Utility of nintedanib for severe idiopathic pulmonary fibrosis: a single-center retrospective study [Letter].
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ABSTRACT:
SUBMITTER: Orsatti L
PROVIDER: S-EPMC6469738 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Utility of nintedanib for severe idiopathic pulmonary fibrosis: a single-center retrospective study [Letter].
Orsatti Leticia L Fortea Josep J Quaresma Manuel M
Drug design, development and therapy 20190412
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Project description:Idiopathic pulmonary fibrosis (IPF), a fibrosing interstitial lung disease, predominantly affects the elderly and is associated with a high mortality risk. Nintedanib, a tyrosine kinase inhibitor, significantly reduces IPF progression. However, data on the tolerability and efficacy of nintedanib in the elderly with IPF are limited. Therefore, this study aimed to examine the tolerability and efficacy of nintedanib in the elderly with IPF in a real-world setting. Medical records of 19 elderly IPF patients (≥ 75 years) and 46 non-elderly IPF patients (< 75 years) newly administered nintedanib were retrospectively analyzed. We compared the forced vital capacity (FVC) level, incidence and severity of adverse events, and continuation rates of nintedanib between the two groups. FVC and percent predicted diffusing capacity of the lung for carbon monoxide (DLco) were lower in the elderly IPF group at baseline. Although the elderly IPF patients had a significantly higher incidence of adverse events, such as diarrhea, nausea, and elevation of hepatic enzymes, the rate of discontinuation of nintedanib owing to adverse events was not different between the groups. The continuation rates of nintedanib treatment at 6 months and 1 year in the elderly IPF group were equivalent. Furthermore, there was a similar trend in the reduction of the annual FVC decline after nintedanib initiation between the groups. Our study demonstrated that nintedanib was tolerable in both the IPF patient groups in a real-world setting. Proper management of adverse events in the elderly with IPF would lead to a better clinical outcome.
| S-EPMC8812933 | biostudies-literature
Project description:BackgroundTwo antifibrotic drugs, pirfenidone and nintedanib, are licensed for the treatment of patients with idiopathic pulmonary fibrosis (IPF). However, there is neither evidence from prospective data nor a guideline recommendation, which drug should be preferred over the other. This study aimed to compare pirfenidone and nintedanib-treated patients regarding all-cause mortality, all-cause and respiratory-related hospitalizations, and overall as well as respiratory-related health care costs borne by the Statutory Health Insurance (SHI).MethodsA retrospective cohort study with SHI data was performed, including IPF patients treated either with pirfenidone or nintedanib. Stabilized inverse probability of treatment weighting (IPTW) based on propensity scores was applied to adjust for observed covariates. Weighted Cox models were estimated to analyze mortality and hospitalization. Weighted cost differences with bootstrapped 95% confidence intervals (CI) were applied for cost analysis.ResultsWe compared 840 patients treated with pirfenidone and 713 patients treated with nintedanib. Both groups were similar regarding two-year all-cause mortality (HR: 0.90 95% CI: 0.76; 1.07), one-year all cause (HR: 1.09, 95% CI: 0.95; 1.25) and respiratory-related hospitalization (HR: 0.89, 95% CI: 0.72; 1.08). No significant differences were observed regarding total (€- 807, 95% CI: €- 2977; €1220) and respiratory-related (€- 1282, 95% CI: €- 3423; €534) costs.ConclusionOur analyses suggest that the patient-related outcomes mortality, hospitalization, and costs do not differ between the two currently available antifibrotic drugs pirfenidone and nintedanib. Hence, the decision on treatment with pirfenidone versus treatment with nintedanib ought to be made case-by-case taking clinical characteristics, comorbidities, comedications, individual risk of side effects, and patients' preferences into account.
| S-EPMC8527681 | biostudies-literature
Project description:BackgroundNintedanib is a multi-kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF); however, its efficacy and safety for patients with IPF and restricted pulmonary function remain unclear. Therefore, the objective of this study was to determine the efficacy and safety of nintedanib for patients with IPF and forced vital capacity (FVC) ≤ 50%.MethodsThis was a multi-center retrospective study performed by the Okayama Respiratory Disease Study Group. Patients were allocated into FVC ≤ 50% and FVC > 50% groups based on their predicted FVC. The primary endpoints were FVC changes from baseline after 6 and 12 months.Results45 patients were eligible for the study. 18 patients had FVC ≤ 50%, and 27 patients had FVC > 50%. Overall, 31 and 19 patients underwent pulmonary function tests at 6 and 12 months after initiating nintedanib, respectively. FVC changes from baseline at 6 and 12 months after initiating nintedanib were comparable between the two groups. Adverse events were seen in all patients, and the rates of patients who discontinued nintedanib were also comparable (38.9% vs. 37.0%, p = 1.000). Multiple regression analysis showed that age and forced expiratory volume in 1 second (FEV1)/FVC were negatively correlated with changes in FVC at 6 months after initiating nintedanib.ConclusionsOur data suggest that nintedanib can be a useful agent for IPF patients, including those with a low FVC, and that age and FEV1/FVC are predictive markers for changes in FVC following nintedanib treatment.
| S-EPMC7451511 | biostudies-literature
Project description:BackgroundNintedanib slows disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF) by reducing decline in Forced Vital Capacity (FVC). The effects of nintedanib on abnormalities on high-resolution computed tomography scans have not been previously studied.ObjectiveWe conducted a Phase IIIb trial to assess the effects of nintedanib on changes in Quantitative Lung Fibrosis (QLF) score and other measures of disease progression in patients with IPF.Methods113 patients were randomized 1:1 to receive nintedanib 150 mg bid or placebo double-blind for ≥6 months, followed by open-label nintedanib. The primary endpoint was the relative change from baseline in QLF score (%) at month 6. Analyses were descriptive and exploratory.ResultsAdjusted mean relative changes from baseline in QLF score at month 6 were 11.4% in the nintedanib group (n=42) and 14.6% in the placebo group (n=45) (difference 3.2% [95% CI: -9.2, 15.6]). Adjusted mean absolute changes from baseline in QLF score at month 6 were 0.98% and 1.33% in these groups, respectively (difference 0.35% [95% CI: -1.27, 1.96]). Adjusted mean absolute changes from baseline in FVC at month 6 were -14.2 mL and -83.2 mL in the nintedanib (n=54) and placebo (n=54) groups, respectively (difference 69.0 mL [95% CI: -8.7, 146.8]).ConclusionExploratory data suggest that in patients with IPF, 6 months' treatment with nintedanib was associated with a numerically smaller degree of fibrotic change in the lungs and reduced FVC decline versus placebo. These data support previous findings that nintedanib slows the progression of IPF.
| S-EPMC7539538 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a rare lung disease characterised by progressive loss of lung function, dyspnoea and cough. IPF has a variable clinical course but a poor prognosis. Nintedanib, a tyrosine kinase inhibitor, is one of two drugs approved for the treatment of IPF. In clinical trials, nintedanib slowed disease progression by reducing the rate of decline in forced vital capacity (FVC) in patients with IPF and mild or moderate lung function impairment. The effect of nintedanib was consistent across patient subgroups defined by baseline characteristics including FVC % predicted, diffusion capacity of the lung for carbon monoxide % predicted and the presence of emphysema. Recently, it has been shown that the rate of decline in FVC and the treatment effect of nintedanib are the same in patients with preserved lung volume (FVC >90% predicted) as in patients with greater impairment in FVC, supporting the value of early treatment of IPF. The adverse events most commonly associated with nintedanib, both in clinical trials and real-world clinical practice, are mild gastrointestinal events, particularly diarrhoea. Side effects are manageable in a majority of patients through symptomatic treatment, dose reductions and treatment interruptions, enabling most patients to stay on treatment in the long term.
| S-EPMC5531305 | biostudies-literature
Project description:BackgroundPhase 3 trials have shown that nintedanib reduces the decline in forced vital capacity (FVC) in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF) with acceptable safety profiles; however, its effects on advanced IPF are unclear. We investigated the efficacy and safety of nintedanib in patients with advanced IPF.MethodsProspective data were obtained from 108 IPF patients administered at least one dose of nintedanib. Of these patients, 47.2% had advanced IPF (FVC < 50% predicted, or diffusing capacity < 30% predicted).ResultsThe median treatment duration was 42.2 weeks. Nintedanib significantly reduced the decline rate in both FVC (- 0.55% [before] vs. -0.32% [after] predicted/month, p = 0.020) and total lung capacity (TLC) (- 0.35% vs. -0.06% predicted/month, p < 0.001) in all patients. A significant improvement in FVC decline rate after treatment was also observed in the advanced group (- 0.77% vs. -0.22% predicted/month, p = 0.003), but not in the non-advanced group (- 0.41% vs. -0.33% predicted/month, p = 0.564). Adverse events occurred in 97.2% of the cohort, including diarrhoea (50.0%) and anorexia (45.4%). Following adjustment for treatment duration, no inter-group difference in odds ratio was observed for the occurrence of adverse events. However, the advanced group showed a higher frequency of treatment interruption (68.0% vs. 40.0%), mainly as a result of disease progression (47.1% vs. 36.4%).ConclusionsThe efficacy and safety profiles of nintedanib in the advanced group were comparable to those in the non-advanced group except for a higher frequency of discontinuation, which may be due to the advanced status itself.
| S-EPMC6194688 | biostudies-literature
Project description:RationaleThere is no consensus as to when treatment for idiopathic pulmonary fibrosis (IPF) should be initiated. Some physicians prefer not to treat patients with preserved lung volume.ObjectiveTo investigate whether patients with IPF and preserved lung volume receive the same benefit from nintedanib as patients with more impaired lung volume.MethodsPost hoc subgroup analyses of pooled data from the two replicate phase III INPULSIS trials by baseline FVC % predicted (≤90%, >90%).ResultsAt baseline, 274 patients had FVC >90% predicted and 787 patients had FVC ≤90% predicted. In patients treated with placebo, the adjusted annual rate of decline in FVC was consistent between patients with FVC >90% predicted and FVC ≤90% predicted (-224.6 mL/year and -223.6 mL/year, respectively). There was no statistically significant difference between these subgroups in the effect of nintedanib on annual rate of decline in FVC, change from baseline in St George's Respiratory Questionnaire total score or time to first acute exacerbation. In patients with baseline FVC >90% predicted and ≤90% predicted, respectively, the adjusted annual rate of decline in FVC with nintedanib was -91.5 mL/year (difference vs placebo: 133.1 mL/year (95% CI 68.0 to 198.2)) and -121.5 mL/year (difference vs placebo: 102.1 mL/year (95% CI 61.9 to 142.3)). Adverse events associated with nintedanib were similar in both subgroups.ConclusionsPatients with IPF and preserved lung volume (FVC >90% predicted) have the same rate of FVC decline and receive the same benefit from nintedanib as patients with more impaired lung volume.Trial registration numberNCT01335464 and NCT01335477.
| S-EPMC5520269 | biostudies-literature
Project description:Nintedanib, a tyrosine kinase inhibitor, is approved for the treatment of idiopathic pulmonary fibrosis. We report a case of left ventricular dysfunction in a patient with idiopathic pulmonary fibrosis treated with nintedanib, which recovered after cessation of nintedanib. Nintedanib may induce left ventricular dysfunction, and early recognition is important since this condition is potentially reversible.
| S-EPMC7017142 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a fatal progressive disease with a median survival of 2-5 years. Nintedanib is a small tyrosine kinase inhibitor that reduces IPF progression, significantly slowing the annual decline in Forced Vital Capacity (FVC). Very little data is available on the molecular mechanisms of this treatment in IPF, despite a growing interest in the definition of IPF pathogenesis and target therapy. A functional proteomic approach was applied to the analysis of serum samples from IPF patients in order to highlight differential proteins potentially indicative of drug-induced molecular pathways modifications and response to therapy. Twelve serum samples were collected from six IPF patients in care at Siena Regional Referral Center for Interstitial Lung Diseases (ILDs) and treated with nintedanib for one year. Serum samples were analyzed at baseline (T0 before starting therapy) and after one year of treatment (T1) and underwent differential proteomic and bioinformatic analysis. Proteomic analysis revealed 13 protein species that were significantly increased after one year of treatment. When the targets of nintedanib (VEGFR, FGFR and PDGFR) were added, enrichment analysis extracted molecular pathways and process networks involved in cell differentiation (haptoglobin and albumin), coagulation (antithrombin III), epithelial mesenchymal transition, cell proliferation and transmigration. PI3K and MAPK induced up-regulation of apolipoprotein C3. Proteomic study found 13 protein species up-regulated in IPF patients after one year of nintedanib treatment. Haptoglobin, a central hub of our analysis was validated by 2D-WB and ELISA as theranostic marker in a more numerous populations of patients.
| S-EPMC7287088 | biostudies-literature
Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by dyspnea and loss of lung function.MethodsUsing pooled data from the replicate, randomized, 52-week, placebo-controlled INPULSIS(®) trials, we characterized the safety and tolerability of nintedanib 150 mg twice daily in patients with IPF and described how adverse events were managed during these trials.ResultsOne thousand and sixty- one patients were treated (nintedanib 638; placebo 423). Higher proportions of patients in the nintedanib group than the placebo group had ≥ 1 dose reduction to 100 mg bid (27.9% versus 3.8%) or treatment interruption (23.7% versus 9.9%). Adverse events led to permanent treatment discontinuation in 19.3% and 13.0% of patients in the nintedanib and placebo groups, respectively. Diarrhea was the most frequent adverse event, reported in 62.4% of patients in the nintedanib group versus 18.4% in the placebo group; however, only 4.4% of nintedanib-treated patients discontinued trial medication prematurely due to diarrhea. Monitoring of liver enzymes before and periodically during nintedanib treatment was recommended so that liver enzyme elevations could be managed through dose reduction or treatment interruption.ConclusionNintedanib had a manageable safety and tolerability profile in patients with IPF. Recommendations for adverse event management minimized permanent treatment discontinuations in the INPULSIS(®) trials.Trial registrationclinicaltrials.gov NCT01335464 and NCT01335477.
| S-EPMC4581488 | biostudies-literature