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European Review For Medical and... Nov 2022The incidence of idiopathic pulmonary fibrosis is increasing year by year in the world, which has a greater impact on the quality of life of patients. In the past,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The incidence of idiopathic pulmonary fibrosis is increasing year by year in the world, which has a greater impact on the quality of life of patients. In the past, symptomatic treatment was used in clinical practice, but the overall effect is still not good. Multiple clinical studies have demonstrated the efficacy of pirfenidone in the treatment of idiopathic pulmonary fibrosis; however, adverse reactions have been reported. We, therefore, systematically evaluated the effectiveness and safety of pirfenidone in patients with idiopathic pulmonary fibrosis.
PATIENTS AND METHODS
Relevant studies were retrieved from the Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature (CBM), Wanfang and Weipu databases between January 1999 and May 2020, including the keywords "pirfenidone" and "idiopathic pulmonary fibrosis", were included in our systematic review. Review Manager 5.4 software was used for data synthesis, and analyses of publication bias and sensitivity.
RESULTS
Our systematic review included 13 studies involving a total of 13247 patients with idiopathic pulmonary fibrosis. Pirfenidone was associated with reduced declines in vital capacity (VC) and forced vital capacity (FVC) from baseline in patients with hermansky-pudlak syndrome (HPS)-related pulmonary fibrosis and to moderate idiopathic pulmonary fibrosis (IPF). Pirfenidone treatment was associated with lower reductions in FVC, lower reductions in 6-minute walking test distance, lower decreases in minimum oxygen saturation during the 6-minute walking test, lower all-cause death, lower relative risk of IPF-related death and increased progression-free survival compared to placebo. Progression-free survival was significantly longer in the pirfenidone group. The incidence of gastrointestinal, skin, nervous system, and liver function-related adverse events was significantly higher in the pirfenidone group compared to the control group.
CONCLUSIONS
Pirfenidone has efficacy in delaying the progression of idiopathic pulmonary fibrosis. Pirfenidone is well-tolerated by the majority of patients; however, mild adverse reactions related to the gastrointestinal tract, skin, nervous system, and liver function are common. Overall, Pirfenidone may be an effective and well-tolerated treatment option for idiopathic pulmonary fibrosis.
Topics: Humans; Hermanski-Pudlak Syndrome; Quality of Life; Idiopathic Pulmonary Fibrosis; Vital Capacity; Skin
PubMed: 36459024
DOI: 10.26355/eurrev_202211_30377 -
BMJ Open Dec 2021Idiopathic pulmonary fibrosis (IPF) has been defined as a distinctive type of chronic fibrotic disease, characterised by a progressive decline in lung function and a... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Idiopathic pulmonary fibrosis (IPF) has been defined as a distinctive type of chronic fibrotic disease, characterised by a progressive decline in lung function and a common histological pattern of interstitial pneumonia. To analyse the efficacy and safety of pirfenidone in the treatment of IPF, a systematic review and meta-analysis was performed.
DESIGN
This is a meta-analysis study.
PARTICIPANTS
Patients were diagnosed as IPF.
INTERVENTIONS
Use of pirfenidone.
PRIMARY AND SECONDARY OUTCOME
Progression-free survival (PFS), acute exacerbation and worsening of IPF and Impact on adverse events.
MEASURES
The inverse variance method for the random-effects model was used to summarise the dichotomous outcomes, risk ratios and 95% CIs.
RESULTS
A total of 9 randomised controlled trials with 1011 participants receiving pirfenidone and 912 controls receiving placebo were summarised. The pooled result suggested a statistically significant difference inall-cause mortality after pirfenidone use, with a summarised relative ratio of 0.51 (p<0.01). Longer PFS was observed in patients receiving pirfenidone compared with those who were given placebo (p<0.01). The IPF groups presented a high incidence of adverse events with a pooled relative ratio of 3.89 (p<0.01).
CONCLUSIONS
Pirfenidone can provide survival benefit for patients with IPF. Pirfenidone treatment was also associated with a longer PFS, a lower incidence of acute exacerbation and worsening of IPF.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Progression-Free Survival; Pyridones; Randomized Controlled Trials as Topic; Treatment Outcome; Vital Capacity
PubMed: 34972762
DOI: 10.1136/bmjopen-2021-050004 -
BMC Pulmonary Medicine Dec 2021Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic... (Comparative Study)
Comparative Study Meta-Analysis
Efficacy of antifibrotic drugs, nintedanib and pirfenidone, in treatment of progressive pulmonary fibrosis in both idiopathic pulmonary fibrosis (IPF) and non-IPF: a systematic review and meta-analysis.
BACKGROUND
Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic therapy (grouping nintedanib and pirfenidone together) in patients with IPF versus patients with progressive lung fibrosis not classified as IPF.
STUDY DESIGN AND METHODS
A search of databases including MEDLINE, EMBASE, PubMed, and clinicaltrials.gov was conducted. Studies were included if they were randomised controlled trials of pirfenidone or nintedanib in adult patients with IPF or non-IPF patients, and with extractable data on mortality or decline in forced vital capacity (FVC). Random effects meta-analyses were performed on changes in FVC and where possible on mortality in the selected studies.
RESULTS
13 trials of antifibrotic therapy were pooled in a meta-analysis (with pirfenidone and nintedanib considered together as anti-fibrotic therapy). The change in FVC was expressed as a standardised difference to allow pooling of percentage and absolute changes. The mean effect size in the IPF studies was - 0.305 (SE 0.043) (p < 0.001) and in the non-IPF studies the figures were - 0.307 (SE 0.063) (p < 0.001). There was no evidence of any difference between the two groups for standardised rate of FVC decline (p = 0.979). Pooling IPF and non-IPF showed a significant reduction in mortality, with mean risk ratio of 07.01 in favour of antifibrotic therapy (p = 0.008). A separate analysis restricted to non-IPF did not show a significant reduction in mortality (risk ratio 0.908 (0.547 to 1.508), p = 0.71.
INTERPRETATION
Anti-fibrotic therapy offers protection against the rate of decline in FVC in progressive lung fibrosis, with similar efficacy shown between the two anti-fibrotic agents currently in clinical use. There was no significant difference in efficacy of antifibrotic therapy whether the underlying condition was IPF or non-IPF with progressive fibrosis, supporting the hypothesis of a common pathogenesis. The data in this analysis was insufficient to be confident about a reduction in mortality in non-IPF with anti-fibrotic therapy. Trial Registration PROSPERO, registration number CRD42021266046.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antifibrotic Agents; Cause of Death; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pulmonary Fibrosis; Pyridones; Treatment Outcome
PubMed: 34895203
DOI: 10.1186/s12890-021-01783-1 -
European Journal of Medical Research Oct 2021It is necessary to systematically evaluate the efficacy and adverse reactions of pirfenidone in the treatment of patients with idiopathic pulmonary fibrosis (IPF). (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is necessary to systematically evaluate the efficacy and adverse reactions of pirfenidone in the treatment of patients with idiopathic pulmonary fibrosis (IPF).
METHODS
Pubmed et al. databases were searched up to March 15, 2021 for randomized controlled trials (RCT) of pirfenidone in the treatment of IPF. Two authors collected and compared the indicators including progression-free survival (PFS), vital capacity (VC), forced vital capacity (FVC), and adverse reactions. RevMan 5.3 software and Stata 15.0 software were used for meta-analysis.
RESULTS
A total of 8 reports with 9 RCTs involving 1824 IPF patients were included. Meta-analysis results showed that compared with the control group, pirfenidone could prolong the PFS phase of IPF patients (HR = 0.65, 95% CI 0.55 ~ 0.76, P < 0.001), slow down the VC of IPF patients (SMD = 0.43, 95% CI 0.21 ~ 0.66, P < 0.001), and decrease FVC (SMD = 0.31, 95% CI 0.14 ~ 0.48, P < 0.001). The main adverse reactions of pirfenidone were gastrointestinal reactions, photosensitivity and skin rashes.
CONCLUSION
Pirfenidone is beneficial to prolong the PFS of IPF patients, improve lung function, and it is safe for clinical use. However, more high-quality RCTs are still needed to provide reliable evidence for the treatment of IPF.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diarrhea; Exanthema; Humans; Idiopathic Pulmonary Fibrosis; Lung; Nausea; Progression-Free Survival; Pyridones; Treatment Outcome; Vital Capacity
PubMed: 34717762
DOI: 10.1186/s40001-021-00601-y -
Arthritis Research & Therapy Jun 2021New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years,... (Review)
Review
New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study and the results obtained were reviewed. Of the 973 references identified, 21 (4 conference abstracts and 17 articles) were included in the systematic review. A total of 15 phase 1/phase 2 clinical trials, 2 phase 3 clinical trials and 2 observation studies were analysed. The drugs studied in phase 1/phase 2 studies included the following: inebilizumab, dabigatran, C-82, pomalidomide, rilonacept, romilkimab, tocilizumab, tofacitinib, pirfenidone, lenabasum, abatacept, belimumab, riociguat, SAR100842 and lanifibranor. All but 3 studies were performed in early diffuse SSc patients with different inclusion criteria, while 3 studies were performed in SSc patients with interstitial lung disease (ILD). Phase 3 clinical trials investigated nintedanib and tocilizumab. Nintedanib was investigated in SSc-ILD patients whereas tocilizumab focused on early diffuse SSc patients with inflammatory features. Two observational studies including > 50 patients with rituximab as the targeted drug were also evaluated. All these studies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc.
Topics: Humans; Lung Diseases, Interstitial; Scleroderma, Diffuse; Scleroderma, Systemic
PubMed: 34074331
DOI: 10.1186/s13075-021-02536-5 -
BMC Pulmonary Medicine May 2020While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression. Antioxidative therapy with N-acetylcysteine (NAC) is considered a potential additional therapy that can be combined with antifibrotics in some patients in clinical practice. However, data on the efficacy, tolerability, and safety of this combination are scarce. We performed a systematic review and meta-analysis to appraise the safety, tolerability, and efficacy of the combination compared to treatment with pirfenidone alone.
METHODS
We systematically reviewed all the published studies with combined pirfenidone (PFD) and NAC (PFD + NAC) treatment in IPF patients. The primary outcomes referred to decline in pulmonary function tests (PFTs) and the rates of IPF patients with side effects.
RESULTS
In the meta-analysis, 6 studies with 319 total IPF patients were included. The PFD + NAC group was comparable to the PFD alone group in terms of the predicted forced vital capacity (FVC%) and predicted diffusion capacity for carbon monoxide (DLco%) from treatment start to week 24. Side effects and treatment discontinuation rates were also comparable in both groups.
CONCLUSION
This systematic review and meta-analysis suggests that combination with NAC does not alter the efficacy, safety, or tolerability of PFD in comparison to PFD alone in IPF patients.
Topics: Humans; Acetylcysteine; Administration, Inhalation; Anti-Inflammatory Agents, Non-Steroidal; Carbon Monoxide; Drug Therapy, Combination; Free Radical Scavengers; Idiopathic Pulmonary Fibrosis; Pyridones; Randomized Controlled Trials as Topic; Treatment Outcome; Vital Capacity
PubMed: 32380989
DOI: 10.1186/s12890-020-1121-2 -
Journal of Drug Assessment 2019Clinical practice guidelines for the treatment of idiopathic pulmonary fibrosis (IPF) currently recommend pirfenidone and nintedanib. However, there is a lack of...
Clinical practice guidelines for the treatment of idiopathic pulmonary fibrosis (IPF) currently recommend pirfenidone and nintedanib. However, there is a lack of evidence from head-to-head comparisons. To perform a systematic review and network meta-analysis (NMA) to access the efficacy and tolerability of two new treatments for IPF, pirfenidone and nintedanib. : Randomized controlled trials (RCTs) selection (CENTRAL, MEDLINE, Embase), data extraction, risk of bias analysis, and GRADE assessment were carried out by two authors separately. Direct estimates were calculated using standard pairwise meta-analysis. A Bayesian mixed treatment comparison approach for NMA estimates, with 95% confidence intervals (CI), was used to compare the treatments, calculating odds ratios (OR) and number needed to treat (NNTB) or harm (NNTH). The NMA on 10 randomized controlled trials showed that each drug had a positive effect on percentage of forced vital capacity (FVC) decline ≥ 10% (pirfenidone OR = 0.54 [95% CI = 0.37-0.80], NNTB = 9 [95% CI = 7-22]; nintedanib OR = 0.59 [95% CI = 0.41-0.84], NNTB = 9 [95% CI = 6-23]), but no significant differences were noted when comparing pirfenidone and nintedanib with respect to acute exacerbations, mortality, and serious adverse events (FVC decline OR = 0.91 [95% CI = 0.45-2.03]) or dropouts (OR = 0.75 [95% CI = 0.33-1.27]). Nintedanib showed an effect on dropouts, OR = 1.61 (1.13-2.28) and NNTH = 14 (8-61). Based on RCTs of 12 month duration in patients with IPF, a positive effect on FVC decline was noted for both treatments and on dropouts for nintedanib, but no significant differences were noted between treatments.
PubMed: 31044096
DOI: 10.1080/21556660.2019.1597726 -
ERJ Open Research Oct 2018Narrative reviews are frequently accessed; however, the content and quality of review articles on idiopathic pulmonary fibrosis (IPF) have not been assessed. A...
Narrative reviews are frequently accessed; however, the content and quality of review articles on idiopathic pulmonary fibrosis (IPF) have not been assessed. A systematic review assessed content and quality of narrative review articles that addressed the diagnosis or management of IPF and were published from 2001 to 2015. Article recommendations were assessed relative to contemporary IPF guidelines. Quality was assessed using the DISCERN instrument. Articles were predominantly written by physicians and published in respiratory journals. Conflicts of interest and sources of funding were reported in 52% and 24% of reviews, respectively. European authors were more likely to recommend bronchoscopy (adjusted p=0.02) and were more likely to recommend pirfenidone or nintedanib prior to publication of definitive clinical trials (adjusted p=0.04). A total of 39% of management-focused articles suggested therapies that were never recommended in guidelines. Predictors of higher article quality were citation of the contemporary IPF guideline (p=0.01) and more recent publication (p=0.001). Quality of reviews increased over time; however, review articles frequently made discordant recommendations compared to IPF guidelines. These findings indicate the need for authors, peer reviewers, editors and readers to critically appraise the content and quality of narrative reviews on IPF, and the need for frequent guideline updates to reflect new evidence.
PubMed: 30588478
DOI: 10.1183/23120541.00156-2018 -
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 -
Journal of Clinical Medicine Dec 2016Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disorder showcasing an interaction between genetic predisposition and environmental... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disorder showcasing an interaction between genetic predisposition and environmental risks. This usually involves the coaction of a mixture of cell types associated with abnormal wound healing, leading to structural distortion and loss of gas exchange function. IPF bears fatal prognosis due to respiratory failure, revealing a median survival of approximately 2 to 3 years. This review showcases the ongoing progress in understanding the complex pathophysiology of IPF and it highlights the latest potential clinical treatments. In IPF, various components of the immune system, particularly clotting cascade and shortened telomeres, are highly involved in disease pathobiology and progression. This review also illustrates two US Food and Drug Administration (FDA)-approved drugs, nintedanib (OFEV, Boehringer Ingelheim, Ingelheim am Rhein, Germany) and pirfenidone (Esbriet, Roche, Basel, Switzerland), that slow IPF progression, but unfortunately neither drug can reverse the course of the disease. Although the mechanisms underlying IPF remain poorly understood, this review unveils the past and current advances that encourage the detection of new IPF pathogenic pathways and the development of effective treatment methods for the near future.
PubMed: 28035951
DOI: 10.3390/jcm6010002