Antifibrotic therapy of idiopathic pulmonary fibrosis: history of discovery, mechanism of action, efficacy and safety assessment (literature review)
REVIEWS
Abstract
Introduction.Idiopathic pulmonary fibrosis is a fibrotic interstitial pneumonia characterized by the development of respiratory failure and high mortality in patients. The disease has shown resistance to anti-inflammatory and immunosuppressive therapy. However, a deep understanding of the pathogenesis contributed to the discovery of antifibrotic drugs: pirfenidone and nintedanib.Materials and methods.When writing the review, both domestic and foreign studies, 4 randomized controlled trials and 11 cohort clinical trials of drugs were studied.Results and discussion.Attempts to treat idiopathic pulmonary fibrosis using anti-inflammatory therapy proved ineffective, as its use was associated with an increased number of hospitalizations, complications, and deaths. This led to a detailed study of the pathogenesis of the disease and the development of new drugs with antifibrotic effect. The study of pirfenidone began with the discovery of protective properties of the drug in relation to respiratory organs, which served as an impetus for further research of the substance in models of pulmonary fibrosis induced in animals. During the analysis of the antitumor drugnintedanib, an antifibrotic effect was revealed in an animal model, which required additional study of this substance. After the publication of the results of randomized controlled trials of ASCEND (pirfenidone) and INPULSIS-1, INPULSIS-2 (nintedanib) drugs were approved by the Food and Drug Administration. During clinical trials of antifibrotic drugs, their effectiveness and safety were evaluated.Conclusions. The antifibrotic drugs pirfenidone and nintedanib have demonstrated their safety and efficacy in the treatment of idiopathic pulmonary fibrosis, which is manifested by slowing the progression of accelerated lung capacity, reducing mortality and increasing patient survival. However, the drugs do not affect the prognosis of the disease, which requires further investigation of the problem.
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