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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 -
International Journal of Molecular... Apr 2023Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use... (Review)
Review
Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use worldwide. These drugs have been shown to reduce the rate of decline in forced vital capacity and the risk of acute exacerbation among patients with idiopathic pulmonary fibrosis. Recent data suggest that different interstitial lung diseases with a progressive pulmonary fibrosis phenotype can share similar pathogenetic and biological pathways and could be amenable to antifibrotic therapies. Indeed, historical management strategies in interstitial lung disease have failed to identify potential treatments once progression has occurred despite available drugs. In this systematic review, we summarized data on the efficacy of pirfenidone and nintedanib in interstitial lung diseases other than idiopathic pulmonary fibrosis as well as ongoing and upcoming clinical trials. We identify two well-designed trials regarding nintedanib demonstrating the efficacy of this drug in slowing disease progression in patients with interstitial lung diseases other than idiopathic pulmonary fibrosis. On the other hand, results on the use of pirfenidone in interstitial lung diseases other than idiopathic pulmonary fibrosis should be interpreted with more caution on the basis of trial limitations. Several randomized control trials are underway to improve the quality of evidence in the interstitial lung disease field.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Indoles; Pyridones; Treatment Outcome
PubMed: 37175556
DOI: 10.3390/ijms24097849 -
Respiratory Medicine Sep 2023The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) ranges from asymptomatic findings on radiographic imaging to a rapidly progressive illness leading to respiratory failure and death. The treatment is always challenging due to the paucity of proven effective treatments. Nintedanib and pirfenidone are recently approved antifibrotics in idiopathic pulmonary fibrosis. This study aimed to investigate the efficacy and safety of antifibrotic agents in the treatment of CTD-ILD and RA-ILD.
METHODS
Relevant databases were searched for randomized controlled trials that compared pirfenidone or nintedanib with placebo in patients with CTD-ILD and RA-ILD. The primary outcome was the change in forced vital capacity (FVC). The odds ratio or risk ratio with 95% confidence interval (CI) was estimated for categorical data, and the mean difference with 95% CI was estimated for continuous data. The I statistic was used to assess heterogeneity, and meta-analysis was performed when possible.
RESULTS
Ten studies with a total of 880 participants met the inclusion criteria. Of these, four studies were included in the meta-analysis. According to the pooled result, the annual decline of FVC was significantly decreased in the antifibrotic agent arm compared to that in the placebo arm (MD 70.58 mL/yr, 95% CI 40.55 to 100.61).
CONCLUSION
This review suggests a potential benefit and safety of antifibrotic treatment in slowing the decline of FVC in patients with CTD-ILD and RA-ILD. Further large-sample, random-controlled, high-quality trials are needed to provide more evidence in the decision-making regarding the use of antifibrotics in this group of patients.
CLINICAL TRIAL REGISTRATION
PROSPERO; No: CRD42022369112; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Antifibrotic Agents; Lung Diseases, Interstitial; Connective Tissue Diseases; Idiopathic Pulmonary Fibrosis; Vital Capacity
PubMed: 37315742
DOI: 10.1016/j.rmed.2023.107329 -
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 -
Journal of Immunology (Baltimore, Md. :... May 2023The mammalian heart is characterized by the presence of striated myocytes, which allow continuous rhythmic contraction from early embryonic development until the last...
The mammalian heart is characterized by the presence of striated myocytes, which allow continuous rhythmic contraction from early embryonic development until the last moments of life. However, the myocardium contains a significant contingent of leukocytes from every major class. This leukocyte pool includes both resident and nonresident immune cells. Over recent decades, it has become increasingly apparent that the heart is intimately sensitive to immune signaling and that myocardial leukocytes exhibit an array of critical functions, both in homeostasis and in the context of cardiac adaptation to injury. Here, we systematically review current knowledge of all major leukocyte classes in the heart, discussing their functions in health and disease. We also highlight the connection between the myocardium, immune cells, lymphoid organs, and both local and systemic immune responses.
Topics: Animals; Myocytes, Cardiac; Myocardium; Leukocytes; Signal Transduction; Mammals
PubMed: 37068299
DOI: 10.4049/jimmunol.2200924 -
Cureus Feb 2024Idiopathic pulmonary fibrosis (IPF), which shares a radiographic pattern with the usual interstitial pneumonia (UIP), is a specific form of chronic and progressive... (Review)
Review
Idiopathic pulmonary fibrosis (IPF), which shares a radiographic pattern with the usual interstitial pneumonia (UIP), is a specific form of chronic and progressive interstitial lung disorder resulting in persistent fibrosis and impaired lung function. Most of the patients suffer from dyspnea which adversely affects health-related quality of life (HRQOL). The underlying etiology of the disease is not yet understood, but research done on the subject reveals that aberrant repair mechanisms and dysregulated immune responses may be the cause. It can affect any age group but predominantly affects patients who are above 50 years of age. It has been observed that in addition to age, the reasons are also related to smoking, pollution, and inhalation of harmful elements. As the cause of IPF is still unknown and there is no cure yet, presently, it is treated to delay lung function loss with antifibrotic medications, nintedanib, and pirfenidone. However, both nintedanib and perfenidone have side effects which affect different patients in different ways and with different levels of severity, thereby making the treatment even more challenging for medical practitioners. The present systematic review aims at studying the efficacy of pirfenidone and nintedanib in relieving symptoms and in extending survival in patients. A detailed search was done in relevant articles listed in PubMed, ScienceDirect, and the New England Journal of Medicine between 2018 and 2023. It was observed that the most accepted way of measuring the progression of IPF is the evaluation of pulmonary function by assessing the forced vital capacity (FVC). Several studies have shown that the decline in FVC over a period of 6-12 months is directly associated with a higher mortality rate. The outcomes were similar in both male and female irrespective of age, gender, and ethnicity. However, some patients being treated with pirfenidone and nintedanib experienced various side-effects which were mainly gastrointestinal like diarrhea, dyspepsia, and vomiting. In the case of pirfenidone, some patients also experienced photosensitivity and skin rashes. In cases where the side-effects are extremely severe and are more threatening than the disease itself, the treatment has to be discontinued. The survival rate in patients with IPF is marked by a median of 3-5 years that is even lower than many cancers; hence, the treatment should be started as soon as the disease is detected. However, further research is needed to establish the etiology of IPF and to establish treatments that can stop its progression.
PubMed: 38500898
DOI: 10.7759/cureus.54268 -
EClinicalMedicine Jul 2023Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis and a high economic burden for individuals and healthcare resources....
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis and a high economic burden for individuals and healthcare resources. Studies of the costs associated with the efficiency of IPF medications are scarce. We aimed to conduct a network meta-analysis (NMA) and cost-effectiveness analysis to identify the optimum pharmacological strategy among all currently available IPF regimens.
METHODS
We first performed a systematic review and network meta-analysis. We searched eight databases for eligible randomised controlled trials (RCTs) published, in any language, between January 1, 1992 and July 31, 2022, that investigated the efficacy or tolerability (or both) of drug therapies for the treatment of IPF. The search was updated on February 1, 2023. Eligible RCTs were enrolled, with no restriction on dose, duration, or length of follow-up, if they included at least one of: all-cause mortality, acute exacerbation rate, disease progression rate, serious adverse events, and any adverse events under investigation. A subsequent Bayesian NMA within random-effects models was performed, followed by a cost-effectiveness analysis using the data obtained from our NMA, by developing a Markov model from the US payer's perspective. Assumptions were checked by deterministic and probabilistic sensitivity approaches to identify sensitive factors. We prospectively registered the protocol (CRD42022340590) in PROSPERO.
FINDINGS
51 publications comprising 12,551 participants with IPF were analysed for the NMA, and the findings indicated that pirfenidone and -acetylcysteine (NAC) + pirfenidone were the most efficacious and tolerable. The pharmacoeconomic analysis showed that NAC + pirfenidone was associated with the highest potentiality of being cost-effective at willingness-to-pay (WTP) thresholds of US$150,000 and $200,000, on the basis of quality-adjusted life years (QALYs), disability-adjusted life years (DALYs) and mortality, with the probability ranging from 53% to 92%. NAC was the minimum cost agent. Compared with placebo, NAC + pirfenidone improved effectiveness by increasing QALYs by 7.02, and reducing DALYs by 7.10 and deaths by 8.40, whilst raising overall costs by $516,894.
INTERPRETATION
This NMA and cost-effectiveness analysis suggests that NAC + pirfenidone is the most cost-effective option for treatment of IPF at WTP thresholds of $150,000 and $200,000. However, given that clinical practice guidelines have not addressed the application of this therapy, large well-designed and multicentre trials are warranted to provide a better picture of IPF management.
FUNDING
None.
PubMed: 37434745
DOI: 10.1016/j.eclinm.2023.102071 -
Life (Basel, Switzerland) Dec 2023Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular clinical manifestation of rheumatoid arthritis (RA) that has negative... (Review)
Review
BACKGROUND
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular clinical manifestation of rheumatoid arthritis (RA) that has negative impacts on morbidity and mortality. In addition, there has been no proven treatment for RA-ILD to date. Thus, we planned a meta-analysis of a literature search to confirm the clinical effects of antifibrotic agents in RA-ILD patients.
MATERIALS AND METHODS
We conducted the literature search in Ovid MEDLIVE databases, Cochrane Library databases, EMBASE, and KoreaMed and identified references elucidating the role of nintedanib or pirfenidone in adult patients with RA-ILD. Among the identified studies, those with comparative interventions, complete results of clinical trials, and available full text were included in the analysis. The primary outcome was the effect of the antifibrotic agent on disease progression in RA-ILD patients assessed with a mean difference in the change of forced vital capacity (FVC) and the proportion of patients with an increase in percent predicted FVC of 10% or more over 52 weeks. Analysis for heterogeneity was assessed through I statistics. Meta-analysis with a fixed effect model was performed on changes in FVC.
RESULTS
A total of 153 articles were identified through database searches, of which 28 were excluded because of duplication. After additional screening, 109 studies were selected with full text and two articles qualified for analysis according to the set inclusion and exclusion criteria. As a result, two randomized controlled studies were selected, comparing nintedanib and pirfenidone to placebo, respectively. The meta-analysis revealed that antifibrotic agents showed a significant reduction in FVC decline compared to placebo in patients with RA-ILD (mean difference, 88.30; 95% CI, 37.10-139.50). Additionally, there were significantly fewer patients experienced an increase in percent predicted FVC of 10% or more in the antifibrotic agent group compared to the placebo group (Odds ratio 0.42; 95% CI 0.19-0.95, = 0.04). There was no significant heterogeneity between the two included studies (χ = 0.35, = 0.0007, I = 0%).
CONCLUSIONS
The meta-analysis suggests that nintedanib and pirfenidone may have clinical utility in reducing disease progression in patients with RA-ILD. Further research is needed to confirm the clinical benefits of antifibrotic agents in RA-ILD.
PubMed: 38137919
DOI: 10.3390/life13122318 -
BMC Pulmonary Medicine Nov 2023Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
RCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated.
RESULTS
Two independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty).
CONCLUSION
Moderate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.
Topics: Humans; Acetylcysteine; Pyridones; Treatment Outcome; Idiopathic Pulmonary Fibrosis
PubMed: 38031002
DOI: 10.1186/s12890-023-02778-w -
Journal of Thoracic Disease Nov 2023The role of combination treatments with two antifibrotic agents, pirfenidone and nintedanib, has been not established in idiopathic pulmonary fibrosis (IPF). This study...
BACKGROUND
The role of combination treatments with two antifibrotic agents, pirfenidone and nintedanib, has been not established in idiopathic pulmonary fibrosis (IPF). This study was performed to investigate the safety and tolerability of combination antifibrotic treatment in patients with IPF.
METHODS
We conducted a proportional meta-analysis and searched PubMed, EMBASE, and the Cochrane Central Register for relevant clinical trials. The primary outcome was the proportion of discontinuation of combination treatment over the treatment period. We also examined the pooled proportions of serious and any adverse drug reactions (ADRs).
RESULTS
Four clinical trials involving 191 patients were analyzed. In pooled estimates, 29% of patients discontinued treatment during the study period [95% confidence interval (CI): 17-41%, I=65.42%]. The pooled proportions of serious and any ADRs were 10% (95% CI: 1-19%; I=79.13%) and 82% (95% CI: 75-90%; I=39.20%), respectively. During the follow-up period, gastrointestinal symptoms were the most frequent ADR. Acute exacerbation (AE) of IPF was reported in 7.0% of patients.
CONCLUSIONS
Our findings showed relatively frequent incidence of discontinuation and ADRs for combination therapy in IPF. Further large-scale, randomized, controlled trials are needed to support our results because of the methodological limitations of the included trials and a scarcity of trials for analysis.
PubMed: 38090320
DOI: 10.21037/jtd-23-946