Recap trial pirfenidone

AEs were reported in nine out of 17 patients receiving nintedanib alone and ten out of 21 patients receiving nintedanib added to pirfenidone. All AEs were mild or moderate in intensity with gastrointestinal disorders such as nausea and vomiting having been the most common ones.

Nintedanib had no effect on the pharmacokinetics of pirfenidone, but a trend toward lower exposure of nintedanib when it was added to pirfenidone has been observed. Plainly, the short duration of the study is an important limitation, and in the future, longer studies are needed to confirm these results, and moreover, to provide evidence regarding the efficacy of the combination.

As already mentioned, patients with comorbidities have been excluded from the trials. Pulmonary hypertension, infections, and gastroesophageal reflux are very common and have been associated with disease progression. A combination of an antifibrotic drug with antireflux agents, antibiotics, and drugs that target the vascular component has been recently suggested.

In the recently revised guidelines, it has been suggested that clinicians use regular antiacid treatment for patients with IPF. On the other hand, there is no recommendation regarding the treatment of pulmonary hypertension in IPF, and specifically, there is a conditional recommendation against the use of sildenafil. The year was an amazing year for IPF. There are two drugs, pirfenidone and nintedanib, which are currently recommended for the treatment of the disease, and since our knowledge on the pathogenesis of IPF is in continuous progress, we may expect the development of other efficacious agents in the future.

Combination of drugs that target different pathogenetic pathways, a treatment approach widely used in other respiratory diseases, such as asthma, COPD, tuberculosis, and lung cancer, seems to be the basis for the design of future clinical trials. Until then and after years of waiting, we are more than happy to be able to offer our patients two weapons to combat this dismal disease.

Both drugs are efficacious and safe with a close collaboration between doctors, nurses, and patients being important in order to overcome side effects that can develop, mainly at the beginning of treatment. This approach will allow patients to gain as much benefits as possible from the antifibrotic therapy.

National Center for Biotechnology Information , U. Journal List Core Evid v. Core Evid. Published online Jul 1. Author information Copyright and License information Disclaimer. This work is published and licensed by Dove Medical Press Limited. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. This article has been cited by other articles in PMC.

Abstract The landscape of idiopathic pulmonary fibrosis IPF has changed. Keywords: antifibrotic, pirfenidone, photosensitivity, nausea. Open in a separate window.

Introduction There is no doubt that a new era has risen for idiopathic pulmonary fibrosis IPF treatment. Table 1 Completed clinical trials in IPF. Positive randomized controlled trials in IPF Nintedanib Nintedanib is an intracellular inhibitor that targets multiple tyrosine kinases, including the PDGF receptor, vascular endothelial growth factor receptors 1 and 2, and fibroblast growth factor receptors 1—3. Pirfenidone Preclinical studies Pirfenidone 5-methylphenyl[1 H ]-pyridone is an orally administered drug with antifibrotic, anti-inflammatory, and antioxidant effects.

Table 2 Prevention of side effects related to pirfenidone. Long-term safety and tolerability trials As shown in clinical trials, pirfenidone is efficacious because it can slow the rate of the progression of the disease. Open questions It is now well recognized that there are delays in the referral of patients with IPF to expert centers and consequently in the diagnosis of the disease. Conclusion The year was an amazing year for IPF.

Footnotes Disclosure The authors report no conflicts of interest in this work. References 1. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med.

Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. An update of the clinical practice guideline. Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence, and survival, — Lancet Respir Med. An update on idiopathic pulmonary fibrosis.

Panminerva Med. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med. Idiopathic pulmonary fibrosis: multiple causes and multiple mechanisms?

Eur Respir J. Armanios M. Syndromes of telomere shortening. Ann Rev Genomics Hum Genet. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis.

Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Smoking-related idiopathic interstitial pneumonia: a review.

Detection of herpes simplex virus type-1 in patients with fibrotic lung diseases. PLoS One. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Progression of idiopathic pulmonary fibrosis: lessons from asymmetrical disease. Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials. Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis.

Int J Biochem Cell Biol. MicroRNAs in idiopathic pulmonary fibrosis. Transl Res. Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology. American Thoracic Society; European Respiratory Society Idiopathic pulmonary fibrosis: diagnosis and treatment: international consensus statement.

High-dose acetylcysteine in idiopathic pulmonary fibrosis. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis INSPIRE : a multicentre, randomised, placebo-controlled trial.

Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis.

BUILD a randomized placebocontrolled trial of bosentan in idiopathic pulmonary fibrosis. BUILD a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomized controlled MUSIC trial.

Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis.

Imatinib treatment for idiopathic pulmonary fibrosis: randomized placebo-controlled trial results. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. Pirfenidone in idiopathic pulmonary fibrosis. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis.

Anticoagulant therapy for idiopathic pulmonary fibrosis. Warfarin in idiopathic pulmonary fibrosis: friend or foe, is it a matter of genes and heparin? BIBF triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. Life Sci. Effect of pirfenidone on rat hepatic stellate cell proliferation and collagen production.

J Hepatol. Eur J Pharm Sci. A novel anti-fibrotic agent pirfenidone suppresses tumor necrosis factor-alpha at the translational level. Eur J Pharmacol. Pirfenidone suppresses tumor necrosis factor-alpha, enhances interleukin and protects mice from endotoxic shock. Inhibition of tumor necrosis factor and subsequent endotoxin shock by pirfenidone. Int J Immunopharmacol. Pirfenidone blocks the in vitro and in vivo effects of staphylococcal enterotoxin B.

Infect Immun. Effects of pirfenidone on the generation of reactive oxygen species in vitro. J Environ Pathol Toxicol Oncol. Misra HP, Rabideau C. Mol Cell Biochem. In our survival analysis, we included all patients who received Pirfenidone at baseline, even those who interrupted the treatment for different reasons. However, patients who interrupted the treatment were not included in this analysis and as observed in trials outside IPF, withdrawals from drug trials have worse outcome [ 19 , 20 , 21 ].

Therefore, the open-label data do not actually show true mortality outcome on intention to treat with Pirfenidone. In the UHH cohort, 30 patients reported gastrointestinal discomfort and 17 patients have experienced photosensitivity. Three patients discontinued treatment due to gastrointestinal adverse events, 9 due to photosensitivity and 10 due to non-compliance. The rate of discontinuation due to adverse effects is One of the most frequent adverse events was a photosensitivity reaction, which is totally expected keeping in mind the weather condition in south Greece.

The rate of discontinuation due to a photosensitivity reaction is lower than in phase III trials and recently published real-life studies [ 6 , 22 , 23 , 24 , 25 ]. This is mainly due to a very detailed discussion between the treating physicians and the patient prior to the introduction of treatment.

A leaflet with helpful recommendations was given to every patient as a skin protection guide. Real-life studies have highlighted the importance of a frequent review of the patients by a specialist nurse as well as the importance of a contact number given to the patients so that they can communicate whenever they have questions about the drug or when they experience side effects. In UHH, a dedicated research fellow provides regular specialist input to provide support and education in order to improve concordance to treatment.

The effect of Pirfenidone on survival is remarkable if ones takes into account that patients with comorbidities and severe disease have been included in the UHH cohort unlike what happens in pharmaceutical trials. More real life studies with a higher number of patients who are unlikely to be eligible for inclusion in pharmaceutical trials are needed to evaluate the effect of Pirfenidone on disease progression.

Recent advances in the pathogenesis and clinical evaluation of pulmonary fibrosis. Eur Respir Rev. Cancer statistics, CA Cancer J Clin. Article Google Scholar.

Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur Respir J. Pirfenidone in the treatment of idiopathic pulmonary fibrosis: an evidence-based review of its place in therapy. Core Evidence. An update of the clinical practice guideline. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis.

Lancet Respir Med. Hot of the breath: mortality as a primary end-point in IPF treatment trials: the best is the enemy of the good. An open-label study of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis RECAP.

Comorbidities in interstitial lung diseases. Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study. Idiopathic pulmonary fibrosis: a composite physiologic index derived from disease extent observed by computed tomography. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. Effect of nintedanib in subgroups of idiopathic pulmonary fibrosis by diagnostic criteria.

Wells AU. Efficacy data in treatment extension studies of idiopathic pulmonary fibrosis: interpret with caution. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. Predicting life expectancy for pirfenidone in idiopathic pulmonary fibrosis.

J Manag Care Spec Pharm. PubMed Google Scholar. Arch Cardiovasc Dis. Clin Respir J. Lancet London, England. Pirfenidone treatment in idiopathic pulmonary fibrosis: nationwide Danish results. Eur Clin Respir J. Real world experiences: pirfenidone and nintedanib are effective and well tolerated treatments for idiopathic pulmonary fibrosis.

J Clin Med. Front Med. Download references. The authors would like to thank Dr. Konstantinos Karagiannis, Dr. Evangelia Stamataki and Mrs. Despoina Moraitaki Respiratory Medicine Department, University Hospital of Heraklion, Crete, Greece for their participation in the collection of the data and for the performance of the lung function tests.

George A. Antoniou contributed equally to this work. You can also search for this author in PubMed Google Scholar. WAW is on the speaker bureaus for F. FG is an employee of F. K-UK is an employee and shareholder of F. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Carlo Albera, Email: ti. Marilyn K. Glassberg, Email: ude. Lisa H.

Lancaster, Email: gro. Wim A. Wuyts, Email: eb. Ute Petzinger, Email: ten. Frank Gilberg, Email: moc. Klaus-Uwe Kirchgaessler, Email: moc. Paul W. Noble, Email: gro. National Center for Biotechnology Information , U. Journal List Respir Res v. Respir Res. Published online Mar Glassberg , 3 Lisa H.

Lancaster , 4 Wim A. Noble 8. Frank Gilberg 7 F. Klaus-Uwe Kirchgaessler 7 F. Author information Article notes Copyright and License information Disclaimer.