Emerging Therapeutic Innovations for Treatment of Idiopathic Pulmonary Fibrosis

Published in the journal European Respiratory Review, researchers highlight new therapeutic attempts and potential future approaches to treating idiopathic pulmonary fibrosis (IPF), a chronic, fibrosing idiopathic interstitial lung disease (ILD).

Study authors note that while the recent introduction of antifibrotic drugs pirfenidone and nintedanib has led to significant reduction in lung function decline, clinical trials have yet to find a cure for IPF. The potentially fatal disease is characterized by progressive scarring of the lung and linked with a steady worsening of respiratory symptoms and decline of pulmonary function.

Development of Biomarkers for Treatment of IPF

The development of biomarkers to personalize therapy for IPF is an innovation that researchers say can guide diagnostic, therapeutic, and prognostic approaches in managing IPF.

As the current standard for diagnosing IPF is performing a lung biopsy, which is not possible in all patients due to its significant risk, developing biomarkers to assist in accurately diagnosing the disease would be crucial for administering timely and effective treatment. Biomarkers such as Krebs von den Lungen (KL)-6, leucocytes, and circulating innate immune cells have all been shown to discriminate IPF from healthy individuals, with KL-6 additionally showing potential in discriminating ILDs from other benign lung diseases.

The development of therapeutic biomarkers has become a focus in clinical trials as different biomarkers were tested in a recent study to interact with pirfenidone treatment. Researchers wanted to see whether any could serve as a prognostic, predictive, or pharmacodynamic biomarker, but for this study, pirfenidone treatment exhibited no significant pharmacodynamic effect on the plasma levels of the biomarkers.

In a Japanese retrospective analysis, the biomarker SP-D exhibited prognostic effects in an IPF cohort receiving pirfenidone. This result shows a potential therapeutic biomarker in the pipeline of IPF treatment, but researchers noted that further research is warranted. “Reliable predictive therapeutic biomarkers are still missing and the search for informative biomarkers in IPF must be continued,” the study authors concluded.

New Developments in IPF Treatment

As the response to antifibrotic treatment is heterogeneous and may be limited by adverse effects, researchers stress that the development of novel therapeutic approaches in treating IPF is vital to expand effective care. Combination therapies have been hypothesized as potentially effective treatments of IPF due to its ability to target multiple pathways with current established therapies, but the combined adverse effects are a cause for concern.

In the INJOURNEY trial, researchers tested nintedanib with add-on pirfenidone to test the safety of the combination. Results found similar adverse effects between patients with the combination therapy and with solely nintedanib, indicating feasible safety and tolerability for patients with IPF. Further expanding these trials to examine the efficacy of these combination therapies on the IPF population was highlighted as an important next step by the study authors.

A variety of clinical trials with positive outcomes were listed by researchers, such as PRAISE and FLORA, with a focus on the repetitive alveolar epithelial cell injury being recognized by clinicians as a crucial mediator of the fibrotic process. “The activation of multiple pathways leading to fibroblast migration, proliferation and myofibroblast differentiation has identified numerous potential molecular targets of novel therapeutic agents currently being explored in early clinical trials,” wrote the study authors.

Reference

Somogyi V, Chaudhuri N, Torrisi SE, et al. The therapy of idiopathic pulmonary fibrosis: what is next? [published online September 30, 2019]. Eur Respir Rev. doi: 10.1183/16000617.0021-2019.