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

Abstract

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 À125 ml (95% CI À163, À87) among patients with mild-moderate IPF, and +28 ml (95% CI À96, +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.

Comparison of different reference values for lung function: implications of inconsistent use among centers

“…PFTs from 577 adult individuals, aged 18-85 years, all of Caucasian ethnicity, were included in the study. The PFTs were obtained from subjects who had participated in recent clinical studies (15,(29)(30)(31)(32)(33) and comprised four different groups (long-term survivors of severe blood disorders, n = 229, pulmonary brosis, n = 148, lung transplantation, n = 88, and healthy, never-smoking controls, n = 112). The clinical studies had all been approved by the hospital's Data Protection O cer and the Regional Committee for Medical and Health Research Ethics.…”

“…Consistent interpretation of PFTs across centers is important to ensure equity of care. Percent predicted values for PFTs are often included in criteria for diagnosis and severity of pulmonary diseases, in guidelines for treatment, inclusion criteria for clinical studies, and legal assessment for health bene ts (12)(13)(14)(15)(16)(17)(18)(19). Further, since the lower limit of normal (LLN) will vary with different sets of reference equations, the ability to discriminate health from disease may be affected.…”

Contemporary Concise Review 2021: Interstitial lung disease

“…Durheim et al examined disease progression and mortality following initiation of antifibrotics in patients with advanced IPF (n = 66) compared to mild to moderate IPF (n = 436). 80 They identified that patients with advanced IPF did not demonstrate more rapid lung function decline but did have higher mortality, indicating that prospective studies in high-risk groups are required. Glaspole et al assessed the efficacy of nintedanib in patients with IPF who were elderly and had multiple comorbidities from pooled data of five separate clinic trials.…”

“…Whether antifibrotics should be commenced in advanced disease or in older patients were also addressed. Durheim et al examined disease progression and mortality following initiation of antifibrotics in patients with advanced IPF ( n = 66) compared to mild to moderate IPF ( n = 436) 80 . They identified that patients with advanced IPF did not demonstrate more rapid lung function decline but did have higher mortality, indicating that prospective studies in high‐risk groups are required.…”

Circadian clock molecule REV-ERBα regulates lung fibrotic progression through collagen stabilization

“…Currently, nintedanib and pirfenidone are the only Food and Drug Administration (FDA)-approved drugs for the treatment of pulmonary fibrosis, which only serve to slow the progression of pulmonary fibrosis 7 . Investigating new promising molecular pathways involved in fibrogenic responses is urgently needed, and Rev-erbα has become a promising candidate 8,9 .…”