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The Annals of Pharmacotherapy Dec 2019Provide information for pharmacists on idiopathic pulmonary fibrosis (IPF) and its treatment. All articles with data from randomized controlled trials of nintedanib or... (Review)
Review
Provide information for pharmacists on idiopathic pulmonary fibrosis (IPF) and its treatment. All articles with data from randomized controlled trials of nintedanib or pirfenidone were reviewed. IPF is a progressive and ultimately fatal interstitial lung disease characterized by decline in lung function and worsening dyspnea. It is uncommon and mainly occurs in individuals aged >60 years, particularly men with a history of smoking. Nintedanib and pirfenidone were approved in the United States for the treatment of IPF in 2014 and received conditional recommendations in the 2015 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association treatment guidelines. These drugs slow the progression of IPF by reducing the rate of decline in lung function. Their adverse event profile is characterized mainly by gastrointestinal events, which can be managed through dose adjustment and symptom management. Management of IPF should also include smoking cessation, vaccinations, and supportive care such as patient education, pulmonary rehabilitation, and the use of supplemental oxygen as well as optimizing the management of comorbidities. This review provides clinical pharmacists with information on the course of IPF, what can be expected of current treatments, and how to help patients manage their drug therapy. IPF is a progressive disease, but treatments are available that can slow the progression of the disease. Clinical pharmacists can play an important role in the care of patients with IPF through patient education, monitoring medication compliance and safety, ensuring drugs for comorbidities are optimized, and preventive strategies such as immunizations.
Topics: Comorbidity; Disease Progression; Female; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Male; Medication Adherence; Middle Aged; Patient Education as Topic; Pharmacists; Pyridones
PubMed: 31280590
DOI: 10.1177/1060028019862497 -
Advances in Therapy Sep 2023In the European Union (EU), the indication for the antifibrotic pirfenidone prior to April 2023 did not include patients with advanced idiopathic pulmonary fibrosis... (Clinical Trial)
Clinical Trial
INTRODUCTION
In the European Union (EU), the indication for the antifibrotic pirfenidone prior to April 2023 did not include patients with advanced idiopathic pulmonary fibrosis (IPF). This analysis compared the efficacy and safety of pirfenidone in advanced IPF versus non-advanced IPF.
METHODS
Data were included from the following studies of pirfenidone: ASCEND (NCT01366209); CAPACITY (004 [NCT00287716] and 006 [NCT00287729]); RECAP (NCT00662038; advanced IPF defined as percent predicted forced vital capacity [%FVC] < 50% and/or percent predicted carbon monoxide diffusing capacity [%DLco] < 35% at baseline); PASSPORT (NCT02699879; advanced IPF defined as baseline %FVC < 50%); and SP-IPF (NCT02951429; patients with advanced IPF [defined as %DLco ≤ 40% at screening] at risk of group 3 pulmonary hypertension).
RESULTS
In the pooled ASCEND/CAPACITY studies, the annual mean rate of FVC decline from baseline to Week 52 was significantly lower for pirfenidone versus placebo in advanced (p = 0.0035) and non-advanced IPF (p = 0.0001). Rate of all-cause mortality over 52 weeks was numerically lower for pirfenidone versus placebo in advanced and non-advanced IPF. In RECAP, the mean annual rate of FVC decline from baseline to Week 180 of pirfenidone treatment was similar in patients with advanced (- 141.5 mL) and non-advanced IPF (- 153.5 mL). In SP-IPF, the mean annual rate of FVC decline and rate of all-cause mortality from baseline to Week 52 in patients treated with placebo + pirfenidone were - 93.0 mL and 20.2%, respectively. No new safety signals were identified, and the safety profile of pirfenidone in patients with advanced IPF was generally consistent with that of non-advanced IPF.
CONCLUSIONS
These results highlight the benefit of pirfenidone treatment in patients with advanced and non-advanced IPF. As such, the indication for pirfenidone in the EU has now been updated to include the treatment of adult patients with advanced IPF.
TRIAL REGISTRATIONS
ASCEND (NCT01366209), CAPACITY 004 (NCT00287716), CAPACITY 006 (NCT00287729), RECAP (NCT00662038), PASSPORT (NCT02699879), and SP-IPF (NCT02951429).
Topics: Adult; Humans; Anti-Inflammatory Agents, Non-Steroidal; Idiopathic Pulmonary Fibrosis; Pyridones; Treatment Outcome; Vital Capacity
PubMed: 37391667
DOI: 10.1007/s12325-023-02565-3 -
Acta Pharmacologica Sinica Apr 2022Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs....
Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs. Pirfenidone has been shown to exert anti-inflammatory and anti-fibrotic properties in the lung. However, whether and how pirfenidone is effective against silicosis remains unknown. Here, we evaluated the efficacy of pirfenidone in the treatment of early and advanced silicosis in an experimental mouse model and explored its potential pharmacological mechanisms. We found that pirfenidone alleviated silica-induced lung dysfunction, secretion of inflammatory cytokines (TNF-α, IL-1β, IL-6) and deposition of fibrotic proteins (collagen I and fibronectin) in both early and advanced silicosis models. Moreover, we observed that both 100 and 200 mg/kg pirfenidone can effectively treat early-stage silicosis, while 400 mg/kg was recommended for advanced silicosis. Mechanistically, antibody array and bioinformatic analysis showed that the pathways related to IL-17 secretion, including JAK-STAT pathway, Th17 differentiation, and IL-17 pathway, might be involved in the treatment of silicosis by pirfenidone. Further in vivo experiments confirmed that pirfenidone reduced the production of IL-17A induced by silica exposure via inhibiting STAT3 phosphorylation. Neutralizing IL-17A by anti-IL-17A antibody improved lung function and reduced pulmonary inflammation and fibrosis in silicosis animals. Collectively, our study has demonstrated that pirfenidone effectively ameliorated silica-induced lung dysfunction, pulmonary inflammation and fibrosis in mouse models by inhibiting the secretion of IL-17A.
Topics: Animals; Disease Models, Animal; Fibrosis; Inflammation; Interleukin-17; Janus Kinases; Lung; Mice; Mice, Inbred C57BL; Pneumonia; Pyridones; STAT Transcription Factors; Signal Transduction; Silicon Dioxide
PubMed: 34316030
DOI: 10.1038/s41401-021-00706-4 -
Respiratory Medicine Oct 2017Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease. After many drugs failed in clinical trials, improvements in the... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease. After many drugs failed in clinical trials, improvements in the understanding of the pathogenesis of IPF led to the approval of two drugs that slow the progression of the disease. However, the prognosis for patients with IPF remains poor and the search continues for drugs that inhibit the pathogenic pathways active in IPF to reduce or even halt the progression of the disease. In this article, we review the mechanisms of action of the two approved therapies for IPF (nintedanib and pirfenidone) and of the investigational compounds that are in Phase II trials and discuss the potential for combination therapy in the treatment of IPF.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Disease Progression; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Molecular Targeted Therapy; Pyridones; Receptors, Fibroblast Growth Factor; Receptors, Platelet-Derived Growth Factor; Receptors, Vascular Endothelial Growth Factor
PubMed: 28947042
DOI: 10.1016/j.rmed.2017.07.062 -
Clinical Medicine (London, England) Feb 2016Idiopathic pulmonary fibrosis (IPF) is characterised by progressive accumulation of scar tissue in the lung and is associated with a median life expectancy of 2-4 years.... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is characterised by progressive accumulation of scar tissue in the lung and is associated with a median life expectancy of 2-4 years. Until recently, treatment options were limited, focusing on ineffective anti-inflammatory therapy, palliation, transplant or trial recruitment. Significant recent advances in the field have led to two novel anti-fibrotic agents, pirfenidone and nintedanib, which have been shown to significantly slow disease progression in IPF. This article outlines the approach to management of IPF, the role of specialist centres and specialist interstitial lung disease multidisciplinary review, and explores both the trial evidence and practical considerations in the use of these anti-fibrotic agents.
Topics: Anti-Inflammatory Agents; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pyridones
PubMed: 26833513
DOI: 10.7861/clinmedicine.16-1-42 -
The European Respiratory Journal Apr 2010
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Idiopathic Pulmonary Fibrosis; Pyridones; Randomized Controlled Trials as Topic
PubMed: 20356985
DOI: 10.1183/09031936.00006610 -
European Journal of Pharmacology Jun 2024Idiopathic pulmonary fibrosis (IPF) associated to pulmonary hypertension (PH) portends a poor prognosis, characterized by lung parenchyma fibrosis and pulmonary artery...
Idiopathic pulmonary fibrosis (IPF) associated to pulmonary hypertension (PH) portends a poor prognosis, characterized by lung parenchyma fibrosis and pulmonary artery remodeling. Serum and parenchyma levels of Interleukin 11 (IL-11) are elevated in IPF-PH patients and contributes to pulmonary artery remodeling and PH. However, the effect of current approved therapies against IPF in pulmonary artery remodeling induced by IL-11 is unknown. The aim of this study is to analyze the effects of nintedanib and pirfenidone on pulmonary artery endothelial and smooth muscle cell remodeling induced by IL-11 in vitro. Our results show that nintedanib (NTD) and pirfenidone (PFD) ameliorates endothelial to mesenchymal transition (EnMT), pulmonary artery smooth muscle cell to myofibroblast-like transformation and pulmonary remodeling in precision lung cut slices. This study provided also evidence of the inhibitory effect of PFD and NTD on IL-11-induced endothelial and muscle cells proliferation and senescence. The inhibitory effect of these drugs on monocyte arrest and angiogenesis was also studied. Finally, we observed that IL-11 induced canonical signal transducer and activator of transcription 3 (STAT3) and non-canonical mitogen-activated protein kinase 1/2 (ERK1/2) phosphorylation, but, PFD and NTD only inhibited ERK1/2 phosphorylation. Therefore, this study provided evidence of the inhibitory effect of NTD and PFD on markers of pulmonary artery remodeling induced by IL-11.
Topics: Pulmonary Artery; Interleukin-11; Indoles; Animals; Myocytes, Smooth Muscle; STAT3 Transcription Factor; Endothelial Cells; Pyridones; Cell Proliferation; Rats; Humans; Male; Cellular Senescence; MAP Kinase Signaling System; Idiopathic Pulmonary Fibrosis; Monocytes; Vascular Remodeling
PubMed: 38561103
DOI: 10.1016/j.ejphar.2024.176547 -
La Revue Du Praticien Sep 2014Idiopathic pulmonary fibrosis is a chronic disease, which affects more frequently subjects older than 60 years, males, and smokers or ex-smokers. The diagnosis is based... (Review)
Review
Idiopathic pulmonary fibrosis is a chronic disease, which affects more frequently subjects older than 60 years, males, and smokers or ex-smokers. The diagnosis is based on a pattern of usual interstitial pneumonia at high resolution computed tomography of the chest and/or at the video- assisted thoracic surgical lung biopsy, and by multidisciplinary discussion in a specialized center, after ruling out possible causes and specific contexts (as connective tissue disease). The disease progresses inexorably to chronic respiratory insufficiency, occasionally with episodes of acute exacerbation, and death after a median of 3 years. Treatment with pirfenidone in patients with mild to moderate disease slows the progression of disease, and reduces the risk of death at one year, with skin and gastro-intestinal adverse events. Drug therapy should be part of a global care management. Several approaches are considered for an earlier diagnosis and treatment.
Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Disease Progression; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Pyridones
PubMed: 25362769
DOI: No ID Found -
The European Respiratory Journal Oct 2022Systemic sclerosis (SSc) is an autoimmune disease characterised by severe vasculopathy and fibrosis of various organs including the lung. Targeted treatment options for...
BACKGROUND
Systemic sclerosis (SSc) is an autoimmune disease characterised by severe vasculopathy and fibrosis of various organs including the lung. Targeted treatment options for SSc-associated interstitial lung disease (SSc-ILD) are scarce. We assessed the effects of pirfenidone in a mouse model of SSc-ILD.
METHODS
Pulmonary function, inflammation and collagen deposition in response to pirfenidone were assessed in Fra-2-overexpressing transgenic (Fra-2 TG) and bleomycin-treated mice. In Fra-2 TG mice, lung transcriptome was analysed after pirfenidone treatment. , pirfenidone effects on human eosinophil and endothelial cell function were analysed using flow cytometry-based assays and electric cell-substrate impedance measurements, respectively.
RESULTS
Pirfenidone treatment attenuated pulmonary remodelling in the bleomycin model, but aggravated pulmonary inflammation, fibrosis and vascular remodelling in Fra-2 TG mice. Pirfenidone increased interleukin (IL)-4 levels and eosinophil numbers in lung tissue of Fra-2 TG mice without directly affecting eosinophil activation and migration . A pronounced immune response with high levels of cytokines/chemokines and disturbed endothelial integrity with low vascular endothelial (VE)-cadherin levels was observed in pirfenidone-treated Fra-2 TG mice. In contrast, eosinophil and VE-cadherin levels were unchanged in bleomycin-treated mice and not influenced by pirfenidone. , pirfenidone exacerbated the IL-4 induced reduction of endothelial barrier resistance, leading to higher leukocyte transmigration.
CONCLUSION
This study shows that antifibrotic properties of pirfenidone may be overruled by unwanted interactions with pre-injured endothelium in a setting of high T-helper type 2 inflammation in a model of SSc-ILD. Careful ILD patient phenotyping may be required to exploit benefits of pirfenidone while avoiding therapy failure and additional lung damage in some patients.
Topics: Humans; Mice; Animals; Interleukin-4; Scleroderma, Systemic; Bleomycin; Lung Diseases, Interstitial; Lung; Fibrosis; Disease Models, Animal; Inflammation; Collagen; Cytokines; Chemokines; Cadherins
PubMed: 35332068
DOI: 10.1183/13993003.02347-2021 -
Heart Failure Reviews Mar 2022Myocardial fibrosis is a common feature of several heart diseases. The progressive deposition of extracellular matrix due to a persistent injury to cardiomyocytes may... (Review)
Review
Myocardial fibrosis is a common feature of several heart diseases. The progressive deposition of extracellular matrix due to a persistent injury to cardiomyocytes may trigger a vicious cycle that leads to persistent structural and functional alterations of the myocardium. Some drugs (like renin-angiotensin-aldosterone system inhibitors) have been shown to reduce extracellular matrix deposition, but no primarily anti-fibrotic medications are currently used to treat patients with heart failure (HF). Pirfenidone is an oral antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis. Although its exact mechanism of action is not fully understood, pirfenidone might reduce the expression of profibrotic factors such as transforming growth factor-β (TGF-β), and proinflammatory cytokines, like tumor necrosis factor-α (TNF-α), interleukin (IL)-4, and IL-13, which could modulate the inflammatory response and inhibit collagen synthesis in lung tissue. There is some evidence that pirfenidone has antifibrotic activity in various animal models of cardiac disease. Furthermore, the positive results of the PIROUETTE trial, evaluating pirfenidone in patients with HF with preserved ejection fraction, have been very recently announced. This review summarizes the data about pirfenidone as a potential cardioprotective treatment.
Topics: Animals; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis; Myocytes, Cardiac; Pyridones
PubMed: 34671871
DOI: 10.1007/s10741-021-10175-w