Long-Term Follow-Up of Patients With Idiopathic Pulmonary Fibrosis Treated With Pirfenidone or Nintedanib: A Real-Life Comparison Study

Cameli, Paolo; Refini, Rosa Metella; Bergantini, Laura; d’Alessandro, Miriana; Alonzi, Valerio; Magnoni, Carlo; Rottoli, Paola; Sestini, Piersante; Bargagli, Elena

doi:10.3389/fmolb.2020.581828

Cited by 57 publications

(52 citation statements)

References 36 publications

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“…Data from the INPULSIS trials are supported by those from the randomized, double-blind, multinational, phase III INSTAGE trial evaluating nintedanib plus sildenafil versus nintedanib alone in the treatment of patients with advanced IPF [12] and numerous real-world studies (e.g. [13][14][15][16][17][18][19][20]).…”

Section: Nintedanib: Clinical Considerations In Fibrotic Ildsmentioning

confidence: 92%

“…Oral nintedanib had a manageable tolerability profile in clinical trials in patients with fibrotic ILDs [9,11,12,36,52,53] and in real-world studies in patients with IPF (e.g. [13][14][15][16]). In a pooled analysis of safety data from the 52-week INPUL-SIS-1 and INPULSIS-2 trials (n = 638 and 423 treated with nintedanib and placebo; mean duration of exposure 10.3 months and 10.8 months respectively), the most frequent AEs with nintedanib were diarrhoea, nausea, nasopharyngitis, cough, vomiting, decreased appetite, bronchitis and IPF progression (Fig.…”

Section: Tolerability Of Nintedanibmentioning

confidence: 99%

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Nintedanib: A Review in Fibrotic Interstitial Lung Diseases

Lamb

2021

Drugs

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Progressive fibrosing interstitial lung diseases (ILDs) involve similar pathophysiological processes, indicating the potential for common approaches to treatment. Nintedanib (Ofev ® ), an intracellular tyrosine kinase inhibitor (TKI) with antifibrotic properties, was one of the first drugs approved for use in idiopathic pulmonary fibrosis (IPF) and has more recently been approved for use in other chronic fibrosing ILDs with a progressive phenotype and systemic sclerosis-associated ILD (SSc-ILD). In multinational phase III trials, nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) in adults with IPF, other progressive fibrosing ILDs and SSc-ILD. Reductions in FVC decline with nintedanib in patients with IPF and severe gas exchange impairment were comparable to those in patients with milder disease. Real-world experience in patients with IPF supports the effectiveness of nintedanib in slowing ILD progression. Nintedanib had a manageable tolerability profile in patients with fibrotic ILDs in clinical trials and real-world studies. No new safety signals have emerged from global pharmacovigilance data. Nintedanib continues to represent an important therapeutic option in patients with IPF and is the first drug to be approved for use in patients with other chronic fibrosing ILDs with a progressive phenotype or SSc-ILD, with these approvals expanding the range of fibrotic ILDs for which nintedanib can be prescribed. Plain language summaryTreatment options for fibrotic interstitial lung diseases (ILDs) that involve progressive lung function decline have historically been limited. Nintedanib (Ofev ® ) was one of the first antifibrotic drugs to be approved for use in idiopathic pulmonary fibrosis and is now also approved for use in other chronic fibrosing ILDs with a progressive phenotype and systemic sclerosisassociated ILD (SSc-ILD). Nintedanib reduced lung function deterioration in patients with idiopathic pulmonary fibrosis, other chronic fibrosing ILDs with a progressive phenotype and SSc-ILD in well-designed clinical trials. In patients with idiopathic pulmonary fibrosis, the clinical benefit of nintedanib was shown to persist over more than 4 years of treatment. The most common adverse events in nintedanib recipients were diarrhoea and nausea, which were manageable in the majority of patients. Real-world experience supports the effectiveness and acceptable safety of nintedanib. Nintedanib remains an important treatment option for patients with idiopathic pulmonary fibrosis and is the first drug to be approved for use in patients with other chronic fibrosing ILDs with a progressive phenotype and SSc-ILD.

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Section: Nintedanib: Clinical Considerations In Fibrotic Ildsmentioning

confidence: 92%

Section: Tolerability Of Nintedanibmentioning

confidence: 99%

Nintedanib: A Review in Fibrotic Interstitial Lung Diseases

Lamb

2021

Drugs

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“…IPF shares various genetic, molecular, and cell processes with lung cancer [ 13 ]. Today, an “antifibrotic” approach is widely accepted and the only drugs approved for the treatment of IPF are pirfenidone and Nintedanib [ 14 , 15 ]. Nintedanib, a tyrosine-kinase inhibitor, was first developed as an anticancer drug because it suppresses angiogenesis, but it was later recognized as an anti-fibrotic agent and approved for the treatment of IPF [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Concentrations of KL-6 in Patients with IPF and Lung Cancer and Serial Measurements of KL-6 in IPF Patients Treated with Antifibrotic Therapy

d’Alessandro

Bergantini

Cameli

et al. 2021

Cancers

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Background: Krebs von den Lungen-6 (KL-6) was suggested as ILD biomarker including idiopathic pulmonary fibrosis (IPF). Lung cancer is one of the most severe comorbidity of IPF patients. This study aims to serially analyze KL-6 in IPF patients after 24 months of Nintedanib and to first investigate the biomarker behavior in IPF associated with adenocarcinoma. Materials and methods: One hundred and forty-two ILD patients (median (IQR), 69 (63–75) years; 86 males) were retrospectively enrolled. Serial serum samples were collected from IPF patients before starting antifibrotic therapy and after 12 months. Serum KL-6 levels were measured by KL-6 reagent assay (Fujirebio Europe, UK). Results: Increased KL-6 concentrations were identified in IPF-LC patients than IPF, fibrotic hypersensitivity pneumonitis, and pulmonary fibrosis associated with autoimmune disease groups. A cut-off value was calculated to distinguish IPF and IPF-LC patients. IPF patients monitored for 24 months with Nintedanib showed persisted increased levels of KL-6 with a progressive decline of FVC percentages. Conclusion: This preliminary study offers a first demonstration that very high serum concentrations of KL-6 in IPF-LC patients are associated with poor prognosis. Moreover, serial evaluation of serum KL-6 in IPF patients over 24 months of Nintedanib treatment revealed that most patients experienced a stabilization of lung function parameters and of serum concentrations of KL-6.

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“…Blood samples were obtained from patients before starting antifibrotic therapy [ 16 , 17 ]. Lung function tests and high-resolution computed tomography (HRCT) of the chest were performed for all patients for diagnostic purposes.…”

Section: Methodsmentioning

confidence: 99%

Extracellular Vesicle Surface Signatures in IPF Patients: A Multiplex Bead-Based Flow Cytometry Approach

d’Alessandro

Soccio

Bergantini

et al. 2021

Cells

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Background: Extracellular vesicles (EVs) are secreted by cells from their membrane within circulation and body fluids. Knowledge of the involvement of EVs in pathogenesis of lung diseases is increasing. The present study aimed to evaluate the expression of exosomal surface epitopes in a cohort of idiopathic pulmonary fibrosis (IPF) patients followed in two Italian Referral Centres for Interstitial Lung Diseases, comparing them with a group of healthy volunteers. Materials and Methods: Ninety IPF patients (median age and interquartile range (IQR) 71 (66–75) years; 69 males) were selected retrospectively. Blood samples were obtained from patients before starting antifibrotic therapy. A MACSPlex Exosome Kit, human, (Miltenyi Biotec, Bergisch-Gladbach, Germany), to detect 37 exosomal surface epitopes, was used. Results: CD19, CD69, CD8, and CD86 were significantly higher in IPF patients than in controls (p = 0.0023, p = 0.0471, p = 0.0082, and p = 0.0143, respectively). CD42a was lower in IPF subjects than in controls (p = 0.0153), while CD209, Cd133/1, MCSP, and ROR1 were higher in IPF patients than in controls (p = 0.0007, p = 0.0050, p = 0.0139, and p = 0.0335, respectively). Kaplan–Meier survival analysis for IPF patients: for median values and a cut-off of 0.48 for CD25, the two subgroups showed a significant difference in survival rate (p = 0.0243, hazard ratio: 0.52 (95%CI 0.29–0.92); the same was true for CD8 (cut-off 1.53, p = 0.0309, hazard ratio: 1.39 (95%CI 0.75–2.53). Conclusion: Our multicenter study showed for the first time the expression of surface epitopes on EVs from IPF patients, providing interesting data on the communication signatures/exosomal profile in serum from IPF patients and new insights into the pathogenesis of the disease and a promising reliability in predicting mid-term survival of IPF patients.

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Long-Term Follow-Up of Patients With Idiopathic Pulmonary Fibrosis Treated With Pirfenidone or Nintedanib: A Real-Life Comparison Study

Cited by 57 publications

References 36 publications

Nintedanib: A Review in Fibrotic Interstitial Lung Diseases

Nintedanib: A Review in Fibrotic Interstitial Lung Diseases

Serum Concentrations of KL-6 in Patients with IPF and Lung Cancer and Serial Measurements of KL-6 in IPF Patients Treated with Antifibrotic Therapy

Extracellular Vesicle Surface Signatures in IPF Patients: A Multiplex Bead-Based Flow Cytometry Approach

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