Real-World Clinical Effectiveness and Safety of Antifibrotics in Progressive Pulmonary Fibrosis Associated with Rheumatoid Arthritis

Abstract

Background/Objectives: Interstitial lung disease (ILD) is one of the most severe complications of rheumatoid arthritis (RA). Real-world data on antifibrotic treatment are needed. Our objective was to evaluate the real-world effectiveness and tolerability of antifibrotic agents in patients with progressive fibrosing RA-ILD. Methods: A longitudinal, retrospective, observational study was conducted on a cohort of RA-ILD patients treated with either nintedanib or pirfenidone. The data collected included pulmonary function test (PFT) results, adverse events (AEs), tolerability, and drug retention. Results: Twenty-seven patients were included; 25 (92.5%) initiated nintedanib, while two initiated pirfenidone. The median follow-up duration was 25 months (IQR 7-27). The mean decline in %pFVC and %pDLCO from ILD diagnosis to the initiation of antifibrotic therapy were -8.9% and -14.8%, respectively. After 6 months of treatment, most patients achieved stabilization in PFT: a ∆%pFVC of +1.2% (p = 0.611 compared with baseline) and a ∆%pDLCO of +3.9% (p = 0.400). Eighteen patients completed one year of therapy, with a modest improvement in %pFVC (+4.7%; p = 0.023) and stabilization in %pDLCO (-3.8%; p = 0.175). This trend persisted among the nine patients who completed 2 years of treatment (%pFVC +7.7%; p = 0.037 and %pDLCO -2.2%; p = 0.621). During the follow-up period, 15% of patients died, and 4% underwent lung transplantation. Adverse events occurred in 81% of patients, leading to discontinuation in 18.5% of cases. The most frequent adverse events were gastrointestinal events and hepatitis, leading to a permanent dose reduction of 40% for nintedanib and 14% for pirfenidone. A second antifibrotic agent was prescribed for 18.5% of the patients. At the end of the follow-up period, 63% of the total cohort remained on antifibrotic therapy. Conclusions: According to our results, antifibrotic initiation was associated with a modest improvement in the trajectory of %pFVC and stabilization in %pDLCO. The discontinuation rate in our cohort (37%) was higher than that reported in clinical trials but similar to that reported in previously published real-world studies.

Keywords: antifibrotics; interstitial lung diseases; nintedanib; pirfenidone; rheumatoid arthritis.

Figure 1

Evolution of the predicted forced vital capacity (%pFVC) and the predicted diffusing capacity for carbon monoxide corrected for hemoglobin (%pDLCO) before initiation of antifibrotic therapy and after 1 year of treatment.

Figure 2

Lung function test results (as defined by the ATS) after 12 months of antifibrotic therapy.