Two approved anti-fibrotics are proving to be safe and effective in treating idiopathic pulmonary fibrosis (IPF), a study with real-world data reports.
The data showed Esbriet (pirfenidone) and Ofev (nintedanib) increased progression-free survival, slowed down lung function decline, and reduced mortality in IPF patients. Ofev appears to be better tolerated than Esbriet in the early stages of treatment, suggesting it may be the preferred first-line medication.
The study, “Real-world retrospective observational study exploring the effectiveness and safety of antifibrotics in idiopathic pulmonary fibrosis,” was published in BMJ Open Respiratory Research and was conducted by researchers in the U.K.
Esbriet (marketed by Genentech) and Ofev (marketed by Boehringer Ingelheim and sold as Vargatef in the European Union) have been shown to slow disease progression in clinical trials. In the new study, researchers provide more insights from the day-to-day practice of physicians treating IPF patients.
“Is the efficacy of antifibrotics shown in clinical trials being translated to everyday clinical practice?” the researchers wrote. “Our aim was to test their effectiveness and safety in clinical practice.”
The study, undertaken at the Queen Elizabeth Hospital in Birmingham, included 104 patients on anti-fibrotics and 64 IPF patients who had never received anti-fibrotics and who served as controls. The researchers stated this was the first study of its kind to include such a control group of patients, “allowing comparisons to be made and the effectiveness and tolerability of antifibrotics to be elicited.”
Of the 104 patients on anti-fibrotics, 62 patients were first started on Esbriet and 42 on Ofev. Of these patients, 14 (13.5%) switched from one anti-fibrotic to the other at some point during the treatment.
The researchers analyzed the effect of the two anti-fibrotics on progression-free survival, which was defined as the time a patient lived with the disease without it getting worse — specifically without experiencing a decline of 10% or more in forced vital capacity (FVC), which is a measure of lung function.
At six months, the rate of progression-free survival was significantly higher in the anti-fibrotic group (75%) than in the control group (56.3%), but this difference was not maintained after 12 or 18 months.
Next, the researchers analyzed the effect of anti-fibrotics on lung function. They found that the mean rate of decline in the percentage of predicted FVC at 12 months after treatment initiation was significantly lower (4.6%) than that at 12 months prior to treatment (10.4%), indicating that the anti-fibrotics slowed down lung function decline.
Side effects associated with both anti-fibrotics was identical to that observed in previous clinical trials, and included nausea as the most common side effect of Esbriet treatment (36.8%) and diarrhea as the most common side effect of Ofev (62%).
The rate of treatment discontinuation at three and six months was significantly higher for Esbriet (29% and 40.3%, respectively) than for Ofev (7.1% and 21.4%). No differences were observed at 12 months post-treatment (46.8% for Esbriet and 38.1% for Ofev) or at 18 months (58.3% Esbriet vs. 52.5% Ofev).
“Both antifibrotics have been shown to have acceptable safety profiles, although the data suggest nintedanib [Ofev] is better tolerated, which could have an influence on survival,” the researchers wrote.
The findings favor the use of Ofev “as first-line antifibrotic therapy, given the lower rates of early treatment discontinuation,” the team added, noting, however, that “further studies are required to investigate this.”
In the study, the mortality rates were higher (26% in the anti-fibrotic group vs. 34.4% in the control group) than those reported in previous clinical trials, which might reflect the broader characteristics of patients in a real-world setting.
“This highlights the importance of real-world data to inform clinical decision making as the availability of counselling and resources may be different in these settings when compared with trial conditions,” the researchers wrote.
Consistent with data from clinical trials, the anti-fibrotics had no significant effect on mortality rates. However, after excluding patients who discontinued treatment within the first six months, the rate of mortality at 12 months was significantly lower in the anti-fibrotic group (15.7%) compared with the control group (34.4%). Similar findings were obtained at 18 months, at which point the mortality rate was 25% in the anti-fibrotic group and 44.4% in the control group.
By analyzing multiple variables at the same time, the researchers identified two independent predictors of 12-month mortality: a body mass index (BMI, a measure of body fat based on height and weight) equal to or less than 25, and a diffusing capacity for carbon monoxide — a measure of the lungs’ ability to transfer oxygen to red blood cells — equal to or less than 35% of predicted.
In addition, the researchers identified three risk factors linked to treatment discontinuation: age of 75 years or older, female sex, and a BMI equal to or less than 25.
“The identification of clinical predictors of mortality and discontinuation may lead to a more stratified approach to the treatment of patients with IPF in the future,” the researchers wrote.
Overall, “this real-world study revealed that antifibrotics are having promising effects on progression-free survival, lung function and mortality, and nintedanib [Ofev] appears better tolerated than pirfenidone [Esbriet] in the early stages of antifibrotic therapy,” the team concluded.
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