Effectiveness of biological disease-modifying antirheumatic drugs in progressive pulmonary fibrosis associated with rheumatoid arthritis
Ryuichiro Kanda, Yoshiya Tanaka, Yusuke Miyazaki, Satoshi Kubo, Midori Ueno, Takako Kawaguchi, Shunsuke Fukuyo, Ippei Miyagawa, Ayako Yamaguchi, Yurie Satoh-Kanda, Naoaki Ohkubo, Yasuyuki Todoroki, Masanobu Ueno, Yuya Fujita, Katsuhide Kusaka, Hidenori Sakai, Shunpei Kosaka, Satsuki Matsunaga, Hirotsugu Nohara, Kazuhiro Yatera, Takatoshi Aoki, Shingo NakayamadaAbstract
Objectives
To evaluate the effectiveness and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA)-associated progressive pulmonary fibrosis (PPF).
Methods
Real-world data were retrospectively collected in RA-associated PPF during the first year after bDMARD initiation. The primary outcome was change in pulmonary function and computed tomography (CT) visual scores at week 52. The secondary outcomes included comparisons of pulmonary function, CT scores, Clinical Disease Activity Index (CDAI), drug retention rates, and adverse event rates over 52 weeks among the tumour necrosis factor inhibitor (TNFi), cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig), and interleukin-6 receptor inhibitor (IL-6Ri), using propensity score–based inverse probability of treatment weighting (PS-IPTW).
Results
Among 2,484 patients with RA initiating bDMARDs, 443 had RA-associated interstitial lung disease (ILD), and 135 had RA-associated PPF (TNFi, n = 35; CTLA4-Ig, n = 45; IL-6Ri, n = 55). Treatment with bDMARDs markedly improved CDAI at week 52, and pulmonary function and CT scores remained stable. PS-IPTW-adjusted comparisons showed no significant differences in CDAI, CT scores, or drug retention rates among the bDMARD groups. However, forced vital capacity (FVC) improved in IL-6Ri compared with TNFi (−3.2% vs + 3.3%, p = 0.011; Cohen’s d = 0.630). Adverse events were less frequent in CTLA4-Ig. Multivariate logistic regression analysis identified IL-6Ri treatment, non-usual interstitial pneumonia (UIP) pattern, and lower CDAI at week 52 as independent predictors of FVC improvement.
Conclusions
Tight control of RA disease activity with bDMARDs appears crucial in RA-associated PPF. In this real-world comparative study, IL-6Ri may have contributed to improved FVC, whereas CTLA4-Ig may have a favourable safety profile.