Ofev (nintedanib) shows a similar ability to reduce lung function decline in patients with advanced idiopathic pulmonary fibrosis (IPF) as those with milder disease, according to a real-world clinical study.
However, a higher number of patients with advanced IPF stopped Ofev treatment.
The study, “Efficacy and safety of nintedanib in advanced idiopathic pulmonary fibrosis,” was published in the journal Respiratory Research.
Ofev, manufactured by Boehringer Ingelheim, is a tyrosine-kinase inhibitor that targets growth factors, such as the vascular endothelial growth factor receptor, shown to contribute to IPF development. The U.S. Food and Drug Administration approved Ofev as an IPF treatment in October 2014.
Data from the Phase 3 INPULSIS trials (NCT01335464 and NCT01335477) showed the therapeutic benefits of Ofev for patients with mild to moderate IPF, reducing lung function decline (measured using forced vital capacity, or FVC), and efficiently slowing disease progression.
However, Ofev’s overall effectiveness in patients with advanced IPF was still unclear.
Researchers at the University of Ulsan College of Medicine in South Korea analyzed data from 108 IPF patients — 51 with advanced IPF and the remaining 57 with mild to moderate disease — who received at least one dose of Ofev and underwent pulmonary function tests before and after treatment.
Advanced IPF was defined as an FVC below 50 percent at the beginning of the study, or a diffusing capacity for carbon monoxide (DLco) — another parameter of lung function — below 30 percent of the predicted value.
Participants, at a mean age of 66.7 years, received Ofev for a median duration of 42.2 weeks (about nine months) — a median of 26.7 weeks in the advanced group and 57 weeks in the non-advanced group.
Patients in the advanced group had poorer lung function and exercise capacity, along with higher pulmonary arterial pressure. They also used corticosteroids more frequently than those with mild to moderate IPF.
Results showed that after treatment with Ofev, all patients had a significant reduction in the decline rate of lung function, as measured by FVC and total lung capacity (the maximum amount of air that can fill the lungs). FVC values, in particular, were reduced from a loss of 0.55% per month at the start of the study to a loss of 0.32% per month after Ofev treatment.
In contrast, no significant changes in DLco decline rates were seen after treatment.
While before treatment, the FVC decline rates were statistically different between the advanced and non-advanced groups (-0.77% vs. -0.41% per month, respectively), no difference was detected between both groups after treatment with Ofev (-0.22% vs. -0.33%, respectively), suggesting that the treatment also has a strong effect in patients with advanced disease.
The rate of disease progression was reduced in the overall group of patients, from 61.1% to 33.3% after Ofev treatment. Looking specifically at the two different groups in the study, the rate of disease progression was significantly lessened in the advanced group, dropping from 78.9% (before treatment) to 9.1% (after Ofev treatment). The non-advanced group also showed a tendency toward reduction, but the difference was not statistically significant (51.4% vs. 41.2% after Ofev treatment).
“Compared with the non-advanced group, the rate of disease progression in the advanced group was significantly higher (78.9% [advanced] vs. 51.4% [non-advanced]) before treatment and lower (9.1% vs. 41.2%) after treatment,” the researchers wrote.
Almost all patients (97.2%) experienced adverse events, with the most frequent being diarrhea (50%), followed by anorexia (45.4%). Researchers found no difference in the incidence of adverse events between the advanced and non-advanced groups.
Patients with advanced IPF, however, showed a higher rate of treatment interruption than the non-advanced group — 68% vs. 40%, respectively. Among all patients, the most frequent reasons for permanent treatment discontinuation were disease progression (42.9%), anorexia (16.1%), and weight loss (10.7%). Patients with advanced IPF, in particular, experienced a high rate of anorexia (23.5% vs. 4.5% in the non-advanced group).
These results show that “the 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,” the researchers wrote.
“In conclusion, the present data suggest that nintedanib may stabilize lung function decline in patients with IPF treated in the real-world setting, irrespective of baseline lung function,” they added. “Nintedanib could therefore represent a treatment option for patients with advanced IPF.”
Another recent study also conducted in IPF patients in a real-world setting suggested that in terms of survival and prognosis, Ofev’s benefits are “reduced in patients with severe IPF when compared to those with mild to moderate IPF,” but that “an improvement in prognosis may be expected when side effects are controlled and the drug is administered over long-term,” suggesting that controlling adverse effects in patients with advanced/severe IPF is crucial for better patient outcomes, according to the researchers who conducted the study.