Ofev’s Ability to Slow Decline in Progressing ILDs Not Dependent on Prior Therapy

The ability of Ofev (nintedanib) to improve lung function in people with progressive fibrosing interstitial lung diseases (ILDs) is not influenced by their use of immunomodulatory therapies, a study indicates.

The study, “Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases,” was published in the journal Respiratory Research.

Ofev, by Boehringer Ingelheim, is an oral anti-fibrotic therapy that works to reduce lung tissue scarring (fibrosis). It was recently approved to treat people with chronic progressive ILDs in the U.S., Canada, and Europe, after years as an approved treatment of idiopathic pulmonary fibrosis (IPF) and scleroderma-associated ILD.

The Phase 3 INBUILD trial (NCT02999178) evaluated the efficacy and safety of 52 weeks of treatment with Ofev (150 mg, twice daily), compared with a placebo, in 663 adults with progressive fibrosing ILDs other than IPF (randomized 1:1 to treatment or placebo). All showed disease progression over the prior two years, despite trying to manage their disease, typically with glucocorticoids or immunomodulatory therapies.

Trial data showed that Ofev consistently reduced the rate of disease progression — by slowing lung function decline — across  patient groups with manageable side effects.

In the present study, INBUILD researchers investigated the potential impact of immunomodulatory therapies on Ofev’s safety and efficacy.

Certain immunomodulatory therapies were restricted, including those “commonly used in the treatment of ILDs,” and had to be discontinued for the first six months of the study. These included azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, high-dose glucocorticoids (over 20 mg per day), or the combination of glucocorticoids, azathioprine and N-acetylcysteine, cyclophosphamide, and rituximab.

After those months of treatment, patients who saw their health deteriorate were allowed to resume their use as “rescue” treatments.

Most of those enrolled had been diagnosed with chronic hypersensitivity pneumonitis (26.1%), followed by autoimmune disease-related ILDs (25.6%), and idiopathic non-specific interstitial pneumonia (18.9%). Unclassifiable ILDs were in 17.2% of these patients, and other ILDs in 12.2%.

Lung function decline was assessed by measuring changes in forced vital capacity (FVC) — a measure of the total amount of air a person is able to exhale after a deep breath — in patients taking a low or high dose of glucocorticoids (under or over 20 mg per day, respectively) or no glucocorticoids.

At the study’s start (baseline), its 663 participants (mean age 65.8, 53.7% male) had a mean FVC of 69.0%. Most patients (62.1%) showed signs of lung tissue scarring (fibrosis) on high-resolution computed tomography (HRCT) chest scans.

All received at least one dose of Ofev over the trial’s 52 weeks, the study reported.

Over half of the patients (54.4%) were using glucocorticoids — eight on high dose and 353 on low dose — when they entered the study, while 4.7% were taking biologic disease-modifying anti-rheumatic drugs (DMARDs) and 11.6% were on non-biologic DMARDs. The trial placed no limitations on people with stable DMARDs doses; most had autoimmune disease-related ILDs.

Among placebo group patients, the adjusted rate of FVC decline over 52 weeks was numerically greater in those using  glucocorticoids than in those not taking these medications (−206.4 vs. −165.8 milliliter per year or mL/year).

The difference in adjusted FVC decline rate between Ofev-treated and placebo group patients was 133.3 mL/year among those taking glucocorticoids, and 76.1 mL per year among those not on glucocorticoids.

“These data should be interpreted with caution given that there were differences between these subgroups at baseline,” the researchers wrote. “[H]owever, other studies have found no benefit of glucocorticoids in reducing the progression of fibrosing ILDs.”

No indication of variability in Ofev’s effectiveness at lowering the rate of FVC decline was seen among patient subgroups receiving high or low glucocorticoid doses, or not taking these medications.

More placebo group patients (27.5%) returned to using restricted immunomodulatory therapies than did Ofev group patients (16.0%). In contrast, a higher proportion of people in the Ofev group used low-dose glucocorticoids than did people in the placebo group (52.4% vs. 45.9%).

Ofev’s efficacy in slowing the rate of FVC decline, in an analysis that excluded those patients “who took ≥ 1 prohibited or restricted therapy over 52 weeks” and those FVC measures taken after use of such therapies, was “similar” to the trial’s primary analysis favoring the therapy, the researchers wrote.

Ofev’s safety profile among treated patients taking immunomodulatory therapies at the study’s beginning or during the trial, and those who did not, was also similar.

“Our analyses suggest that the use of glucocorticoids at baseline, or the introduction of immunomodulatory therapies during the trial, did not affect the benefit of nintedanib in reducing the rate of FVC decline in patients with chronic fibrosing ILDs and a progressive [disease],” the researchers concluded.