Outcomes of patients with advanced idiopathic pulmonary fibrosis treated with nintedanib or pirfenidone in a real‐world multicentre cohort

• Published in: Respirology (Carlton, Vic.) Vol. 26; no. 10; pp. 982 - 988
• Main Authors: Durheim, Michael T., Bendstrup, Elisabeth, Carlson, Lisa, Sutinen, Eva M., Hyldgaard, Charlotte, Kalafatis, Dimitrios, Myllärniemi, Marjukka, Sköld, C. Magnus, Sjåheim, Tone
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.10.2021; Wiley Subscription Services, Inc
• Subjects: advanced idiopathic pulmonary fibrosis; antifibrotic therapy; Carbon monoxide; Clinical trials; Fibrosis; interstitial lung disease; Lung diseases; Medicin och hälsovetenskap; Mortality; nintedanib; Patients; pirfenidone; Pulmonary fibrosis; Respiratory diseases; Respiratory function; Survival; transplant‐free survival
• ISSN: 1323-7799; 1440-1843; 1440-1843
• DOI: 10.1111/resp.14116

Background and objective Antifibrotic therapy with nintedanib or pirfenidone slows disease progression and reduces mortality in patients with idiopathic pulmonary fibrosis (IPF). However, patients with advanced IPF, as defined by forced vital capacity (FVC) < 50% and/or diffusion capacity for carbon monoxide (DLCO) < 30% of predicted, have not been included in randomized trials, and the outcomes of such patients who initiate treatment are not well understood. We determined lung function, disease progression and mortality outcomes following initiation of antifibrotic therapy in patients with advanced IPF at the time of treatment initiation compared to those with mild–moderate IPF. Methods We included 502 patients enrolled in IPF registries from four Nordic countries. Linear mixed models were used to assess change in FVC and DLCO over time. Cox proportional hazards models were used to assess transplant‐free survival and progression‐ and transplant‐free survival. Results Of 502 patients, 66 (13%) had advanced IPF. Annual change in FVC was −125 ml (95% CI −163, −87) among patients with mild–moderate IPF, and +28 ml (95% CI −96, +152) among those with advanced IPF. Advanced IPF at treatment initiation was associated with poorer transplant‐free survival (hazard ratio [HR] 2.39 [95% CI 1.66, 3.43]) and progression‐ and transplant‐free survival (HR 1.60 [95% CI 1.15, 2.23]). Conclusion In a broadly representative IPF population, patients with advanced IPF at the initiation of antifibrotic therapy did not have greater lung function decline over time compared with those with mild–moderate IPF, but had substantially higher mortality. Prospective studies are needed to determine the effect of antifibrotic therapy in patients with advanced IPF. Patients with advanced idiopathic pulmonary fibrosis (IPF) have not been included in randomized trials of nintedanib or pirfenidone, but are often treated with these drugs. We show that in a real‐world setting, patients with severe compared to mild–moderate IPF may not have lung function decline during treatment, but show substantially greater mortality.