Antifibrotics in rheumatoid arthritis-associated interstitial lung disease – real-world data from a nationwide cohort
Authors:   Serviço de Reumatologia, Hospital Garcia de Orta, Unidade  Local de Saúde de Almada-Seixal, Duarte AC ,   Unidade de Investigação em  Reumatologia, Instituto de Medicina Molecular, Faculdade de  Medicina, Universidade de Lisboa, Marques Gomes C ,   Serviço de Reumatologia,  Centro Hospitalar Universitário de São João, Unidade Local de  Saúde de São João; Departamento de Medicina, Faculdade  de Medicina, Universidade do Porto, Correia M ,   Serviço de Reumatologia,  Hospital de Braga, Unidade Local de Saúde de Braga, Mendes B ,   Serviço  de Reumatologia, Hospitais da Universidade de Coimbra, Unidade  Local de Saúde de Coimbra, Mazeda C ,   Serviço de Reumatologia, Hospital  Infante D. Pedro, Unidade Local de Saúde da Região de Aveiro; Centro Académico Clínico Egas Moniz, Health Alliance, Aveiro; EpiDoc Unit, Nova Medical School, NOVA University Lisbon, Guimarães F ,   Serviço de Reumatologia, Unidade Local de Saúde do Alto Minho, Abelha-Aleixo J ,   Serviço de Reumatologia, Hospital de Vila Nova de Gaia,  Unidade Local de Saúde de Gaia/Espinho, Guerra M ,   Serviço de  Reumatologia, Centro Hospitalar Universitário Cova da Beira,  Unidade Local de Saúde da Cova da Beira, Pereira da Costa R ,   Unidade de Investigação em  Reumatologia, Instituto de Medicina Molecular, Faculdade de  Medicina, Universidade de Lisboa;  Serviço de  Reumatologia, Hospital de Santa Maria, Unidade Local de Saúde  Santa Maria, Lisbon Academic Medical Center (CAML), Meirinhos T ,   Serviço de  Reumatologia, Unidade Local de Saúde do Tâmega e Sousa, Santos MJ ,   Serviço de Reumatologia, Hospital Garcia de Orta, Unidade  Local de Saúde de Almada-Seixal; Unidade de Investigação em  Reumatologia, Instituto de Medicina Molecular, Faculdade de  Medicina, Universidade de Lisboa
Published: October 2024

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 antifi brotics, 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 pirfeni done. 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 discontinu ation 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.