Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients

Fournier, D.; Jouneau, S.; Bouzillé, Guillaume; Polard, Élisabeth; Osmont, Marie-Noëlle; Scailteux, Lucie‐Marie

doi:10.1016/j.pupt.2022.102149

Cited by 11 publications

(12 citation statements)

References 36 publications

(49 reference statements)

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“…Our study confirms the efficacy of NTD in slowing disease progression in terms of stabilizing lung function without, as already known, allowing a marked improvement in fibrotic damage. Patients with IPF may have a variable clinical course also influenced by comorbidities, smoking habits first and foremost, which affected 61% of the enrolled patients and by any NTD-associated therapies; however, the existence of a phenotype associated with a rapid decline in FVC leading rapidly to death, which occurred within a year in 5% of the cases in our cluster, should also be kept in mind [ 22 , 23 , 24 , 25 ]. In the studies performed in the 1990s and the early 2000s, before the era of the new American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and the introduction of antifibrotic medication, the median survival of IPF patients was 2–3 years [ 26 , 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…FVC, FEV1, and DLCO were described as a percentage of the predicted values for the patient’s age, sex, and height [ 21 ]. Abnormalities of PFTs were defined as predicted values of forced vital capacity (FVC) < 80% and diffusing capacity of the lung for carbon monoxide (DLCO) < 70% [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

“…The repetitive exposures aberrantly activate the alveolar epithelial cells of genetically susceptible individuals, promoting epitelial apoptosis, recruitment of mesenchymal cells and increased vascular permeability. Unregulated epithelial/mesenchymal interaction results in the secretion of various profibrotic cytokines, metalloproteinases and procoagulant mediators, which promote uncontrolled migration and proliferation, and differentiation in fibroblasts to myofibroblasts as well as fibrosis in the extracellular matrix [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. The main pro-inflammatory cytokines involved in fibrosis are tumour necrosis factor (TNF)-α and interleukin (IL)-1, as well as some fibrous factors such as transforming growth factor (TGF)-β and platelet-derived growth factor (PDGF) [ 28 , 29 , 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…Caution should be exercised with concomitant administration of nintedanib with CYP3A4 and P-gp inhibitors (e.g., ketoconazole) with inducers (e.g., rifampin), which may result in increased or decreased exposure to nintedanib, respectively. The main route of elimination is fecal/biliary excretion (about 93% of the administered dose), while renal excretion contributes little to the total clearance [ 1 , 14 , 15 , 16 , 17 , 18 ]; the resulting half-life is 9.5 h. The main adverse effects include, first and foremost, diarrhea (61.5 percent of cases), but also increased liver enzymes (which should be checked before initiating therapy and then monitored), abdominal pain, nausea, vomiting, and weight loss, all of which are generally manageable by reducing the dose (200 mg/day), discontinuing treatment, and applying symptomatic measures (e.g., loperamide) [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Nintedanib in Idiopathic Pulmonary Fibrosis: Tolerability and Safety in a Real Life Experience in a Single Centre in Patients also Treated with Oral Anticoagulant Therapy

et al. 2023

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Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ~3 years. Nintedanib (NTD) has been shown to be useful in controlling interstitial lung disease (ILD) in IPF. Here we describe the experience of NTD use in IPF in a real-life setting. Objective. Our objective was to examine the safety profile and efficacy of nintedanib even in subjects treated with anticoagulants. Clinical data of patients with IPF treated with NTD at our center were retrospectively evaluated at baseline and at 6 and 12 months after the introduction of NTD. The following parameters were recorded: IPF clinical features, NTD tolerability, and pulmonary function tests (PFT) (i.e., Forced Vital Capacity (FVC) and carbon monoxide diffusing capacity (DLCO)). In total, 56 IPF patients (34% female and 66% male, mean onset age: 71 ± 11 years, mean age at baseline: 74 ± 9 years) treated with NTD were identified. At enrollment, HRCT showed an UIP pattern in 45 (80%) and a NSIP in 11 (20%) patients. For FVC and FEV1 we found no significant change between baseline and 6 months, but for DLCO we observed a decrease (p = 0.012). We identified a significant variation between baseline and 12 months for FEV1 (p = 0.039) and for DLCO (p = 0.018). No significant variation was observed for FVC. In the cohort, 18 (32%) individuals suspended NTD and 10 (18%) reduced the dosage. Among individuals that suspended the dosage, 14 (78%) had gastrointestinal (GI) collateral effects (i.e., diarrhea being the most common complaint (67%), followed by nausea/vomiting (17%) and weight loss (6%). Bleeding episodes have also not been reported in patients taking anticoagulant therapy. (61%). One patient died within the first 6 months and two subjects died within the first 12 months. In a real-life clinical scenario, NTD may stabilize the FVC values in IPF patients. However, GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in IPF patients. This study confirms the safety of NTD, even in patients treated with anticoagulant drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nintedanib in Idiopathic Pulmonary Fibrosis: Tolerability and Safety in a Real Life Experience in a Single Centre in Patients also Treated with Oral Anticoagulant Therapy

et al. 2023

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“…Few cardiovascular events have been reported in patients treated with nintedanib in real-world studies [ 18 – 23 , 28 , 55 , 56 ]. In the largest real-world study to report data on cardiovascular events, among 244 patients treated with nintedanib for an average of 24 months at seven centres in Greece, ischaemic events (MI or ischaemic stroke) were reported in 2.9% of patients [ 28 ].…”

Section: Cardiovascular Eventsmentioning

confidence: 99%

A Narrative Review of Real-World Data on the Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis

Podolanczuk

Cottin

2023

Adv Ther

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Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF) and other progressive fibrosing interstitial lung diseases. Placebocontrolled trials showed that the adverse event profile of nintedanib was characterised mainly by gastrointestinal events, particularly diarrhoea. We review the data from all published real-world studies of the safety of nintedanib in patients with IPF. These real-world data were consistent with the safety profile observed in clinical trials and described in the product label. The most common adverse events were diarrhoea, nausea and vomiting, but these infrequently led to permanent treatment discontinuation. Liver enzyme elevations were observed, supporting the recommendation for regular monitoring of liver enzymes, particularly in the first few months of treatment.Bleeding and cardiovascular adverse events were rarely reported. As in clinical trials, in real-world studies, reductions of the nintedanib dose, treatment interruptions and use of anti-diarrhoeal medications were frequently employed to manage adverse events. Few data are available on the use of nintedanib in patients who are elderly or have advanced disease, but there are some data to suggest a greater rate of treatment discontinuation in these patients. Effective management of adverse events associated

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Lung regeneration: diverse cell types and the therapeutic potential

Chen,

Li,

et al. 2024

MedComm

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Lung tissue has a certain regenerative ability and triggers repair procedures after injury. Under controllable conditions, lung tissue can restore normal structure and function. Disruptions in this process can lead to respiratory system failure and even death, causing substantial medical burden. The main types of respiratory diseases are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS). Multiple cells, such as lung epithelial cells, endothelial cells, fibroblasts, and immune cells, are involved in regulating the repair process after lung injury. Although the mechanism that regulates the process of lung repair has not been fully elucidated, clinical trials targeting different cells and signaling pathways have achieved some therapeutic effects in different respiratory diseases. In this review, we provide an overview of the cell type involved in the process of lung regeneration and repair, research models, and summarize molecular mechanisms involved in the regulation of lung regeneration and fibrosis. Moreover, we discuss the current clinical trials of stem cell therapy and pharmacological strategies for COPD, IPF, and ARDS treatment. This review provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials.

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Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients

Cited by 11 publications

References 36 publications

Nintedanib in Idiopathic Pulmonary Fibrosis: Tolerability and Safety in a Real Life Experience in a Single Centre in Patients also Treated with Oral Anticoagulant Therapy

Nintedanib in Idiopathic Pulmonary Fibrosis: Tolerability and Safety in a Real Life Experience in a Single Centre in Patients also Treated with Oral Anticoagulant Therapy

A Narrative Review of Real-World Data on the Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis

Lung regeneration: diverse cell types and the therapeutic potential

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