# Nerandomilast in Autoimmune-Associated Interstitial Lung Diseases: Translating Evidence from Progressive Pulmonary Fibrosis Studies

## TL;DR

Nerandomilast, a new drug targeting PDE4B, shows promise in treating autoimmune-related lung diseases by reducing fibrosis and inflammation.

## Contribution

The paper introduces nerandomilast as a novel PDE4B inhibitor with dual antifibrotic and immunomodulatory potential in autoimmune-associated lung diseases.

## Key findings

- Preclinical studies suggest PDE4B inhibition reduces fibroblast activation and extracellular matrix deposition.
- Clinical trials show reduced lung function decline in progressive pulmonary fibrosis, with potential benefits in autoimmune-related cases.
- Safety profile includes gastrointestinal adverse events, with ongoing evaluation of neuropsychiatric effects.

## Abstract

Systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) comprises a heterogeneous group of fibrosing lung disorders frequently complicated by progressive pulmonary fibrosis, a phenotype associated with accelerated lung function decline and increased mortality. Although antifibrotic therapies have improved clinical outcomes, significant unmet needs remain, particularly regarding treatment tolerability and integration with background immunosuppressive strategies. Preferential phosphodiesterase-4B (PDE4B) inhibition has emerged as a novel therapeutic approach targeting both inflammatory and fibrotic pathways through modulation of intracellular cyclic adenosine monophosphate signaling. This narrative review summarizes the biological rationale and emerging clinical evidence supporting nerandomilast, an oral preferential PDE4B inhibitor, in autoimmune-associated interstitial lung diseases. Preclinical data indicate that PDE4B inhibition may attenuate fibroblast activation, inflammatory signaling, and extracellular matrix deposition. Clinical trials conducted in progressive pulmonary fibrosis populations have demonstrated a reduction in lung function decline, with subgroup analyses suggesting potential benefit in autoimmune-related diseases, although evidence remains limited. The safety profile appears mainly characterized by gastrointestinal adverse events, with ongoing evaluation of neuropsychiatric safety and drug interactions in complex autoimmune populations. Overall, nerandomilast represents a promising investigational strategy bridging antifibrotic and immunomodulatory mechanisms, warranting further dedicated studies in SARD-ILD.