-
European Journal of Clinical... Nov 2020SARS-CoV-2 infection has been divided by scientific opinion into three phases: the first as asymptomatic or slightly symptomatic and the second and the third with... (Review)
Review
The added value of pirfenidone to fight inflammation and fibrotic state induced by SARS-CoV-2 : Anti-inflammatory and anti-fibrotic therapy could solve the lung complications of the infection?
AIM
SARS-CoV-2 infection has been divided by scientific opinion into three phases: the first as asymptomatic or slightly symptomatic and the second and the third with greater severity, characterized by a hyperinflammatory and fibrotic state, responsible for lung lesions, in some cases fatal. The development of antiviral drugs directed against SARS-CoV-2 and effective vaccines is progressing; meanwhile, the best pharmacological objective is related to the management of all the complications caused by this viral infection, mainly controlling the inflammatory and fibrotic state and preventing the infection from moving into the most serious phases.
SUBJECT AND METHOD
Describe the scientific rationale related to the use of an antifibrotic therapy with pirfenidone, as monotherapy and/or in combination with anti-inflammatory drugs to manage and control complications of SARS-CoV-2 infection.
RESULTS
Based on the scientific literature and epidemiological results and considering the pathophysiological, biological, and molecular characteristics of SARS-CoV-2, an antifibrotic drug such as pirfenidone as monotherapy or in combination with anti-inflammatory drugs can be (acting early, at the right doses and at the right time) therapeutically effective to avoid serious complications during viral infection. The same approach can also be effective as postinfection therapy in patients with residual pulmonary fibrotic damage. Management of inflammation and fibrotic status with a combination therapy of pirfenidone and IL-6 or IL-1 inhibitors could represent a pharmacological synergy with added value.
CONCLUSION
In this article, we consider the role of antifibrotic therapy with pirfenidone in patients with SARS-CoV-2 infection on going or in the stage of postinfection with pulmonary fibrotic consequences. The scientific rationale for its use is also described.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Betacoronavirus; COVID-19; Coronavirus Infections; Drug Therapy, Combination; Humans; Inflammation; Interleukin-1; Interleukin-6; Pandemics; Pneumonia, Viral; Pulmonary Fibrosis; Pyridones; SARS-CoV-2
PubMed: 32594204
DOI: 10.1007/s00228-020-02947-4 -
Frontiers in Cardiovascular Medicine 2021Heart failure with preserved ejection fraction (HFpEF) is a major public health problem with growing prevalence and poor outcomes, mainly due to the lack of an effective... (Review)
Review
Heart failure with preserved ejection fraction (HFpEF) is a major public health problem with growing prevalence and poor outcomes, mainly due to the lack of an effective treatment. HFpEF pathophysiology is heterogeneous and complex. Recently a "new paradigm" has been proposed, suggesting that cardiovascular and non-cardiovascular coexisting comorbidities lead to a systemic inflammatory state, perturbing the physiology of the endothelium and the perivascular environment and engaging molecular pathways that ultimately converge to myocardial fibrosis. If inflammation and fibrosis are the "" in the heterogeneous spectrum of HFpEF, anti-fibrotic and anti-inflammatory drugs may have a role in its treatment. Pirfenidone is an orally bioavailable drug with antifibrotic and anti-inflammatory properties already approved for the treatment of idiopathic pulmonary fibrosis. Pirfenidone has been recently tested in animal models of myocardial fibrosis with promising results. Here we will review the rationale underlying the potential therapeutic effect of Pirfenidone in HFpEF.
PubMed: 33969025
DOI: 10.3389/fcvm.2021.678530 -
Cureus Jul 2021Idiopathic pulmonary fibrosis is a chronic and progressive disease with a significant mortality rate. Pirfenidone is one of two oral antifibrotic therapies approved to...
Idiopathic pulmonary fibrosis is a chronic and progressive disease with a significant mortality rate. Pirfenidone is one of two oral antifibrotic therapies approved to treat idiopathic pulmonary fibrosis (IPF). Pirfenidone helps decrease disease progression in patients with IPF and reduces vital capacity. This has led to widespread use of this medication in recent years. In this case report, we present a 60-year-old male who started treatment with pirfenidone for IPF and had severe skin reactions after initiation of therapy.
PubMed: 34458037
DOI: 10.7759/cureus.16626 -
Cells Mar 2020Intestinal fibrosis is a common complication of inflammatory bowel disease. So far, there is no safe and effective drug for intestinal fibrosis. Pirfenidone is an...
Intestinal fibrosis is a common complication of inflammatory bowel disease. So far, there is no safe and effective drug for intestinal fibrosis. Pirfenidone is an anti-fibrotic compound available for the treatment of idiopathic pulmonary fibrosis. Here, we explored the anti-proliferative and anti-fibrotic properties of pirfenidone on primary human intestinal fibroblasts (p-hIFs). p-hIFs were cultured in the absence and presence of pirfenidone. Cell proliferation was measured by a real-time cell analyzer (xCELLigence) and BrdU incorporation. Cell motility was monitored by live cell imaging. Cytotoxicity and cell viability were analyzed by Sytox green, Caspase-3 and Water Soluble Tetrazolium Salt-1 (WST-1) assays. Gene expression of fibrosis markers was determined by quantitative reverse transcription PCR (RT-qPCR). The mammalian target of rapamycin (mTOR) signaling was analyzed by Western blotting and type I collagen protein expression additionally by immunofluorescence microscopy. Pirfenidone dose-dependently inhibited p-hIF proliferation and motility, without inducing cell death. Pirfenidone suppressed mRNA levels of genes that contribute to extracellular matrix production, as well as basal and TGF-β1-induced collagen I protein production, which was associated with inhibition of the rapamycin-sensitive mTOR/p70S6K pathway in p-hIFs. Thus, pirfenidone inhibits the proliferation of intestinal fibroblasts and suppresses collagen I production through the TGF-β1/mTOR/p70S6K signaling pathway, which might be a novel and safe anti-fibrotic strategy to treat intestinal fibrosis.
Topics: Cell Death; Cell Proliferation; Cells, Cultured; Collagen Type I; Extracellular Matrix Proteins; Fibroblasts; Humans; Intestines; Phosphorylation; Pyridones; RNA, Messenger; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; TOR Serine-Threonine Kinases; Transforming Growth Factor beta1
PubMed: 32235767
DOI: 10.3390/cells9030775 -
The American Journal of Managed Care Jul 2017Idiopathic pulmonary fibrosis (IPF) is the most prevalent type of idiopathic interstitial pneumonia, accounting for at least half of all diagnosed cases. Because it...
Idiopathic pulmonary fibrosis (IPF) is the most prevalent type of idiopathic interstitial pneumonia, accounting for at least half of all diagnosed cases. Because it lacks a cure, the goal of treatment for IPF is to stabilize or reduce the rate of disease progression. Nonpharmacologic treatment options for IPF consist of long-term oxygen treatment, lung transplantation, and pulmonary rehabilitation. In the past, pharmacologic therapies for IPF included anticoagulants and anti-inflammatory or immunosuppressive agents. However, in late 2014, 2 therapies were approved by the US FDA for use in IPF: nintedanib and pirfenidone. While treatment of IPF was previously significantly impeded by a lack of effective agents and a paucity of clinical trial data on which to base guideline recommendations, these new agents provide notable breakthroughs in management of IPF, and continued research may break further, new fertile ground for management.
Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Disease Progression; Enzyme Inhibitors; Female; Humans; Idiopathic Pulmonary Fibrosis; Immunosuppressive Agents; Indoles; Lung; Male; Middle Aged; Pyridones; United States
PubMed: 28978213
DOI: No ID Found -
Respirology (Carlton, Vic.) Jun 2021
Topics: Humans; Idiopathic Pulmonary Fibrosis; Pyridones
PubMed: 33890384
DOI: 10.1111/resp.14068 -
The Korean Journal of Internal Medicine Mar 2022Pirfenidone slows the progression of idiopathic pulmonary fibrosis (IPF). We investigated its efficacy and safety in terms of dose and disease severity in real-world...
BACKGROUND/AIMS
Pirfenidone slows the progression of idiopathic pulmonary fibrosis (IPF). We investigated its efficacy and safety in terms of dose and disease severity in real-world patients with IPF.
METHODS
This multicenter retrospective cohort study investigated 338 patients treated with pirfenidone between July 2012 and March 2018. Demographics, pulmonary function, mortality, and pirfenidone-related adverse events were also investigated. Efficacy was analyzed according to pirfenidone dose and disease severity using linear mixed-effects models to assess the annual decline rate of forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO).
RESULTS
The mean %FVCpredicted and %DLCOpredicted values were 72.6% ± 13.1% and 61.4% ± 17.9%, respectively. The mean duration of pirfenidone treatment was 16.1 ± 9.0 months. In the standard dose (1,800 mg/day) group, the mean %FVCpredicted was -6.56% (95% confidence interval [CI], -9.26 to -3.87) per year before, but -4.43% (95% CI, -5.87 to -3.00) per year after treatment with pirfenidone. In the non-standard lower dose group, the mean %FVCpredicted was -4.96% (95% CI, -6.82 to -3.09) per year before, but -1.79% (95% CI, -2.75 to -0.83) per year after treatment with pirfenidone. The FVC decline rate was significantly reduced, regardless of the Gender-Age-Physiology (GAP) stage. Adverse events and mortality were similar across dose groups; however, they were more frequent in GAP stages II-III than in the stage I group.
CONCLUSION
The effect of pirfenidone on reducing disease progression of IPF persisted even with a consistently lower dose of pirfenidone.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Idiopathic Pulmonary Fibrosis; Pyridones; Retrospective Studies; Treatment Outcome; Vital Capacity
PubMed: 34293852
DOI: 10.3904/kjim.2020.559 -
Core Evidence 2016The landscape of idiopathic pulmonary fibrosis (IPF) has changed. The significant progress regarding our knowledge on the pathogenesis of the disease together with the... (Review)
Review
The landscape of idiopathic pulmonary fibrosis (IPF) has changed. The significant progress regarding our knowledge on the pathogenesis of the disease together with the experience achieved after a series of negative trials has led to the development of two drugs for the treatment of IPF. Both pirfenidone and nintedanib can slow significantly the rate of disease progression. They are safe with side effects that can be either prevented by close collaboration between health care professionals and patients or treated successfully when they occur, rarely leading to treatment discontinuation. However, there are still few unanswered questions regarding the application of the beneficial results of pharmaceutical trials in the general population of IPF patients. Long-term "real-life" studies are being undertaken to answer these questions. In this article, we focus on the advances that have led to the development of the antifibrotic agents with particular focus on pirfenidone.
PubMed: 27445644
DOI: 10.2147/CE.S76549 -
PloS One 2022There is no clear evidence whether pirfenidone has a benefit in patients with probable or possible UIP, i.e. when idiopathic pulmonary fibrosis (IPF) is diagnosed with a...
BACKGROUND
There is no clear evidence whether pirfenidone has a benefit in patients with probable or possible UIP, i.e. when idiopathic pulmonary fibrosis (IPF) is diagnosed with a lower degree of diagnostic certainty. We report on outcomes of treatment with pirfenidone in IPF patients diagnosed with various degrees of certainty.
METHODS AND FINDINGS
We followed patients in the multi-national European MultiPartner IPF Registry (EMPIRE) first seen between 2015 and 2018. Patients were assessed with HRCT, histopathology and received a multi-disciplinary team (MDT) IPF diagnosis. Endpoints of interest were overall survival (OS), progression-free survival (PFS) and lung function decline.
RESULTS
A total of 1626 patients were analysed, treated with either pirfenidone (N = 808) or receiving no antifibrotic treatment (N = 818). When patients treated with pirfenidone were compared to patients not receiving antifibrotic treatment, OS (one-, two- and three-year probability of survival 0.871 vs 0.798; 0.728 vs 0.632; 0.579 vs 0.556, P = 0.002), and PFS (one-, two- and three-year probability of survival 0.597 vs 0.536; 0.309 vs 0.281; 0.158 vs 0.148, P = 0.043) was higher, and FVC decline smaller (-0.073 l/yr vs -0.169 l/yr, P = 0.017). The benefit of pirfenidone on OS and PFS was also seen in patients with probable or possible IPF.
CONCLUSIONS
This EMPIRE analysis confirms the favourable outcomes observed for pirfenidone treatment in patients with definitive IPF and indicates benefits also for patients with probable or possible IPF.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Idiopathic Pulmonary Fibrosis; Lung; Probability; Pyridones; Retrospective Studies; Treatment Outcome; Vital Capacity
PubMed: 36048805
DOI: 10.1371/journal.pone.0273854 -
Cell Death & Disease Jan 2023Hepatocellular carcinoma (HCC) with lung metastasis is associated with poor prognosis and poor therapeutic outcomes. Studies have demonstrated that stiffened stroma can...
Hepatocellular carcinoma (HCC) with lung metastasis is associated with poor prognosis and poor therapeutic outcomes. Studies have demonstrated that stiffened stroma can promote metastasis in various tumors. However, how the lung mechanical microenvironment favors circulating tumor cells remains unclear in metastatic HCC. Here, we found that the expression of cell migration-inducing hyaluronan-binding protein (CEMIP) was closely associated with lung metastasis and can promote pre-metastatic niche formation by increasing lung matrix stiffness. Furthermore, upregulated serum CEMIP was indicative of lung fibrotic changes severity in patients with HCC lung metastasis. By directly targeting CEMIP, pirfenidone can inhibit CEMIP/TGF-β1/Smad signaling pathway and reduce lung metastases stiffening, demonstrating promising antitumor activity. Pirfenidone in combination with sorafenib can more effectively suppress the incidence of lung metastasis compared with sorafenib alone. This study is the first attempt to modulate the mechanical microenvironment for HCC therapy and highlights CEMIP as a potential target for the prevention and treatment of HCC lung metastasis. CEMIP mediating an HCC-permissive microenvironment through controlling matrix stiffness. Meanwhile, Pirfenidone could reduce metastasis stiffness and increases the anti-angiogenic effect of Sorafenib by directly targeting CEMIP.
Topics: Humans; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Liver Neoplasms; Lung Neoplasms; Signal Transduction; Sorafenib; Tumor Microenvironment; Hyaluronoglucosaminidase
PubMed: 36639658
DOI: 10.1038/s41419-023-05550-4