INTRODUCTION: The antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry. PATIENTS/METHODS: Data of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed. The influence of nintedanib on overall survival (OS), pulmonary function parameters as forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO), as well as GAP score (gender, age, physiology) and and CPI (composite physiological index) were investigated. RESULTS: During 2 year follow-up we observed that nintedanib treated patients had longer OS, compared to those treated with no-antifibrotic drugs (p < 0.00001). Nintedanib reduces risk of mortality over no-antifibrotic treatment by 55% (p < 0.001). We have observed no significant difference in the rate of FVC and DLCO decline between the NIN and NAF group. Changes within 24 months from baseline in CPI were not significant between the groups (NAF and NIN). CONCLUSION: Our real-practice study showed the benefit of nintedanib treatment on survival. There were no significant differences between NIN and NAF groups in changes from baseline in FVC %, DLCO % predicted and CPI.

• Klíčová slova
• Idiopathic pulmonary fibrosis, Lung function decline, Nintedanib, Overall survival,
• MeSH
• idiopatická plicní fibróza * farmakoterapie   MeSH
• lidé MeSH
• plíce MeSH
• registrace MeSH
• vitální kapacita MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• nintedanib MeSH Prohlížeč

BACKGROUND: There is no clear evidence whether pirfenidone has a benefit in patients with probable or possible UIP, i.e. when idiopathic pulmonary fibrosis (IPF) is diagnosed with a lower degree of diagnostic certainty. We report on outcomes of treatment with pirfenidone in IPF patients diagnosed with various degrees of certainty. METHODS AND FINDINGS: We followed patients in the multi-national European MultiPartner IPF Registry (EMPIRE) first seen between 2015 and 2018. Patients were assessed with HRCT, histopathology and received a multi-disciplinary team (MDT) IPF diagnosis. Endpoints of interest were overall survival (OS), progression-free survival (PFS) and lung function decline. RESULTS: A total of 1626 patients were analysed, treated with either pirfenidone (N = 808) or receiving no antifibrotic treatment (N = 818). When patients treated with pirfenidone were compared to patients not receiving antifibrotic treatment, OS (one-, two- and three-year probability of survival 0.871 vs 0.798; 0.728 vs 0.632; 0.579 vs 0.556, P = 0.002), and PFS (one-, two- and three-year probability of survival 0.597 vs 0.536; 0.309 vs 0.281; 0.158 vs 0.148, P = 0.043) was higher, and FVC decline smaller (-0.073 l/yr vs -0.169 l/yr, P = 0.017). The benefit of pirfenidone on OS and PFS was also seen in patients with probable or possible IPF. CONCLUSIONS: This EMPIRE analysis confirms the favourable outcomes observed for pirfenidone treatment in patients with definitive IPF and indicates benefits also for patients with probable or possible IPF.

• MeSH
• antiflogistika nesteroidní farmakologie   MeSH
• idiopatická plicní fibróza * diagnóza   MeSH
• lidé MeSH
• plíce MeSH
• pravděpodobnost MeSH
• pyridony farmakologie   MeSH
• retrospektivní studie MeSH
• vitální kapacita MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• pirfenidone MeSH Prohlížeč
• pyridony MeSH

BACKGROUND: The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the association of common profibrotic polymorphisms in MUC5B (mucin 5B, rs35705950) and DSP (desmoplakin, rs2076295) on antifibrotic treatment outcomes in IPF. METHODS: MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients (n = 210, 139 men/71 women) from the Czech EMPIRE registry and age- or sex-matched healthy individuals (n = 205, 125 men/80 women). Genetic data were collated with overall survival (OS), acute exacerbation episodes, worsening lung function and antifibrotic treatment. RESULTS: We confirmed overexpression of the MUC5B rs35705950*T allele (55.2% versus 20.9%, p < 0.001) and the DSP rs2076295*G allele (80.4% versus 68.3%, p < 0.001) in IPF compared with controls. On antifibrotic drugs, lower mortability was observed in IPF patients with DSP G* allele (p = 0.016) and MUC5B T* allele (p = 0.079). Carriers of the DSP rs2076295*G allele benefitted from nintedanib treatment compared with TT genotype by a longer OS [hazard ratio (HR) = 7.99; 95% confidence interval (CI) = 1.56-40.90; p = 0.013] and a slower decline in lung function (HR = 8.51; 95% CI = 1.68-43.14; p = 0.010). Patients with a TT genotype (rs2076295) benefitted from treatment with pirfenidone by prolonged OS (p = 0.040; HR = 0.35; 95% CI = 0.13-0.95) compared with nintedanib treatment. Both associations were confirmed by cross-validation analysis. After stratifying by MUC5B rs35705950*T allele carriage, no difference in treatment outcome was observed for nintedanib or pirfenidone (p = 0.784). In the multivariate model, smoking, age, forced vital capacity (FVC) and DLCO (diffuse lung capacity) at the IPF diagnosis were associated with survival. CONCLUSION: Our real-world study showed that IPF patients with MUC5B T* allele or DSP G* allele profit from antifibrotic treatment by lower mortability. Moreover, carriers of the DSP rs2076295*G allele benefit from treatment with nintedanib, and TT genotype from treatment with pirfenidone. MUC5B rs35705950 did not impact the outcome of treatment with either nintedanib or pirfenidone. Our single-registry pilot study should be confirmed with an independent patient cohort.

• Klíčová slova
• IPF, antifibrotic treatment, desmoplakin, mucin 5, single nucleotide polymorphisms,
• MeSH
• desmoplakiny * genetika   MeSH
• idiopatická plicní fibróza * farmakoterapie   genetika   MeSH
• indoly * terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• pilotní projekty MeSH
• pyridony * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• desmoplakiny * MeSH
• indoly * MeSH
• nintedanib MeSH Prohlížeč
• pirfenidone MeSH Prohlížeč
• pyridony * MeSH