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Morán-Mendoza O, Khalil M, Aldhaheri S, Xing J, Johnson AP. Real World Experience: Impact of a Specialist Interstitial Lung Disease Nurse on Health Care Utilization. OPEN RESPIRATORY ARCHIVES 2025; 7:100400. [PMID: 40028261 PMCID: PMC11869855 DOI: 10.1016/j.opresp.2025.100400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2025] Open
Affiliation(s)
- Onofre Morán-Mendoza
- Department of Medicine, Queen's University, Kingston, ON, Canada
- Kingston Health Sciences Center, Kingston, ON, Canada
| | | | | | - Jiayi Xing
- Department of Medicine, Queen's University, Kingston, ON, Canada
| | - Ana P. Johnson
- Faculty of Health Sciences, Queen's University, Kingston, ON, Canada
- Department of Public Health Sciences, Queen's University, Kingston, ON, Canada
- Institute for Clinical Evaluative Sciences Queen's, Kingston, ON, Canada
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Mohamed BME, Abdelrahim MEA. Timing impact on the initiation of pirfenidone therapy on idiopathic pulmonary fibrosis disease progression. World J Clin Cases 2024; 12:6538-6542. [PMID: 39554893 PMCID: PMC11438636 DOI: 10.12998/wjcc.v12.i32.6538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/25/2024] [Accepted: 07/31/2024] [Indexed: 09/24/2024] Open
Abstract
In this editorial, we comment on the article by Lei et al, with a specific focus on the timing of the initiation of the antifibrotic agent pirfenidone (PFD) in the management of idiopathic pulmonary fibrosis (IPF) and its impact on lung function of IPF patients. PFD is an antifibrotic agent that is widely used in the management of IPF in both early and advanced stages. It inhibits various pathways and has antifibrotic, anti-inflammatory, and antioxidant properties. Despite dosage lowering, PFD slowed IPF progression and maintained functional capacity. The 6-min walk distance test indicated that patients tolerated adverse events well, and PFD significantly reduced the incidence of progression episodes and death. Even when a single disease-progression event occurred, continuing PFD treatment had benefits.
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Affiliation(s)
- Basma M E Mohamed
- Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 343433, Egypt
| | - Mohamed E A Abdelrahim
- Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 343433, Egypt
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Kou M, Jiao Y, Li Z, Wei B, Li Y, Cai Y, Wei W. Real-world safety and effectiveness of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis. Eur J Clin Pharmacol 2024; 80:1445-1460. [PMID: 38963453 DOI: 10.1007/s00228-024-03720-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 06/23/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUND AND OBJECTIVE Multiple randomized controlled studies have shown that pirfenidone and nintedanib are effective and safe for treating idiopathic pulmonary fibrosis. This study aimed to evaluate their efficacy, safety, and tolerability in a real-world setting. METHODS We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for real-world studies published up to March 3, 2023, on pirfenidone and nintedanib for idiopathic pulmonary fibrosis. RESULTS A total of 74 studies with 23,119 participants were included. After 12 months of treatment, the change from baseline in percent predicted FVC (%FVC) was - 0.75% for pirfenidone and - 1.43% for nintedanib. The change from baseline in percent predicted DLCO (%DCLO) was - 2.32% for pirfenidone and - 3.95% for nintedanib. The incidence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) was 12.5% for pirfenidone and 14.4% for nintedanib. The IPF-related mortality rates of pirfenidone and nintedanib were 13.4% and 7.2%, respectively. The all-cause mortality was 20.1% for pirfenidone and 16.6% for nintedanib. In the pirfenidone group, 16.6% of patients discontinued treatment because of adverse events, and in the nintedanib group, 16.2% of patients discontinued treatment because of adverse events. The incidence of adverse events was 56.4% and 69.7% for pirfenidone and nintedanib, respectively. CONCLUSION The results of this study indicate that pirfenidone and nintedanib are both effective in slowing down the decline of lung function in IPF patients in real-world settings. The incidence of adverse events with pirfenidone is lower than that with nintedanib, but both are below the clinical trial data, and no new major adverse events have been observed. The discontinuation rates due to adverse reactions of the two drugs are consistent with clinical trial data, indicating good tolerability. However, the mortality rates and AE-IPF incidence rates of these two drugs in real-world settings are higher than those in previous clinical trials, with pirfenidone patients showing a higher mortality rate. Further large-sample studies are needed to investigate the risks of these drugs in these aspects. Additionally, we recommend that future real-world studies pay more attention to patients' subjective symptoms and conduct stratified analyses of the efficacy and safety of pirfenidone and nintedanib based on factors such as patients' baseline lung function, comorbidities, and age, in order to provide more personalized medication advice for IPF patients in clinical practice.
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Affiliation(s)
- Mengjia Kou
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yang Jiao
- Department of Respiration, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, 100078, China
| | - Zhipeng Li
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Bin Wei
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yang Li
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yaodong Cai
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Wan Wei
- Department of Respiration, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, 100078, China.
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Chang CY, Wei YF, Chen CY, Lai YC, Hu PW, Hung JC, Chu CH, Chuang HT, Chang SC. Real world experience on the effectiveness and safety of pirfenidone in patients with idiopathic pulmonary fibrosis in Taiwan. Front Med (Lausanne) 2023; 10:1242260. [PMID: 37964885 PMCID: PMC10642852 DOI: 10.3389/fmed.2023.1242260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Accepted: 10/04/2023] [Indexed: 11/16/2023] Open
Abstract
Introduction Randomized controlled trials have demonstrated a reduction in the decline of lung function and a reduced risk of acute exacerbation in patients with idiopathic pulmonary fibrosis treated with the antifibrotic prifenidone. The present study aimed to investigate the real-world effectiveness and safety profile of pirfenidone treatment for patients with IPF in Taiwan. Methods Between January 1, 2019 and December 31, 2020, we enrolled 50 patients who were newly diagnosed with IPF and had at least 12 months follow-up period after pirfenidone administration. Result The primary outcome of pharmacologic effect showed that the mean differences in the absolute values of forced vital capacity from baseline were 0.2 liter (n = 36), 0.13 liter (n = 32), 0.04 liter (n = 26), and - 0.004 liter (n = 26) after 3, 6, 9, and 12 months of administration, respectively. A slight improvement in quality of life, including scores of chronic obstructive pulmonary disease assessment test and St. George's respiratory questionnaire scores. The most common adverse effects were gastrointestinal upset and dermatological problems. No new safety concerns were observed in the present study. Conclusion Our real-world study describe for the first time in Taiwan, the use of pirfenidone over a 12 months period. This drug preserves the lung function and improves quality of life with tolerable side effects.
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Affiliation(s)
- Cheng-Yu Chang
- Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei, Taiwan
- Department of Nursing, Cardinal Tien Junior College of Healthcare and Management, New Taipei, Taiwan
| | - Yu-Feng Wei
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chung-Yu Chen
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Chun Lai
- Division of Chest Medicine, Department of Internal Medicine, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan
- Faculty of Medicine, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Po-Wei Hu
- Division of Chest Medicine, Department of Internal Medicine, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan
- Faculty of Medicine, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Jui-Chi Hung
- Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei, Taiwan
| | - Chi-Hsiang Chu
- Department of Statistics, Tunghai University, Taichung, Taiwan
| | - Hsin-Tzu Chuang
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shih-Chieh Chang
- Division of Chest Medicine, Department of Internal Medicine, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan
- Faculty of Medicine, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
- Department of Critical Care Medicine, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan
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Lee EG, Lee TH, Hong Y, Ryoo J, Heo JW, Gil BM, Kang HS, Kwon SS, Kim YH. Effects of low-dose pirfenidone on survival and lung function decline in patients with idiopathic pulmonary fibrosis (IPF): Results from a real-world study. PLoS One 2021; 16:e0261684. [PMID: 34941933 PMCID: PMC8699661 DOI: 10.1371/journal.pone.0261684] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 12/07/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown etiology. In several randomized clinical trials, and in the clinical practice, pirfenidone is used to effectively and safely treat IPF. However, sometimes it is difficult to use the dose of pirfenidone used in clinical trials. This study evaluated the effects of low-dose pirfenidone on IPF disease progression and patient survival in the real-world. METHODS This retrospective, observational study enrolled IPF patients seen at the time of diagnosis at a single center from 2008 to 2018. Longitudinal clinical and laboratory data were prospectively collected. We compared the clinical characteristics, survival, and pulmonary function decline between patients treated and untreated with various dose of pirfenidone. RESULTS Of 295 IPF patients, 100 (33.9%) received pirfenidone and 195 (66.1%) received no antifibrotic agent. Of the 100 patients who received pirfenidone, 24 (24%), 50 (50%), and 26 (26%), respectively, were given 600, 1200, and 1800 mg pirfenidone daily. The mean survival time was 57.03 ± 3.90 months in the no-antifibrotic drug group and 73.26 ± 7.87 months in the pirfenidone-treated group (p = 0.027). In the unadjusted analysis, the survival of the patients given pirfenidone was significantly better (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.48-0.99, p = 0.04). After adjusting for age, gender, body mass index, and the GAP score [based on gender (G), age (A), and two physiological lung parameters (P)], survival remained better in the patients given pirfenidone (HR = 0.56, 95% CI: 0.37-0.85, p = 0.006). In terms of pulmonary function, the decreases in forced vital capacity (%), forced expiratory volume in 1 s (%) and the diffusing capacity of lung for carbon monoxide (%) were significantly smaller (p = 0.000, p = 0.001, and p = 0.007, respectively) in patients given pirfenidone. CONCLUSIONS Low-dose pirfenidone provided beneficial effects on survival and pulmonary function decline in the real-world practice.
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Affiliation(s)
- Eung Gu Lee
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Tae-Hee Lee
- Department of Statistics and Data Science, Yonsei University, Seoul, South Korea
| | - Yujin Hong
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jiwon Ryoo
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung Won Heo
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Bo Mi Gil
- Department of Radiology, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic university of Korea, Seoul, Republic of Korea
| | - Hye Seon Kang
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Soon Seog Kwon
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yong Hyun Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Delameillieure A, Vandekerkhof S, Van Grootven B, Wuyts WA, Dobbels F. Care programs and their components for patients with idiopathic pulmonary fibrosis: a systematic review. Respir Res 2021; 22:229. [PMID: 34399748 PMCID: PMC8365984 DOI: 10.1186/s12931-021-01815-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 07/29/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The multidimensional and complex care needs of patients with idiopathic pulmonary fibrosis (IPF) call for appropriate care models. This systematic review aimed to identify care models or components thereof that have been developed for patients with IPF in the outpatient clinical care, to describe their characteristics from the perspective of chronic integrated care and to describe their outcomes. METHODS A systematic review was conducted using state-of-the-art methodology with searches in PubMed/Medline, Embase, CINAHL and Web Of Science. Researchers independently selected studies and collected data, which were described according to the Chronic Care Model (CCM). RESULTS Eighteen articles were included describing 13 new care models or components. The most commonly described CCM elements were 'delivery system design' (77%) and 'self-management support' (69%), with emphasis on team-based and multidisciplinary care provision and education. The most frequently described outcome was health-related quality of life. CONCLUSIONS Given the high need for integrated care and the scarcity and heterogeneity of data, developing, evaluating and implementing new models of care for patients with IPF and the comprehensive reporting of these endeavours should be a priority for research and clinical care.
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Affiliation(s)
- Anouk Delameillieure
- Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery, KU Leuven, Leuven, Belgium
- Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Kapucijnenvoer 35 blok D-box 7001, 3000 Leuven, Belgium
| | - Sarah Vandekerkhof
- Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Kapucijnenvoer 35 blok D-box 7001, 3000 Leuven, Belgium
| | - Bastiaan Van Grootven
- Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Kapucijnenvoer 35 blok D-box 7001, 3000 Leuven, Belgium
- Research Foundation-Flandres, Brussels, Belgium
| | - Wim A. Wuyts
- Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery, KU Leuven, Leuven, Belgium
- Department of Respiratory Diseases, Unit for Interstitial Lung Diseases, University Hospitals Leuven, Leuven, Belgium
| | - Fabienne Dobbels
- Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Kapucijnenvoer 35 blok D-box 7001, 3000 Leuven, Belgium
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Hisata S, Bando M, Homma S, Kataoka K, Ogura T, Izumi S, Sakamoto S, Watanabe K, Saito Y, Shimizu Y, Kato M, Nishioka Y, Hara H, Waseda Y, Tanino Y, Yatera K, Hashimoto S, Mukae H, Inase N. Safety and tolerability of combination therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis: A multicenter retrospective observational study in Japan. Respir Investig 2021; 59:819-826. [PMID: 33994347 DOI: 10.1016/j.resinv.2021.04.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 03/23/2021] [Accepted: 04/15/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Phase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited. METHODS The retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records. RESULTS Nintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender-Age-Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax). CONCLUSIONS Real-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile.
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Affiliation(s)
- Shu Hisata
- Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan
| | - Masashi Bando
- Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
| | - Sakae Homma
- Department of Advanced and Integrated Interstitial Lung Diseases Research, School of Medicine, Toho University, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan
| | - Kensuke Kataoka
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan
| | - Takashi Ogura
- Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama, 236-0051, Japan
| | - Shinyu Izumi
- Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Susumu Sakamoto
- Department of Respiratory Medicine, Toho University Omori Medical Center, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan
| | - Kizuku Watanabe
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Yoshinobu Saito
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan
| | - Yasuo Shimizu
- Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi, 321-0293, Japan
| | - Motoyasu Kato
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Yasuhiko Nishioka
- Graduate School of Biomedical Sciences, Tokushima University, Department of Respiratory Medicine and Rheumatology, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Hiromichi Hara
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yuko Waseda
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Yoshinori Tanino
- Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima, 960-1295, Japan
| | - Kazuhiro Yatera
- Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Kitakyushu, 807-8555, Japan
| | - Seishu Hashimoto
- Department of Respiratory Medicine, Tenri Hospital, 200, Mishima-cho, Tenri, 632-8552, Japan
| | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
| | - Naohiko Inase
- Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
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Role of pirfenidone in TGF-β pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection: a theoretical perspective. Pharmacol Rep 2021; 73:712-727. [PMID: 33880743 PMCID: PMC8057922 DOI: 10.1007/s43440-021-00255-x] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/14/2021] [Accepted: 03/23/2021] [Indexed: 12/13/2022]
Abstract
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pulmonary injury or multiple-organ injury by various pathological pathways. Transforming growth factor-beta (TGF-β) is a key factor that is released during SARS-CoV-2 infection. TGF-β, by internalization of the epithelial sodium channel (ENaC), suppresses the anti-oxidant system, downregulates the cystic fibrosis transmembrane conductance regulator (CFTR), and activates the plasminogen activator inhibitor 1 (PAI-1) and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kB). These changes cause inflammation and lung injury along with coagulopathy. Moreover, reactive oxygen species play a significant role in lung injury, which levels up during SARS-CoV-2 infection. Drug Suggestion Pirfenidone is an anti-fibrotic drug with an anti-oxidant activity that can prevent lung injury during SARS-CoV-2 infection by blocking the maturation process of transforming growth factor-beta (TGF-β) and enhancing the protective role of peroxisome proliferator-activated receptors (PPARs). Pirfenidone is a safe drug for patients with hypertension or diabetes and its side effect tolerated well. Conclusion The drug as a theoretical perspective may be an effective and safe choice for suppressing the inflammatory response during COVID-19. The recommendation would be a combination of pirfenidone and N-acetylcysteine to achieve maximum benefit during SARS-CoV-2 treatment.
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Satsuma Y, Ikesue H, Kusuda K, Maeda M, Muroi N, Mori R, Kogo M, Hirabayashi R, Nagata K, Nakagawa A, Tachikawa R, Tomii K, Hashida T. Effectiveness of Pharmacist-Physician Collaborative Management for Patients With Idiopathic Pulmonary Fibrosis Receiving Pirfenidone. Front Pharmacol 2020; 11:529654. [PMID: 33324201 PMCID: PMC7725709 DOI: 10.3389/fphar.2020.529654] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Accepted: 10/16/2020] [Indexed: 11/13/2022] Open
Abstract
Background: Pirfenidone is an anti-fibrotic agent used to treat patients with idiopathic pulmonary fibrosis (IPF). Managing adverse drug events and ensuring compliance with pirfenidone treatment for a prolonged period are important to reduce the rate of disease progression. To maximize the benefits of pirfenidone treatment, we established and evaluated an ambulatory care pharmacy practice, a model of pharmacist-physician collaborative management, for patients receiving pirfenidone. Methods: We conducted a retrospective chart review of 76 consecutive patients treated with pirfenidone in the Kobe City Medical Center General Hospital, Japan, between January 2012 and January 2019. The first group (61 patients) received pirfenidone treatment as conventional management, whereas the second group (15 patients) started pirfenidone based on collaborative pharmacist-physician management. The drug discontinuation rate and time to drug discontinuation were compared between the groups. To analyze factors associated with pirfenidone discontinuation, we used a multivariate Cox regression analysis to evaluate the baseline characteristics of patients, including those receiving the collaborative management. Clinical outcomes were compared using a propensity score matched analysis. Results: In the collaborative management group, pharmacists made 56 suggestions, including suggestions for supportive care (51 suggestions), to the physicians. Among these suggestions, 52 were accepted by the physicians. The discontinuation rates at 3 [6.7% (1/15) vs. 26.2% (16/61)] and 6 [9.1% (1/11) vs. 36.1% (22/61)] months were lower in the collaborative management group than in the conventional management group. Multivariate analysis revealed that collaborative management [hazard ratio (HR) 0.34, 95% CI 0.08-0.96, p = 0.041] and predicted baseline forced vital capacity <60% (HR 2.13, 95% CI 1.17-3.85, p = 0.015) were significantly associated with pirfenidone discontinuation. The time to drug discontinuation was also significantly longer in the collaborative management group than in the conventional management group (p = 0.034, log-rank test). Propensity score matched analysis confirmed a significant correlation between collaborative management and drug discontinuation time (HR 0.20, 95% CI 0.03-0.84, p = 0.027). Conclusions: We established an ambulatory care pharmacy practice for out-patients with IPF receiving pirfenidone. The results suggest that collaborative management may help prevent pirfenidone discontinuation compared with conventional management.
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Affiliation(s)
- Yukari Satsuma
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Hiroaki Ikesue
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Kaori Kusuda
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Mami Maeda
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Nobuyuki Muroi
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Ryobu Mori
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Mariko Kogo
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Ryosuke Hirabayashi
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Kazuma Nagata
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Atsushi Nakagawa
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Ryo Tachikawa
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Keisuke Tomii
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Tohru Hashida
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
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Eaden JA, Barber CM, Renshaw SA, Chaudhuri N, Bianchi SM. Real world experience of response to pirfenidone in patients with idiopathic pulmonary fibrosis: a two centre retrospective study. SARCOIDOSIS, VASCULITIS, AND DIFFUSE LUNG DISEASES : OFFICIAL JOURNAL OF WASOG 2020; 37:218-224. [PMID: 33093786 PMCID: PMC7569563 DOI: 10.36141/svdld.v37i2.8587] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 06/15/2020] [Indexed: 11/17/2022]
Abstract
Introduction: Pirfenidone has been shown to reduce the decline in forced vital capacity (FVC) compared to placebo in patients with idiopathic pulmonary fibrosis (IPF). Previous studies have suggested that patients with a more rapid decline in FVC during the period before starting pirfenidone experience the greatest benefit from treatment. The purpose of this retrospective observational study was to investigate the response to pirfenidone in IPF patients, comparing two groups stratified by the annual rate of decline in FVC % predicted prior to treatment. Methods: Using the rate of decline in FVC % predicted in the 12 months prior to pirfenidone, patients were stratified into slow (<5%) or rapid (≥5%) decliner groups. Comparisons in the lung function response to pirfenidone in these two groups were performed. Results: Pirfenidone resulted in no statistically significant reduction in the median annual rate of decline in FVC or FVC % predicted. In the rapid decliners, pirfenidone significantly reduced the median (IQR) annual rate of decline in FVC % predicted (-8.7 (-14.2 – -7.0) %/yr vs 2.0 (-7.1 – 6.0) %/yr; n=17; p<0.01). In the slow decliners, pirfenidone did not reduce the median (IQR) annual rate of decline in FVC % predicted (-1.3 (-3.2 – 1.3) %/yr vs -5.0 (-8.3 – -0.35) %/yr; n=17; p=0.028). Conclusions: We demonstrate the greater net effect of pirfenidone in IPF patients declining rapidly. We suggest that using an annual rate of decline in FVC of <5% and ≥5% may be useful in counselling patients with regard to pirfenidone treatment. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 218-224)
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Affiliation(s)
- James A Eaden
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.,Respiratory Medicine Department, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
| | - Christopher M Barber
- Respiratory Medicine Department, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
| | - Stephen A Renshaw
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.,Respiratory Medicine Department, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
| | - Nazia Chaudhuri
- Interstitial Lung Disease Unit, University of Manchester NHS Foundation Trust, Manchester, United Kingdom
| | - Stephen M Bianchi
- Respiratory Medicine Department, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
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11
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Ruwanpura SM, Thomas BJ, Bardin PG. Pirfenidone: Molecular Mechanisms and Potential Clinical Applications in Lung Disease. Am J Respir Cell Mol Biol 2020; 62:413-422. [PMID: 31967851 DOI: 10.1165/rcmb.2019-0328tr] [Citation(s) in RCA: 143] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Pirfenidone (PFD) is a pharmacological compound with therapeutic efficacy in idiopathic pulmonary fibrosis. It has been chiefly characterized as an antifibrotic agent, although it was initially developed as an antiinflammatory compound because of its ability to diminish the accumulation of inflammatory cells and cytokines. Despite recent studies that have elucidated key mechanisms, the precise molecular activities of PFD remain incompletely understood. PFD modulates fibrogenic growth factors, thereby attenuating fibroblast proliferation, myofibroblast differentiation, collagen and fibronectin synthesis, and deposition of extracellular matrix. This effect is mediated by suppression of TGF-β1 (transforming growth factor-β1) and other growth factors. Here, we appraise the impact of PFD on TGF-β1 production and its downstream pathways. Accumulating evidence indicates that PFD also downregulates inflammatory pathways and therefore has considerable potential as a viable and innovative antiinflammatory compound. We examine the effects of PFD on inflammatory cells and the production of pro- and antiinflammatory cytokines in the lung. In this context, recent evidence that PFD can target inflammasome pathways and ensuing lung inflammation is highlighted. Finally, the antioxidant properties of PFD, such as its ability to inhibit redox reactions and regulate oxidative stress-related genes and enzymes, are detailed. In summary, this narrative review examines molecular mechanisms underpinning PFD and its recognized benefits in lung fibrosis. We highlight preclinical data that demonstrate the potential of PFD as a nonsteroidal antiinflammatory agent and outline areas for future research.
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Affiliation(s)
- Saleela M Ruwanpura
- Monash Lung and Sleep, Monash Health, Monash Medical Centre, Clayton, Victoria, Australia; and
| | - Belinda J Thomas
- Monash Lung and Sleep, Monash Health, Monash Medical Centre, Clayton, Victoria, Australia; and.,Hudson Institute of Medical Research, Clayton, Victoria, Australia
| | - Philip G Bardin
- Monash Lung and Sleep, Monash Health, Monash Medical Centre, Clayton, Victoria, Australia; and.,Hudson Institute of Medical Research, Clayton, Victoria, Australia
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12
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Gulati S, Luckhardt TR. Updated Evaluation of the Safety, Efficacy and Tolerability of Pirfenidone in the Treatment of Idiopathic Pulmonary Fibrosis. DRUG HEALTHCARE AND PATIENT SAFETY 2020; 12:85-94. [PMID: 32440226 PMCID: PMC7213901 DOI: 10.2147/dhps.s224007] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 01/29/2020] [Indexed: 11/28/2022]
Abstract
Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrotic disease characterized by a progressive decline in lung function with a median survival of 3–5 years after diagnosis. The course of disease is highly variable and unpredictable, often punctuated by episodes of acute respiratory failure, known as acute exacerbations. The incidence of IPF is on the rise due to the aging population, as age is the most important risk factor for this disease. Pirfenidone and nintedanib are the two anti-fibrotic drugs approved for IPF which have shown reduction in lung function decline. This review will discuss the efficacy, safety and tolerability profile of pirfenidone from clinical trials and the real-world clinical experience. Pirfenidone reduces the decline in lung function and improves progression-free survival in patients with IPF. It is generally well tolerated with the most common side effects being gastrointestinal and phototoxicity.
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Affiliation(s)
- Swati Gulati
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Tracy R Luckhardt
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.,Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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13
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Majewski S, Białas AJ, Buchczyk M, Gomółka P, Górska K, Jagielska-Len H, Jarzemska A, Jassem E, Jastrzębski D, Kania A, Koprowski M, Krenke R, Kuś J, Lewandowska K, Martusewicz-Boros MM, Roszkowski-Śliż K, Siemińska A, Sładek K, Sobiecka M, Szewczyk K, Tomczak M, Tomkowski W, Wiatr E, Ziora D, Żołnowska B, Piotrowski WJ. A multicentre retrospective observational study on Polish experience of pirfenidone therapy in patients with idiopathic pulmonary fibrosis: the PolExPIR study. BMC Pulm Med 2020; 20:122. [PMID: 32366291 PMCID: PMC7199354 DOI: 10.1186/s12890-020-1162-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 04/20/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Pirfenidone is an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). The drug is available for Polish patients with IPF since 2017. The PolExPIR study aimed to describe the real-world data (RWD) on the Polish experience of pirfenidone therapy in IPF with respect to safety and efficacy profiles. METHODS This was a multicentre, retrospective, observational study collecting clinical data of patients with IPF receiving pirfenidone from January 2017 to September 2019 across 10 specialized pulmonary centres in Poland. Data collection included baseline characteristics, pulmonary function tests (PFTs) results and six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), treatment persistence, and survival were also collected up to 24 months post-inclusion. RESULTS A total of 307 patients receiving pirfenidone were identified for analysis. The mean age was 68.83 (8.13) years and 77% were males. The median time from the first symptoms to IPF diagnosis was 15.5 (9.75-30) months and from diagnosis to start of pirfenidone treatment was 6 (2-23) months. Patients were followed on treatment for a median of 17 (12-22.75) months. Seventy-four patients (24.1%) required dose adjustments and 35 (11.4%) were chronically treated with different than the full recommended dose. A total of 141 patients (45.92%) discontinued therapy due to different reasons including ADRs (16.61%), death (8.79%), disease progression (6.51%), patient's own request (5.54%), neoplastic disease (3.91%) and lung transplantation (0.33%). Over up to 24 months of follow-up, the pulmonary function remained largely stable. The median annual decline in forced vital capacity (FVC) during the first year of pirfenidone therapy was -20 ml (-200-100) and during the second year was -120 ml (-340-30). Over a study period, 33 patients (10.75%) died. CONCLUSIONS The PolExPIR study is a source of longitudinal RWD on pirfenidone therapy in the Polish cohort of patients with IPF supporting its long-term acceptable safety and efficacy profiles and reinforce findings from the previous randomised clinical trials and observational studies.
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Affiliation(s)
- Sebastian Majewski
- Department of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland.
| | - Adam J Białas
- Department of Pathobiology of Respiratory Diseases, Medical University of Lodz, Lodz, Poland
| | - Małgorzata Buchczyk
- Department of Lung Diseases and Tuberculosis, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Paweł Gomółka
- Department of Pulmonology, Jagiellonian University Medical College, Cracow, Poland
| | - Katarzyna Górska
- Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, Poland
| | - Hanna Jagielska-Len
- Clinical Department of Lung Diseases, K. Marcinkowski University Hospital, Zielona Gora, Poland
| | - Agnieszka Jarzemska
- Department of Pneumonology, Oncology and Tuberculosis, Kuyavian and Pomeranian Pulmonology Centre, Bydgoszcz, Poland
| | - Ewa Jassem
- Department of Allergology and Pneumonology, Medical University of Gdansk, Gdansk, Poland
| | - Dariusz Jastrzębski
- Department of Lung Diseases and Tuberculosis, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Aleksander Kania
- Department of Pulmonology, Jagiellonian University Medical College, Cracow, Poland
| | - Marek Koprowski
- Department of Civilization Diseases and Lung Diseases, John Paul II Specialist Hospital, Cracow, Poland
| | - Rafał Krenke
- Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, Poland
| | - Jan Kuś
- 1st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - Katarzyna Lewandowska
- 1st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - Magdalena M Martusewicz-Boros
- 3rd Lung Diseases and Oncology Department, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - Kazimierz Roszkowski-Śliż
- 3rd Lung Diseases and Oncology Department, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - Alicja Siemińska
- Department of Allergology and Pneumonology, Medical University of Gdansk, Gdansk, Poland
| | - Krzysztof Sładek
- Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, Poland
| | - Małgorzata Sobiecka
- 1st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - Karolina Szewczyk
- Department of Pathobiology of Respiratory Diseases, Medical University of Lodz, Lodz, Poland
| | - Małgorzata Tomczak
- Department of Pulmonology, E.J. Zeyland Wielkopolska Center of Pulmonology and Thoracic Surgery, Poznan, Poland
| | - Witold Tomkowski
- 1st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - Elżbieta Wiatr
- 3rd Lung Diseases and Oncology Department, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - Dariusz Ziora
- Department of Lung Diseases and Tuberculosis, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Beata Żołnowska
- 1st Department of Lung Diseases, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
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Real-life comparison of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis: A 24-month assessment. Respir Med 2019; 159:105803. [PMID: 31670147 DOI: 10.1016/j.rmed.2019.105803] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/28/2019] [Accepted: 10/17/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Real-life data on the use of pirfenidone and nintedanib to treat patients with idiopathic pulmonary fibrosis (IPF) are still scarce. METHODS We compared the efficacy of either pirfenidone (n = 78) or nintedanib (n = 28) delivered over a 24-month period in patients with IPF, followed at two regional clinic centers in Italy, with a group of patients who refused the treatment (n = 36), and who were considered to be controls. All patients completed regular visits at 1- to 3-month intervals, where primary [forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)] and secondary outcomes (side effects, treatment compliance, and mortality) were recorded. RESULTS Over time, the decline in FVC and DLCO was significantly higher (p = 0.0053 and p = 0.037, respectively) in controls when compared with the combined treated group, with no significant difference between the two treated groups. Compared to patients with less advanced disease (GAP (Gender, Age, Physiology) stage I), those in GAP stages II and III showed a significantly higher decline in both FVC and DLCO irrespective of the drug taken. Side effects were similarly reported in patients receiving pirfenidone and nintedanib (5% and 7%, respectively), whereas mortality did not differ among the three groups. CONCLUSION This real-life study demonstrated that both pirfenidone and nintedanib were equally effective in reducing the decline of FVC and DLCO versus non-treated patients after 24 months of treatment; however, patients with more advanced disease were likely to show a more rapid decline in respiratory function.
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15
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Mason W, McLaughlin S, Dedopoulos S, Mahoney E, Meadows T, Stauffer JL, Lancaster LH. Real-World Comprehensive Disease Management of Patients With Idiopathic Pulmonary Fibrosis. CURRENT RESPIRATORY MEDICINE REVIEWS 2019. [DOI: 10.2174/1573398x15666190212155051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Idiopathic pulmonary fibrosis (IPF) is a debilitating, progressive, and fatal fibrotic lung disease with a poor prognosis. Antifibrotic therapy slows but does not halt disease progression. Patient education and management needs change during disease progression. Management is complicated by comorbidities, adverse events associated with antifibrotic therapy, and difficulties with long-term oxygen therapy and pulmonary rehabilitation. Treating IPF requires coordination between physicians and nurses in community and interstitial lung disease center settings. This review provides guidance for the healthcare professional who manages the essential aspects of care in IPF from diagnosis, through disease progression, and to the end of life.
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Affiliation(s)
- Wendi Mason
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, TN, United States
| | - Sally McLaughlin
- University of California, San Francisco, California, CA, United States
| | | | - Erin Mahoney
- Loyola University Medical Center, Maywood, Illinois, IL, United States
| | - Tonja Meadows
- University of Alabama at Birmingham, Birmingham, Alabama, AL, United States
| | - John L. Stauffer
- Genentech, Inc., South San Francisco, California, CL, United States
| | - Lisa H. Lancaster
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, TN, United States
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16
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Vancheri C, Sebastiani A, Tomassetti S, Pesci A, Rogliani P, Tavanti L, Luppi F, Harari S, Rottoli P, Ghirardini A, Kirchgaessler KU, Albera C. Pirfenidone in real life: A retrospective observational multicentre study in Italian patients with idiopathic pulmonary fibrosis. Respir Med 2019; 156:78-84. [PMID: 31445389 DOI: 10.1016/j.rmed.2019.08.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Revised: 07/08/2019] [Accepted: 08/12/2019] [Indexed: 10/26/2022]
Abstract
RATIONALE Real-world data on pirfenidone treatment of patients with idiopathic pulmonary fibrosis (IPF) are limited. This study assessed the effectiveness of pirfenidone in a large real-life Italian IPF cohort. METHODS IRENE was an observational, retrospective study of patients with IPF treated with pirfenidone in routine clinical practice (18 centres). At Month 6, a mandatory re-evaluation of forced vital capacity (FVC) decline (absolute change < 10%) was required to continue pirfenidone. The primary effectiveness outcomes were absolute change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12. Safety was described by adverse event (AE) occurrence. Prespecified subgroups included sex, age, presence/absence of emphysema, usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and baseline lung function. RESULTS The study included 379 patients (mean age, 67.6 years; 78.1% male). Mean change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12 were -81.8 mL (SD, 419.6 mL; P = 0.002) and 16.0% (95% CI, 12.2-20.9%), respectively. Disease progression was similar across prespecified subgroups, including patients with definite vs possible UIP. Overall, 211 AEs occurred in 149 patients (39.3%), with serious AEs in 31 patients (8.2%) and 9 discontinuations due to AEs. Skin and gastrointestinal AEs were most frequent. Fifteen patients (4.0%) died. CONCLUSIONS The decline in FVC and the safety profile observed in this real-world IPF cohort were consistent with the findings of the Phase III pirfenidone trials.
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Affiliation(s)
| | | | - Sara Tomassetti
- Department of Diseases of the Thorax, Ospedale GB Morgagni, Forlì, Italy
| | | | - Paola Rogliani
- Respiratory Unit, University of Rome, Tor Vergata, Rome, Italy
| | | | - Fabrizio Luppi
- University Hospital Policlinico di Modena, Modena, Italy
| | - Sergio Harari
- Ospedale San Giuseppe, MultiMedica IRCCS, Milan, Italy
| | - Paola Rottoli
- Respiratory Diseases Unit, AOUS-University of Siena, Siena, Italy
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17
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Sakayori M, Terada J, Abe M, Hirasawa Y, Suzuki K, Yoshioka K, Tsushima K, Tatsumi K. Differences in tolerability of pirfenidone between elderly and younger patients with idiopathic pulmonary fibrosis. Drug Des Devel Ther 2019; 13:2295-2303. [PMID: 31371923 PMCID: PMC6630358 DOI: 10.2147/dddt.s208733] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 06/14/2019] [Indexed: 01/28/2023] Open
Abstract
PURPOSE Although pirfenidone (PFD) is a key drug for the treatment of idiopathic pulmonary fibrosis (IPF), differences in tolerability between elderly and young patients remain unclear. This study aimed to investigate age-related differences in adverse drug reactions to PFD and to evaluate whether patient age influences the safety and tolerability of PFD in clinical practice. PATIENTS AND METHOD One hundred fifty-four patients with IPF were treated with PFD in our institution between May 2009 and April 2017; these patients were classified into 2 groups on the basis of age: ≥75 years of age (elderly patients) and <75 years of age (younger patients). In each group, the clinical course, laboratory data, radiographic findings, adverse events, and tolerability of PFD at 6 months and 1 year after administration were retrospectively analyzed. RESULTS Among the 120 patients examined in this study, 31 patients (26%) were ≥75 years of age. The continuation rate of PFD at 1 year in the elderly patient group was significantly lower (n=11 [35%] vs 57 [64%], p=0.007) than in the younger patient group. Regarding adverse drug reactions to PFD, the incidence of gastrointestinal disorders including anorexia (n=24 [77%] vs 40 [45%], p=0.002) and the discontinuation caused by gastrointestinal disorders (n=11 [35%] vs 13 [15%], p=0.019) were significantly higher in elderly patients than those in younger patients. However, with the exception of gastrointestinal disorders, other adverse drug reactions did not significantly differ between elderly and younger patients. CONCLUSIONS Compared with younger patients, elderly patients with IPF had a higher incidence of gastrointestinal disorders, along with an increased discontinuation rate of PFD. More careful management of gastrointestinal disorders may be required to ensure continuation of PFD in elderly patients.
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Affiliation(s)
- Masashi Sakayori
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Jiro Terada
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Mitsuhiro Abe
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Yasutaka Hirasawa
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Kenichi Suzuki
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Keiichiro Yoshioka
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Kenji Tsushima
- Department of Pulmonary Medicine, International University of Health and Welfare, School of Medicine, Chiba286-8686, Japan
| | - Koichiro Tatsumi
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
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Moran-Mendoza O, Colman R, Kalluri M, Cabalteja C, Harle I. A comprehensive and practical approach to the management of idiopathic pulmonary fibrosis. Expert Rev Respir Med 2019; 13:601-614. [PMID: 31177864 DOI: 10.1080/17476348.2019.1627204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Introduction: Idiopathic pulmonary fibrosis (IPF) is a debilitating, progressive, and fatal fibrotic pulmonary disease with a prognosis comparable to that of lung cancer. IPF management is a complex process that involves pharmacological and nonpharmacological interventions, extensive patient education, and addressing patient needs that change through the course of the illness. Areas covered: This review summarizes the key aspects of a multifaceted, multidisciplinary, individualized approach to IPF care that incorporates available treatment options, strategies to improve compliance with antifibrotic therapies, pulmonary rehabilitation, and the integration of palliative care for symptom management. Aspects of care discussed include the use of antifibrotic therapy and nonpharmacological treatments, targeted education and psychosocial support, evaluation and management of comorbidities, and early integration of palliative care. Expert opinion: By incorporating this comprehensive approach to disease management, physicians can address most aspects of care for a patient with IPF to optimize survival and quality of life.
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Affiliation(s)
- Onofre Moran-Mendoza
- a Division of Respiratory Medicine, Department of Medicine , Queen's University , Kingston , ON , Canada
| | - Rebecca Colman
- b Division of Respirology, Department of Medicine , University Health Network , Toronto , ON , Canada
| | - Meena Kalluri
- c Division of Pulmonary Medicine, Department of Medicine , University of Alberta , Edmonton , AB , Canada
| | | | - Ingrid Harle
- e Division of Palliative Medicine, Department of Medicine and Department of Oncology , Queen's University , Kingston , ON , Canada
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The Effectiveness, Safety, and Tolerability of Pirfenidone in Idiopathic Pulmonary Fibrosis: A Retrospective Study. Adv Ther 2019; 36:1126-1131. [PMID: 30900199 DOI: 10.1007/s12325-019-00928-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Indexed: 10/27/2022]
Abstract
INTRODUCTION In this study we aimed to investigate the effectiveness and safety profile of pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF) in a real-life setting. METHODS Clinical records of patients diagnosed with mild-to-moderate IPF and receiving pirfenidone treatment across three centers in Turkey between January and September 2017 were retrospectively collected. Pulmonary function measurements, including percentage of forced vital capacity (FVC%) and percentage of diffusion capacity (DLCO%) were analyzed in patients who received pirfenidone treatment for at least 6 months. Decline in lung function, defined as an absolute decline of at least 10% in FVC from baseline, or death at 6 months was also analyzed. Safety data were included for all follow-up visits. RESULTS In the pooled cohort (n = 60), patients were mostly men (73.4%) and current or former smokers (61.7%). Average baseline FVC% and DLCO% were 68.4% and 48.7%, respectively. Forty-seven patients (78.3%) had a high-resolution computed tomography scan with a definite interstitial pneumonia (UIP) pattern, and 18 patients (30%) had a surgically proven UIP pattern. Forty-six (76.7%) patients with IPF remained stable and 14 (23.3%) patients had progressed according to decline in FVC of at least 10% during the therapy course. After 6 months of therapy, cough decreased in 58.3% of patients. At least one side effect due to therapy was encountered in 33 (55.0%) IPF patients. Dyspepsia (36.4%), nausea (27.3%), and rash/photosensitivity (24.2%) were the most frequent side effects in our cohort. Sixteen patients (26.7%) needed dose adjustment, one patient (1.7%) discontinued therapy, and one patient (1.7%) died in the study period. CONCLUSIONS This study shows that pirfenidone seems to be an effective treatment for IPF and also had tolerable and relatively acceptable side effects. FUNDING Roche.
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20
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van Cleemput J, Sonaglioni A, Wuyts WA, Bengus M, Stauffer JL, Harari S. Idiopathic Pulmonary Fibrosis for Cardiologists: Differential Diagnosis, Cardiovascular Comorbidities, and Patient Management. Adv Ther 2019; 36:298-317. [PMID: 30554332 PMCID: PMC6824347 DOI: 10.1007/s12325-018-0857-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Indexed: 02/06/2023]
Abstract
The presence of rare comorbidities in patients with cardiovascular disease (CVD) presents a diagnostic challenge to cardiologists. In evaluating these patients, cardiologists are faced with a unique opportunity to shorten diagnosis times and direct patients towards correct treatment pathways. Idiopathic pulmonary fibrosis (IPF), a type of interstitial lung disease (ILD), is an example of a rare disease where patients frequently demonstrate comorbid CVD. Both CVD and IPF most commonly affect a similar patient demographic: men over the age of 60 years with a history of smoking. Moreover, IPF and heart failure (HF) share a number of symptoms. As a result, patients with IPF can be misdiagnosed with HF and vice versa. This article aims to increase awareness of IPF among cardiologists, providing an overview for cardiologists on the differential diagnosis of IPF from HF, and describing the signs and symptoms that would warrant referral to a pulmonologist with expertise in ILD. Once patients with IPF have received a diagnosis, cardiologists can have an important role in managing patients who are candidates for a lung transplant or those who develop pulmonary hypertension (PH). Group 3 PH is one of the most common cardiovascular complications diagnosed in patients with IPF, its prevalence varying between reports but most often cited as between 30% and 50%. This review summarizes the current knowledge on Group 3 PH in IPF, discusses data from clinical trials assessing treatments for Group 1 PH in patients with IPF, and highlights that treatment guidelines recommend against these therapies in IPF. Finally, this article provides the cardiologist with an overview on the use of the two approved treatments for IPF, the antifibrotics pirfenidone and nintedanib, in patients with IPF and CVD comorbidities. Conversely, the impact of treatments for CVD comorbidities on patients with IPF is also discussed.Funding: F. Hoffmann-La Roche, Ltd.Plain Language Summary: Plain language summary available for this article.
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Affiliation(s)
| | - Andrea Sonaglioni
- U.O. di Cardiologia, Ospedale San Giuseppe - MultiMedica IRCCS, Milan, Italy
| | - Wim A Wuyts
- Department of Respiratory Medicine, Unit for Interstitial Lung Diseases, University Hospitals Leuven, Leuven, Belgium
| | | | | | - Sergio Harari
- U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria - Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe - MultiMedica IRCCS, Milan, Italy
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21
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Zurkova M, Kriegova E, Kolek V, Lostakova V, Sterclova M, Bartos V, Doubkova M, Binkova I, Svoboda M, Strenkova J, Janotova M, Plackova M, Lacina L, Rihak V, Petrik F, Lisa P, Bittenglova R, Tyl R, Ondrejka G, Suldova H, Lnenicka J, Psikalova J, Snizek T, Homolka J, Kralova R, Kervitzer J, Vasakova M. Effect of pirfenidone on lung function decline and survival: 5-yr experience from a real-life IPF cohort from the Czech EMPIRE registry. Respir Res 2019; 20:16. [PMID: 30665416 PMCID: PMC6341650 DOI: 10.1186/s12931-019-0977-2] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 01/06/2019] [Indexed: 01/03/2023] Open
Abstract
Introduction Pirfenidone, an antifibrotic drug, slows-down the disease progression in idiopathic pulmonary fibrosis (IPF) over 12 months, however limited data on the decline of lung function and overall survival (OS) in real-world cohorts on longer follow-up exists. Patients/methods Of the enrolled Czech IPF patients (n = 841) from an EMPIRE registry, 383 (45.5%) received pirfenidone, 218 (25.9%) no-antifibrotic treatment and 240 (28.5%) were excluded (missing data, nintedanib treatment). The 2- and 5-yrs OS and forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO) were investigated at treatment initiation and 6, 12, 18 and 24 months’ follow-up. Results During a 2-yr follow-up, less than a quarter of the patients progressed on pirfenidone as assessed by the decline of ≥10% FVC (17.0%) and ≥ 15% DLCO (14.3%). On pirfenidone, the DLCO (≥10%) declines at 6, 12, 18 and 24 months’ and DLCO (≥15%) declines at 6, 18 and 24 months’ follow-up were associated with increased mortality. The DLCO decline showed higher predictive value for mortality than FVC decline. In patients with no-antifibrotics, FVC and DLCO declines were not predictive for mortality. Pirfenidone increased 5-yrs OS over no-antifibrotic treatment (55.9% vs 31.5% alive, P = 0.002). Conclusion Our study observed the 2-yrs sustained effect of pirfenidone on the decline of lung function and survival in the real-world patient’s IPF cohort. DLCO decline of ≥10% shows a potential as a mortality predictor in IPF patients on pirfenidone, and should be routinely evaluated during follow-up examinations.
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Affiliation(s)
- Monika Zurkova
- Department of Pulmonary Diseases and Tuberculosis, Faculty of Medicine and Dentistry, Palacky University in Olomouc, University Hospital Olomouc, Olomouc, Czech Republic
| | - Eva Kriegova
- Department of Immunology, Faculty of Medicine and Dentistry, University Hospital Olomouc, Palacky University in Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic.
| | - Vitezslav Kolek
- Department of Pulmonary Diseases and Tuberculosis, Faculty of Medicine and Dentistry, Palacky University in Olomouc, University Hospital Olomouc, Olomouc, Czech Republic
| | - Vladimira Lostakova
- Department of Pulmonary Diseases and Tuberculosis, Faculty of Medicine and Dentistry, Palacky University in Olomouc, University Hospital Olomouc, Olomouc, Czech Republic
| | - Martina Sterclova
- Department of Respiratory Medicine, 1st Faculty of Medicine Charles University in Prague, Thomayer Hospital, Prague, Czech Republic
| | - Vladimir Bartos
- Department of Pulmonary Medicine, Faculty of Medicine in Hradec Kralove at Charles University in Prague, University Hospital Hradec Kralove, Prague, Czech Republic
| | - Martina Doubkova
- Department of Pulmonary Diseases and Tuberculosis, Faculty of Medicine at Masaryk University, University Hospital Brno, Brno, Czech Republic
| | - Ilona Binkova
- Department of Pulmonary Diseases and Tuberculosis, Faculty of Medicine at Masaryk University, University Hospital Brno, Brno, Czech Republic
| | - Michal Svoboda
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Jana Strenkova
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Marketa Janotova
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Martina Plackova
- Department of Pulmonary Diseases and Tuberculosis, Faculty of Medicine at University of Ostrava, University Hospital Ostrava, Ostrava, Czech Republic
| | - Ladislav Lacina
- Department of Pulmonary Medicine and Thoracic Surgery, Hospital Na Bulovce, Prague, Czech Republic
| | - Vladimir Rihak
- Department of Pulmonary Medicine, Tomas Bata Regional Hospital, Zlin, Czech Republic
| | - Frantisek Petrik
- Department of Pulmonary Medicine, 2nd Faculty of Medicine at Charles University in Prague, University Hospital in Motol, Prague, Czech Republic
| | - Pavlina Lisa
- Department of Pulmonary Medicine, 2nd Faculty of Medicine at Charles University in Prague, University Hospital in Motol, Prague, Czech Republic
| | - Radka Bittenglova
- Department of Pulmonary Medicine, University Hospital Plzen, Pilsen, Czech Republic
| | - Richard Tyl
- Department of Pulmonary Diseases and Tuberculosis, Faculty of Medicine at University of Ostrava, University Hospital Ostrava, Ostrava, Czech Republic
| | - Gustav Ondrejka
- Department of Pulmonary Medicine, Hospital Novy Jicin, Novy Jicin, Czech Republic
| | - Hana Suldova
- Department of Pulmonary Medicine, Hospital Ceske Budejovice, Ceske Budejovice, Czech Republic
| | - Jaroslav Lnenicka
- Department of Pulmonary Diseases and Tuberculosis, Regional Medical Association, JSC - Masaryk Hospital in Usti nad Labem, Usti nad Labem, Czech Republic
| | - Jana Psikalova
- Department of Pulmonary Medicine and Allergology, Hospital Kromeriz, Kromeriz, Czech Republic
| | - Tomas Snizek
- Department of Pulmonary Medicine, Hospital Jihlava, Jihlava, Czech Republic
| | - Jiri Homolka
- Department of Respiratory Medicine, 1st Faculty of Medicine Charles University in Prague, Thomayer Hospital, Prague, Czech Republic
| | - Renata Kralova
- Department of Pulmonary Medicine, Regional Hospital Pardubice, Pardubice, Czech Republic
| | - Jan Kervitzer
- Department of Pulmonary Medicine, Hospital Znojmo, Znojmo, Czech Republic
| | - Martina Vasakova
- Department of Respiratory Medicine, 1st Faculty of Medicine Charles University in Prague, Thomayer Hospital, Prague, Czech Republic
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22
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Kwapiszewska G, Gungl A, Wilhelm J, Marsh LM, Thekkekara Puthenparampil H, Sinn K, Didiasova M, Klepetko W, Kosanovic D, Schermuly RT, Wujak L, Weiss B, Schaefer L, Schneider M, Kreuter M, Olschewski A, Seeger W, Olschewski H, Wygrecka M. Transcriptome profiling reveals the complexity of pirfenidone effects in idiopathic pulmonary fibrosis. Eur Respir J 2018; 52:13993003.00564-2018. [DOI: 10.1183/13993003.00564-2018] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 08/03/2018] [Indexed: 11/05/2022]
Abstract
Despite the beneficial effects of pirfenidone in treating idiopathic pulmonary fibrosis (IPF), it remains unclear if lung fibroblasts (FB) are the main therapeutic target.To resolve this question, we employed a comparative transcriptomic approach and analysed lung homogenates (LH) and FB derived from IPF patients treated with or without pirfenidone.In FB, pirfenidone therapy predominantly affected growth and cell division pathways, indicating a major cellular metabolic shift. In LH samples, pirfenidone treatment was mostly associated with inflammation-related processes. In FB and LH, regulated genes were over-represented in the Gene Ontology node “extracellular matrix”. We identified lower expression of cell migration-inducing and hyaluronan-binding protein (CEMIP) in both LH and FB from pirfenidone-treated IPF patients. Plasma levels of CEMIP were elevated in IPF patients compared to healthy controls and decreased after 7 months of pirfenidone treatment. CEMIP expression in FB was downregulated in a glioma-associated oncogene homologue-dependent manner and CEMIP silencing in IPF FB reduced collagen production and attenuated cell proliferation and migration.Cumulatively, our approach indicates that pirfenidone exerts beneficial effects via its action on multiple pathways in both FB and other pulmonary cells, through its ability to control extracellular matrix architecture and inflammatory reactions.
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Vartiainen V, Raula J, Bimbo LM, Viinamäki J, Backman JT, Ugur N, Kauppinen E, Sutinen E, Joensuu E, Koli K, Myllärniemi M. Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice. Int J Pharm 2018; 544:121-128. [PMID: 29655797 DOI: 10.1016/j.ijpharm.2018.04.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 04/09/2018] [Accepted: 04/10/2018] [Indexed: 11/17/2022]
Abstract
The aim of this work was to study the antifibrotic effect of pulmonary administration of tilorone to lung fibrosis. L-leucine coated tilorone particles were prepared and their aerosolization properties were analyzed using two dry powder inhalers (Easyhaler and Twister). In addition, the biological activity and cell monolayer permeation was tested. The antifibrotic effect of tilorone delivered by oropharyngeal aspiration was studied in vivo using a silica-induced model of pulmonary fibrosis in mice in a preventive setting. When delivered from the Easyhaler in an inhalation simulator, the emitted dose and fine particle fraction were independent from the pressure applied and showed dose repeatability. However, with Twister the aerosolization was pressure-dependent indicating poor compatibility between the device and the formulation. The formulation showed more consistent permeation through a differentiated Calu-3 cell monolayer compared to pristine tilorone. Tilorone decreased the histological fibrosis score in vivo in systemic and local administration, but only systemic administration decreased the mRNA expression of type I collagen. The difference was hypothesized to result from 40-fold higher drug concentration in tissue samples in the systemic administration group. These results show that tilorone can be formulated as inhalable dry powder and has potential as an oral and inhalable antifibrotic drug.
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Affiliation(s)
- Ville Vartiainen
- Department of Clinical Medicine, Division of Pulmonary Medicine, University of Helsinki, Finland; Research Programs Unit, Translational Cancer Biology, University of Helsinki, Finland.
| | - Janne Raula
- Department of Applied Physics, Aalto University School of Science, Finland
| | - Luis M Bimbo
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, United Kingdom; Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland
| | - Jenni Viinamäki
- Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Finland
| | - Janne T Backman
- Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Finland
| | - Nurcin Ugur
- Department of Applied Physics, Aalto University School of Science, Finland
| | - Esko Kauppinen
- Department of Applied Physics, Aalto University School of Science, Finland
| | - Eva Sutinen
- Department of Clinical Medicine, Division of Pulmonary Medicine, University of Helsinki, Finland
| | - Emmi Joensuu
- Research Programs Unit, Translational Cancer Biology, University of Helsinki, Finland
| | - Katri Koli
- Research Programs Unit, Translational Cancer Biology, University of Helsinki, Finland
| | - Marjukka Myllärniemi
- University of Helsinki and Helsinki University Hospital, Heart and Lung Center and HUH Diagnostics, Pulmonary Medicine, Finland
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24
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Gotfried MH, Girod CE, Antin-Ozerkis D, Burgess T, Strombom I, Stauffer JL, Kirchgaessler KU, Padilla ML. An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002). Pulm Ther 2018; 4:59-71. [PMID: 32026243 PMCID: PMC6967037 DOI: 10.1007/s41030-018-0053-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Indexed: 11/26/2022] Open
Abstract
INTRODUCTION PIPF-002 was a phase 2, multicenter, open-label study of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) or other types of pulmonary fibrosis (PF). PIPF-002 terminated after pirfenidone became commercially available in the United States. The goal of PIPF-002 was to characterize the long-term safety of pirfenidone in these patients. METHODS Between August 2003 and September 2006, 83 patients (IPF: 81, PF: 2) enrolled. Patients received pirfenidone in three divided doses daily, with the maintenance dose and schedule determined by enrollment group assignment. Treatment continued until patient withdrawal or study termination (2015). Treatment-emergent adverse events (TEAEs) were assessed by descriptive statistics. RESULTS At baseline, median age was 70 years, mean percent predicted forced vital capacity was 67.7%, 33.7% of patients had cardiac disorders, 51.8% had gastroesophageal reflux disease, and 63.9% were receiving concomitant prednisone. Median pirfenidone dose and exposure duration were 2400 mg/day and 3.0 years, respectively. Cumulative total exposure was 279.7 patient-exposure years (PEY). Most patients (98.8%) reported ≥ 1 TEAE, with an overall incidence rate of 460.5 per 100 PEY. The most frequent TEAEs (incidence rate per 100 PEY) were nausea (23.6), IPF progression (16.1), fatigue (11.8), dyspnea (11.4), upper respiratory tract infection (11.4), and cough (10.7). Serious TEAEs were reported in 49 patients; the most frequent serious TEAEs were IPF progression and pneumonia. The most common reason for discontinuation was TEAEs (35 patients; 12.5 patients per 100 PEY), most frequently IPF progression and nausea. Overall, 21 patients died (7.5 per 100 PEY); 16 deaths were IPF-related. CONCLUSIONS Long-term safety and tolerability of pirfenidone findings in this study were consistent with the known safety profile of pirfenidone; no new safety signals were identified. These data support the continued use of pirfenidone in patients with IPF. FUNDING F. Hoffmann-La Roche Ltd./Genentech, Inc. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT00080223. Plain language summary available for this article.
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Affiliation(s)
| | - Carlos E Girod
- The University of Texas Southwestern Medical Center, Dallas, TX, USA
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25
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Harari S, Caminati A, Poletti V, Confalonieri M, Gasparini S, Lacedonia D, Luppi F, Pesci A, Sebastiani A, Spagnolo P, Vancheri C, Balestro E, Bonifazi M, Cerri S, De Giacomi F, Della Porta R, Foschino Barbaro MP, Fui A, Pasquinelli P, Rosso R, Tomassetti S, Specchia C, Rottoli P. A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis. Respiration 2018; 95:433-440. [PMID: 29587263 DOI: 10.1159/000487711] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 02/13/2018] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. OBJECTIVES This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. METHODS All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. RESULTS Forty-one patients with a forced vital capacity (FVC) ≤50% and/or a diffusing capacity of the lung for carbon monoxide (DLCO) ≤35% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute DLCO at the -6-month, T0, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. CONCLUSIONS This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted DLCO but does not have significant impact on FVC or other lung parameters.
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Affiliation(s)
- Sergio Harari
- U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, IRCCS MultiMedica, Milan, Italy
| | - Antonella Caminati
- U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, IRCCS MultiMedica, Milan, Italy
| | - Venerino Poletti
- U.O. di Pneumologia, Dipartimento dell'Apparato Respiratorio e del Torace, Ospedale G.P. Morgagni-L. Pierantoni, Forlì, Italy
| | - Marco Confalonieri
- Department of Pulmonology, University Hospital of Cattinara, Azienda Ospedaliero-Universitaria "Ospedali Riuniti" di Trieste, Trieste, Italy
| | - Stefano Gasparini
- Pulmonology Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Azienda Ospedaliera-Universitaria "Ospedali Riuniti", Ancona, Italy
| | - Donato Lacedonia
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Fabrizio Luppi
- Center for Rare Lung Diseases, University Hospital Policlinico di Modena, Modena, Italy
| | - Alberto Pesci
- Respiratory Unit, Department of Health Science, University of Milano-Bicocca, AO San Gerardo, Monza, Italy
| | - Alfredo Sebastiani
- Department of Respiratory Diseases, S. Camillo-Forlanini Hospital, Rome, Italy
| | - Paolo Spagnolo
- Section of Respiratory Disease, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy
| | - Carlo Vancheri
- Regional Referral Centre for Rare Lung Disease, University of Catania, A.O.U. Policlinico-Vittorio Emanuele, Catania, Italy
| | - Elisabetta Balestro
- Section of Respiratory Disease, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy
| | - Martina Bonifazi
- Pulmonology Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Azienda Ospedaliera-Universitaria "Ospedali Riuniti", Ancona, Italy
| | - Stefania Cerri
- Center for Rare Lung Diseases, University Hospital Policlinico di Modena, Modena, Italy
| | - Federica De Giacomi
- Respiratory Unit, Department of Health Science, University of Milano-Bicocca, AO San Gerardo, Monza, Italy
| | - Rossana Della Porta
- Department of Pulmonology, University Hospital of Cattinara, Azienda Ospedaliero-Universitaria "Ospedali Riuniti" di Trieste, Trieste, Italy
| | | | - Annalisa Fui
- Respiratory Diseases and Lung Transplant Unit, Department of Internal and Specialist Medicine, AOUS, Siena, Italy
| | | | - Roberta Rosso
- Regional Referral Centre for Rare Lung Disease, University of Catania, A.O.U. Policlinico-Vittorio Emanuele, Catania, Italy
| | - Sara Tomassetti
- U.O. di Pneumologia, Dipartimento dell'Apparato Respiratorio e del Torace, Ospedale G.P. Morgagni-L. Pierantoni, Forlì, Italy
| | - Claudia Specchia
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.,IRCCS MultiMedica, Milan, Italy
| | - Paola Rottoli
- Respiratory Diseases and Lung Transplant Unit, Department of Internal and Specialist Medicine, AOUS, Siena, Italy
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Lancaster LH, de Andrade JA, Zibrak JD, Padilla ML, Albera C, Nathan SD, Wijsenbeek MS, Stauffer JL, Kirchgaessler KU, Costabel U. Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis. Eur Respir Rev 2017; 26:170057. [PMID: 29212837 PMCID: PMC9488585 DOI: 10.1183/16000617.0057-2017] [Citation(s) in RCA: 165] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Accepted: 09/07/2017] [Indexed: 12/31/2022] Open
Abstract
Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequent post hoc analyses have demonstrated that pirfenidone reduces lung function decline, decreases mortality and improves progression-free survival. Long-term extension trials, registries and real-world studies have also shown similar treatment effects with pirfenidone. However, for patients with IPF to obtain the maximum benefits of pirfenidone treatment, the potential adverse events (AEs) associated with pirfenidone need to be managed. This review highlights the well-known and established safety profile of pirfenidone based on randomised controlled clinical trials and real-world data. Key strategies for preventing and managing the most common pirfenidone-related AEs are described, with the goal of maximising adherence to pirfenidone with minimal AEs.
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Affiliation(s)
| | | | | | - Maria L Padilla
- Mount Sinai - National Jewish Health Respiratory Institute, New York, NY, USA
| | | | | | | | | | | | - Ulrich Costabel
- Ruhrlandklinik, University of Duisberg-Essen, Essen, Germany
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27
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Tzouvelekis A, Karampitsakos T, Ntolios P, Tzilas V, Bouros E, Markozannes E, Malliou I, Anagnostopoulos A, Granitsas A, Steiropoulos P, Dimakou K, Chrysikos S, Koulouris N, Bouros D. Longitudinal "Real-World" Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece. Front Med (Lausanne) 2017; 4:213. [PMID: 29238708 PMCID: PMC5712559 DOI: 10.3389/fmed.2017.00213] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 11/13/2017] [Indexed: 12/23/2022] Open
Abstract
Background Pirfenidone is an antifibrotic compound able to slow down disease progression in patients with idiopathic pulmonary fibrosis (IPF). Objective To investigate the safety and efficacy of pirfenidone in patients with IPF in a real-life setting. Methods This was a multicenter, retrospective, real-life, observational study for patients with IPF receiving pirfenidone. Results We identified 92 patients with IPF receiving pirfenidone. Eighty patients (70 males and 10 females, mean age ± SD: 68.1 + 7.5, mean %FVC ± SD = 74.9 ± 17.2, mean %DLCO ± SD = 48.1 ± 16.9) were included in the analysis. Skin-related (25%) and gastrointestinal (17.5%) adverse events were the most common and led to drug discontinuation in 22.5% of cases. The majority (87%) of patients experienced side effects during the first 6 months of treatment. At 36 months, changes in %FVC and %DLCO were -9.25 ± 16.34 and -9.26 ± 15.26, respectively. At 6, 12, and 24 months after treatment initiation (n = 80, 60, and 26), 18, 15, and 5 patients (22.5, 25, and 19.2%) experienced significant (>10%) and 11, 3, and 3 patients (13.8, 5, and 11.5%) experienced marginal (5-10%) %FVC improvement; and 13, 6, and 1 patient (16.2, 10, and 3.9%) experienced marginal (-5 to -10%) and 20, 21, and 8 patients (25, 35, and 30.8%) experienced significant decline (<-10%) in %FVCpred. Median survival was 851 days, and 41 patients died during the study period. Conclusion Pirfenidone demonstrated an acceptable safety and therapeutic profile in patients with IPF on a longitudinal basis. Prospective observational registries are urgently needed to provide a real-world view of outcomes of pirfenidone in clinical practice.
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Affiliation(s)
- Argyrios Tzouvelekis
- First Academic Department of Pneumonology, Hospital for Diseases of the Chest "Sotiria", Medical School, National and Kapodistrian University of Athens, Athens, Greece.,Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece
| | | | - Paschalis Ntolios
- Department of Pneumonology, University Hospital of Alexandroupolis, Democritus University of Thrace, Komotini, Greece
| | - Vasilios Tzilas
- First Academic Department of Pneumonology, Hospital for Diseases of the Chest "Sotiria", Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Bouros
- First Academic Department of Pneumonology, Hospital for Diseases of the Chest "Sotiria", Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Markozannes
- First Academic Department of Pneumonology, Hospital for Diseases of the Chest "Sotiria", Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioanna Malliou
- First Academic Department of Pneumonology, Hospital for Diseases of the Chest "Sotiria", Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Aris Anagnostopoulos
- First Academic Department of Pneumonology, Hospital for Diseases of the Chest "Sotiria", Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Andreas Granitsas
- First Academic Department of Pneumonology, Hospital for Diseases of the Chest "Sotiria", Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Paschalis Steiropoulos
- Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece
| | - Katerina Dimakou
- 5th Respiratory Department, Hospital for Diseases of the Chest "Sotiria", Athens, Greece
| | - Serafeim Chrysikos
- Department of Pneumonology, University Hospital of Alexandroupolis, Democritus University of Thrace, Komotini, Greece
| | - Nikolaos Koulouris
- First Academic Department of Pneumonology, Hospital for Diseases of the Chest "Sotiria", Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Demosthenes Bouros
- First Academic Department of Pneumonology, Hospital for Diseases of the Chest "Sotiria", Medical School, National and Kapodistrian University of Athens, Athens, Greece
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28
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Shaw J, Marshall T, Morris H, Hayton C, Chaudhuri N. Idiopathic pulmonary fibrosis: a holistic approach to disease management in the antifibrotic age. J Thorac Dis 2017; 9:4700-4707. [PMID: 29268540 DOI: 10.21037/jtd.2017.10.111] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Idiopathic pulmonary fibrosis (IPF) is the most common cause of interstitial lung disease (ILD) and carries a worse prognosis than many cancers. Until recently, there were no active treatment options available for patients with IPF, meaning palliation or lung transplantation in selected patients were the only options. The management of IPF has changed dramatically over the last decade with the advent of two antifibrotic agents; pirfenidone and nintedanib. These new agents have been shown to reduce decline in lung function and pirfenidone has been shown to reduce mortality. The changing landscape of IPF diagnosis and management present a number of issues that may be encountered including management of side effects related to antifibrotic therapy. This article aims to give an overview of the holistic approach to the management of patients with IPF, including antifibrotic management, symptom management and the invaluable role of the ILD specialist nurse.
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Affiliation(s)
- Jonathon Shaw
- North West Interstitial Lung Disease Unit, Manchester University Foundation Trust, Wythenshawe, Manchester, UK
| | - Tracey Marshall
- North West Interstitial Lung Disease Unit, Manchester University Foundation Trust, Wythenshawe, Manchester, UK
| | - Helen Morris
- North West Interstitial Lung Disease Unit, Manchester University Foundation Trust, Wythenshawe, Manchester, UK
| | - Conal Hayton
- North West Interstitial Lung Disease Unit, Manchester University Foundation Trust, Wythenshawe, Manchester, UK
| | - Nazia Chaudhuri
- North West Interstitial Lung Disease Unit, Manchester University Foundation Trust, Wythenshawe, Manchester, UK
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Caminati A, Cassandro R, Torre O, Harari S. Severe idiopathic pulmonary fibrosis: what can be done? Eur Respir Rev 2017; 26:170047. [PMID: 28954763 PMCID: PMC9488930 DOI: 10.1183/16000617.0047-2017] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Accepted: 06/21/2017] [Indexed: 12/11/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with mild-to-moderate IPF. This means that early diagnosis is mandatory, because there are no proven effective therapies for severe IPF. This lack of proven therapies may be at least partially due to the fact that severe IPF patients are usually not enrolled in randomised, prospective, multicentre, international trials. Clinical observation experiences and preliminary results of long-term, open-label extensions of clinical trials suggest that both pirfenidone and nintedanib may also slow or decrease progression in patients with severe IPF. However, data are sparse and obtained from a relatively small number of patients. Lung transplantation should be taken into account early and discussed with patients, when indicated. Rehabilitative strategies are important and effective supportive therapies. The needs of patients with severe IPF are similar to those of patients with an advanced neoplastic disease. Palliative care and psychological support play an important role in the relief of symptoms of anxiety and depression. Accordingly, these therapeutic approaches should start early in IPF patients.
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Affiliation(s)
- Antonella Caminati
- U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, MultiMedica IRCCS, Milan, Italy
| | - Roberto Cassandro
- U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, MultiMedica IRCCS, Milan, Italy
| | - Olga Torre
- U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, MultiMedica IRCCS, Milan, Italy
| | - Sergio Harari
- U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, MultiMedica IRCCS, Milan, Italy
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Costabel U, Albera C, Lancaster LH, Lin CY, Hormel P, Hulter HN, Noble PW. An Open-Label Study of the Long-Term Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (RECAP). Respiration 2017; 94:408-415. [PMID: 28898890 DOI: 10.1159/000479976] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 08/01/2017] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND RECAP (NCT00662038) was an open-label extension study in patients with idiopathic pulmonary fibrosis (IPF) who completed either the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) 016 phase 3 trial or the Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY) 004/006 phase 3 trials. OBJECTIVE To obtain long-term safety data for pirfenidone in patients with IPF in RECAP. METHODS Of the 1,334 patients who participated in the phase 3 trials, 1,058 entered RECAP. The final analysis from enrollment (September 2008) to June 2015 is presented. RESULTS Mean (SD) and median (range) pirfenidone exposures in RECAP were 122 (98) weeks and 88 (>0 to 349) weeks, respectively, with a mean daily dose of 2,091.1 mg. Cumulative total exposure was 2,482 patient exposure years (PEY). The treatment-emergent adverse event (TEAE) rate was 701.9 per 100 PEY. The serious TEAE rate was 53.5 per 100 PEY, with the most common serious TEAE being IPF (11.1 per 100 PEY). Of the 231 deaths (9.3 per 100 PEY), the most common cause was IPF (5.4 per 100 PEY). The treatment discontinuation rate due to a TEAE was 17.9 per 100 PEY; discontinuations were due to IPF (7.2 per 100 PEY), pneumonia, respiratory failure, acute respiratory failure, rash (0.5 per 100 PEY each), and nausea (0.4 per 100 PEY). For patients from CAPACITY 004/006 who entered RECAP, the mean change in percent predicted forced vital capacity from RECAP baseline at 180 weeks was -9.6%. Median on-treatment survival from the first pirfenidone dose in RECAP was 77.2 months. CONCLUSIONS RECAP provides long-term follow-up and safety data for pirfenidone that were consistent with the known profile, with no new safety signals observed.
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Affiliation(s)
- Ulrich Costabel
- Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany
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Khazaei A, Sarmasti N, Seyf JY, Rostami Z, Zolfigol MA. QSAR study of the non-peptidic inhibitors of procollagen C-proteinase based on Multiple linear regression, principle component regression, and partial least squares. ARAB J CHEM 2017. [DOI: 10.1016/j.arabjc.2015.02.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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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. Respirology 2017; 22:1171-1178. [DOI: 10.1111/resp.13024] [Citation(s) in RCA: 111] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 11/30/2016] [Accepted: 01/03/2017] [Indexed: 11/27/2022]
Affiliation(s)
- Jonathan A. Galli
- Department of Thoracic Medicine and Surgery; Lewis Katz School of Medicine at Temple University; Philadelphia Pennsylvania USA
| | - Aloknath Pandya
- Department of Thoracic Medicine and Surgery; Lewis Katz School of Medicine at Temple University; Philadelphia Pennsylvania USA
| | - Michelle Vega-Olivo
- Department of Thoracic Medicine and Surgery; Lewis Katz School of Medicine at Temple University; Philadelphia Pennsylvania USA
| | - Chandra Dass
- Department of Thoracic Medicine and Surgery; Lewis Katz School of Medicine at Temple University; Philadelphia Pennsylvania USA
| | - Huaqing Zhao
- Department of Thoracic Medicine and Surgery; Lewis Katz School of Medicine at Temple University; Philadelphia Pennsylvania USA
| | - Gerard J. Criner
- Department of Thoracic Medicine and Surgery; Lewis Katz School of Medicine at Temple University; Philadelphia Pennsylvania USA
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George PM, Wells AU. Pirfenidone for the treatment of idiopathic pulmonary fibrosis. Expert Rev Clin Pharmacol 2017; 10:483-491. [PMID: 28266906 DOI: 10.1080/17512433.2017.1295846] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Idiopathic pulmonary fibrosis (IPF) is a diffuse parenchymal lung disease with no cure. Up until recently, no treatment had been proven to alter its natural history as judged by rate of lung function decline. In 2014 however, the emergence of two novel anti-fibrotic agents, Pirfenidone and Nintedanib revolutionized the management of this condition. Both have demonstrated the ability to deliver a major reduction in the rate of chronic IPF progression. Areas Covered: This review article focuses on Pirfenidone - a pyridone derivative initially designed as an analgesic and anti-pyretic agent. Here we describe the history of the drug from its inception through to exploratory pre-clinical in-vitro and in-vivo studies where its anti-fibrotic potential was identified, and eventually to large multicenter randomized controlled trials. Expert Commentary: This article also summarizes some of the difficulties surrounding clinical end-point selection in IPF trials and addresses some of the challenges facing the IPF community over the coming years.
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Affiliation(s)
- Peter M George
- a Department of Respiratory Medicine, Royal Brompton Hospital , Interstitial Lung Disease Unit , London , SW3 6NP, UK
| | - Athol U Wells
- a Department of Respiratory Medicine, Royal Brompton Hospital , Interstitial Lung Disease Unit , London , SW3 6NP, UK
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Salih GN, Shaker SB, Madsen HD, Bendstrup E. Pirfenidone treatment in idiopathic pulmonary fibrosis: nationwide Danish results. Eur Clin Respir J 2016; 3:32608. [PMID: 27616539 PMCID: PMC5018656 DOI: 10.3402/ecrj.v3.32608] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 08/17/2016] [Indexed: 11/16/2022] Open
Abstract
Background Pirfenidone was approved by the European Medicines Agency and introduced in most European countries in 2011 for treatment of idiopathic pulmonary fibrosis (IPF). Objective To describe the national Danish experiences of pirfenidone treatment for IPF during 30 months with respect to target population, safety, adherence to the treatment and effect analysis in a well-characterised IPF population in a real-life setting. Methods Retrospective data collection from medical records of all patients in Denmark with IPF from 2011 to 2014. Data included baseline demographics, high-resolution computed tomography (HRCT), histopathology, forced vital capacity (FVC) and 6-min walk test (6MWT). Longitudinal data on FVC, walk test, adherence to the treatment and vital status were also collected. Results Pirfenidone treatment was initiated in 113 patients. Mean age was 69.6±8.1 years (±SD), and 71% were male. Definite IPF diagnosis required thoracoscopic lung biopsy in 45 patients (39.8%). The remaining 68 cases had a definite (64 patients) or possible usual interstitial pneumonia (four patients) pattern on HRCT. Patients were followed for 0.1–33.8 months (median 9.4 months). Fifty-one patients (45.2%) needed dose adjustment, 18 (16%) patients discontinued therapy and 13 patients (11.5%) died. The annual mean decline in FVC was 164 ml (SE 33.2). The decline in 6MWT was 18.2 m (SE 11.2). Nausea (44.2%), fatigue (38.9%) and skin reactions (32.7%) were frequent adverse events. Conclusion Patients with IPF treated with pirfenidone experienced tolerable adverse events. Patients were maintained on treatment due to a careful follow-up and dose adjustment programme. The annual decline in physiological parameters and mortality rate was comparable to previous randomised controlled trials.
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Affiliation(s)
- Goran Nadir Salih
- Department of Respiratory Medicine, Gentofte University Hospital, Hellerup, Denmark;
| | - Saher Burhan Shaker
- Department of Respiratory Medicine, Gentofte University Hospital, Hellerup, Denmark
| | - Helle Dall Madsen
- Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark
| | - Elisabeth Bendstrup
- Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
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Real World Experiences: Pirfenidone and Nintedanib are Effective and Well Tolerated Treatments for Idiopathic Pulmonary Fibrosis. J Clin Med 2016; 5:jcm5090078. [PMID: 27598213 PMCID: PMC5039481 DOI: 10.3390/jcm5090078] [Citation(s) in RCA: 136] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Revised: 08/24/2016] [Accepted: 08/30/2016] [Indexed: 11/22/2022] Open
Abstract
Idiopathic Pulmonary Fibrosis (IPF) now has two licensed treatments available. Pirfenidone was the first drug to be licensed and approved for use, followed by nintedanib. We set out our real world experience with these agents in terms of their adverse events profile outside the restrictions of a clinical trial. We have demonstrated in the real world setting, that side effects are common and predominantly gastrointestinal with both therapies. Our study shows that the side effects can be effectively managed in the majority of patients with an acceptable discontinuation rate similar to that seen in the clinical trials. These findings are compelling despite the fact that the patients in our study are older, have severer disease as depicted by baseline lung function and more co-morbidities. Our data provides ongoing evidence of the safety and tolerability of both pirfenidone and nintedanib in patients who would not have met the rigorous criteria to be included in a clinical trial. Both these agents are effective in the management of IPF and slow the progression of this debilitating life limiting condition.
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Fletcher S, Jones MG, Spinks K, Sgalla G, Marshall BG, Limbrey R, Richeldi L. The safety of new drug treatments for idiopathic pulmonary fibrosis. Expert Opin Drug Saf 2016; 15:1483-1489. [DOI: 10.1080/14740338.2016.1218470] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Affiliation(s)
- Sophie Fletcher
- Department of Respiratory Medicine, University Hospital Southampton, Southampton, UK
- Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK
| | - Mark G. Jones
- Department of Respiratory Medicine, University Hospital Southampton, Southampton, UK
- Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK
- Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, UK
| | - Katherine Spinks
- Department of Respiratory Medicine, University Hospital Southampton, Southampton, UK
| | - Giacomo Sgalla
- Department of Respiratory Medicine, University Hospital Southampton, Southampton, UK
- Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK
- Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, UK
| | - Ben G. Marshall
- Department of Respiratory Medicine, University Hospital Southampton, Southampton, UK
- Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK
| | - Rachel Limbrey
- Department of Respiratory Medicine, University Hospital Southampton, Southampton, UK
| | - Luca Richeldi
- Department of Respiratory Medicine, University Hospital Southampton, Southampton, UK
- Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK
- Academic Unit of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, UK
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Greig SL, Lyseng-Williamson KA, Kim ES, Keating GM. Pirfenidone in idiopathic pulmonary fibrosis: a guide to its use in the EU. DRUGS & THERAPY PERSPECTIVES 2016. [DOI: 10.1007/s40267-016-0321-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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38
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Margaritopoulos GA, Vasarmidi E, Antoniou KM. Pirfenidone in the treatment of idiopathic pulmonary fibrosis: an evidence-based review of its place in therapy. CORE EVIDENCE 2016; 11:11-22. [PMID: 27445644 PMCID: PMC4936814 DOI: 10.2147/ce.s76549] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The landscape of idiopathic pulmonary fibrosis (IPF) has changed. The significant progress regarding our knowledge on the pathogenesis of the disease together with the experience achieved after a series of negative trials has led to the development of two drugs for the treatment of IPF. Both pirfenidone and nintedanib can slow significantly the rate of disease progression. They are safe with side effects that can be either prevented by close collaboration between health care professionals and patients or treated successfully when they occur, rarely leading to treatment discontinuation. However, there are still few unanswered questions regarding the application of the beneficial results of pharmaceutical trials in the general population of IPF patients. Long-term “real-life” studies are being undertaken to answer these questions. In this article, we focus on the advances that have led to the development of the antifibrotic agents with particular focus on pirfenidone.
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Affiliation(s)
| | - Eirini Vasarmidi
- Department of Thoracic Medicine and Laboratory of Molecular and Cellular Pneumonology, Interstitial Lung Disease Unit, University Hospital of Heraklion, Heraklion, Greece
| | - Katerina M Antoniou
- Department of Thoracic Medicine and Laboratory of Molecular and Cellular Pneumonology, Interstitial Lung Disease Unit, University Hospital of Heraklion, Heraklion, Greece
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Anderson A, Shifren A, Nathan SD. A safety evaluation of pirfenidone for the treatment of idiopathic pulmonary fibrosis. Expert Opin Drug Saf 2016; 15:975-82. [PMID: 27177012 DOI: 10.1080/14740338.2016.1187129] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Pirfenidone is a novel oral anti-fibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). Since IPF is a chronic and progressive disease most commonly encountered in an older population, therapeutic options should be not only effective, but also free from drug interactions and as safe and tolerable as possible. AREAS COVERED Comprehensive data from randomized controlled trials, meta-analyses, safety studies, and post-marketing data are available to assess the efficacy and safety of pirfenidone in the treatment of IPF. Information on efficacy, adverse events, drug tolerability and discontinuation rates both in clinical trials and real-world clinical experiences are reported. EXPERT OPINION Pirfenidone has an abundance of data supporting its use in mild-to-moderate IPF. Observational evidence suggests a similar efficacy in severe IPF. In clinical trials, observational studies and real-world use, adverse events are frequent, though generally mild and well tolerated, especially with adequate patient education. Preventative strategies, along with timely and appropriate management of adverse events are critical in improving patient compliance, thereby ensuring the benefits of long-term treatment with pirfenidone.
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Affiliation(s)
- Adam Anderson
- a Department of Internal Medicine , Washington University School of Medicine , St. Louis , MO , USA
| | - Adrian Shifren
- a Department of Internal Medicine , Washington University School of Medicine , St. Louis , MO , USA
| | - Steven D Nathan
- b Department of Internal Medicine , Virginia Commonwealth University, Inova Fairfax Hospital , Falls Church , VA , USA
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Borie R, Justet A, Beltramo G, Manali ED, Pradère P, Spagnolo P, Crestani B. Pharmacological management of IPF. Respirology 2016; 21:615-25. [PMID: 27072575 DOI: 10.1111/resp.12778] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 01/17/2016] [Accepted: 01/18/2016] [Indexed: 12/23/2022]
Abstract
Idiopathic pulmonary fibrosis (IPF) is a deadly disease with a median survival of approximately three years in historical cohorts. Despite increased knowledge of disease pathophysiology and selection of more targeted therapy, main clinical trials yielded negative results. However, two agents, pirfenidone and nintedanib, were recently shown to be effective in IPF and received marketing authorization worldwide. Both drugs significantly reduce functional decline and disease progression with an acceptable safety profile. Yet, none of these drugs actually improves or even stabilizes the disease or the symptoms perceived by the patient. Several other treatments and combinations are currently tested, and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF.
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Affiliation(s)
- Raphael Borie
- APHP, Bichat Hospital, Department of Pneumology A, Centre de competence des maladies pulmonaires rares, DHU Fire, Paris, France.,INSERM, Paris, France.,Paris Diderot University, Paris, France
| | - Aurelien Justet
- APHP, Bichat Hospital, Department of Pneumology A, Centre de competence des maladies pulmonaires rares, DHU Fire, Paris, France.,INSERM, Paris, France.,Paris Diderot University, Paris, France
| | - Guillaume Beltramo
- APHP, Bichat Hospital, Department of Pneumology A, Centre de competence des maladies pulmonaires rares, DHU Fire, Paris, France.,INSERM, Paris, France.,Paris Diderot University, Paris, France
| | - Effrosyni D Manali
- 2nd Respiratory Medicine Department, 'Attikon' University Hospital, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Pauline Pradère
- APHP, Bichat Hospital, Department of Pneumology A, Centre de competence des maladies pulmonaires rares, DHU Fire, Paris, France.,INSERM, Paris, France.,Paris Diderot University, Paris, France
| | - Paolo Spagnolo
- Clinica di Malattie dell'Apparato Respiratorio, Università degli Studi di Padova, Padova, Italy
| | - Bruno Crestani
- APHP, Bichat Hospital, Department of Pneumology A, Centre de competence des maladies pulmonaires rares, DHU Fire, Paris, France.,INSERM, Paris, France.,Paris Diderot University, Paris, France
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Trawinska MA, Rupesinghe RD, Hart SP. Patient considerations and drug selection in the treatment of idiopathic pulmonary fibrosis. Ther Clin Risk Manag 2016; 12:563-74. [PMID: 27114711 PMCID: PMC4833375 DOI: 10.2147/tcrm.s81144] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown cause. Approximately 5,000 people are diagnosed with IPF in the UK every year. People with IPF suffer significant morbidity and, without any curative treatment at present, survival rates remain poor with a median survival of 3 years. While treatment remains largely supportive, many drug therapies have been trialed in IPF over the years. Pirfenidone and nintedanib are newly licensed treatments for IPF and the first drugs to have shown convincing evidence of slowing disease progression. In addition to evaluating clinical evidence, we also discuss elements affecting drug choice from the viewpoint of patients and health care professionals. We discuss pharmacological and nonpharmacological aspects of providing best supportive care for patients with IPF. However, few good quality studies exist focusing on controlling symptoms specifically in patients with IPF, and recommendations are often extrapolated from evidence in other chronic diseases. In covering these topics, we hope to provide readers with a comprehensive review of the available evidence pertaining to all aspects of care for patients suffering with IPF.
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Affiliation(s)
- Maria A Trawinska
- Hull and East Yorkshire Hospitals NHS Trust, Cottingham, East Yorkshire, UK
| | | | - Simon P Hart
- Hull and East Yorkshire Hospitals NHS Trust, Cottingham, East Yorkshire, UK
- Hull York Medical School, Academic Respiratory Medicine, Castle Hill Hospital, Cottingham, East Yorkshire, UK
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Zhou Y, Yang J, Sun GY, Liu T, Duan JX, Zhou HF, Lee KS, Hammock BD, Fang X, Jiang JX, Guan CX. Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice. Cell Tissue Res 2016; 363:399-409. [PMID: 26310139 PMCID: PMC4738109 DOI: 10.1007/s00441-015-2262-0] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 07/29/2015] [Indexed: 10/23/2022]
Abstract
Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 (CYP450) epoxygenases, are mainly metabolized by soluble epoxide hydrolase (sEH) to their corresponding diols. EETs but not their diols, have anti-inflammatory properties and inhibition of sEH might provide protective effects against inflammatory fibrosis. We test the effects of a selected sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on bleomycin-induced pulmonary fibrosis (PF) in mice. A mouse model of PF was established by intratracheal injection of bleomycin and TPPU was administered for 21 days after bleomycin injection. We found TPPU treatment improved the body weight loss and survival rate of bleomycin-stimulated mice. Histological examination showed that TPPU treatment alleviated bleomycin-induced inflammation and maintained the alveolar structure of the pulmonary tissues. TPPU also decreased the bleomycin-induced deposition of collagen and the expression of procollagen I mRNA in lung tissues of mice. TPPU decreased the transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β) and IL-6 levels in the serum of bleomycin-stimulated mice. Furthermore, TPPU inhibited the proliferation and collagen synthesis of mouse fibroblasts and partially reversed TGF-β1-induced α-smooth muscle actin expression. Our results indicate that the inhibition of sEH attenuates bleomycin-induced inflammation and collagen deposition and therefore prevents bleomycin-induced PF in a mouse model.
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Affiliation(s)
- Yong Zhou
- Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, People's Republic of China
| | | | - Guo-Ying Sun
- Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, People's Republic of China
| | - Tian Liu
- Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, People's Republic of China
| | - Jia-Xi Duan
- Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, People's Republic of China
| | - Hui-Fang Zhou
- Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, People's Republic of China
| | - Kin Sing Lee
- Department of Entomology and the UC Davis Cancer Center, University of California Davis, Davis, CA 95616, USA
| | - Bruce D Hammock
- Department of Entomology and the UC Davis Cancer Center, University of California Davis, Davis, CA 95616, USA
| | - Xiang Fang
- Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Jian-Xin Jiang
- State Key Laboratory of Trauma, Burns, and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, Sichuan, 400042, People's Republic of China.
| | - Cha-Xiang Guan
- Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, People's Republic of China.
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Practical considerations in the pharmacologic treatment of idiopathic pulmonary fibrosis. Curr Opin Pulm Med 2015; 21:479-89. [DOI: 10.1097/mcp.0000000000000190] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Harari S, Caminati A. Idiopathic pulmonary fibrosis: from clinical trials to real-life experiences. Eur Respir Rev 2015; 24:420-7. [PMID: 26324803 PMCID: PMC9487689 DOI: 10.1183/16000617.0042-2015] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Randomised controlled clinical trials are fundamental in medicine to develop new effective drugs and new therapeutic regimens and are the strength of evidence-based medicine. These studies allow us to avoid the repetition of misleading experiences that have been reported in the past, where drugs or associations were utilised without compelling evidence and ultimately proven to be ineffective. In recent years, randomised clinical trials have been conducted and concluded for many rare diseases, including idiopathic pulmonary fibrosis. However, clinical trials do not always reflect the real-life scenario. Patients selected for clinical trials present fewer comorbidities, they fall between certain age limits, and the severity of their disease is defined; therefore, they do not always reflect the whole of the population affected by a specific disease. These are the reasons why we also need data that mirror real-life experience. The limitations that these kind of studies present are always several and the studies should be interpreted with caution, although they can fill the important gap between efficacy and effectiveness. In this article, we will review the existing clinical data on real-life treatment of idiopathic pulmonary fibrosis. Real-life studies are useful in confirming the experimental data obtained from randomised controlled clinical trialshttp://ow.ly/PYUCC
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Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study. Respir Med 2015; 109:904-13. [DOI: 10.1016/j.rmed.2015.04.010] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2014] [Revised: 04/03/2015] [Accepted: 04/13/2015] [Indexed: 11/24/2022]
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Wijsenbeek MS, Grutters JC, Wuyts WA. Early Experience of Pirfenidone in Daily Clinical Practice in Belgium and The Netherlands: a Retrospective Cohort Analysis. Adv Ther 2015; 32:691-704. [PMID: 26173796 PMCID: PMC4522034 DOI: 10.1007/s12325-015-0225-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Indexed: 10/28/2022]
Abstract
INTRODUCTION This analysis aimed to investigate the effectiveness and safety profile of pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF) in clinical practice. METHODS Clinical records of patients diagnosed with mild-to-moderate IPF (as per European Medicines Agency indication) and receiving pirfenidone treatment across three centers in Belgium and the Netherlands between April 2011 and October 2013 were retrospectively collected from patient notes at 3-month intervals. Pulmonary function measurements, including % predicted forced vital capacity (%FVC) and % predicted diffusing capacity of the lungs for carbon monoxide (%DLCO), were analyzed from 6 months prior to pirfenidone treatment up to 12 months of treatment. Decline in lung function, defined as an absolute ≥10% decline in FVC from baseline or death at 12 months, was also analyzed. Safety data were included for all follow-up visits. RESULTS In the pooled cohort (n = 63), patients were mostly men (84.1%) and current or former smokers (79.4%). Average baseline %FVC and %DLCO were 75.0% and 47.9%, respectively. 69.8% of patients had a high-resolution computed tomography scan with a definite usual interstitial pneumonia pattern, and 46% had a surgical lung biopsy. The mean decline in %FVC for 32 patients with available data was 4.8% from -6 months to baseline (p = 0.002) and 0.8% from baseline to 6 months (p = 0.516). Across these time intervals, a lesser decline in DLCO was similarly observed during therapy. At 12 months, ten patients had an %FVC decline ≥10% or died. Loss of appetite (25.3%) and nausea (11.1%) were the most frequent gastrointestinal side effects. Nausea was the most highly cited reason for discontinuation (7.9%). CONCLUSIONS In this clinical practice cohort, pirfenidone showed effectiveness and safety profiles consistent with those seen in the Phase III clinical study ASCEND (ClinicalTrials.gov #NCT01366209). These results highlight the challenges and benefits associated with pirfenidone treatment in clinical practice.
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Cottin V, Maher T. Long-term clinical and real-world experience with pirfenidone in the treatment of idiopathic pulmonary fibrosis. Eur Respir Rev 2015; 24:58-64. [DOI: 10.1183/09059180.00011514] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible, progressively destructive lung disease that culminates in respiratory failure and death. Randomised controlled trials have demonstrated that treatment of IPF patients with pirfenidone reduces lung function decline, improves progression-free survival and significantly reduces the risk of all-cause mortality at 1 year. Pirfenidone has been shown to have a favourable safety profile and was generally well tolerated over the long term in clinical trials and real-world experience. However, side-effect management is critical to help some patients remain on treatment over the long term. The primary treatment-related adverse events associated with pirfenidone therapy are gastrointestinal upset, rash and photosensitivity. Gastrointestinal events may be mitigated by ensuring that pirfenidone is taken with food, while skin symptoms may be reduced by avoiding sun exposure and frequent use of sunblock. Educating patients about the potential for these adverse events to occur and providing instructions prior to treatment to avoid adverse drug reactions are an important means of ensuring patients may derive the important benefits provided by long-term treatment with pirfenidone.
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Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible fibrotic disease of the lung that has greatly frustrated clinicians for a long time. The prognosis of IPF (median survival 2–5 years following diagnosis) is poorer than that of some cancers and for many years no significant advances were made in its management. However, between 2011 and 2014 a number of pivotal developments were made that have improved the outlook for patients with IPF. Herein, we review this rapidly changing landscape, discussing key events whilst still acknowledging that IPF remains a challenging disease to diagnose and manage. Idiopathic pulmonary fibrosis has become a treatable disease, with two drugs now approved for this indicationhttp://ow.ly/GhCEE
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Duck A, Pigram L, Errhalt P, Ahmed D, Chaudhuri N. IPF Care: a support program for patients with idiopathic pulmonary fibrosis treated with pirfenidone in Europe. Adv Ther 2015; 32:87-107. [PMID: 25691376 PMCID: PMC4349950 DOI: 10.1007/s12325-015-0183-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Indexed: 12/02/2022]
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible fibrotic lung disease that requires long-term treatment. Given the importance of adherence to treatment and management of adverse events (AEs), patients with IPF need long-term, high-quality support in living with their condition, and adhering to therapy so they can derive maximum benefit. The IPF Care Patient Support Program (IPF Care) provides support, education, and empowerment to patients receiving pirfenidone for the treatment of IPF in Europe, through the provision of frequent, patient-managed discussions with specialist IPF nurses. In this review, we describe the structure of IPF Care in the United Kingdom (UK) and Austria, two of the longest-running IPF Care programs to date, and describe the benefits that these programs provide to patients with IPF. Analysis of results demonstrates a low rate of discontinuation from the program, and provides insight into the questions and concerns that patients express, not only with respect to pirfenidone (the only approved treatment for IPF at the time of analysis), but also in relation to other aspects of living with IPF. Pirfenidone dose modifications are common in patients in IPF Care and AEs most commonly occur early in treatment, with the majority of affected patients continuing on a stable maintenance dose. This highlights the value of the advice and support that patients receive in IPF Care regarding management of AEs and staying on treatment. Patient satisfaction was high in a survey of the UK program, with patients reporting high scores regarding ‘feeling in control of their condition’, ‘knowing what to expect from treatment’, and ‘feeling confident about how their disease is managed’. IPF Care in Europe will continue to evolve over time, striving to provide individually tailored support and patient-friendly information to improve treatment outcomes and quality of life for patients living with IPF.
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