Nearly 40% of IPF Patients in US Not Prescribed Esbriet or Ofev Despite Effectiveness, Study Reports

In the U.S., 61% of people with idiopathic pulmonary fibrosis (IPF) are prescribed approved anti-fibrotic therapies, namely Ofev (nintedanib) and Esbriet (pirfenidone), analysis of data from the U.S. Pulmonary Fibrosis (PF) Foundation Patient Registry shows.

In turn, almost 40% of IPF patients are not prescribed either of these medications, which have been found to slow disease progression and reduce the risk of acute respiratory deterioration.

The study, “Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry,” was published in the journal Respiratory Research.

To date, the U.S. Food and Drug Administration (FDA) has granted approvals for two medicines for the treatment of IPF: Boehringer Ingelheim’s Ofev, and Genentech’s Esbriet, both approved in 2014.

Ofev inhibits receptor tyrosine kinases, which are thought to be involved in IPF development. For its part, Esbriet acts as an anti-fibrotic agent by blocking transforming growth factor (TGF)-beta and tumor necrosis factor (TNF)-alpha, thus decreasing inflammation and excessive collagen production.

Despite the availability of these medicines, “little is known about prescription patterns for anti-fibrotic medications in a real-world United States (US) setting,” the researchers said.

To learn more, a team led by scientists at the University of Michigan and Genentech made a detailed analysis of how the two treatments are prescribed. They collected records from 1,999 cases registered in the Pulmonary Fibrosis Foundation Patient Registry. A total of 1,218 cases of individuals diagnosed with IPF for whom prescription information was available were included in the analysis.

About 76% of the patients analyzed were male, with a mean age of 70 years.

The data revealed that 740 patients (60.7%) were taking at least one anti-fibrotic medication, and that only 37 people used both medications in the prior year. A large number of patients — 703 of the total, or 57.7% — were taking a single anti-fibrotic medication at the time of the study. Among these, 312 (44.4%) were taking Ofev, while 391 (55.6%) were on Esbriet.

“One surprising finding is that nearly 40% of persons with IPF were not prescribed one of these disease-altering medications,” the researchers said.

“It is possible that provider unfamiliarity with these newer medications, concerns about side effects, or concerns about financial cost may be reasons for deferral of medication initiation,” they added.

Among the individuals taking anti-fibrotic medication, only 71 (9.6%) had a forced-vital capacity (FVC, a lung function measure) above 90%. Meanwhile, 107 (14.5%) had FVC below 50% — corresponding to a severe decline in lung function.

“In general, more severe lung disease … was associated with anti-fibrotic use,” the researchers said.

This finding led the team to suggest that the lack of treatment “may be due to providers and patients deferring anti-fibrotic initiation in patients with less severe disease.”

However, the team questioned why such a decision would be made.

“Such a strategy is not supported by evidence that shows anti-fibrotic use prevents irreversible lung function loss at all levels of disease severity,” they said.

Further analysis showed that the use of anti-fibrotic medications decreased with a patient’s age. In addition, people with IPF using supplemental oxygen therapy and patients who participated in clinical trials were more likely to use anti-fibrotics. However, clinical trial participation among the patients analyzed was not frequent, with only 13.5% having recently been enrolled in a study.

The researchers also found that a 10% increase in the percent-predicted diffusing capacity for carbon monoxide (DLCO) — the ability of the lungs to transfer oxygen from the air to blood — reduced the likelihood of using anti-fibrosis medications.  Yet, increased DLCO was associated with the use of Esbriet.

In the analysis, the researchers were able to identify additional factors that predicted the use of Esbriet. These included increased days since diagnosis, patients from the Midwest region compared with the south region, recent clinical trial participation, and the use of anticoagulants.

The rates of treatment discontinuation were modest for both medications, and of similar proportions: 10.7% for Esbriet, and 10.6% for Ofev. Discontinuation was mainly due to side effects of the treatment with both medicines.

Overall, the study provides “a detailed characterization of IPF treatment patterns in the US,” including patients at every disease stage. The results suggest that anti-fibrotic use varies by registry site across the U.S., and that about “39% of patients potentially helped by these medications [Ofev and Esbriet] were not prescribed one of the medications.”

The team also noted that “many users of anti-fibrotic medications may not have qualified for inclusion in clinical trials,” as PF patients with more severe lung disease are typically excluded from such studies.

“More research is needed to better understand variations in medical decision-making regarding use, including at different stages of disease severity, and selection of anti-fibrotic medication,” the researchers concluded.