Pharmacological Management of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a common interstitial lung disease (ILD) caused by environmental exposures, infections, or traumatic injuries and subsequent epithelial damage. Since IPF is a progressively fatal disease without remission, treatment is both urgent and necessary. The two medications indicated solely for treatment include the tyrosine kinase inhibitor nintedanib (Ofev®) and the anti-fibrotic agent pirfenidone (Esbriet®). This chapter discusses in detail the current treatment options for clinical management of IPF, specifically the mentioned two pharmacotherapeutic agents that decrease physiological progression and likely improve progression-free survival. The chapter also discusses the evolution of drug therapy in IPF management and the drawbacks and limitations learned throughout historical trials and observational studies.

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Treatment of Advanced Hormone Receptor-Positive (HR+) HER2-negative Breast Cancer

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-1037-5205 ◽

2019 ◽

Vol 79 (12) ◽

pp. 1328-1335

Author(s):

Nina Ditsch ◽

Marcus Schmidt

Keyword(s):

Breast Cancer ◽

Hormone Receptor ◽

Treatment Options ◽

Clinical Status ◽

Progression Free Survival ◽

Current Treatment ◽

Free Survival ◽

Cyclin Dependent Kinases ◽

Hormone Receptor Positive ◽

Study Results

AbstractThe article gives an overview of current treatment options for metastatic hormone receptor-positive and HER2-negative breast cancer. The focus is on combined therapies, e.g., with CDK4/6 inhibition compared with purely endocrine-based therapies in the pre- and postmenopause, presenting the latest study results. The addition of a CDK4/6 inhibitor to endocrine-based therapy with an aromatase inhibitor or fulvestrant leads to a marked improvement in progression-free survival and is independently beneficial whether palbociclib, ribociclib or abemaciclib is involved. The particular clinical status of inhibition of cyclin-dependent kinases argues for its use in the first-line treatment of women with metastatic, hormone receptor-positive and HER2-negative breast cancer compared with the available purely endocrine-based therapies.

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Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials

European Respiratory Journal ◽

10.1183/13993003.00026-2015 ◽

2015 ◽

Vol 47 (1) ◽

pp. 243-253 ◽

Cited By ~ 177

Author(s):

Paul W. Noble ◽

Carlo Albera ◽

Williamson Z. Bradford ◽

Ulrich Costabel ◽

Roland M. du Bois ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Progression ◽

Vital Capacity ◽

Progression Free Survival ◽

Phase 3 ◽

Treatment Benefit ◽

Free Survival ◽

Pooled Data ◽

Three Phase

Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression.All patients randomised to pirfenidone 2403 mg·day−1 or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol.A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3–55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0–96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation.Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF.

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LATE-BREAKING ABSTRACT: Antiacid therapy and progression free survival in idiopathic pulmonary fibrosis (IPF)

10.1183/13993003.congress-2015.oa3478 ◽

2015 ◽

Cited By ~ 1

Author(s):

Michael Kreuter ◽

Wim Wuyts ◽

Elisabetta Renzoni ◽

Dirk Koschel ◽

Toby M. Maher ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Progression Free Survival ◽

Free Survival

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Genetic Variation in CCL18 Gene Influences CCL18 Expression and Correlates with Survival in Idiopathic Pulmonary Fibrosis—Part B

Journal of Clinical Medicine ◽

10.3390/jcm9061993 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1993

Author(s):

Canay Caliskan ◽

Benjamin Seeliger ◽

Benedikt Jäger ◽

Jan Fuge ◽

Tobias Welte ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Progressive Disease ◽

Progression Free Survival ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Free Survival ◽

Antifibrotic Therapy ◽

Level Measurement ◽

Chemokine Ligand

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality. CC-chemokine ligand 18 (CCL18) is predictive of survival in IPF. We described correlation of CCL18 serum levels with the genotype of rs2015086 C > T polymorphism the CCL18-gene, which was associated with survival in a pre-antifibrotic cohort (Part-A). Herein (Part-B), we aimed to validate these findings and to study the effects of antifibrotics. Two cohorts were prospectively recruited, cohort-A (n = 61, pre-antifibrotic) and cohort B (n = 101, received antifibrotics). Baseline CCL18 serum level measurement by enzyme-linked immunosorbent assay (ELISA, serially in cohort B) and genotyping of rs2015086 was performed and correlated with clinical outcomes. The CT genotype was present in 15% and 31% of patients. These patients had higher CCL18 levels compared to the TT-genotype (cohort-A: 234 vs. 115.8 ng/mL, p < 0.001; cohort B: 159.5 vs. 120 ng/mL, p = 0.0001). During antifibrotic therapy, CCL18 increased (p = 0.0036) regardless of rs2015086-genotype and antifibrotic-agent. In cohort-A, baseline CCL18-cutoff (>120 ng/mL) and CT-genotype were associated with mortality (p = 0.041 and p = 0.0051). In cohort-B, the CCL18-cutoff (>140 ng/mL) was associated with mortality (p = 0.003) and progression (p = 0.004), but not the CT/CC-genotype. In conclusion, we validated the correlation between rs2015086-genotype and CCL18 serum levels, which was predictive of (progression-free)-survival in two prospective validation cohorts.

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[18F]FDG PET/CT predicts progression-free survival in patients with idiopathic pulmonary fibrosis

Respiratory Research ◽

10.1186/s12931-017-0556-3 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 28

Author(s):

Aurélien Justet ◽

Astrid Laurent-Bellue ◽

Gabriel Thabut ◽

Arnaud Dieudonné ◽

Marie-Pierre Debray ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Fdg Pet ◽

Progression Free Survival ◽

Free Survival ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

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Histologic factors associated with nintedanib efficacy in patients with idiopathic pulmonary fibrosis

PLoS ONE ◽

10.1371/journal.pone.0245147 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245147

Author(s):

Masahiro Nemoto ◽

Yoshiaki Zaizen ◽

Kensuke Kataoka ◽

Kishio Kuroda ◽

Kazuhiro Tabata ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Progression Free Survival ◽

Available P ◽

Radiological Progression ◽

Free Survival ◽

Factors Associated ◽

Interlobular Septum ◽

Microscopic Features ◽

Histopathologic Evaluation

Background Histopathologic factors predictive of nintedanib efficacy in idiopathic pulmonary fibrosis have not been studied. We aimed to describe the characteristics, focusing on histopathology, of idiopathic pulmonary fibrosis patients who did and did not respond to nintedanib. Methods This study retrospectively examined the clinicoradiopathologic features of 40 consecutive patients with surgical lung biopsy-confirmed idiopathic pulmonary fibrosis treated with nintedanib. Additionally, we compared the histopathologic scoring of 21 microscopic features between patients with functional or radiological progression and those with non-progression during 12 months of treatment. Results The histopathologic evaluation showed edematous changes in the interlobular septum as the only histologic finding observed more frequently in patients with both functional and radiological progression than in those without (58% vs. 14%, P = 0.007 and 50% vs. 0%, P = 0.003, respectively). Regarding per-year change, patients with edematous changes in the interlobular septum showed greater progression in median changes in spared area (-12%, interquartile range: [-25%–-5%], vs. -3% [-7%–0%], P = 0.004) and reticular shadow (7% [3%–13%], vs. 0% [0%–5%], P = 0.041) on computed tomography. Functional and radiological progression-free survival were shorter in patients with edematous changes in the interlobular septum than in those without (6.6 months, 95% confidence interval: [5.9–25.3], vs. event <50%, [12.1–Not available], P = 0.0009, and 6.1 months, [5.2–6.6] vs. 14.5 months [7.8–not available], P<0.0001). Conclusions Edematous changes in the interlobular septum may indicate poor nintedanib efficacy in idiopathic pulmonary fibrosis. Further studies are needed to validate these findings and address the mechanism behind ECIS.

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The effects and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis: a meta-analysis and systematic review

European Journal of Medical Research ◽

10.1186/s40001-021-00601-y ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Chenchen Zang ◽

Yan Zheng ◽

Yanqing Wang ◽

Lisha Li

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Vital Capacity ◽

Adverse Reactions ◽

Meta Analysis ◽

Progression Free Survival ◽

Control Group ◽

High Quality ◽

Free Survival ◽

Randomized Controlled

Abstract Background It is necessary to systematically evaluate the efficacy and adverse reactions of pirfenidone in the treatment of patients with idiopathic pulmonary fibrosis (IPF). Methods Pubmed et al. databases were searched up to March 15, 2021 for randomized controlled trials (RCT) of pirfenidone in the treatment of IPF. Two authors collected and compared the indicators including progression-free survival (PFS), vital capacity (VC), forced vital capacity (FVC), and adverse reactions. RevMan 5.3 software and Stata 15.0 software were used for meta-analysis. Results A total of 8 reports with 9 RCTs involving 1824 IPF patients were included. Meta-analysis results showed that compared with the control group, pirfenidone could prolong the PFS phase of IPF patients (HR = 0.65, 95% CI 0.55 ~ 0.76, P < 0.001), slow down the VC of IPF patients (SMD = 0.43, 95% CI 0.21 ~ 0.66, P < 0.001), and decrease FVC (SMD = 0.31, 95% CI 0.14 ~ 0.48, P < 0.001). The main adverse reactions of pirfenidone were gastrointestinal reactions, photosensitivity and skin rashes. Conclusion Pirfenidone is beneficial to prolong the PFS of IPF patients, improve lung function, and it is safe for clinical use. However, more high-quality RCTs are still needed to provide reliable evidence for the treatment of IPF.

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Small bowel wall edema induced by regorafenib is associated with regorafenib intolerance and shorter survival in patients with metastatic colorectal cancer: A retrospective study

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220978471 ◽

2020 ◽

pp. 107815522097847

Author(s):

Melek Karakurt Eryılmaz ◽

Ülkü Kerimoğlu ◽

Mustafa Karaağaç ◽

Fatma Yalçın Müsri ◽

Murat Araz ◽

...

Keyword(s):

Small Bowel ◽

Receptor Tyrosine Kinase ◽

Bowel Wall ◽

Kinase Inhibitor ◽

Progression Free Survival ◽

Current Treatment ◽

Metastatic Colorectal Carcinoma ◽

Free Survival ◽

Targeted Agent ◽

The Relationship

Introduction Regorafenib, a receptor tyrosine kinase inhibitor, is a routinely used targeted agent in the current treatment of patients with refractory metastatic colorectal carcinoma (mCRC). The aims of this study were to detect the presence of bowel wall edema during regorafenib treatment via computed tomography (CT) and to assess the relationship between survival and regorafenib-induced bowel wall edema in patients with mCRC receiving regorafenib. Patients and methods We retrospectively evaluated the presence of bowel wall edema on CT of 25 mCRC patients who received regorafenib and analyzed its relationship with progression free survival (PFS) and overall survival (OS). Results Among the 25 patients, 25 had small bowel wall edema (SBWE) and 14 had large bowel wall edema (LBWE) on at least one CT examination. The median SBWE value was 4.85 milimeters (mm). Of the 25 patients, 14 had SBWE ≤4.85 mm and 11 had SBWE >4.85 mm. Regorafenib intolerance was significantly higher at SBWE >4.85 mm patients (p = 0.03). The median PFS was 4.6 months (95% CI: 2.4–6.8) and median OS was 9.3 months (95% CI: 3.1–15.4). Median PFS and OS were shorter in patients with SBWE > 4.85 mm than in those with ≤4.85 mm, but not statistically significant (median PFS: 3.9 vs 4.6 months, p: 0.523; median OS: 5.6 vs 9.3 months, p: 0.977). Conclusions Regorafenib caused SBWE in patients with mCRC. Patients who developed more SBWE had a higher regorafenib intolerance and a shorter survival. Further studies are needed to confirm the predictor value of SBWE on the survival outcomes of patients with mCRC receiving regorafenib.

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