Idiopathic pulmonary fibrosis (IPF) patients taking antifibrotic therapies Ofev (nintedanib) or Esbriet (pirfenidone) had a mortality risk that was 37% lower than patients not treated with such therapies, a large registry-based study reports.
The study, “Survival and Course of Lung Function in the Presence or Absence of Antifibrotic Treatment in Patients With Idiopathic Pulmonary Fibrosis: Long-Term Results of the INSIGHTS-IPF Registry,” was published in the European Respiratory Journal.
Approved antifibrotic therapies, such as Ofev by Boehringer Ingelheim, and Esbriet by the Roche subsidiary Genentech, are designed to prevent the progression of the disease, manage its symptoms, and prolong patients’ lives.
Since the efficacy of these treatments was assessed in randomized clinical trials with selected patients, getting real-life data from general, unselected IPF patients is warranted, researchers say.
“Observational data in unselected IPF patients are needed to provide a more comprehensive picture,” they wrote.
The German INSIGHTS-IPF registry (NCT01695408), launched in November 2012, is one of the largest IPF registries worldwide allowing researchers to analyze the course of disease and the long-term efficacy of antifibrotic therapies in IPF under real-life conditions.
In the new study, researchers analyzed data from 588 IPF patients registered in INSIGHTS-IPF. The mean age of the patient group analyzed was 69.8 years, and the majority were men (81%).
Symptoms lasted on average 3.5 years before the first clinical visit. More than half of the patients (58%) were diagnosed with IPF in less than 12 months, and 47% of the cases were diagnosed in less than six months.
According to the GAP staging system — a risk-prediction index for IPF — 20.4% of the patients were at stage 1, 49.9% at stage 2, and 29.7 % at stage 3.
The scores of two lung function measures — forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO or TLCO) — at the initial visit were 68.6% for FVC and 37.8% for DLCO.
Patients were followed for a mean of 1.2 years up to a maximum of two years.
In total, 298 patients received antifibrotic therapy, either Esbriet or Ofev, and 290 patients had never been treated with this type of therapy.
A first analysis showed that, after two years of follow-up, the mean predicted FVC% remained stable, and no differences were detected between the group of patients treated with antifibrotic therapy and those who were untreated. Similarly, no significant differences were seen in the decline of DLCO between both groups.
In a second analysis restricted to patients diagnosed with IPF for 12 months or less, researchers saw a better outcome in FVC% and DLCO%, and in the six-minute walk distance test (6MWD, which assesses exercise capacity and endurance) for patients on antifibrotic therapy. However, the difference was not statistically significant.
Researchers then evaluated the mortality risk in patients who were treated with Esbriet (139 patients) and Ofev (159 patients) in follow-up.
During the two-year follow-up period, 194 patients (33%) died. Seventy-nine patients (41%) died of IPF-related reasons — in 20% of the cases due to respiratory failure, followed by infections of the respiratory tract or pneumonia (8%), as a result of complications associated with IPF (8%), and due to other causes (9%). In 71 patients (37%), the cause of death was unknown.
Overall mortality risk was significantly lower by 37% in patients treated with antifibrotic therapy compared to those who were not treated. The survival rate after one year of follow-up was 87% for patients treated with antifibrotic therapy versus 46% in the control group. In the second year of follow-up, the rates were 62% vs. 21%.
No statistically significant differences in overall mortality rates were seen between Esbriet- and Ofev-treated patients.
The risk of death due to IPF, however, showed no differences between patients receiving antifibrotic therapy and those who did not. In contrast, the risk of death for unknown reasons was 56% lower in patients on antifibrotic therapy. However, “due to the lower numbers of events in this sub-group analysis this result should be interpreted with caution,” the researchers wrote.
Then the team compared the mortality risk between patients with stable FVC — those with a 10% decline or less during follow-up — to those with worsening decline of FVC (above 10%) during follow-up. This was done regardless of the therapy used.
Results showed that the mortality risk was slightly lower in patients with stable IPF. A 64% decrease in the risk of mortality was also seen among patients treated with antifibrotic therapy and who had IPF for less than 12 months.
Overall, “we were able to demonstrate a significant lower all-cause mortality in IPF patients treated with antifibrotic drugs when compared to a matched cohort of IPF patients not treated with antifibrotic drugs,” the researchers wrote.
“Moreover, our analysis provides the basis for a hypothesis that stability of lung function parameters over time, especially FVC and DLco, in untreated IPF patients may be misleading as our data indicate that stability of these parameters probably do not protect from premature death,” they concluded.
Of note, some of the researchers report receiving grants or personal fees from Boehringer Ingelheim — which also supported the study — and/or Roche.
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