New abilities in therapy of idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is progressive fibrosing lung disease with average survival of 2 to 3 years after the diagnosis. Nintedanib is tyro sine kinase inhibitor targeted to receptors of PDGF, FGF and VEGF growth factors. Use of nintedanib in IPF was approved in many countries on the basis of results of TOMORROW phase 2 clinical trial and two phase 3 INPULSIS replicate studies. Significant reduction in the annual FVC decline was shown under the therapy with nintedanib in the INPULSIS studies. Improvement in time to the first exacerbation and stabilization of quality of life measured by SGRQ scale were obtained in the INPULSIS1 study. In pooled analysis of TOMORROW and INPULSIS study results, nintedanib decreased mortality in IPF patients compared to placebo. FVC decline was not differed between patients with typical and possible IPF (i.e., patients with traction bronchiectasis in HRCT, but without surgical lung biopsy) in the INPULSIS trials. In subgroup analysis in INPULSIS trials, the efficacy of nintedanib was confirmed in all IPF patients independently on age, gender, race, baseline FVC and DLCO, presence of emphy sema, use of antireflux therapy or systemic steroids. Frequency of severe adverse events (AE) did not differed between groups of nintedanib and placebo in the INPULSIS trials. The most frequent AE was diarrhea (60%), mostly mild or moderate, which did not require withdrawal the treat ment. Further investigations are needed to study efficacy of nintedanib in IPF patients with more extended inclusion criteria and other fibrosing interstitial lung diseases, as well as efficacy and safety of combinations of nintedanib and pirfenidone. Ideally, the therapeutic strategy in IPF patients should be individualized according to characteristics of the patient.