Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study
Ryu Watanabe, Kosuke Ebina, Takaho Gon, Tadashi Okano, Koichi Murata, Kosaku Murakami, Yuichi Maeda, Sadao Jinno, Iku Shirasugi, Yonsu Son, Hideki Amuro, Masaki Katayama, Ryota Hara, Kenichiro Hata, Ayaka Yoshikawa, Wataru Yamamoto, Shotaro Tachibana, Shinya Hayashi, Yuki Etani, Masao Katsushima, Kazuo Fukumoto, Shinsuke Yamada, Motomu HashimotoAbstract
Objectives
To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi).
Methods
Retrospective analysis was conducted on data from the ANSWER cohort comprising 3,623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention.
Results
Of these, 450 (12.4%) met the first two criteria of EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared to those under 65, HR = 0.46, 95% CI: 0.31 to 0.69), higher rheumatoid factor (RF) titres (HR = 1.005, 95% CI: 1.00 to 1.01), higher clinical disease activity index (HR = 1.02, 95% CI: 1.01 to 1.03), lower methotrexate dosage (HR = 0.97, 95% CI: 0.95 to 0.99), and comorbidities like hypertension (HR = 1.53, 95% CI: 1.2 to 1.95) and diabetes (HR = 1.37, 95% CI: 1.09 to 1.73). Anti-interleukin 6 receptor antibodies (aIL-6R, HR = 0.53, 95% CI: 0.37 to 0.75) and JAKi (HR = 0.64, 95% CI: 0.46 to 0.90) were associated with fewer discontinuations due to ineffectiveness compared to tumour necrosis factor inhibitors. Oral glucocorticoids usage (HR = 1.65, 95% CI: 1.11 to 2.47) was linked to increased discontinuation due to toxic adverse events.
Conclusion
Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.