Role of antifibrotics in progressive pulmonary fibrosis associated to autoimmune diseases: multicenter study from NEREA registry
Maria Asunción Nieto, Cristina Vadillo, Olga Sánchez‐Pernaute, Fredeswinda Romero-Bueno, María Jesús Rodríguez‐Nieto, Rosalía Laporta, Hilda Godoy, Jesús Loarce, Juan Rigual, Leticia León, Lydia Abásolo
Abstract
BACKGROUND: To assess the incidence of functional respiratory impairment in interstitial lung disease (ILD) of autoimmune origin, starting progressive pulmonary fibrosis (PPF), and to evaluate the effectiveness of antifibrotics and other variables. METHODS: A longitudinal multicenter study was conducted in ILD of autoimmune origin (ILD with autoimmune rheumatic diseases, IPAF, and unclassifiable autoimmune ILD) from 2006 to 2023 and followed until September 2024 in Madrid. Patients were those enrolled in NEREA [pNEumology RhEumatology Autoinmune] registry who met PPF criteria. MAIN OUTCOME: functional respiratory impairment (≥ 5% absolute decline in predicted forced vital capacity (FVC%) within a year). Pulmonary function was assessed at baseline and every 6-12 months. INDEPENDENT VARIABLE: antifibrotics. Covariates: sociodemographics, clinical, other treatments. Survival techniques were used to estimate the incidence rate (IR) and [95%CI] of functional respiratory impairment, (per 100 patients-year). Cox multivariate regression models were run to examine the influence of antifibrotics and other covariates on, main outcome (results expressed as hazard ratio (HR) and [95%CI]). RESULTS: Among 150 patients, 21 were on antifibrotics at baseline, increasing to 52 during follow-up. Functional respiratory impairment occurred in 118 patients with 292 events (IR 57.4 [51.2-64.4]). Regarding multivariate analysis: antifibrotics lowered functional respiratory impairment risk (nintedanib: HR 0.58 [0.39-0.85], pirfenidone: HR 0.68 [0.5-0.94]). Emphysema (HR 1.32 [1.04-1.68]), smoking (HR 1.40 [1.06-1.84]), and cardiovascular risk (HR 1.02 [1.02-1.63]) increased the risk. CONCLUSIONS: The rate of worsening in PPF-ILD of autoimmune origin was considerable. Both antifibrotics reduced functional respiratory impairment risk in these patients, supporting prior clinical trials. Additional risk factors were identified. CLINICAL TRIAL NUMBER: Not applicable.