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Clinical Medicine (London, England) Dec 2014Idiopathic pulmonary fibrosis (IPF) is a devastating condition with a poor prognosis and few treatment options. However, recent research into this condition has led to... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a devastating condition with a poor prognosis and few treatment options. However, recent research into this condition has led to considerable insights into the pathophysiology of the disease, resulting in the identification of potential biomarkers to aid diagnosis and stratification of patients and the development of novel therapies. In this review we will discuss the recent developments in this field and review how this knowledge has been translated into clinical trials and a paradigm shift in our approach to patients with IPF.
Topics: Biomarkers; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pyridones
PubMed: 25468919
DOI: 10.7861/clinmedicine.14-6-s45 -
Therapeutic Advances in Respiratory... Apr 2012Pirfenidone is the first antifibrotic agent to be approved for the treatment of pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is one of the idiopathic... (Review)
Review
Pirfenidone is the first antifibrotic agent to be approved for the treatment of pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is one of the idiopathic interstitial pneumonias with the worst prognoses; approximately half of patients die within 3-5 years, and the need for an effective treatment has been unmet until recently. The etiology of IPF is still unknown and its pathogenesis is poorly understood. Anti-inflammatory drugs, such as corticosteroids and some immunosuppressants, have been empirically used to treat IPF, although they have not been objectively proven to be effective by large-scale randomized, controlled trials. Pirfenidone is an agent that can inhibit the decline of forced vital capacity (FVC)/vital capacity (VC) and that thereby can be hoped to decrease the mortality rate. The number of clinical trials of pirfenidone completed, ongoing, or planned is growing, and the present status of pirfenidone as treatment for IPF is summarized in this review.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Humans; Idiopathic Pulmonary Fibrosis; Pyridones; Vital Capacity
PubMed: 22333982
DOI: 10.1177/1753465812436663 -
European Journal of Hospital Pharmacy :... Nov 2020To assess the long-term effectiveness of pirfenidone in idiopathic pulmonary fibrosis (IPF) treatment and to establish its adverse effects profile. (Observational Study)
Observational Study
OBJECTIVES
To assess the long-term effectiveness of pirfenidone in idiopathic pulmonary fibrosis (IPF) treatment and to establish its adverse effects profile.
METHODS
Retrospective observational study in patients with IPF who initiated treatment with pirfenidone between 2011 and 2016. We collected demographic variables (age, sex); date of first and last treatment; reason for discontinuation; pulmonary function measures (forced vital capacity (FVC), carbon monoxide diffusion capacity (DLCO), and 6 min walk test (6MWT)) at treatment initiation (baseline) and at 1, 2 and 3 year follow-up; adherence to pirfenidone treatment; recorded adverse effects; and mortality.
RESULTS
Thirty-one patients treated with pirfenidone were included; mean±SD age was 69±8 years, 74% were men, and 59% had a smoking history. Mean baseline values were: FVC 2.43±0.66 L (61.8±12.1%); DLCO 46.1±19.4%; and 6MWT 334±125 m. Median duration of treatment was 14±13 months, and treatment was discontinued in 58% of patients. The most frequently observed adverse effects were gastrointestinal disturbances and photosensitivity. Twenty (65%) patients were evaluated at 1 year, when mean FVC was 2.41±0.86 L (64.7±20.3%); DLCO 50.8±26.8%; and 6MWT 341±139 m. At 2 years' follow-up, 11 patients (36%) who were still taking pirfenidone were evaluated. Mean FVC was 2.34±0.79 L (66.2±14.7%); DLCO 50.0±28.3%; and 6MWT 265±121 m. At 3 years, five patients were still taking the treatment. Mean FVC was 2.71±0.84 L (71.0±24.7%); DLCO 52.6±26.7%; and 6MWT 286±139 m. Nineteen per cent of patients were non-adherent to treatment.
CONCLUSIONS
Pirfenidone seems to be effective for long-term control of IPF despite substantial variability in response among individual patients. The most frequent adverse effects were digestive and cutaneous, prompting in some cases a reduction in dose or even discontinuation of the treatment.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Exercise Test; Fatigue; Female; Follow-Up Studies; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Myalgia; Pyridones; Retrospective Studies; Treatment Outcome
PubMed: 33020058
DOI: 10.1136/ejhpharm-2018-001806 -
Expert Opinion on Investigational Drugs Feb 2010Many chronic diseases of various etiologies lead to fibrosis and organ dysfunction. Despite many advances in medicine in recent years, options to slow the progression of... (Review)
Review
IMPORTANCE OF THE FIELD
Many chronic diseases of various etiologies lead to fibrosis and organ dysfunction. Despite many advances in medicine in recent years, options to slow the progression of fibrotic diseases have remained limited. The recent availability of pirfenidone, an antifibrotic and anti-inflammatory investigational agent, thus offers a new hope for treating progressive fibrotic diseases.
AREAS COVERED IN THIS REVIEW
This review provides concise review of the available data regarding the mechanism and pharmacokinetics of pirfenidone and preclinical and clinical data regarding efficacy and safety in fibrotic diseases of the kidney. It also reviews results of clinical trials involving pirfenidone in other fibrotic diseases.
WHAT THE READER WILL GAIN
The review will provide in-depth review of pirfenidone with a renal focus.
TAKE HOME MESSAGE
Because many of the available clinical trials have been small and/or uncontrolled, conclusive evidence regarding efficacy and safety of pirfenidone is lacking, particularly in patients with renal or hepatic dysfunction. Larger studies are needed to better understand long-term efficacy and safety of this medication in various patient populations.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Clinical Trials as Topic; Disease Models, Animal; Disease Progression; Drug Evaluation; Fibrosis; Humans; Kidney; Kidney Diseases; Pyridones
PubMed: 20050822
DOI: 10.1517/13543780903501539 -
Scientific Reports Nov 2023Chronic kidney disease (CKD) is a comorbidity in idiopathic pulmonary fibrosis (IPF), and managing IPF with CKD is challenging due to limited options for antifibrotic...
Chronic kidney disease (CKD) is a comorbidity in idiopathic pulmonary fibrosis (IPF), and managing IPF with CKD is challenging due to limited options for antifibrotic therapy. The aim of this study was to examine the prevalence of CKD and prescription status of pirfenidone in IPF patients and to analyze its impact on mortality. Data from the Korean National Health Insurance Service (NHIS) database between October 2015 and September 2021 were used. IPF and CKD were defined based on both International Classification of Diseases 10th Revision (ICD-10) codes and Rare Intractable Disease (RID) codes. The risk of mortality was assessed based on accompanying CKD with or without antifibrotic therapy. Among 5038 patients with IPF, 8.4% had comorbid CKD and 83.3% with CKD did not receive renal replacement therapy (RRT). Patients with IPF and CKD were older, predominantly male, and had more frequent comorbidities such as cardiovascular disease and diabetes mellitus than subjects without CKD. Pirfenidone was prescribed to 105 (24.6%) of 426 CKD patients, and 89.5% of them did not receive RRT. Pirfenidone was also prescribed to 775 (16.8%) of 4612 IPF patients without CKD. Significant difference was not found in all-cause mortality between the IPF patients with or without CKD regardless of pirfenidone treatment. The use of antifibrotics in IPF patients with CKD is limited due to CKD severity; however, evidence is lacking. Mortality did not increase with accompanying CKD regardless of antifibrotic use. Further research on IPF and CKD is needed.
Topics: Humans; Male; Female; Idiopathic Pulmonary Fibrosis; Pyridones; Comorbidity; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 37935732
DOI: 10.1038/s41598-023-46506-0 -
International Journal of Molecular... May 2023There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone...
There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone (PFD) on alveolar bone loss in ligature-induced periodontitis in mice and identify the relevant mechanisms. Experimental periodontitis was established by ligating the unilateral maxillary second molar for 7 days in mice (n = 8 per group), and PFD was administered daily via intraperitoneal injection. The micro-computed tomography and histology analyses were performed to determine changes in the alveolar bone following the PFD administration. For in vitro analysis, bone marrow macrophages (BMMs) were isolated from mice and cultured with PFD in the presence of RANKL or LPS. The effectiveness of PFD on osteoclastogenesis, inflammatory cytokine expression, and NF-κB activation was determined with RT-PCR, Western blot, and immunofluorescence analyses. PFD treatment significantly inhibited the ligature-induced alveolar bone loss, with decreases in TRAP-positive osteoclasts and expression of inflammatory cytokines in mice. In cultured BMM cells, PFD also inhibited RANKL-induced osteoclast differentiation and LPS-induced proinflammatory cytokine (IL-1β, IL-6, TNF-a) expression via suppressing the NF-κB signal pathway. These results suggest that PFD can suppress periodontitis progression by inhibiting osteoclastogenesis and inflammatory cytokine production via inhibiting the NF-κB signal pathway, and it may be a promising candidate for controlling periodontitis.
Topics: Mice; Animals; NF-kappa B; Alveolar Bone Loss; X-Ray Microtomography; Lipopolysaccharides; Signal Transduction; Osteoclasts; Periodontitis; Cytokines; RANK Ligand
PubMed: 37240020
DOI: 10.3390/ijms24108682 -
Journal of Managed Care & Specialty... Mar 2017The antifibrotics pirfenidone and nintedanib are both approved for the treatment of idiopathic pulmonary fibrosis (IPF) by regulatory agencies and are recommended by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The antifibrotics pirfenidone and nintedanib are both approved for the treatment of idiopathic pulmonary fibrosis (IPF) by regulatory agencies and are recommended by health technology assessment bodies. Other treatments such as N-acetylcysteine are used in clinical practice but have not received regulatory approval. No head-to-head trials have been conducted to directly compare the efficacy of these therapies in IPF.
OBJECTIVE
To compare the efficacy of treatments for IPF.
METHODS
A systematic review was conducted up to April 2015. Phase II/III randomized controlled trials in adults with IPF were eligible. A Bayesian network meta-analysis (NMA) was used to compare pirfenidone, nintedanib, and N-acetylcysteine with respect to forced vital capacity (FVC) and mortality.
RESULTS
Nine studies were included in the NMA. For change from baseline in FVC, the NMA indicated that pirfenidone and nintedanib were more effective than placebo after 1 year (pirfenidone vs. placebo: difference = 0.12 liter (L), 95% credible interval [CrI] = 0.03-0.21 L; nintedanib vs. placebo: difference = 0.11 L, 95% CrI = 0.00-0.22 L). There was no evidence that N-acetylcysteine had an effect on FVC compared with placebo (N-acetylcysteine vs. placebo: difference = 0.01 L, 95% CrI = -0.15-0.17 L). Patients treated with pirfenidone also had a lower risk of experiencing a decline in percent predicted FVC of ≥ 10% over 1 year (odds ratio [OR]: 0.58, 95% CrI = 0.40-0.88), whereas there was no conclusive evidence of a difference between nintedanib and placebo (OR: 0.65, 95% CrI = 0.42-1.02). The NMA indicated that pirfenidone reduced all-cause mortality relative to placebo over 1 year (hazard ratio [HR]: 0.52, 95% CrI = 0.28-0.92). There was no evidence of a difference in all-cause mortality between nintedanib and placebo (HR: 0.70, 95% CrI = 0.32-1.55), or N-acetylcysteine and placebo (HR: 2.00, 95% CrI=0.46-8.62).
CONCLUSIONS
Our primary analysis of the available evidence indicates that over 1 year, pirfenidone and nintedanib are effective at reducing lung-function decline, and pirfenidone may reduce the odds of experiencing a decline in percent predicted FVC of ≥10% compared with placebo in the first year of treatment. The results of our analysis also suggest that pirfenidone improves survival.
DISCLOSURES
Fleetwood is an employee of Quantics Consulting. McCool and Glanville are employees of York Health Economics Consortium (YHEC). Quantics and YHEC received funding from F. Hoffmann-La Roche for conducting the systematic review and network meta-analysis reported in this paper. Edwards, Gsteiger, and Daigl are employees of F. Hoffmann-La Roche. Fisher was employed by InterMune UK, a wholly owned Roche subsidiary, until July 2015. He is currently employed by FIECON, which has received funding from F. Hoffmann-La Roche for consulting services. The systematic review and network meta-analysis reported in this paper were conducted by Fleetwood (Quantics Consulting) and McCool and Glanville (YHEC), funded by F. Hoffmann-La Roche. The original network analysis was funded by InterMune. Study concept and design were contributed by Edwards, Gsteiger, and Daigl, along with Fleetwood, McCool, and Glanville. Fleetwood, McCool, and Glanville collected the data, with assistance from Edwards, Gsteiger, and Daigl. Data interpretation was performed by Fleetwood and Fisher, with assistance from the other authors. The manuscript was written by Fleetwood, McCool, and Glanville, with assistance from Edwards, Daigl, and Fisher, and revised by all the authors.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Enzyme Inhibitors; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pyridones; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28287346
DOI: 10.18553/jmcp.2017.23.3-b.s5 -
Respiratory Medicine and Research Nov 2023GAP (gender-age-physiology) and TORVAN are multi-parametric prognostication scores for idiopathic pulmonary fibrosis (IPF). We compared their prognostic value in...
BACKGROUND
GAP (gender-age-physiology) and TORVAN are multi-parametric prognostication scores for idiopathic pulmonary fibrosis (IPF). We compared their prognostic value in patients treated with nintedanib or pirfenidone and explored their effect on patient survival in relation to disease staging.
STUDY DESIGN AND PATIENTS
Retrospective evaluation of 235 naïve IPF patients (M = 179; mean age 69.8 yrs±7.1; 102 treated with nintedanib and 133 with pirfenidone), referred to two Italian academic centers between February 2012 and December 2019.
RESULTS
During a median follow-up of 4.2 years, the incidence rate of death was 14.5 per 100 person-years (95% CI: 12 to 17.4), with no differences between nintedanib and pirfenidone (log-rank p = 0.771). According to time-ROC analysis, GAP and TORVAN showed a similar discrimination performance at 1, 2, and 5 years. Survival of GAP-2/GAP-3 IPF patients treated with nintedanib was worse than that of patients in GAP-1 (HR 4.8, 95% CI: 2.2 to 10.5 and HR 9.4, 95% CI: 3.8 to 23.2). TORVAN I patients treated with nintedanib exhibited better survival than those in stages III (HR 3.1, 95% CI: 1.4 to 6.6) and IV (HR 10.5, 95% CI: 3.5 to 31.6). A significant treatment x stage interaction was observed for both disease staging indexes (p = 0.042 for treatment by GAP interaction and p = 0.046 for treatment by TORVAN interaction). A better survival was associated with nintedanib in patients with mild disease (GAP-1 or TORVAN I stage) and with pirfenidone in GAP-3 or TORVAN IV cases, although these findings did not always reach statistical significance.
CONCLUSIONS
GAP and TORVAN similarly perform in IPF patients on anti-fibrotic therapy. However, the survival of patients treated with nintedanib and pirfenidone appears to be differently affected by disease staging.
Topics: Humans; Aged; Retrospective Studies; Treatment Outcome; Idiopathic Pulmonary Fibrosis
PubMed: 37302161
DOI: 10.1016/j.resmer.2023.101013 -
International Journal of Medical... 2015Pirfenidone (PFD) is a non-peptide synthetic molecule issued as a broad-spectrum anti-fibrotic drug with the ability to decrease TGF-β1, TNF-α, PDGF and COL1A1... (Review)
Review
Pirfenidone (PFD) is a non-peptide synthetic molecule issued as a broad-spectrum anti-fibrotic drug with the ability to decrease TGF-β1, TNF-α, PDGF and COL1A1 expression, which is highly related to prevent or remove excessive deposition of scar tissue in several organs. Basic and clinical evidence suggests that PFD may safely slow or inhibit the progressive fibrosis swelling after tissue injuries. Furthermore, a number of evidence suggests that this molecule will have positive effects in the treatment of other inflammatory diseases. This review contains current research in which PFD has been used as the treatment of several diseases, and focus mainly in the outcomes related to improve inflammation and fibrogenesis. Therefore, the main goal of this review is to focus on the novel findings of PFD efficacy rather than deepen in the chemical aspects of the molecule.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Eye; Fibrosis; Humans; Kidney; Liver Cirrhosis; Myocardium; Pulmonary Fibrosis; Pyridones
PubMed: 26640402
DOI: 10.7150/ijms.11579 -
European Respiratory Review : An... Sep 2011Currently, there are no approved pharmacological treatments for the management of patients with idiopathic pulmonary fibrosis (IPF) in the USA or Europe. Pirfenidone is... (Review)
Review
Currently, there are no approved pharmacological treatments for the management of patients with idiopathic pulmonary fibrosis (IPF) in the USA or Europe. Pirfenidone is an orally bio-available small molecule that exhibits antifibrotic and anti-inflammatory properties in a variety of in vitro and animal models. Pirfenidone has been evaluated in four randomised, double-blind, placebo-controlled clinical trials conducted in Japan, North America and Europe. The totality of the data from these trials indicates that pirfenidone is able to reduce the rate of decline in lung function, measured as change in per cent predicted forced vital capacity (FVC) or vital capacity. There was also an effect on secondary end-points of progression free survival, categorical change in per cent predicted FVC, and the 6-min walk test. A recent meta-analysis of the three phase III studies in IPF demonstrated that pirfenidone significantly reduced the risk of disease progression by 30%. The efficacy of pirfenidone is associated with an acceptable tolerability and safety profile.
Topics: Animals; Clinical Trials as Topic; Evidence-Based Medicine; Humans; Idiopathic Pulmonary Fibrosis; Lung; Pyridones; Respiratory System Agents; Treatment Outcome
PubMed: 21881148
DOI: 10.1183/09059180.00002011