Adverse Events and Persistency of Biologics in Rheumatoid Arthritis Patients with Interstitial Lung Disease

Abstract

Background/Purpose: Interstitial lung disease (ILD) is one of the most important extra-articular manifestations of rheumatoid arthritis (RA). The prevalence of RA associated ILD (RA-ILD) is reported as 1-58% depending on the study population and the definition of ILD, and RA-ILD is known to be associated with increased respiratory infection and higher mortality in RA patients. Recently, use of biologics is increasing; however, the safety and persistency of biologics in RA-ILD patients are not established. We aimed to compare the incidence of adverse events (AEs) and persistency of biologics in RA patients with or without ILD.

Methods: A total of 981 RA patients with chest radiograph or chest computed tomography (CT) data at enrollment were extracted from BIOlogics Pharmacoepidemiologic StudY (BIOPSY) cohort, a nationwide multicenter prospective inception cohort for biologic users of RA patients in Korea. We classified them into two groups: 1) RA-ILD group as patients with ILD, and 2) RA-non ILD group as patients without ILD detected by chest radiograph or CT. We compared the incidence of AEs including respiratory infection and mortality during use of biologics between two groups, and then tested the differences of drug discontinuation rates due to AEs, infection, and respiratory infection between RA-ILD and RA-non ILD groups using Kaplan-Meier survival analysis and log-rank test. In addition, crude and multivariable Cox proportional hazard model were used to identify the impact of ILD on AEs in RA patients with biologics.

Results: The 42 patients (4.3%) revealed to have RA-ILD by chest radiograph or chest CT, and the rest of 939 patients were included in RA-non ILD group. Patients in RA-ILD group were older (62.6 ± 9.6 vs. 51.8 ± 13.2 years, p<0.01), and male patients were more in RA-ILD group (31.0% vs. 13.3%, p<0.01). During mean follow-up of 20 months with 1,611 person years (PY), the incidence of AEs was higher in RA-ILD group compared with RA-non ILD group (IRR 1.55, CI 1.11-2.17). In addition, the incidence of infection and respiratory infection were higher in RA-ILD group (IRR 2.38, CI 1.32-4.30 for infection, IRR 3.00, CI 1.50-5.99 for respiratory infection, respectively). The biologics discontinuation rate due to AEs was comparable in two groups (p=0.13), whereas the biologics discontinuation rate due to infection (p=0.03) and respiratory infection (p<0.01) were significantly higher in RA-ILD group. After adjusting for variables, age (HR 1.27, CI 1.15-1.41) and having ILD (HR 10.77, CI 2.26-51.41) were risk factors for mortality in RA patients with biologics.

Conclusion: The incidence of adverse events, especially respiratory infections were higher in RA-ILD patients with biologics compared with RA-non ILD patients. In addition, the biologics discontinuation rate due to infection, especially respiratory infection was significantly higher in RA-ILD patients. Concerning the mortality, ILD increased the mortality in RA patients with biologics.