[Treatment of pulmonary fibrosis: Beginning of a new era].
Behr Jürgen J, Veit Tobias T
Interstitial lung diseases (ILD) comprise a heterogeneous group of inflammatory and fibrotic disorders of the lung parenchyma. Idiopathic pulmonary fibrosis (IPF) is the prototype of a progressive pulmonary fibrosis and is associated with a particularly poor prognosis. 18-32% of other ILD evolve into a progressive phenotype called progressive pulmonary fibrosis (PPF), with behavior similar to IPF in terms of prognosis and mortality. IPF and PPF share key pathophysiological mechanisms. Currently available antifibrotic therapies can slow disease progression; however, their benefits on quality of life and mortality are not undisputably proven in controlled clinical trials, and adverse effects often limit their use. Consequently, there remains a substantial need for effective and better-tolerated therapeutic options. To present current developments and emerging pharmacological treatment strategies, as well as their potential implications for clinical practice. A systematic search in PubMed and ClinicalTrials.gov was conducted to identify relevant clinical studies on established and novel therapeutic approaches. The most clinically advanced compounds currently under investigation for the treatment of progressive pulmonary fibrosis include nerandomilast and inhaled treprostinil. Nerandomilast, a preferential PDE4B inhibitor with antifibrotic, anti-inflammatory and vascular properties, significantly reduced the decline in forced vital capacity (FVC) in the Phase III FIBRONEER trials in patients with IPF and PPF and was associated with a manageable tolerability profile as well as favourable signals regarding mortality risk. For inhaled treprostinil, TETON-2, TETON-1 and the pre-specified pooled analysis demonstrated significant positive effects on the primary endpoint (FVC) and in part on the secondary endpoints. Both agents may therefore broaden the range of therapeutic options for progressive pulmonary fibrosis in the future. The current Phase III data indicate that new therapeutic approaches may meaningfully complement the previously limited treatment options for IPF and PPF in the future, particularly through novel mechanisms of action, additional possibilities for combination therapy, and potentially better-tolerated treatment options.