Meta-Analysis of Effect of Nintedanib on Mortality in Subjects with Idiopathic Pulmonary Fibrosis (IPF) and Other Forms of Progressive Pulmonary Fibrosis (PPF)

The study conducted meta-analyses to assess nintedanib's effects on several outcomes, including time to death, time to the first acute exacerbation, and time to the first acute exacerbation or death. in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). Previous individual trials had shown numerical reductions in mortality with nintedanib, but the study aimed to provide a more comprehensive analysis across multiple trials. The methods involved collecting data from randomized placebo-controlled trials involving nintedanib in both IPF and PPF patients. These trials had varying durations of double-blind periods. Heterogeneity across trials was also examined. Based on data from 5 clinical trials involving 2007 patients, the results indicated that nintedanib reduced the risk of death and the risk of acute exacerbation of interstitial lung disease (ILD) or death compared to placebo. These findings were consistent across all the trials analyzed. In conclusion, the study demonstrated that nintedanib consistently reduced mortality risk and acute exacerbations across clinical trials in IPF and PPF patients. These results support using nintedanib as a treatment option to improve meaningful clinical outcomes in patients with progressive pulmonary fibrosis, including those with IPF.

Poster ID 2875, European Respiratory Society (ERS) International Congress 2023, Milan, Italy, 9-13 September 2023.

Real-World Study Evaluating Anti-Fibrotic Therapy on Survival in Idiopathic Pulmonary Fibrosis

The study investigated the impact of antifibrotic therapies on the survival of patients with idiopathic pulmonary fibrosis (IPF) and identified key factors influencing outcomes. Conducted at Royal Papworth Hospital from 2007 to 2020, the study retrospectively analyzed a cohort of 410 IPF patients. Patient information, including demographics, lung function, 6-minute walk test results, and the use of antifibrotic drugs, was collected, and the analysis continued until June 1, 2022, or until patients underwent transplantation or experienced mortality. The patients were categorized based on their GAP index, a measure of disease severity, and Kaplan-Meier analysis compared survival between those who received antifibrotic therapy (255 patients) and those who did not (155 patients). The results revealed a significant survival benefit associated with antifibrotic therapy, with treated patients exhibiting a median survival duration of 1148 days compared to 1003 days for untreated patients. Moreover, the study observed worse survival for patients in GAP stage 3. However, antifibrotic therapy still conferred a survival advantage for both GAP stage 2 and 3 patients. Through multivariate Cox regression analysis, the study identified two robust predictors of survival in the treated cohort: the duration of antifibrotic therapy and baseline DLCO (diffusion capacity of the lung for carbon monoxide). In addition to assessing survival, the study examined changes in lung function over a 12-month period for both treated and untreated IPF cohorts. For untreated IPF patients, there was a notable decline in FVC% predicted over the first 6 months (189 days, IQR 53), with a decrease of -2.8% (p=0.01), and over 12 months (359 days, IQR 66.5), with a more substantial decline of -4.4% (p<0.001). While DLCO% predicted showed no significant change over the initial 6 months (183 days, IQR 56), with only a slight decrease of -0.2% (p=1.00), a significant decline of -3.6% (p=0.004) was observed over 12 months (356 days, IQR 64.5). Conversely, the treated IPF cohort displayed no significant difference in FVC% predicted changes over the first 6 months (191 days, IQR 57), with a decrease of -1.1% (p=0.09), or over 12 months (378 days, IQR 56), with a negligible decline of -0.3% (p=1.00). Regarding DLCO% predicted, there was no significant alteration over the initial 6 months (190 days, IQR 50), with a minor decrease of -0.5% (p=1.00). However, over 12 months (372 days, IQR 61), a significant decline of -3.7% (p<0.001) was evident. The real-world study highlighted the survival benefits of antifibrotic therapy in IPF patients, particularly in GAP stages 2 and 3. It identified baseline DLCO and the duration of antifibrotic treatment as crucial predictors of patient outcomes.

Poster ID 2888, European Respiratory Society (ERS) International Congress 2023, Milan, Italy, 9-13 September 2023

Idiopathic Pulmonary Fibrosis Treated by Nintedanib: Evaluation of Safety Even in Patients Treated with Anticoagulants

The study aimed to assess the safety and effectiveness of nintedanib (NTD) in managing idiopathic pulmonary fibrosis (IPF) patients, including those concurrently receiving oral anticoagulants. The research involved the retrospective analysis of clinical data from 64 IPF patients at baseline (T0), 6 months (T6), and 12 months (T12) after initiating NTD treatment. The study included 31% women and 69% men, with a mean age of onset of 73 years and a mean age at baseline of 72 years. High-resolution computed tomography (HRCT) scans showed a usual interstitial pneumonia (UIP) pattern in 77% of patients and a nonspecific interstitial pneumonia (NSIP) pattern in 23% of patients. There was no significant change in forced vital capacity (FVC) from T0 to T6 and T12 (p=0.06). However, a significant change in diffusion capacity (DLCO) was observed from T0 to T12 (p=0.02), suggesting a potential benefit in lung function preservation with NTD treatment. Among the patients receiving anticoagulant therapy (72%), no bleeding episodes were reported, indicating that NTD can be safely administered alongside anticoagulants. Some patients experienced gastrointestinal (GI) symptoms, with diarrhoea being the most common (75%). In response, 29% of patients discontinued NTD, and 19% reduced the dosage. Gastrointestinal side effects were the primary reason for discontinuation. Three patients died during the study follow-up at T12. The study suggests that NTD treatment can stabilize FVC values in IPF patients and demonstrates the safety of using NTD in combination with anticoagulant therapy. It also highlights the importance of dose adjustment to manage gastrointestinal side effects in some individuals.