Background/Purpose: Nintedanib and pirfenidone are antifibrotic drugs indicated for the treatment of idiopathic pulmonary fibrosis (IPF) and other forms of progressive pulmonary fibrosis. Antifibrotics have also been tested in RA-associated interstitial lung disease (ILD) within two recent randomized clinical trials (RCT). However, there are limited real-world studies regarding the use of antifibrotics, and none in RA-ILD. RA-ILD patients may be different from IPF patients since they often need concomitant immunosuppression for articular disease. Our aim was to investigate the tolerability and effectiveness of antifibrotics in a real-world cohort of patients with RA-ILD.

Methods: In this retrospective cohort study, we identified RA-ILD patients initiating antifibrotics at a large multi-hospital healthcare system. We used electronic query to find all patients with at least two RA diagnosis codes and a prescription for either nintedanib or pirfenidone (2014-2023). We then performed medical record review to confirm all patients met 2010 ACR/EULAR classification criteria for RA and had definite RA-ILD by Bongartz criteria. Data regarding adverse events (AEs), tolerability, pulmonary function test (PFT) results, and clinical data were collected. Drug retention was estimated using a Kaplan-Meier curve. A linear mixed model with random intercept was used to compare the within-patient trajectory of the percent predicted forced vital capacity (%FVC) within 18-months before to 18-months after antifibrotic initiation among those with these PFT data.

Results: We analyzed 74 patients with RA-ILD that initiated antifibrotics (mean age 67.8 years, 53% male); 40 patients initiated nintedanib and 34 initiated pirfenidone (Table 1). Median follow-up was 89 weeks (min 4, max 387). AEs were reported in 41 (55%) patients, with gastrointestinal (GI) AEs (n=30) being most common, followed by disease progression (n=6), rash (n=3), and hepatitis (n=2). The initial antifibrotic was discontinued in 34 (46%) patients due to: GI AEs (n=19), rash (n=3), transaminitis (n=2), and financial reasons (n=1). The median drug survival was 147.7 weeks (95%CI 79.1, NA; Figure 1). There was no difference in drug retention between nintedanib and pirfenidone (p=0.68). A second antifibrotic was prescribed in 14 patients, with 4 discontinuations. Change of %FVC trajectory was analyzed for 49 patients with available PFTs within 18 months pre- and post-antifibrotic (median number of PFT/patient = 4). There was a statistical difference in the estimated %FVC slope after initiation (-0.3% per year compared to -6.2% per year before initiation, p=0.031, Figure 2). Twenty-six patients (35%) died (17 due to ILD) and 4 (5%) had lung transplantation during follow-up.

Conclusion: In this first real-world study of antifibrotic use in RA-ILD, AEs were frequently reported, particularly GI, and discontinuation was common (46% compared to 20% for nintedanib and 24% for pirfenidone in their respective RCTs). However, antifibrotic initiation was associated with a modestly improved trajectory in %FVC. Death and/or lung transplant were frequent, emphasizing the need for additional safe and effective RA-ILD treatment options.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tolerability-and-effectiveness-of-antifibrotics-in-rheumatoid-arthritis-associated-interstitial-lung-disease/