The Changing Antifibrotic Landscape for the APP

The Changing Antifibrotic Landscape for the APP

Kelsey Cramer DNP

Antifibrotic therapy for Interstitial lung disease is shifting from a narrow, IPF- only focus with two modestly effective drugs to a broader, more patient centered and potentially better set of options that span multiple progressive pulmonary fibrosis. For Pulmonary APPs this means more patients are candidates, more drugs and more combinations are emerging, and monitoring plans and patient counseling all need to evolve.

Two Drug History

For a decade antifibrotic conversations were essentially about pirfenidone and nintedanib for IPF slowing FVC decline and exacerbations but with frequent GI side effects.

•       Perfenidone (oral TGF-B- modulating antifibrotic) slows FVC decline and may confer a mortality signal with key toxicities of GI upset, anorexia, and photosensitivity
•       Nintedanib (tyrosine kinase inhibitor) slows FVC decline and may reduce acute exacerbations but is limited by diarrhea, liver enzyme elevation and adherence challenges

The New Kid: nerandomilast

The most recent shift is the arrival of nerandomilast, a selective PDE4B inhibitor with both antifibrotic and possible immunomodulatory effects, representing the first new antifibrotic in more than a decade. Nerandomilast has shown reduced FVC decline, survival benefit signals, and tolerable side effect profiles.

•       Nerandomilast has a more favorable GI profile addresses one of the biggest real-world barriers: long term adherence to nintedanib or pirfenidone
•       Trial design permitted background nintedanib and pirfenidone, opening the door to combination or “add on” antifibrotic

Shifting Indications and Phenotypes

Pulmonary providers are now asked less “is this classic IPF” and more “is this progressive fibrosing ILD phenotype that could benefit from antifibrotic therapy?” Trials like INBUILD and SENSCIS have shown benefit with nintedanib across non-IPF progressive fibrosis ILD and SSC-ILD while pirfenidone and nintedanib have shown benefit in select post- COVID fibrosis cohorts.

What this means for APP practice

The changing antifibrotic landscape reshapes clinic responsibilities from simple prescribing to nuanced, longitudinal management of complex multimorbid patients. Pulmonary APPs sit at the center; they orchestrate monitoring, adverse- effect management and shared decision making across IPF and progressive fibrosing ILD

•       Assessment and timing

○       Incorporate structure FVC trends, 6MWT, oxygen needs and imaging

○       Revisit antifibrotic eligibility at every visit for IPF and Fibrosis ILD who show subtle but consistent decline

•       Drug Selection and Sequencing

○       For patients with significant baseline GI disease or frailty consider agents with more favorable tolerability profiles ( e.g. nerandomilast) while still individualizing based on comorbidities and drug interactions

○       For CTD-ILD or SSC-ILD think in terms of “platform immunosuppression + antifibrotic” and aligning choices with rheumatology and transplant centers

•       Patient education and shared decision

○       From antifibrotics as chronic disease therapy “we are slowing the slope, not curing the disease” and use visuals of FVC to support understanding

○       Discuss newer options in terms that the patient understands

Looking ahead

The next decade is likely to move from one-size-fits-all antifibrotics toward phenotype-driven biomarker-guided therapy and strategic combinations. For the APP, the emerging antifibrotic landscape offers more opportunities to change the trajectory of fibrosing lung disease, but also demands more nuanced clinical reasoning, patient coaching, and team based care.

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