Antifibrotics in rheumatoid arthritis-associated interstitial lung disease – real-world data from a nationwide cohort
Introduction: Interstitial lung disease (ILD) is the most common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with an increased mortality. Clinical trials have shown that antifibrotics (nintedanib and pirfenidone) can slow the progression of connective tissue disease-associated ILD. This study aims to evaluate the effectiveness and tolerability of antifibrotics in a national, real-world cohort of patients with RA-ILD.
Material and methods: We conducted an observational multicenter study of RA-ILD patients treated with antifibrotics, who were prospectively followed in Reuma.pt. Demographic and clinical data, pulmonary function tests (PFTs) results and adverse events (AEs) were collected. A linear mixed model with random intercept was used to compare PFT results within 12 (±6) months before to 12 (±6) months after antifibrotic initiation. Drug persistence was evaluated using Kaplan-Meier curves.
Results: We included 40 RA-ILD patients, 27 (67.5%) initially treated with nintedanib and 13 (32.5%) with pirfenidone. Most of the patients were female (55%), and current or past smokers (52.5%). At antifibrotic initiation, mean age was 70.9 ± 7.1 years and median ILD duration 5.0 [IQR 2.3-7.5] years. A total of 20 patients were included in effectiveness analysis, with the use of antifibrotics interrupting the decline of forced vital capacity (FVC; decline 300 ± 500 mL in the year before antifibrotic initiation vs. improvement of 200 ± 400 mL in the year following antifibrotic initiation, p=0.336) and total lung capacity (TLC; decline 800 ± 300 mL in the year before antifibrotic initiation vs. improvement of 600 ± 900 mL in the year following antifibrotic initiation, p=0.147). However, diffusion capacity for carbon monoxide remained in decline (3% decline in the year before antifibrotic initiation vs. 2.9% decline in the year following antifibrotic initiation, p=0.75). AEs were reported in 16 (40%) patients and led to drug discontinuation in 12 (30%). Median duration of drug persistence was 150.3 weeks (95 %CI 11.0-289.6), with no difference between nintedanib and pirfenidone (p = 0.976).
Conclusion: This study with real-world data corroborates the usefulness of antifibrotics in stabilizing lung function, based on FVC and TLC. However, AEs were frequently reported and were the main cause for drug discontinuation.
Tiago Meirinhos
Unidade Local de Saúde do Tâmega e Sousa
Maria José Santos
Hospital Garcia de Orta, Unidade Local de Saúde Almada-Seixal
Joana Abelha-Aleixo
Hospital de Vila Nova de Gaia, Unidade Local de Saúde de Gaia/Espinho
Miguel Guerra
Centro Hospitalar Universitário Cova da Beira, Unidade Local de Saúde da Cova da Beira
Roberto Pereira da Costa
Hospital Santa Maria, Unidade Local de Saúde Santa Maria, Lisbon Academic Medical Center (CAML)
Margarida Correia
Hospital de Braga, Unidade Local de Saúde de Braga
Ana Catarina Duarte
Hospital Garcia de Orta, Unidade Local de Saúde Almada-Seixal
Francisca Guimarães
Unidade Local de Saúde do Alto Minho
Beatriz Mendes
Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra
Carolina Mazeda
Hospital Infante D. Pedro, Unidade Local de Saúde da Região de Aveiro
Carlos Marques Gomes
Centro Hospitalar Universitário de São João, Unidade Local de Saúde de São João
Unidade Local de Saúde do Tâmega e Sousa
Maria José Santos
Hospital Garcia de Orta, Unidade Local de Saúde Almada-Seixal
Joana Abelha-Aleixo
Hospital de Vila Nova de Gaia, Unidade Local de Saúde de Gaia/Espinho
Miguel Guerra
Centro Hospitalar Universitário Cova da Beira, Unidade Local de Saúde da Cova da Beira
Roberto Pereira da Costa
Hospital Santa Maria, Unidade Local de Saúde Santa Maria, Lisbon Academic Medical Center (CAML)
Margarida Correia
Hospital de Braga, Unidade Local de Saúde de Braga
Ana Catarina Duarte
Hospital Garcia de Orta, Unidade Local de Saúde Almada-Seixal
Francisca Guimarães
Unidade Local de Saúde do Alto Minho
Beatriz Mendes
Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra
Carolina Mazeda
Hospital Infante D. Pedro, Unidade Local de Saúde da Região de Aveiro
Carlos Marques Gomes
Centro Hospitalar Universitário de São João, Unidade Local de Saúde de São João