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INTRODUCTION: Lung injury in severe COVID-19 pneumonia can rapidly evolve to established pulmonary fibrosis, with prognostic implications in the acute phase of the disease and long-lasting impact on the quality of life of COVID-19 survivors. This is an emerging medical need, and it has been hypothesized that antifibrotic treatments could have a role in ameliorating the fibrotic process in the lungs of these patients.Areas covered: The safety and efficacy of available antifibrotic drugs (nintedanib and pirfenidone) and novel promising agents are being assessed in several ongoing clinical trials that were performed either in critically ill patients admitted to intensive care, or in discharged patients presenting fibrotic sequalae from COVID-19. Literature search was performed using Medline and Clinicaltrials.org databases (2001-2021). Expert opinion: Despite the strong rationale support the use of antifibrotic therapies in COVID-related fibrosis, there are several uncertainties regarding the timing for their introduction and the real risks/benefits ratio of antifibrotic treatment in the acute and the chronic phases of the disease. The findings of ongoing clinical trials and the long-term observation of longitudinal cohorts will eventually clarify the best management approach for these patients.

The approval of antifibrotic agents nintedanib and pirfenidone revolutionized the management of idiopathic pulmonary fibrosis (IPF). These treatments showed acceptable tolerability in randomized-clinical trials; however, they have been associated with a spectrum of potential side effects which require careful assessment of risks and benefits in the individual patient before commencing and during antifibrotic therapy.The accrued evidence on safety of nintedanib and pirfenidone is summarized, from the first randomized clinical trials to the open-label extension studies and post-marketing clinical experiences which helped clarify the long-term tolerability of these drugs.The data collected over the last years confirmed the comparable tolerability profile of nintedanib and pirfenidone. The physician's assessment of expected side effects may help decide the optimal first-line therapy for the individual patient. Patient's counseling during treatment remains essential to manage emerging adverse events and eventually inform the decision of drug discontinuation.

The enthusiasm generated by the approval of pirfenidone and nintedanib as the first effective therapies for IPF led the IPF scientific community to investigate an increasing number of novel agents in well-designed randomized controlled trials, in the hope to find a cure for these patients.This reviews the evidence from IPF phase II trials that were completed or started in 2020. Literature search was performed using Medline and Clinicaltrials.org databases.Randomized clinical trials revolutionized the management of IPF, leading to the discovery of the first therapies capable of slowing down functional deterioration in these patients. The recently published findings of the first successful phase II trials since pirfenidone and nintedanib will hopefully inaugurate a new era in the therapeutic scenario of IPF, where consolidated treatments of proven efficacy and novel targeted agents contribute together to reach the final goal of halting the fibrotic process of this dreadful disease.

The last two decades witnessed an increasing number of well-designed late phase trials in patients with Idiopathic Pulmonary Fibrosis (IPF), leading to the approval of the first effective therapies...

Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease characterized by the progressive loss of pulmonary function, ultimately leading to respiratory failure and death. Two novel compounds, nintedanib and pirfenidone, have shown efficacy in reducing the rate of decline of lung function in IPF patients. The multiple tyrosine kinase inhibitor nintedanib has extensively being studied as a potential angiogenesis inhibitor in clinical against various neoplastic disorders. Afterwards, this compound was successfully tested in IPF. Areas covered: Herein, the authors review the working mechanisms of nintedanib, its pharmacological profile, and its efficacy and safety for patients with IPF. Expert opinion: Nintedanib has shown to be safe and effective in patients with IPF, with a favorable long-term safety profile. There is a lack of comparative trials of pirfenidone and nintedanib, and the choice of treatment is left to the physicians' judgement. Future directions of nintedanib use are represented by the treatment of progressive fibrosing interstitial lung disease other than IPF, IPF with advanced functional impairment, and lung fibrosis secondary to connective tissue diseases. A promising safety profile for the combinational use of nintedanib and pirfenidone in IPF has also recently emerged.

Idiopathic Pulmonary Fibrosis (IPF) is a progressive, fatal lung disorder of unknown cause with a highly variable and unpredictable clinical course. The advances made in deciphering IPF pathobiology over the last decades have led to the approval of two anti-fibrotic molecules, pirfenidone and nintedanib, that showed to be effective in significantly reducing the rate of progression of the disease. Such pharmacological breakthroughs represent a dramatic change in the management of these patients and are reflected in updated international guidelines. However, the need to find a cure for this devastating disease remains unmet and the development of novel therapeutic agents remains hurdled by several factors. Here, we review the latest insights into therapeutic approaches for IPF and the available evidence for the most promising novel compounds currently under development, and discuss the challenges and evolution of IPF clinical research over the next few years.