New Findings Highlight the Impact of Lung Function Decline in IPF, PPF

An update to ongoing research into idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) at the European Respiratory Society (ERS) Congress 2024 highlighted the impact of these diseases on lung function and patient outcomes in 2 abstracts.

The studies, which analyzed the decline in forced vital capacity (FVC) and its relationship to mortality risk, underscore the importance of understanding disease progression and the potential benefits of treatment with nintedanib.

FVC Decline in Patients With IPF and PPF

Claudia Valenzuela, MD, pulmonologist at the Hospital Universitario de La Princesa in Madrid, Spain, presented the first abstract at the ERS Congress.¹ It looked at baseline FVC and its decline in individuals with IPF from the INPULSIS trials and those with PPF from the INBUILD trial and compared these with hypothetical healthy references. Values for these healthy references were developed using equations published by the ERS Global Function Initiative.

These trials previously demonstrated that nintedanib reduced the rate of FVC decline by 49% for those with IPF and by 57% for those with PPF in a year compared with placebo. The newest comparison allowed researchers to quantify the physiological impact of IPF and PPF, illustrating how much these diseases accelerate lung function decline compared with individuals without either condition.

The researchers found that patients with IPF and PPF had substantially impaired lung function compared with their healthy counterparts when matched for age, sex, race, and height.

In the INPULSIS trials, patients with IPF treated with nintedanib had a mean baseline FVC of 2714 mL, whereas their healthy references had a much higher baseline FVC of 3597 mL. Similarly, in the INBUILD trial, patients in the nintedanib group had a baseline FVC of 2340 mL compared with 3411 mL in healthy individuals. Both trials also saw much lower baseline FVCs for patients receiving placebo than their healthy references.

Additionally, over 52 weeks of treatment, the rate of FVC decline in the placebo groups was 7 times greater than in the healthy reference group. Meanwhile in the nintedanib groups, the decline was only 3 to 4 times greater than in healthy individuals.

Patients with IPF and PPF had substantially more impaired lung function compared with their healthy counterparts | Image credit: Oranuch – stock.adobe.com

“This analysis demonstrates the physiological impact of IPF and PPF, and support the clinical relevance of the reduction in FVC decline seen with nintedanib,” Valenzuela said during her presentation.

Lung Function Decline Tied to Increased Mortality Risk in IPF

The second abstract was presented by Divya Patel, DO, MBA, director of clinical development and medical affairs at Boehringer Ingelheim and adjunct associate professor of medicine at the University of Florida.²

This study focused on the relationship between changes in lung function and mortality risk in patients with IPF, with data pulled from the IPF-PRO Registry, a real-world cohort of more than 1000 patients enrolled at 46 sites across the US. The study used a joint model to estimate FVC and diffusing capacity of the lungs for carbon monoxide (DLco) as percentages predicted for each day of follow-up, allowing for an in-depth analysis of how changes in lung function influence patient prognosis.

Even small relative declines in lung function had a significant impact on mortality risk or the likelihood of lung transplant, according to the study results. Median relative changes in FVC and DLco over 12 months were –3.3% and –11.2%, respectively, and for each threshold of decline examined—2%, 5%, or 10% for FVC and 15% for DLco—the researchers observed a corresponding increase in the risk of death or lung transplant.

“Generally, for thresholds of FVC decline, the risk was similar for an absolute or relative decline,” Patel noted. “But for thresholds of DLco decline, the risk was greater for relative than for an absolute decline.”

These findings support the value of closely monitoring lung function in patients with IPF, as early detection of even minor declines could have crucial prognostic value.

Taken together, these abstracts highlight the burden of lung function decline in both IPF and PPF, and emphasize the clinical relevance of treatments like nintedanib in mitigating disease progression. By comparing FVC decline with healthy individuals and identifying the mortality risks associated with lung function decline, the studies presented at the ERS Congress 2024 contribute to a growing body of evidence supporting more proactive and tailored treatment approaches for fibrosing lung diseases.

References

1. Valenzuela C, Bonella F, Moor CC, et al. Decline in forced vital capacity (FVC) in subjects with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) compared with healthy references. Presented at: ERS Congress 2024. September 8, 2024. https://live.ersnet.org/programme/presentation/559699
2. Oldham J, Neely M, Wojdyla D, et al. Changes in lung function and mortality risk in patients with idiopathic pulmonary fibrosis (IPF). Presented at: ERS Congress 2024. September 8, 2024. https://live.ersnet.org/programme/presentation/565002