Retention Rate and Safety of Biologic and Targeted Synthetic DMARDs in Patients with RA-Associated Interstitial Lung Disease: A KOBIO Registry Study

Abstract

This study aimed to evaluate the long-term retention and safety of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) and identify the factors associated with drug withdrawal in patients with rheumatoid arthritis (RA) with interstitial lung disease (ILD) enrolled in the Korean College of Rheumatology Biologics and Targeted Therapy registry. We investigated adults with RA (n=2266) administered with bDMARDs or tsDMARDs between 2012 and 2021. Propensity score matching (1:3) was performed between patients with RA with ILD(RA-ILD) and without ILD (RA-no ILD). The Kaplan-Meier method was used to analyse drug survival and a logistic regression model to identify withdrawal-related factors in RA-ILD. One hundred and fifty-nine patients with RA-ILD were matched with 477 patients with RA-no ILD. The 5-year drug retention rate was lower in RA-ILD than in RA-no ILD (log-rank p=0.020), and both the ILD and no-ILD groups had statistical differences of drug retention rate among agents (log-rank p=0.019 and 0.020, respectively). In the RA-ILD group, Janus kinase inhibitors had the highest drug retention rate (64.3%), and tumour necrosis factor-α inhibitors showed the lowest retention rate (30.6%). Approximately 58.5% and 48.4% of the patients with RA-ILD and RA-no ILD, respectively, withdrew from their regimen, and the main cause of withdrawal in RA-ILD was adverse events, followed by inefficacy. In the logistic regression analysis, current smoking had a negative effect on drug retention (odds ratio [OR]: 9.938, 95% confidence interval [CI]: 2.550-38.733; p<0.001), while concomitant corticosteroid use had a protective effect against withdrawal (OR: 0.284, 95% CI: 0.008-0.917; p=0.035) in RA-ILD. The patients with RA-ILD had lower bDMARD and tsDMARD retention rates than those with RA-no ILD. In the RA-ILD group, current smoking and concomitant corticosteroid use were associated factors affecting drug withdrawal.