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Saudi Medical Journal Sep 2017To analyze the efficacy and adverse events (AEs) of pirfenidone in idiopathic pulmonary fibrosis (IPF) trials. Methods: MEDLINE, Cochrane Library, and... (Review)
Review
To analyze the efficacy and adverse events (AEs) of pirfenidone in idiopathic pulmonary fibrosis (IPF) trials. Methods: MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for studies published before June 2016. All studies of clinical trials with the key words IPF or idiopathic pulmonary fibrosis or lung fibrosis and pirfenidone or Esbriet were identified. Quality assessment and data extraction nwere conducted by 2 independent researchers. A meta-analysis of randomized controlled trials (RCTs) was performed, and relative risk (RR) and 95% confidence intervals (95% CIs) were calculated. Results: Five studies were included in this review, involving 1568 participants. The meta-analysis revealed that pirfenidone reduced the risk of decline in forced vital capacity (FVC)% ≥10% from baseline (relative risk: 0.62; 95% CI: 0.51-0.76, p less than 0.001). The pirfenidone group had a significantly higher rate of AEs compared with the placebo group. Pirfenidone did not reduce mortality from any cause significantly (odds ratio: 0.63; 95% CI: 0.36-1.09). Conclusions: This study showed that pirfenidone could reduce disease progression as assessed by the decline in FVC in IPF. Pirfenidone represents a suitable treatment option for patients with IPF.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Meta-Analysis as Topic; Placebos; Pyridones; Randomized Controlled Trials as Topic; Respiratory Function Tests
PubMed: 28889145
DOI: 10.15537/smj.2017.9.19349 -
Heliyon Aug 2023Genetic variations in Idiopathic Pulmonary Fibrosis (IPF) affect survival and outcomes. Current antifibrotic agents are managed based on the patient's reported side...
BACKGROUND
Genetic variations in Idiopathic Pulmonary Fibrosis (IPF) affect survival and outcomes. Current antifibrotic agents are managed based on the patient's reported side effects, although certain single nucleotide polymorphisms (SNPs) might alter treatment response and survival depending on the antifibrotic administered. This study investigated variations in response and outcomes to pirfenidone based on patients-specific genetic profiles.
METHODS
Retrospective clinical data were collected from 56 IPF patients and had blood drawn for DNA extraction between 7/2013 and 3/2016, with the last patient followed until 10/2018. Nine SNPs were selected for pharmacogenetic investigation based on prior associations with IPF treatment outcomes or implications for pirfenidone metabolism. Genetic variants were examined in relation to clinical data and treatment outcomes.
RESULTS
Of the 56 patients, 38 were males (67.85%). The average age of IPF at diagnosis was 66.88 years. At the initiation of pirfenidone, the average percent predicted FVC was 70.7%, and the average DLCO percent predicted was 50.02% (IQR 40-61%). Among the genetic variants tested, the TOLLIP rs5743890 risk allele was significantly associated with improved survival, with increasing pirfenidone duration. This finding was observed with CC or CT genotype carriers but not for those with the TT genotype (p = 0.0457). Similarly, the TGF-B1 rs1800470 risk allele was also significantly associated with improved survival with longer pirfenidone therapy (p = 0.0395), even though it was associated with disease progression.
CONCLUSION
This pilot study suggests that in IPF patients, the TOLLIP rs5743890 genotypes CC and CT, as well as TGF-B1 rs 1800470 may be associated with increased survival when treated with pirfenidone.
PubMed: 37560683
DOI: 10.1016/j.heliyon.2023.e18573 -
Medicina Clinica (English Ed.) Jun 2023Although pulmonary fibrosis secondary to COVID-19 infection is uncommon, it can lead to problems if not treated effectively in the early period. This study aimed to...
BACKGROUND
Although pulmonary fibrosis secondary to COVID-19 infection is uncommon, it can lead to problems if not treated effectively in the early period. This study aimed to compare the effects of treatment with nintedanib and pirfenidone in patients with COVID-19-related fibrosis.
METHODS
Thirty patients who presented to the post-COVID outpatient clinic between May 2021 and April 2022 with a history of COVID-19 pneumonia and exhibited persistent cough, dyspnea, exertional dyspnea, and low oxygen saturation at least 12 weeks after diagnosis were included. The patients were randomized to receive off-label treatment with nintedanib or pirfenidone and were followed up for 12 weeks.
RESULTS
After 12 weeks of treatment, all pulmonary function test (PFT) parameters, 6MWT distance, and oxygen saturation were increased compared to baseline in both the pirfenidone group and nintedanib groups, while heart rate and radiological score levels were decreased ( < 0.05 for all). The changes in 6MWT distance and oxygen saturation were significantly greater in the nintedanib group than in the pirfenidone group ( = 0.02 and 0.005, respectively). Adverse drug effects were more frequent with nintedanib than pirfenidone, with the most common being diarrhea, nausea, and vomiting.
CONCLUSION
In patients with interstitial fibrosis after COVID-19 pneumonia, both nintedanib and pirfenidone were observed to be effective in improving radiological score and PFT parameters. Nintedanib was more effective than pirfenidone in increasing exercise capacity and saturation values but caused more adverse drug effects.
PubMed: 37337553
DOI: 10.1016/j.medcle.2022.12.019 -
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 -
Respiratory Research May 2022Pirfenidone slows down disease progression in idiopathic pulmonary fibrosis (IPF). Recent studies suggest a treatment effect in progressive pulmonary fibrosis other than...
BACKGROUND
Pirfenidone slows down disease progression in idiopathic pulmonary fibrosis (IPF). Recent studies suggest a treatment effect in progressive pulmonary fibrosis other than IPF. However, the safety and effectiveness of pirfenidone in asbestosis patients remain unclear. In this study, we aimed to investigate the safety, tolerability and efficacy of pirfenidone in asbestosis patients with a progressive phenotype.
METHODS
This was a multicenter prospective study in asbestosis patients with progressive lung function decline. After a 12-week observational period, patients were treated with pirfenidone 801 mg three times a day. Symptoms and adverse events were evaluated weekly and patients completed online patient-reported outcomes measures. At baseline, start of therapy, 12 and 24 weeks, in hospital measurement of lung function and a 6 min walking test were performed. Additionally, patients performed daily home spirometry measurements.
RESULTS
In total, 10 patients were included of whom 6 patients (66.7%) experienced any adverse events during the study period. Most frequently reported adverse events were fatigue, rash, anorexia and cough, which mostly occurred intermittently and were reported as not very bothersome. No significant changes in hospital pulmonary function (forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), 6 min walking test or patient-reported outcomes measures before and after start of pirfenidone were found. Home spirometry demonstrated a FVC decline in 12 weeks before start of pirfenidone, while FVC did not decline during the 24 week treatment phase, but this difference was not statistically significant.
CONCLUSIONS
Treatment with pirfenidone in asbestosis has an acceptable safety and tolerability profile and home spirometry data suggest this antifibrotic treatment might attenuate FVC decline in progressive asbestosis. Trial registration MEC-2018-1392; EudraCT number: 2018-001781-41.
Topics: Asbestosis; Humans; Idiopathic Pulmonary Fibrosis; Prospective Studies; Pyridones; Treatment Outcome
PubMed: 35643466
DOI: 10.1186/s12931-022-02061-2 -
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 -
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 -
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 -
Pneumologie (Stuttgart, Germany) Oct 2015Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and a disease of the elderly. Cigarette smoking and longterm exposure to...
Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and a disease of the elderly. Cigarette smoking and longterm exposure to substances harming alveolar epithelial cells are risk factors for the development of IPF. There is also evidence for a genetic susceptibility. IPF is defined as the idiopathic variant of Usual Interstitial Pneumonitis (UIP). Diagnosis of IPF is complex and based on the exclusion of other diseases associated with an UIP pattern. The only cure is lung transplantation. In the last years there was a breakthrough in the treatment of IPF. With pirfenidone and nintedanib there are now two compounds approved for the treatment of IPF.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Evidence-Based Medicine; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pyridones; Respiratory System Agents; Treatment Outcome
PubMed: 26444136
DOI: 10.1055/s-0034-1393036 -
Bone Marrow Transplantation Aug 2022Bronchiolitis obliterans syndrome (BOS) is the most morbid form of chronic graft-versus-host disease (cGVHD) after hematopoietic cell transplantation (HCT). Progressive... (Randomized Controlled Trial)
Randomized Controlled Trial
Bronchiolitis obliterans syndrome (BOS) is the most morbid form of chronic graft-versus-host disease (cGVHD) after hematopoietic cell transplantation (HCT). Progressive airway fibrosis leads to a 5-year survival of 40%. Treatment options for BOS are limited. A single arm, 52-week, Phase I study of pirfenidone was conducted. The primary outcome was tolerability defined as maintaining the recommended dose of pirfenidone (2403 mg/day) without a dose reduction totaling more than 21 days, due to adverse events (AEs) or severe AEs (SAEs). Secondary outcomes included pulmonary function tests (PFTs) and patient reported outcomes (PROs). Among 22 participants treated for 1 year, 13 (59%) tolerated the recommended dose, with an average daily tolerated dose of 2325.6 mg/day. Twenty-two SAEs were observed, with 90.9% related to infections, none were attributed to pirfenidone. There was an increase in the average percent predicted forced expiratory volume in 1 s (FEV%) of 7 percentage points annually and improvements in PROs related to symptoms of cGVHD. In this Phase I study, treatment with pirfenidone was safe. The stabilization in PFTs and improvements in PROs suggest the potential of pirfenidone for BOS treatment and support the value of a randomized controlled trial to evaluate the efficacy of pirfenidone in BOS after HCT. The study is registered in ClinicalTrials.gov (NCT03315741).
Topics: Bronchiolitis Obliterans; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Lung; Pyridones
PubMed: 35641662
DOI: 10.1038/s41409-022-01716-4