Effect of Pirfenidone on All-Cause Mortality in Patients With Idiopathic Pulmonary Fibrosis (IPF): Comparison of Pooled Analysis With Meta-analysis From the ASCEND and CAPACITY Trials

CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 363A
Author(s):  
Steven Nathan ◽  
Carlo Albera ◽  
Williamson Bradford ◽  
Ulrich Costabel ◽  
Monica Daigl ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
All Cause Mortality

scholarly journals The effect of additional antimicrobial therapy on the outcomes of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ching-Yi Chen ◽  
Chao-Hsien Chen ◽  
Cheng-Yi Wang ◽  
Chih-Cheng Lai ◽  
Chien-Ming Chao ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Usual Care ◽  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Meta Analysis ◽  
Lung Function Decline ◽  
Increased Risk ◽  
Significant Difference ◽  
All Cause Mortality

Abstract Background The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. Methods We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs). Results Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI − 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI − 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001). Conclusions In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.

Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis

2020 ◽  
pp. 106002802096445
Author(s):  
Enrica Di Martino ◽  
Alessio Provenzani ◽  
Patrizio Vitulo ◽  
Piera Polidori
Keyword(s):  
Systematic Review ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
World Health ◽  
Effect Model ◽  
All Cause Mortality ◽  
Positive Effect

Background: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown. Objective: To perform a systematic review and meta-analysis (MA) of these drugs for IPF. Methods: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization’s registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen’s d for change from baseline FVC (in percentage predicted and liters) and odds ratio (OR) for 10% reduction in FVC and all-cause mortality (ACM). Results: Six studies were included in the MA. For change from baseline in percentage predicted FVC, the MA indicated that the 3 drugs were more effective than placebo (pirfenidone: d=3.30%, 95% CI=2.15-4.45; nintedanib: d=3.15%, 95% CI=2.35-3.95; pamrevlumab: d=4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: d=0.09L, 95% CI=0.04-0.14; nintedanib: d=0.13L, 95% CI=0.10-0.16; pamrevlumab: d=0.20L, 95% CI=0.05-0.35). Each drug had a positive effect on 10% reduction in FVC (pirfenidone: OR=0.57, 95% CI=0.45-0.74; nintedanib: OR=0.66, 95% CI=0.51-0.85; pamrevlumab: OR=0.24, 95% CI=0.08-0.73), but only pirfenidone showed an effect on ACM (OR=0.50; 95% CI=0.31-0.83). Conclusion and Relevance: This MA provided encouraging results on pamrevlumab efficacy in slowing the decline in FVC compared with pirfenidone and nintedanib. Actually, in phase 3, it could become a potential IPF treatment.

scholarly journals Systematic review and meta-analysis of clinical significance of autoantibodies for idiopathic pulmonary fibrosis

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e027849 ◽  
Author(s):  
Hiroyuki Kamiya ◽  
Ogee Mer Panlaqui
Keyword(s):  
Systematic Review ◽  
Autoimmune Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Clinical Significance ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Quality Of Evidence ◽  
All Cause Mortality

ObjectiveTo clarify clinical significance of the sole presence of autoantibodies for idiopathic pulmonary fibrosis (IPF) without any other symptoms or signs suggestive of autoimmune disease.DesignSystematic review and meta-analysisData sourcesMedline, EMBASE, Science Citation Index Expanded and Google Scholar were searched from 1 January 2002 through 12 February 2019.Eligibility criteria for selecting studiesPrimary studies addressing all-cause mortality and the development of a defined autoimmune disease for IPF with autoantibodies were included for the review.Data extraction and synthesisTwo reviewers extracted relevant data and assessed risk of bias independently. Meta-analysis was conducted using a random-effects model if three or more studies reported the same outcome for a certain autoantibody. The quality of evidence was assessed by the Grades of Recommendation, Assessment, Development and Evaluation system.ResultsOut of 4603 records retrieved nine studies were included in this review. All studies contained some risk of bias. Based on pooled data myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) was significantly associated with microscopic polyangiitis incidence with risk ratio (RR) of 20.2 (95% CI: 7.22 to 56.4) and antinuclear antibody (ANA) was also significantly associated with the development of connective tissue diseases with RR of 7.11 (p=0.001) (10 cases in 157 patients with ANA) in one study. However, there was no significant association of autoantibodies with all-cause mortality aside from MPO-ANCA and proteinase 3-ANCA in one study each. MPO-ANCA was not demonstrated to be associated with all-cause mortality by meta-analysis. The quality of evidence was deemed as either low or very low.ConclusionsThe presence of autoantibodies such as MPO-ANCA and ANA was demonstrated to be associated with the development of some autoimmune diseases for patients with IPF although there was no difference of all-cause mortality. However, the results should be interpreted with caution due to low evidence level.PROSPERO registration numberCRD42017077336.

scholarly journals The effect of additional antimicrobial therapy on the outcomes of patients with idiopathic pulmonary fibrosis: A systematic review and meta-analysis

2021 ◽  
Author(s):  
Ching-Yi Chen ◽  
Chao-Hsien Chen ◽  
Cheng-Yi Wang ◽  
Chih-Cheng Lai ◽  
Chien-Ming Chao ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Usual Care ◽  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Meta Analysis ◽  
Lung Function Decline ◽  
Increased Risk ◽  
Significant Difference ◽  
All Cause Mortality

Abstract Background The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. Methods We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs). Results Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were enrolled in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI, -0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI, -0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR, 1.65; 95% CI, 1.19–2.27; p = 0.002), especially gastrointestinal disorders (OR, 1.54; 95% CI, 1.10–2.15; p = 0.001). Conclusion In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.

Prognostic role of Krebs von den Lungen-6 (KL-6) measurement in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elena Aloisio ◽  
Federica Braga ◽  
Chiara Puricelli ◽  
Mauro Panteghini
Keyword(s):  
Systematic Review ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Binary Data ◽  
Meta Analysis ◽  
Mortality Prediction ◽  
Asian Populations ◽  
Increased Risk ◽  
Using Data ◽  
Patient Prognosis

Abstract Objectives Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease with limited therapeutic options. The measurement of Krebs von den Lungen-6 (KL-6) glycoprotein has been proposed for evaluating the risk of IPF progression and predicting patient prognosis, but the robustness of available evidence is unclear. Methods We searched Medline and Embase databases for peer-reviewed literature from inception to April 2020. Original articles investigating KL-6 as prognostic marker for IPF were retrieved. Considered outcomes were the risk of developing acute exacerbation (AE) and patient survival. Meta-analysis of selected studies was conducted, and quantitative data were uniformed as odds ratio (OR) or hazard ratio (HR) estimates, with corresponding 95% confidence intervals (CI). Results Twenty-six studies were included in the systematic review and 14 were finally meta-analysed. For AE development, the pooled OR (seven studies) for KL-6 was 2.72 (CI 1.22–6.06; p=0.015). However, a high degree of heterogeneity (I2=85.6%) was found among selected studies. Using data from three studies reporting binary data, a pooled sensitivity of 72% (CI 60–82%) and a specificity of 60% (CI 52–68%) were found for KL-6 measurement in detecting insurgence of AE in IPF patients. Pooled HR (seven studies) for mortality prediction was 1.009 (CI 0.983–1.036; p=0.505). Conclusions Although our meta-analysis suggested that IPF patients with increased KL-6 concentrations had a significant increased risk of developing AE, the detection power of the evaluated biomarker is limited. Furthermore, no relationship between biomarker concentrations and mortality was found. Caution is also needed when extending obtained results to non-Asian populations.

scholarly journals Comparative outcomes in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Manon Belhassen ◽  
Faustine Dalon ◽  
Maëva Nolin ◽  
Eric Van Ganse
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Treatment Initiation ◽  
Proportional Hazards Model ◽  
Research Question ◽  
National Health System ◽  
Cox Proportional Hazards Model ◽  
Time To Treatment ◽  
All Cause Mortality ◽  
Time To Treatment Initiation

Abstract Background Real-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. In France, pirfenidone and nintedanib are only reimbursed for documented IPF, with similar reimbursement criteria with respect to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in multidisciplinary discussion. Research question The data of the comprehensive French National Health System were used to evaluate outcomes in patients newly treated with pirfenidone or nintedanib in 2015–2016. Study design and methods Patients aged < 50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. All-cause mortality, acute respiratory-related hospitalisations and treatment discontinuations up to 31 December 2017 were compared using a Cox proportional hazards model adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period. Results During the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical contacts prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.8; 95% confidence interval [CI] 1.3–2.6), a greater risk of acute respiratory-related hospitalisations (HR 1.3; 95% CI 1.0–1.7) and a lower risk of treatment discontinuation at 12 months (HR 0.7; 95% CI 0.6–0.9). Interpretation This observational study identified potential differences in outcome under newly prescribed antifibrotic drugs, deserving further explorations.

scholarly journals Effect of Uric Acid-Lowering Agents on Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

2021 ◽  
Vol 8 ◽  
Author(s):  
Hongxuan Xu ◽  
Yunqing Liu ◽  
Lingbing Meng ◽  
Li Wang ◽  
Deping Liu
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Uric Acid ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Controlled Trials ◽  
Heart Failure Patients ◽  
All Cause Mortality ◽  
Randomised Controlled

Background: Elevated serum uric acid (SUA) level is considered an independent predictor of all-cause mortality and the combined endpoint of death or readmission in cardiovascular disease patients. However, the causal relationship between uric acid-lowering therapies (ULTs) and heart failure is still controversial.Design: Meta-analyses were performed to systematically compile available evidence to determine the overall effect of ULTs on heart failure patients.Method: We conducted this systematic review following the PRISMA statement guidelines. Databases were searched to identify randomised controlled trials related to the influence of a ULT intervention in people with heart failure. Data extracted from the included studies were subjected to a meta-analysis to compare the effects of ULTs to a control.Results: Pooled analysis of left ventricular ejection fraction (LEVF) showed an insignificant result towards the ULT group (MD, 1.63%; 95%CI, −1.61 to 4.88; p = 0.32; three studies). Pooled analysis of the 6-Minute Walk Test (6MWT) showed an insignificant result towards the ULT group (MD, 4.59; 95%CI, −12.683 to 22.00; p = 0.61; four studies). Pooled analysis of BNP/NT-pro-BNP led to a nearly statistically significant result towards the ULT group (SMD, −0.30; 95%CI, −0.64 to 0.04; p = 0.08; five studies). Pooled analysis of all-cause mortality and cardiovascular death between ULTs (all XOIs) and placebo did not show a significant difference (RR, 1.26; 95% CI, 0.74 to 2.15, p = 0.39).Conclusion: ULTs did not improve LVEF, BNP/NT-pro-BNP, 6MWT, all-cause mortality, and CV death in heart failure patients. UA may just be a risk marker of heart failure.

scholarly journals Efficacy and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis patients: a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e050004
Author(s):  
Wenjuan Wu ◽  
Lingxiao Qiu ◽  
Jizhen Wu ◽  
Xueya Liu ◽  
Guojun Zhang
Keyword(s):  
Systematic Review ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Events ◽  
Acute Exacerbation ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomised Controlled

ObjectivesIdiopathic 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.DesignThis is a meta-analysis study.ParticipantsPatients were diagnosed as IPF.InterventionsUse of pirfenidone.Primary and secondary outcomeProgression-free survival (PFS), acute exacerbation and worsening of IPF and Impact on adverse events.MeasuresThe inverse variance method for the random-effects model was used to summarise the dichotomous outcomes, risk ratios and 95% CIs.ResultsA 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).ConclusionsPirfenidone 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.

scholarly journals Morbidity and Mortality Reduction Associated with Polysomnography Testing in Idiopathic Pulmonary Fibrosis: A Population-Based Cohort Study

2021 ◽  
Author(s):  
Nicholas T Vozoris ◽  
Andrew S Wilton ◽  
Peter C Austin ◽  
Tetyana Kendzerska ◽  
Clodagh M Ryan ◽  
...  
Keyword(s):  
Cohort Study ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Health Outcomes ◽  
Index Date ◽  
Population Based ◽  
Sleep Breathing Disorders ◽  
Breathing Disorders ◽  
All Cause Mortality ◽  
Important Health

Abstract Background: It is not well-known if diagnosing and treating sleep breathing disorders among individuals with idiopathic pulmonary fibrosis (IPF) improves health outcomes. We evaluated the association between receipt of laboratory-based polysomnography (which is the first step in the diagnosis and treatment of sleep breathing disorders in Ontario, Canada) and respiratory-related hospitalization and all-cause mortality among individuals with IPF.Methods: We used a retrospective, population-based, cohort study design, analyzing health administrative data from Ontario, Canada, from 2007-2019. Individuals with IPF were identified using an algorithm based on health administrative codes previously developed by IPF experts. Propensity score matching was used to account for potential differences in 41 relevant covariates between individuals that underwent polysomnography (exposed) and individuals that did not undergo polysomnography (controls), in order minimize potential confounding. Respiratory-related hospitalization and all-cause mortality were evaluated up to 12 months after the index date. Results: Out of 5044 individuals with IPF identified, 201 (4.0%) received polysomnography, and 189 (94.0%) were matched to an equal number of controls. Compared to controls, exposed individuals had significantly reduced rates of respiratory-related hospitalization (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.24-0.75), p=0.003) and all-cause mortality (HR 0.49, 95% CI 0.30-0.80), p=0.004). Significantly reduced rate of respiratory-related hospitalization (but not all-cause mortality) was also observed among those with >=1 respiratory-related hospitalization (HR 0.38, 95% CI 0.15-0.99) and systemic corticosteroid receipt (HR 0.37, 95% CI 0.19-0.94) in the year prior to the index date, which reflect sicker subgroups of persons. Conclusions: Undergoing polysomnography was associated with significantly improved clinically-important health outcomes among individuals with IPF, highlighting the potential importance of incorporating this testing in IPF disease management.

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