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Swiss Medical Weekly 2015Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with poor survival. Recent studies have improved understanding of IPF and new discoveries have... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with poor survival. Recent studies have improved understanding of IPF and new discoveries have led to novel treatment options, which now have become available for patients. In face of the newly available therapies we present an update on the pathophysiology and epidemiology of IPF. We discuss the typical clinical findings and elaborate diagnostic procedures according to current guidelines and our daily practice approach. The role of biomarkers will briefly be outlined. Finally, we discuss novel antifibrotic treatment options for IPF (pirfenidone, nintedanib) and the management of patients regarding to comorbidities and complications. Both pirfenidone and nintedanib were shown to reduce the progression of IPF and therefore represent novel therapeutic strategies in this so far untreatable chronic lung disease.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Disease Progression; Enzyme Inhibitors; Gastroesophageal Reflux; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Indoles; Practice Guidelines as Topic; Pyridones
PubMed: 26024356
DOI: 10.4414/smw.2015.14139 -
Respiratory Medicine Aug 2017Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease associated with dyspnoea, cough and impaired quality of life. Currently, the aims... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease associated with dyspnoea, cough and impaired quality of life. Currently, the aims of patient care are to improve outcomes for patients by slowing the progression of the disease, extending life, and improving quality of life. A prompt, accurate diagnosis is important to enable patients to receive treatment early in the course of the disease and to be considered for lung transplantation. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been shown to reduce decline in lung function in patients with IPF. In addition to pharmacological therapy, optimal management of IPF includes treatment of comorbidities, symptom relief, pulmonary rehabilitation, and palliative care. Patient education is important to enable patients to make decisions about their care and to help them manage their disease and the side-effects of anti-fibrotic drugs. Research continues into new treatments and combinations of treatments that may improve outcomes for patients with this devastating disease.
Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Comorbidity; Disease Progression; Enzyme Inhibitors; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung Diseases, Interstitial; Lung Transplantation; Middle Aged; Palliative Care; Patient Education as Topic; Practice Guidelines as Topic; Prevalence; Pyridones; Quality of Life; Young Adult
PubMed: 28732832
DOI: 10.1016/j.rmed.2017.05.017 -
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 -
Eye (London, England) Sep 2017PurposeThe purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of...
PurposeThe purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury.Patients and methodsPenetrating trauma was induced on the retina of rabbit and treated either with 0.1 ml of phosphate-buffered saline (PBS) or 0.1 ml of 0.5% pirfenidone, and development of PVR was evaluated clinically and graded after 1 month. Histopathology and immunohistochemistry with transforming growth factor beta (TGFβ), alpha smooth muscle actin (αSMA), and collagen-1 were performed to assess the fibrotic changes. Expression of cytokines in the vitro-retinal tissues at different time points following pirfenidone and PBS injection was examined by RT-PCR. Availability of pirfenidone in the vitreous of rabbit at various time points was determined by high-performance liquid chromatography following injection of 0.1 ml of 0.5% pirfenidone. In normal rabbit eye, 0.1 ml of 0.5% pirfenidone was injected to evaluate any toxic effect.ResultsClinical assessment and grading revealed prevention of PVR formation in pirfenidone-treated animals, gross histology, and histopathology confirmed the observation. Immunohistochemistry showed prevention in the expression of collagen-I, αSMA, and TGFβ in the pirfenidone-treated eyes compared to the PBS-treated eyes. Pirfenidone inhibited increased gene expression of cytokines observed in control eyes. Pirfenidone could be detected up to 48 h in the vitreous of rabbit eye following single intravitreal injection. Pirfenidone did not show any adverse effect following intravitreal injection; eyes were devoid of any abnormal clinical sign, intraocular pressure, and electroretinography did not show any significant change and histology of retina remained unchanged.ConclusionThis animal study shows that pirfenidone might be a potential therapy for PVR. Further clinical study will be useful to evaluate the clinical application of pirfenidone.
Topics: Actins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Collagen Type I; Cytokines; Disease Models, Animal; Electroretinography; Eye Injuries, Penetrating; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation; Intravitreal Injections; Pyridones; Rabbits; Real-Time Polymerase Chain Reaction; Retina; Vitreoretinopathy, Proliferative; Vitreous Body
PubMed: 28304388
DOI: 10.1038/eye.2017.21 -
European Respiratory Review : An... Sep 2019Two antifibrotic medications (nintedanib and pirfenidone) were recommended (conditionally) for the treatment of patients with idiopathic pulmonary fibrosis (IPF) in the... (Review)
Review
Two antifibrotic medications (nintedanib and pirfenidone) were recommended (conditionally) for the treatment of patients with idiopathic pulmonary fibrosis (IPF) in the 2015 IPF evidence-based guidelines. These medications have been shown to reduce the rate of decline in forced vital capacity among patients with IPF over time and are the only two disease-modulating pharmacological agents approved by regulatory agencies and available for clinical use worldwide. With the evolved standard of care for interstitial lung disease evaluation including routine use of high-resolution computed tomography, fibrotic lung diseases other than IPF are increasingly recognised. In addition, it is becoming evident that genetic and pathophysiological mechanisms as well as disease behaviour in patients manifesting other "non-IPF progressive fibrotic interstitial lung diseases" (non-IPF-PF) may be similar to those in patients with IPF. Thus, it is biologically plausible that pharmacological agents with antifibrotic properties may be efficacious in non-IPF-PF. Indeed, studies are underway or planned to assess the safety and efficacy of nintedanib or pirfenidone among patients with several non-IPF fibrotic lung diseases. In this review, we briefly summarise the use of pirfenidone and nintedanib in IPF as well as the rationale and potential for use of these medications in non-IPF-PF that are being investigated in ongoing and upcoming clinical trials.
Topics: Animals; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung; Lung Diseases, Interstitial; Pyridones; Treatment Outcome; Vital Capacity
PubMed: 31578210
DOI: 10.1183/16000617.0022-2019 -
Expert Opinion on Pharmacotherapy Feb 2014Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and lethal fibrosing interstitial pneumonia. The median survival from the onset of the symptoms is 2.8 -... (Review)
Review
INTRODUCTION
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and lethal fibrosing interstitial pneumonia. The median survival from the onset of the symptoms is 2.8 - 4.2 years and the 5-year survival rate is 20%. Its poor prognosis, combined with the scarcity of treatment options, provides a strong rationale for the development of novel therapeutic strategies. During the past decade there has been a huge rise in clinical trials with anti-fibrotic drugs, although only pirfenidone (Esbriet) has shown a beneficial effect.
AREAS COVERED
This article reviews the medical literature on the effectiveness and safety of pirfenidone in IPF, by means of a PubMed search from 1995 to present, completed with some data on file from the manufacturer.
EXPERT OPINION
Pirfenidone is the only anti-fibrotic drug approved for the treatment of IPF. Pirfenidone provides a meaningful clinical effect on reductions in the decrease in forced vital capacity (FVC), six-minute walk test (6MWT) distance and mortality, and it improves the progression-free survival in IPF patients with mild-to-moderate disease. Pirfenidone is well tolerated, with the most common side-effects being gastrointestinal discomfort and photosensitivity. Pirfenidone has a favorable benefit-risk profile and represents a suitable treatment option for patients with mild-to-moderate IPF.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease-Free Survival; Humans; Idiopathic Pulmonary Fibrosis; Prognosis; Pyridones; Risk Assessment; Severity of Illness Index; Survival Rate; Vital Capacity
PubMed: 24308635
DOI: 10.1517/14656566.2014.867328 -
Chest Dec 2016Among the interstitial lung diseases (ILDs), idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis, and fibrotic connective tissue disease-related... (Review)
Review
Among the interstitial lung diseases (ILDs), idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis, and fibrotic connective tissue disease-related ILD are associated with a worse prognosis, with death occurring as a result of both respiratory failure and serious associated comorbidities. The recent development and approval of the antifibrotic agents nintedanib and pirfenidone, both of which reduced the rate of decline in lung function in patients with IPF in clinical trials, offer hope that it may be possible to alter the increased mortality associated with IPF. Although chronic hypersensitivity pneumonitis and connective tissue disease related-ILD may be associated with an inflammatory component, the evidence for the use of immunosuppressive agents in their treatment is largely limited to retrospective studies. The lack of benefit of immunosuppressive therapy in advanced fibrosis argues for rigorous clinical trials using antifibrotic therapies in these types of ILD as well. Patients with fibrotic ILD may benefit from identification and management of associated comorbid conditions such as pulmonary hypertension, gastroesophageal reflux, and OSA, which may improve the quality of life and, in some cases, survival in affected individuals. Because early assessment may optimize posttransplantation outcomes, lung transplant evaluation should occur early in patients with IPF and those with other forms of fibrotic ILD.
Topics: Alveolitis, Extrinsic Allergic; Anti-Inflammatory Agents, Non-Steroidal; Connective Tissue Diseases; Disease Progression; Enzyme Inhibitors; Humans; Idiopathic Pulmonary Fibrosis; Immunosuppressive Agents; Indoles; Lung Diseases, Interstitial; Prognosis; Pyridones
PubMed: 27521738
DOI: 10.1016/j.chest.2016.07.027 -
European Respiratory Review : An... Sep 2017Idiopathic pulmonary fibrosis (IPF) remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with... (Review)
Review
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.
Topics: Disease Progression; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung; Lung Transplantation; Palliative Care; Pyridones; Respiratory Function Tests; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 28954763
DOI: 10.1183/16000617.0047-2017 -
European Respiratory Review : An... Mar 2014Pirfenidone is an orally active, small molecule that inhibits synthesis of profibrotic and inflammatory mediators. It was approved for the treatment of adults with... (Review)
Review
Pirfenidone is an orally active, small molecule that inhibits synthesis of profibrotic and inflammatory mediators. It was approved for the treatment of adults with mild-to-moderate idiopathic pulmonary fibrosis in the European Union based on the results of two pivotal phase III, double-blind, randomised, placebo-controlled clinical trials (CAPACITY) demonstrating efficacy and safety, and supported by two Japanese clinical trials (SP2 and SP3). Currently, there is increasing interest in experience with pirfenidone in patients relating to the real-world setting. Following the publication of the CAPACITY clinical studies, additional analyses have been conducted to provide further support for pirfenidone in clinical practice, including a modified per-protocol analysis of the CAPACITY study population. New data from the RECAP extension study also provided longer term data for pirfenidone and promising continuation rates with treatment. Pirfenidone is also being evaluated in specialist centre cohorts providing important information on real-world efficacy and safety. Increasing experience with pirfenidone in everyday clinical practice is helping to establish \expert guidance on the management of known adverse events, together with practical recommendations, to ensure adherence to treatment so that the possible longer term benefits of pirfenidone treatment in reducing lung function decline can be maximised.
Topics: Clinical Trials, Phase III as Topic; Evidence-Based Medicine; Humans; Idiopathic Pulmonary Fibrosis; Lung; Pyridones; Randomized Controlled Trials as Topic; Respiratory System Agents; Time Factors; Treatment Outcome
PubMed: 24591668
DOI: 10.1183/09059180.00008513 -
Respirology (Carlton, Vic.) Aug 2017The real-world tolerability of pirfenidone and nintedanib in non-clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical...
BACKGROUND AND OBJECTIVE
The real-world tolerability of pirfenidone and nintedanib in non-clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical co-morbidities or baseline characteristics that exclude them from clinical trial participation.
METHODS
We conducted a retrospective chart review study on subjects prescribed nintedanib or pirfenidone for pulmonary fibrosis treatment (any aetiology) from September 2014 to February 2016. A total of 186 subjects were included: 129 received pirfenidone and 57 were prescribed nintedanib and followed up for mean observation periods of 52 ± 17 weeks for pirfenidone and 41 ± 15 weeks for nintedanib. The primary outcome was drug discontinuation as a result of an adverse event.
RESULTS
Subjects had significant respiratory impairment at baseline, 63% required home oxygen therapy and mean diffusion capacity of carbon monoxide (DLCO) was 36 ± 14% predicted. Drug discontinuation as a result of an adverse event occurred in 20.9% of subjects on pirfenidone and 26.3% on nintedanib. Drug discontinuation rates for both pirfenidone and nintedanib did not significantly differ from corresponding large clinical trials (ASCEND/CAPACITY and INPULSIS 1 and 2, respectively). Adverse events that occurred with highest frequency on pirfenidone were nausea (26.4%), rash/photosensitivity (14.7%) and dyspepsia/gastroesophageal reflux disease (GERD) (12.4%). Diarrhoea (52.6%) and nausea (29.8%) were reported most often with nintedanib therapy.
CONCLUSION
Patients with pulmonary fibrosis treated with nintedanib or pirfenidone in routine clinical practice had drug tolerability and adverse event profiles comparable with subjects enrolled in clinical trials despite having a greater degree of respiratory impairment and a high prevalence of co-morbid medical conditions.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Enzyme Inhibitors; Female; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Male; Middle Aged; Pyridones; Retrospective Studies; Treatment Outcome
PubMed: 28317233
DOI: 10.1111/resp.13024