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.

• Keywords
• Idiopathic pulmonary fibrosis, Lung function decline, Nintedanib, Overall survival,
• MeSH
• Idiopathic Pulmonary Fibrosis * drug therapy   MeSH
• Humans MeSH
• Lung MeSH
• Registries MeSH
• Vital Capacity MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• nintedanib MeSH Browser

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
• Anti-Inflammatory Agents, Non-Steroidal pharmacology   MeSH
• Idiopathic Pulmonary Fibrosis * diagnosis   MeSH
• Humans MeSH
• Lung MeSH
• Probability MeSH
• Pyridones pharmacology   MeSH
• Retrospective Studies MeSH
• Vital Capacity MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Inflammatory Agents, Non-Steroidal MeSH
• pirfenidone MeSH Browser
• Pyridones MeSH

Hypersensitivity pneumonitis (HP) is a complex and heterogeneous interstitial lung disease (ILD) that occurs when susceptible individuals develop an exaggerated immune response to an inhaled antigen. In this review, we discuss the latest guidelines for the diagnostic evaluation of patients with suspected HP, the importance of identifying patients with fibrotic and progressive disease, and the evidence supporting the drugs commonly used in the treatment of HP. Differential diagnosis of HP can be challenging and requires a thorough exposure history, multidisciplinary discussion of clinical and radiologic data, and, in some cases, assessment of bronchoalveolar lavage lymphocytosis and histopathologic findings. Patients with HP may be categorised as having non-fibrotic or fibrotic HP. The presence of fibrosis is associated with worse outcomes. A proportion of patients with fibrotic HP develop a progressive phenotype, characterised by worsening fibrosis, decline in lung function and early mortality. There are no established guidelines for the treatment of HP. Antigen avoidance should be implemented wherever possible. Immunosuppressants are commonly used in patients with HP but have not been shown to slow the worsening of fibrotic disease. Nintedanib, a tyrosine kinase inhibitor, has been approved by the US Food and Drug Administration for slowing the progression of chronic fibrosing ILDs with a progressive phenotype, including progressive fibrotic HP. Non-pharmacological interventions, such as oxygen therapy, pulmonary rehabilitation and supportive care, may be important components of the overall care of patients with progressive HP.

• MeSH
• Diagnosis, Differential MeSH
• Fibrosis MeSH
• Alveolitis, Extrinsic Allergic * diagnosis   therapy   MeSH
• Protein Kinase Inhibitors MeSH
• Lung Diseases, Interstitial * diagnosis   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Geographicals
• United States MeSH
• Names of Substances
• Protein Kinase Inhibitors 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.

• Keywords
• IPF, antifibrotic treatment, desmoplakin, mucin 5, single nucleotide polymorphisms,
• MeSH
• Desmoplakins * genetics   MeSH
• Idiopathic Pulmonary Fibrosis * drug therapy   genetics   MeSH
• Indoles * therapeutic use   MeSH
• Humans MeSH
• Mutation MeSH
• Pilot Projects MeSH
• Pyridones * therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Desmoplakins * MeSH
• Indoles * MeSH
• nintedanib MeSH Browser
• pirfenidone MeSH Browser
• Pyridones * MeSH

A proportion of patients with certain types of interstitial lung disease (ILD), including chronic hypersensitivity pneumonitis and ILDs associated with autoimmune diseases, develop a progressive fibrosing phenotype that shows similarities in clinical course to idiopathic pulmonary fibrosis. Irrespective of the clinical diagnosis, these progressive fibrosing ILDs show commonalities in the underlying pathogenetic mechanisms that drive a self-sustaining process of pulmonary fibrosis. The natural history of progressive fibrosing ILDs is characterized by decline in lung function, worsening of symptoms and health-related quality of life, and early mortality. Greater impairment in forced vital capacity or diffusion capacity of the lungs for carbon monoxide, and a greater extent of fibrotic changes on a computed tomography scan, are predictors of mortality in patients with fibrosing ILDs. However, the course of these diseases is heterogenous and cannot accurately be predicted for an individual patient. Data from ongoing clinical trials and patient registries will provide a better understanding of the clinical course and impact of progressive fibrosing ILDs.

• Keywords
• Connective tissue diseases, Mortality, Pulmonary fibrosis, Rheumatic diseases, Systemic sclerosis, Vital capacity,
• MeSH
• Alveolitis, Extrinsic Allergic diagnostic imaging   epidemiology   MeSH
• Idiopathic Pulmonary Fibrosis diagnostic imaging   epidemiology   MeSH
• Lung Diseases, Interstitial diagnostic imaging   epidemiology   MeSH
• Humans MeSH
• Mortality trends   MeSH
• Disease Progression * MeSH
• Risk Factors MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

INTRODUCTION: Pirfenidone, an antifibrotic drug, slows-down the disease progression in idiopathic pulmonary fibrosis (IPF) over 12 months, however limited data on the decline of lung function and overall survival (OS) in real-world cohorts on longer follow-up exists. PATIENTS/METHODS: Of the enrolled Czech IPF patients (n = 841) from an EMPIRE registry, 383 (45.5%) received pirfenidone, 218 (25.9%) no-antifibrotic treatment and 240 (28.5%) were excluded (missing data, nintedanib treatment). The 2- and 5-yrs OS and forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO) were investigated at treatment initiation and 6, 12, 18 and 24 months' follow-up. RESULTS: During a 2-yr follow-up, less than a quarter of the patients progressed on pirfenidone as assessed by the decline of ≥10% FVC (17.0%) and ≥ 15% DLCO (14.3%). On pirfenidone, the DLCO (≥10%) declines at 6, 12, 18 and 24 months' and DLCO (≥15%) declines at 6, 18 and 24 months' follow-up were associated with increased mortality. The DLCO decline showed higher predictive value for mortality than FVC decline. In patients with no-antifibrotics, FVC and DLCO declines were not predictive for mortality. Pirfenidone increased 5-yrs OS over no-antifibrotic treatment (55.9% vs 31.5% alive, P = 0.002). CONCLUSION: Our study observed the 2-yrs sustained effect of pirfenidone on the decline of lung function and survival in the real-world patient's IPF cohort. DLCO decline of ≥10% shows a potential as a mortality predictor in IPF patients on pirfenidone, and should be routinely evaluated during follow-up examinations.

• Keywords
• Disease progression, Idiopathic pulmonary fibrosis, Mortality prediction, Pirfenidone,
• MeSH
• Anti-Inflammatory Agents, Non-Steroidal pharmacology   therapeutic use   MeSH
• Idiopathic Pulmonary Fibrosis diagnosis   drug therapy   epidemiology   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Survival Rate trends   MeSH
• Follow-Up Studies MeSH
• Disease Progression * MeSH
• Pyridones pharmacology   therapeutic use   MeSH
• Registries * MeSH
• Respiratory Function Tests trends   MeSH
• Aged MeSH
• Vital Capacity drug effects   physiology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Anti-Inflammatory Agents, Non-Steroidal MeSH
• pirfenidone MeSH Browser
• Pyridones MeSH