirfenidone vs nintedanib for treatment of idiopathic pulmonary fibrosis in clinical practice: efficacy, tolerability, and adverse effects. Egypt J Chest Dis Tuberc. 2020 Sep;69(3):549.
Zhao R, Xie B, Wang X, Zhang X, Ren Y, Wang C, et al. The tolerability and efficacy of antifibrotic therapy in patients with idiopathic pulmonary fibrosis: Results from a real-world study. Pulm Pharmacol Ther. 2024;84:102287.
Cerri S, Monari M, Guerrieri A, Donatelli P, Bassi I, Garuti M, et al. Real-life comparison of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis: A 24-month assessment. Respir Med. 2019;159:105803.
Paterniti MO, Bi Y, Rekić D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395–402.
Rogliani P, Calzetta L, Cavalli F, Matera MG, Cazzola M. Pirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Pulm Pharmacol Ther. 2016 Oct;40:95–103.
Fleetwood K, McCool R, Glanville J, Edwards SC, Gsteiger S, Daigl M, et al. Systematic Review and Network Meta-analysis of Idiopathic Pulmonary Fibrosis Treatments. J Manag Care Spec Pharm. 2017 Mar;23(3-b Suppl):10.18553/jmcp.2017.23.3-b.s5.
Ley B, Collard HR, King TE. Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2011 Feb 15;183(4):431–40.
Karman J, Wang J, Bodea C, Cao S, Levesque MC. Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms. Kass DJ, editor. PLOS ONE. 2021 Mar 23;16(3):e0248889.
Bocchino M, Agnese S, Fagone E, Svegliati S, Grieco D, Vancheri C, et al. Reactive Oxygen Species Are Required for Maintenance and Differentiation of Primary Lung Fibroblasts in Idiopathic Pulmonary Fibrosis. PLOS ONE. 2010 Nov 16;5(11):e14003.
Shah RR, Morganroth J, Shah DR. Hepatotoxicity of Tyrosine Kinase Inhibitors: Clinical and Regulatory Perspectives. Drug Saf. 2013 Jul 1;36(7):491–503.
Raschi E, Fusaroli M, Gatti M, Caraceni P, Poluzzi E, De Ponti F. Liver Injury with Nintedanib: A Pharmacovigilance–Pharmacokinetic Appraisal. Pharmaceuticals. 2022 May;15(5):645.
Abdel-Rahman O, Bahie Eldin N, ElHalawani H. Risk of Selected Gastrointestinal and Hepatic Toxicities in Cancer Patients Treated with Nintedanib: A Meta-Analysis. Future Oncol. 2016 Sep 30;12(18):2163–72.
Shah RR, Morganroth J, Shah DR. Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Saf. 2013 Jul;36(7):491–503.
Han D, Shinohara M, Ybanez MD, Saberi B, Kaplowitz N. Signal transduction pathways involved in drug-induced liver injury. Handb Exp Pharmacol. 2010;(196):267–310.
Kato M, Sasaki S, Nakamura T, Kurokawa K, Yamada T, Ochi Y, et al. Gastrointestinal adverse effects of nintedanib and the associated risk factors in patients with idiopathic pulmonary fibrosis. Sci Rep. 2019 Aug 19;9(1):12062.
Koudstaal T, Wijsenbeek MS. Idiopathic pulmonary fibrosis. Presse Médicale. 2023 Sep 1;52(3):104166.
Smith ML. The histologic diagnosis of usual interstitial pneumonia of idiopathic pulmonary fibrosis. Where we are and where we need to go. Mod Pathol. 2022 Jan 1;35:8–14.
Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep;198(5):e44–68.
Duhig EE. Usual interstitial pneumonia: a review of the pathogenesis and discussion of elastin fibres, type II pneumocytes and proposed roles in the pathogenesis. Pathology (Phila). 2022 Aug 1;54(5):517–25.
Honda T, Uehara T, Sano K. Heterogeneous proliferation of type II pneumocytes in usual interstitial pneumonia. Pathology (Phila). 2006 Jan 1;38(5):433–6.
Raghu G, Rochwerg B, Zhang Y, Garcia CAC, Azuma A, Behr J, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015 Jul 15;192(2):e3–19.
Tepede A, Yogaratnam D. Nintedanib for Idiopathic Pulmonary Fibrosis. J Pharm Pract. 2019 Apr;32(2):199–206.
Aimo A, Spitaleri G, Nieri D, Tavanti LM, Meschi C, Panichella G, et al. Pirfenidone for Idiopathic Pulmonary Fibrosis and Beyond. Card Fail Rev. 2022 Apr 14;8:e12.
Conte E, Gili E, Fagone E, Fruciano M, Iemmolo M, Vancheri C. Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts. Eur J Pharm Sci. 2014 Jul 16;58:13–9.
Bocchino M, Bruzzese D, Scioscia G, Capitelli L, Tondo P, Rea G, et al. Disease stage-related survival in idiopathic pulmonary fibrosis patients treated with nintedanib and pirfenidone: An exploratory study. Respir Med Res. 2023;84:101013.
Richeldi L, Bois RM du, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. N Engl J Med. 2014 May 29;370(22):2071–82.
Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. The Lancet. 2011 May 21;377(9779):1760–9.
King TE, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2014 May 29;370(22):2083–92.
Nathan SD, Albera C, Bradford WZ, Costabel U, Glaspole I, Glassberg MK, et al. Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis. Lancet Respir Med. 2017 Jan 1;5(1):33–41.
Richeldi L, Cottin V, du Bois RM, Selman M, Kimura T, Bailes Z, et al. Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials. Respir Med. 2016 Apr 1;113:74–9.
Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2022 May;205(9):e18–47.
Wells G, Shea B, Connell DO, Petersn J, Welch V. Ottawa Hospital Research Institute. [cited 2024 Sep 6]. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
Granholm A, Alhazzani W, Møller MH. Use of the GRADE approach in systematic reviews and guidelines. Br J Anaesth. 2019 Nov;123(5):554–9.
Barratt SL, Mulholland S, Al Jbour K, Steer H, Gutsche M, Foley N, et al. South-West of England’s Experience of the Safety and Tolerability Pirfenidone and Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis (IPF). Front Pharmacol. 2018;9:1480.
Belhassen M, Dalon F, Nolin M, Van Ganse E. Comparative outcomes in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis. Respir Res. 2021;22(1):135.
Cameli P, Refini RM, Bergantini L, d’Alessandro M, Alonzi V, Magnoni C, et al. Long-Term Follow-Up of Patients With Idiopathic Pulmonary Fibrosis Treated With Pirfenidone or Nintedanib: A Real-Life Comparison Study. Front Mol Biosci. 2020;7:581828.
Corral M, DeYoung K, Kong AM. Treatment patterns, healthcare resource utilization, and costs among patients with idiopathic pulmonary fibrosis treated with antifibrotic medications in US-based commercial and Medicare Supplemental claims databases: a retrospective cohort study. BMC Pulm Med. 2020 Jul 11;20(1):188.
Dempsey TM, Sangaralingham LR, Yao X, Sanghavi D, Shah ND, Limper AH. Clinical Effectiveness of Antifibrotic Medications for Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2019;200(2):168–74.
Fournier D, Jouneau S, Bouzillé G, Polard E, Osmont MN, Scailteux LM. Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients. Pulm Pharmacol Ther. 2022;76:102149.
Galli JA, Pandya A, Vega-Olivo M, Dass C, Zhao H, Criner GJ. Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions. Respirol Carlton Vic. 2017;22(6):1171–8.
Holtze CH, Freiheit EA, Limb SL, Stauffer JL, Raimundo K, Pan WT, et al. Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry. Respir Res. 2020;21(1):48.
Honda K, Saraya T, Ishii H. A Real-World Prognosis in Idiopathic Pulmonary Fibrosis: A Special Reference to the Role of Antifibrotic Agents for the Elderly. J Clin Med [Internet]. 2023 [cited 5AD Jan 1];12(10). Available from: https://pubmed.ncbi.nlm.nih.gov/37240670/
Iwasaki K, Wakabayashi H, Saiki A, Ueshiba H, Murakami Y, Matsuzawa Y. Real-World Clinical Efficacy of Antifibrotic Agents for Idiopathic Pulmonary Fibrosis: A Single-Center Retrospective Study in Japan. Drugs - Real World Outcomes. 2024;11(1):43–52.
Khan MA, Ghamdi BA, Alhamadi M, Rajendram R, Alyami S, Al-Gamedi M, et al. A survival analysis of idiopathic pulmonary fibrosis in the context of antifibrotic therapy in Saudi Arabia. Ann Thorac Med. 2023;18(2):79–85.
Khan MA, Sherbini N, Alyami S, Al-Harbi A, Al-Ghamdi M, Alrajhi S, et al. Nintedanib and pirfenidone for idiopathic pulmonary fibrosis in King Abdulaziz Medical City, Riyadh: Real-life data. Ann Thorac Med. 2023;18(1):45–51.
Levra S, Guida G, Sprio AE, Crosa F, Ghio PC, Bertolini F, et al. Long-Term Safety of Antifibrotic Drugs in IPF: A Real-World Experience. Biomedicines [Internet]. 2022 [cited 12AD Jan 1];10(12). Available from: https://pubmed.ncbi.nlm.nih.gov/36551989/
Marijic P, Schwarzkopf L, Schwettmann L, Ruhnke T, Trudzinski F, Kreuter M. Pirfenidone vs. nintedanib in patients with idiopathic pulmonary fibrosis: a retrospective cohort study. Respir Res. 2021;22(1):268.
Noor S, Nawaz S, Chaudhuri N. Real-World Study Analysing Progression and Survival of Patients with Idiopathic Pulmonary Fibrosis with Preserved Lung Function on Antifibrotic Treatment. Adv Ther. 2021;38(1):268–77.
Takehara K, Koga Y, Hachisu Y, Utsugi M, Sawada Y, Saito Y, et al. Differential Discontinuation Profiles between Pirfenidone and Nintedanib in Patients with Idiopathic Pulmonary Fibrosis. Cells [Internet]. 2022 [cited 1AD Jan 1];11(1). Available from: https://pubmed.ncbi.nlm.nih.gov/35011705/
Üzer F, Akanlar S, Çilli A. Real-life data in the treatment and follow-up of idiopathic pulmonary fibrosis: A single-center study. Tuberk Ve Toraks. 2023;71(4):347–55.
Wright WA, Crowley LE, Parekh D, Crawshaw A, Dosanjh DP, Nightingale P, et al. Real-world retrospective observational study exploring the effectiveness and safety of antifibrotics in idiopathic pulmonary fibrosis. BMJ Open Respir Res. 2021 Mar;8(1):e000782.
Romero Ortiz AD, Jiménez-Rodríguez BM, López-Ramírez C, López-Bauzá Á, Pérez-Morales M, Delgado-Torralbo JA, et al. Antifibrotic treatment adherence, efficacy and outcomes for patients with idiopathic pulmonary fibrosis in Spain: a real-world evidence study. BMJ Open Respir Res [Internet]. 2024 [cited 4AD Jan 1];11(1). Available from: https://pubmed.ncbi.nlm.nih.gov/38663886/
Sadon AAEA, Kenawy AS, Abdelsalam AH, Attia HM. Pirfenidone vs nintedanib for treatment of idiopathic pulmonary fibrosis in clinical practice: efficacy, tolerability, and adverse effects. Egypt J Chest Dis Tuberc. 2020 Sep;69(3):549.
Zhao R, Xie B, Wang X, Zhang X, Ren Y, Wang C, et al. The tolerability and efficacy of antifibrotic therapy in patients with idiopathic pulmonary fibrosis: Results from a real-world study. Pulm Pharmacol Ther. 2024;84:102287.
Cerri S, Monari M, Guerrieri A, Donatelli P, Bassi I, Garuti M, et al. Real-life comparison of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis: A 24-month assessment. Respir Med. 2019;159:105803.
Paterniti MO, Bi Y, Rekić D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395–402.
Rogliani P, Calzetta L, Cavalli F, Matera MG, Cazzola M. Pirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Pulm Pharmacol Ther. 2016 Oct;40:95–103.
Fleetwood K, McCool R, Glanville J, Edwards SC, Gsteiger S, Daigl M, et al. Systematic Review and Network Meta-analysis of Idiopathic Pulmonary Fibrosis Treatments. J Manag Care Spec Pharm. 2017 Mar;23(3-b Suppl):10.18553/jmcp.2017.23.3-b.s5.
Ley B, Collard HR, King TE. Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2011 Feb 15;183(4):431–40.
Karman J, Wang J, Bodea C, Cao S, Levesque MC. Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms. Kass DJ, editor. PLOS ONE. 2021 Mar 23;16(3):e0248889.
Bocchino M, Agnese S, Fagone E, Svegliati S, Grieco D, Vancheri C, et al. Reactive Oxygen Species Are Required for Maintenance and Differentiation of Primary Lung Fibroblasts in Idiopathic Pulmonary Fibrosis. PLOS ONE. 2010 Nov 16;5(11):e14003.
Shah RR, Morganroth J, Shah DR. Hepatotoxicity of Tyrosine Kinase Inhibitors: Clinical and Regulatory Perspectives. Drug Saf. 2013 Jul 1;36(7):491–503.
Raschi E, Fusaroli M, Gatti M, Caraceni P, Poluzzi E, De Ponti F. Liver Injury with Nintedanib: A Pharmacovigilance–Pharmacokinetic Appraisal. Pharmaceuticals. 2022 May;15(5):645.
Abdel-Rahman O, Bahie Eldin N, ElHalawani H. Risk of Selected Gastrointestinal and Hepatic Toxicities in Cancer Patients Treated with Nintedanib: A Meta-Analysis. Future Oncol. 2016 Sep 30;12(18):2163–72.
Shah RR, Morganroth J, Shah DR. Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Saf. 2013 Jul;36(7):491–503.
Han D, Shinohara M, Ybanez MD, Saberi B, Kaplowitz N. Signal transduction pathways involved in drug-induced liver injury. Handb Exp Pharmacol. 2010;(196):267–310.
Kato M, Sasaki S, Nakamura T, Kurokawa K, Yamada T, Ochi Y, et al. Gastrointestinal adverse effects of nintedanib and the associated risk factors in patients with idiopathic pulmonary fibrosis. Sci Rep. 2019 Aug 19;9(1):12062.
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