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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