Progress in the treatment of pulmonary fibrosis

Pulmonary fibrosis encompasses a wide range of fibrosing interstitial lung diseases (ILDs) with different underlying causes. In the past two decades, most focus has been on idiopathic pulmonary fibrosis (IPF), the most prevalent and relentlessly progressive type of fibrosing ILD. 1 Raghu G Rochwerg B Zhang Y et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015; 192: e3-e19 Crossref PubMed Scopus (1069) Google Scholar , 2 Raghu G Remy-Jardin M Myers JL et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018; 198: e44-e68 Crossref PubMed Scopus (1207) Google Scholar For other forms of fibrosing ILD, data on the proportion of patients who develop progressive pulmonary fibrosis are still scarce and depend on the disease studied and criteria used. 3 Wijsenbeek M Kreuter M Olson A et al. Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management. Curr Med Res Opin. 2019; 35: 2015-2024 Crossref PubMed Scopus (51) Google Scholar Guidelines seem dedicated to assessing the likelihood of IPF versus another fibrosing ILD, as treatment, trial options, and prognosis differ. 1 Raghu G Rochwerg B Zhang Y et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015; 192: e3-e19 Crossref PubMed Scopus (1069) Google Scholar , 2 Raghu G Remy-Jardin M Myers JL et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018; 198: e44-e68 Crossref PubMed Scopus (1207) Google Scholar For the treatment of IPF, anti-fibrotic therapy in the form of nintedanib or pirfenidone is recommended, whereas, other forms of fibrosing ILD are mostly treated with immunosuppressive medication. 1 Raghu G Rochwerg B Zhang Y et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015; 192: e3-e19 Crossref PubMed Scopus (1069) Google Scholar , 3 Wijsenbeek M Kreuter M Olson A et al. Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management. Curr Med Res Opin. 2019; 35: 2015-2024 Crossref PubMed Scopus (51) Google Scholar This focus on IPF versus other fibrosing ILDs is likely to shift with the progress made in the ILD-field. Communalities in underlying pathobiological mechanisms as well as disease behaviour have been reported for different forms of pulmonary fibrosis regardless of the initial underlying cause that sets off the disease. 4 Kolb M Vašáková M The natural history of progressive fibrosing interstitial lung diseases. Respir Res. 2019; 20: 57 Crossref PubMed Scopus (70) Google Scholar Furthermore, three trials have shown response to anti-fibrotic therapy in patients with various forms of progressive fibrosing ILD, by use of different criteria to define progression. 5 Behr J Neuser P Prasse A et al. Exploring efficacy and safety of oral pirfenidone for progressive, non-IPF lung fibrosis (RELIEF)—a randomized, double-blind, placebo-controlled, parallel group, multi-center, phase II trial. BMC Pulm Med. 2017; 17: 122 Crossref PubMed Scopus (67) Google Scholar , 6 Flaherty KR Wells AU Cottin V et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019; 381: 1718-1727 Crossref PubMed Scopus (457) Google Scholar , 7 Wells AU Flaherty KR Brown KK et al. Nintedanib in patients with progressive fibrosing interstitial lung diseases, subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind,. placebo-controlled, parallel-group trial. Lancet Respir Med. 2020; (published online March 5.)https://doi.org/10.1016/S2213-2600(20)30036-9 Summary Full Text Full Text PDF Scopus (104) Google Scholar , 8 Maher TM Corte TJ Fischer A et al. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2020; 8: 147-157 Summary Full Text Full Text PDF PubMed Scopus (156) Google Scholar Combining two out of three domains of forced vital capacity (FVC), high resolution CT, and symptoms (INBUILD criteria) allowed for identification of patients with fibrosing ILD with a progressive phenotype similar to IPF. 6 Flaherty KR Wells AU Cottin V et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019; 381: 1718-1727 Crossref PubMed Scopus (457) Google Scholar This pragmatic approach of identifying patients with progressive fibrosing ILD is feasible in almost every setting and close to daily practice in which we include more parameters than FVC to assess disease progression. Nintedanib in patients with progressive fibrosing interstitial lung diseases—subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trialThe INBUILD trial was not designed or powered to provide evidence for a benefit of nintedanib in specific diagnostic subgroups. However, its results suggest that nintedanib reduces the rate of ILD progression, as measured by FVC decline, in patients who have a chronic fibrosing ILD and progressive phenotype, irrespective of the underlying ILD diagnosis. Full-Text PDF