New Antifibrotics Are Changing the Treatment Calculus in ILD

The antifibrotic landscape for interstitial lung disease (ILD) has been largely static since 2014, when nintedanib and pirfenidone became the first approved agents for idiopathic pulmonary fibrosis (IPF). Effective at slowing fibrosis progression, both drugs carried a tolerability burden that shaped clinical decision-making in a particular way: in patients who were clinically stable or early in their disease course, many providers opted to wait before initiating therapy, weighing the risk of side effects against the uncertain benefit in a patient who felt well.

That calculus is now shifting, according to Jessica Glennie, MSN, APRN, of the Cleveland Clinic ILD Center in Cleveland, Ohio, who presented as part of the multidisciplinary ILD bootcamp series at the Association of Pulmonary Advanced Practice Providers (APAPP) National Conference, held June 28-20 in Colorado Springs.1

The catalyst is nerandomilast (Jascayd), a first-in-class preferential phosphodiesterase 4B (PDE4B) inhibitor approved by the United States Food and Drug Administration (US FDA) in October 2025 for IPF and subsequently for progressive pulmonary fibrosis (PPF) — the first new antifibrotic mechanism in more than a decade.2 In the FIBRONEER phase 3 trials, nerandomilast significantly reduced the annual rate of forced vital capacity decline versus placebo, with a tolerability profile meaningfully better than existing agents: no requirement for liver function monitoring, no food requirement for administration, and substantially lower rates of gastrointestinal adverse effects.2

"Now I can put a patient on a medication that they're potentially going to tolerate a lot better, not have these side effects and feel worse — so why not try to get them on something that's potentially going to slow the progression of their disease?" Glennie said. She described offering nerandomilast upfront to antifibrotic-naïve patients, switching patients intolerant of nintedanib, and using it as add-on dual therapy in patients who are tolerating their existing antifibrotic but continuing to show functional decline. Insurance coverage remains an obstacle in some cases, but when it is accessible, patient preference has consistently favored nerandomilast given its tolerability advantages.

The evolution in prescribing approach reflects a broader shift: when side effects were the dominant limiting factor, the rational strategy was to withhold therapy until progression was clear. When a well-tolerated option exists, the equation tips toward earlier intervention — preserving function before irreversible fibrosis accrues, rather than waiting for measurable deterioration to justify treatment.

Glennie has no disclosures to report.

References

1. Glennie J. Bridging specialties in ILD: a multidisciplinary bootcamp series for early recognition and targeted treatment; ILD 102. Presented at: Association of Pulmonary Advanced Practice Providers Annual Meeting (APAP 2026); Las Vegas, NV.

2. Richeldi L, Azuma A, Cottin V, et al. Nerandomilast in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2025;392:2193–2202. doi:10.1056/NEJMoa2414108