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The American Journal of Chinese Medicine 2021Idiopathic pulmonary fibrosis (IPF), a tumor-like disease, is a serious and fatal pulmonary inflammatory condition usually characterized by irreversible destruction of...
Idiopathic pulmonary fibrosis (IPF), a tumor-like disease, is a serious and fatal pulmonary inflammatory condition usually characterized by irreversible destruction of the lung parenchyma, excessive matrix accumulation, and decline in lung function. IPF still remains a great burden to the universe. At the moment, the available therapeutic regimens utilized for IPF such as non-pharmacological therapies (lung transplantation) and pharmacological therapies (drugs, nintedanib, pirfenidone, etc.) are normally accompanied by significant limitations, such as adverse reactions, low bioavailability, poor selectivity, low-tissue distribution, instability, systemic toxicity, inconveniency and unsafe usage. There is a need for the exploration and discovery of new novel remedies by researchers and scientists globally. Recent numerous preliminary studies have laid significant emphasis and demonstrated the antifibrotic importance, good curative actions (little or no adverse reactions), and multiple target sites of the active components from traditional herbal medicine (THM) against IPF, which could serve as a modern, alternative and potential therapeutics or drug candidates in treating IPF. This paper extensively summarizes the pharmacological actions and signaling pathways or mechanisms of active components obtained from THM for treating IPF. Moreover, the sources and modernization, markets, relevant FDA and CFDA studies (the USA and China), preclinical analysis, and various compositions of THM currently under clinical trials are also highlighted. Additionally, this present analytical data would be instrumental towards further drug progression or advancement of active components from THM for the potential therapeutics of IPF in the future.
Topics: Herbal Medicine; Humans; Idiopathic Pulmonary Fibrosis; Medicine, Traditional; Phytotherapy; Plants, Medicinal
PubMed: 34107859
DOI: 10.1142/S0192415X2150052X -
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 -
The Annals of Pharmacotherapy Jun 2021The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic... (Meta-Analysis)
Meta-Analysis
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 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: =3.30%, 95% CI=2.15-4.45; nintedanib: =3.15%, 95% CI=2.35-3.95; pamrevlumab: =4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: =0.09L, 95% CI=0.04-0.14; nintedanib: =0.13L, 95% CI=0.10-0.16; pamrevlumab: =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.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pyridones; Treatment Outcome
PubMed: 33054319
DOI: 10.1177/1060028020964451 -
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 -
Biomedicine & Pharmacotherapy =... Sep 2017Pulmonary fibrosis (PF) is a lethal, chronic and progressive respiratory disease leading to interstitial lung damage and serious breathing problems. The pathogenic... (Review)
Review
Pulmonary fibrosis (PF) is a lethal, chronic and progressive respiratory disease leading to interstitial lung damage and serious breathing problems. The pathogenic mechanism involves activation, migration, proliferation and differentiation of fibroblasts into myofibroblats inducing extracellular matrix accumulation that destroy lung parenchyma. Available antifibrotic treatment options are limited to Pirfenidone and Nintedanib that prevent deterioration without an improvement of this disease. The use of plant extracts and natural bioactive compounds for the treatment of PF has been known for more than thirty years in China. Nowadays, phytotherapy has gained a considerable attention in the treatment of PF both in vivo and in vitro using bleomycin (BLM)-induced lung inflammation, oxidative stress and pulmonary fibrosis in rats. In this review, we aimed to focus on the protective effects and the mechanisms of action of several plant extracts described by various research works for the treatment of PF.
Topics: Animals; Fibroblasts; Humans; Oxidative Stress; Phytotherapy; Plant Extracts; Pneumonia; Pulmonary Fibrosis
PubMed: 28688290
DOI: 10.1016/j.biopha.2017.06.052 -
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 -
Pulmonary Pharmacology & Therapeutics Oct 2016The prevalence of idiopathic pulmonary fibrosis (IPF) is increasing every year. Pirfenidone and nintedanib were approved for treatment of IPF in 2014, but they received... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of idiopathic pulmonary fibrosis (IPF) is increasing every year. Pirfenidone and nintedanib were approved for treatment of IPF in 2014, but they received only a conditional recommendation for use and, thus, to date no drugs are strongly recommended for IPF. The aim of this study was to assess the effectiveness and safety of the currently approved drugs for IPF and N-acetylcysteine (NAC), the most debated drug in the last update of guidelines for IPF treatment.
METHODS
RCTs in IPF were identified searching from databases of published and unpublished studies. The influence of pirfenidone, nintedanib and NAC on clinical outcomes, safety, and mortality was assessed via pair-wise meta-analysis.
RESULTS
Ten papers (3847 IPF patients; 2254 treated; 1593 placebo) were included in this study. Our results showed that both pirfenidone and nintedanib, but not NAC, were significantly effective in reducing FVC decline and the risk of FVC ≥10% decline in percent predicted over 12 months. Nintenadib significantly protected against the risk of acute exacerbation and mortality. Pirfenidone and nintedanib showed a similar and good safety profile, whereas NAC provided a signal for increased adverse events.
CONCLUSIONS
The rank of effectiveness emerging from this meta-analysis represents an indirect indicator of potential differences between currently approved doses of pirfenidone and nintedanib. Direct comparisons are necessary to assess this matter, and well designed bench-to-bedside studies would permit to understand the potential of combined, sequential, or adjunctive treatment regimens in which perhaps NAC may have a role for specific clusters of IPF patients.
Topics: Acetylcysteine; Anti-Inflammatory Agents; Enzyme Inhibitors; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Practice Guidelines as Topic; Pyridones; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27481628
DOI: 10.1016/j.pupt.2016.07.009