Immune Protein SP-A Can Predict Esbriet, Ofev Therapy Outcomes in IPF Patients, Study Finds

Iqra Mumal, MSc avatar

by Iqra Mumal, MSc |

Share this article:

Share article via email
pamrevlumab trial update

Changes in blood levels of surfactant protein-A (SP-A) — immune proteins most abundant in the lungs — can help predict treatment outcomes with anti-fibrotic therapies, including Esbriet and Ofev, in people with idiopathic pulmonary fibrosis (IPF), a study found.

According to the new study, serial measurements of SP-A can serve as a useful biomarker to evaluate treatment response and help guide the management of IPF. Assessing changes in SP-A can help predict treatment outcomes with the approved therapies Esbriet (pirfenidone) and Ofev (nintedanib), the researchers said.

Titled “Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis,” the study was published in the journal BMC Pulmonary Medicine.

Currently, lung transplants are the only curative treatment for IPF. Nonetheless, notable advances have been made in pharmacological therapies for the treatment of the disease.

In particular, Esbriet, marketed by Genentech, and Ofev, marketed by Boehringer Ingelheim, are anti-fibrotic therapies — medications that lessen tissue scarring — approved for the treatment of IPF. The use of these medicines is associated with a reduction in the rate of decline in forced vital capacity (FVC), which is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC is a key measure of lung function.

Secretion of SP-A, surfactant protein-D (SP-D), and Krebs von den Lungen (KL)-6 — three different types of proteins — are known to be associated with IPF progression and mortality. However, changes in these blood biomarkers in relation to treatment with Esbriet or Ofev have not been reported.

Thus, researchers at Sapporo Medical University School of Medicine, in Japan, conducted a study to assess the levels of SP-A, SP-D, and KL-6 in people with IPF undergoing anti-fibrotic therapy. Their goal was to determine if the levels of these proteins reflected changes in FVC and in diffusion capacity of the lung for carbon monoxide (DLco), another measure of lung function. Both FVC and DLco also are surrogate markers for clinical monitoring and prognostic assessment.

The team carried out a retrospective study with IPF patients who started treatment with either Esbriet or Ofev between January 2014 and June 2018 at Sapporo Medical University Hospital. Changes in clinical characteristics, as well as SP-A, SP-D, and KL-6 levels were evaluated.

Those who experienced a decline in FVC of 10% or more, or a decline in DLco of 15% or more, from baseline (the start of the study) to after 6 months, were categorized as the progression group. The other patients were classified as the stable group.

Altogether, 49 patients were evaluated, including 23 treated with Esbriet, and 26 given Ofev. The stable group was comprised of 32 patients — 17 receiving Esbriet, and 15 Ofev — while the progression group counted 17 individuals, which included six on Esbriet, and 11 on Ofev.

The results showed that, within the stable group, the levels of SP-A and KL-6 significantly decreased from baseline to three and six months, compared with the progression group. In the stable group, the median decrease in SP-A at three months was 6%, with a 10.2% reduction at six months. Meanwhile, the median decreases in the progression group were 16.7% at three months and 20.2% at six months.

Similarly, the median decrease in KL-6 levels in the stable group were 9.2% at three months and 15.0% at six months. In the progression group, the median decrease was 6.7% at three months and 12.1% at six months.

SP-D levels also decreased by a median change, in the stable group, at three months of 10.6% and at six months of 13.7%. In the progression group, the median changes were 0.4% at three months and 0.5% at six months.

Interestingly, the researchers found that SP-A and SP-D levels were negatively correlated to changes in FVC and DLco. Essentially, the lower the SP-A and SP-D levels, the higher the FVC and DLco, meaning a better lung function.

When the team evaluated the results based on the therapy used by the patients — Esbriet or Ofev — they observed similar results, regardless of which therapy each person was receiving.

Further, a statistical analysis indicated that a change in SP-A was a significant predictive factor of therapeutic outcomes at six months.

Overall, the team found that “changes in serum SP-A reflected the outcomes of anti-fibrotic drug therapy.”

“Serum SP-A has a potential as a biomarker of therapeutic outcomes of anti-fibrotic drugs,” they concluded.

Your PF Community

Woman laying down reading

Visit the Pulmonary Fibrosis News forums to connect with others in the PF community.

View Forums