Ofev effective at slowing lung function decline in RA-ILD patients
Phase 3 INBUILD trial tested more than 650 adults with progressive fibrosing ILDs
Ofev (nintedanib) more than halved the rate of lung function decline in patients who developed interstitial lung disease (ILD) associated with rheumatoid arthritis (RA), an inflammatory disease.
That’s according to data from INBUILD (NCT02999178), a Phase 3 trial of more than 650 adults with progressive fibrosing ILDs in whom lung tissue scarring continued to progress and data supported Ofev’s approval in a broad range of progressive ILDs.
The data from a group of patients with RA-ILD were shared in “Effect of nintedanib in patients with progressive pulmonary fibrosis associated with rheumatoid arthritis: data from the INBUILD trial,” in Clinical Rheumatology.
RA causes pain, swelling, and joint stiffness. Over time, it can cause other parts of the body to become inflamed. When this happens in the lungs or their lining, it can lead to ILD.
Sometimes ILD gets worse and becomes progressive pulmonary fibrosis, wherein the lungs become increasingly scarred and their function declines.
Boehringer Ingelheim’s Ofev reduces scar tissue formation, helping to prevent symptoms from getting worse. It was initially approved for idiopathic pulmonary fibrosis and later to manage other forms of ILD with a progressive course.
Effectiveness of Ofev at slowing lung function decline
In the company-sponsored INBUILD trial, Ofev slowed the rate of lung function decline in patients who developed ILD secondary to an autoimmune disease.
Here, researchers evaluated how well it works in RA-ILD. Of the 663 patients who took part in INBUILD, 89 (13.4%) had RA-ILD and signs of worsening pulmonary fibrosis in the previous two years, even with regular treatment.
They had a mean age of 66.9 and more than half (60.7%) were men. On high-resolution computed tomography scans, most (86.5%) had a typical interstitial pneumonia-like pattern, associated with pulmonary fibrosis.
Most (88.8%) were taking at least one immunomodulatory medication for their RA. More than half (53.9%) were on nonbiologic disease-modifying anti-rheumatic drugs (DMARDs), 21.3% on biologic DMARDs, and 73% on glucocorticoids.
At the trial’s entry, the patients were randomly assigned to receive either Ofev as 150 mg capsules (42 patients) or a placebo (47 patients), twice daily for about a year.
Those on Ofev saw 59% less lung function decline than those on a placebo. This was determined by measuring forced vital capacity (FVC) over a year. FVC represents the total volume of air a person can forcibly exhale from the lungs.
FVC dropped by a mean of 82.6 mL a year with Ofev, but dropped by a mean of 199.3 mL/year with a placebo. This translated into a significant difference of 116.7 mL/year between the groups.
Similar results were obtained regardless of whether patients were taking immunomodulatory medications at the study’s start or had high levels of C-reactive protein, a marker of inflammation linked to worse FVC and survival.
Acute exacerbations (symptom worsening) or death occurred in eight (19%) patients on Ofev and 15 (31.9%) on a placebo, meaning acute exacerbations and death were about half as likely to occur with Ofev.
“This trend may be of clinical relevance given the lack of effective treatments for acute exacerbations of ILD,” the researchers wrote.
The most common side effect was diarrhea, which occurred in 26 (61.9%) patients taking Ofev and 13 (27.7%) on a placebo over a median 17.4 months, or nearly 1.5 years. In the Ofev group, side effects led to a dose reduction in nine (21.4%) patients or to treatment being discontinued in 10 (23.8%).
“The proportions of patients with adverse events leading to dose adjustment or permanent treatment discontinuation over the whole trial were consistent with the overall trial population,” the researchers wrote in a graphical abstract.
The side effects were manageable, however, and the researchers concluded that Ofev was effective in slowing lung function decline with RA-ILD. “The efficacy and safety of [Ofev] in these patients were consistent with the overall trial population,” they wrote.