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 Hashimoto

doi:10.1093/rheumatology/keae265

Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study

Rheumatology (Oxford). 2024 May 9:keae265. doi: 10.1093/rheumatology/keae265. Online ahead of print.

Authors

Ryu Watanabe¹, Kosuke Ebina^{2

3}, Takaho Gon¹, Tadashi Okano⁴, Koichi Murata⁵, Kosaku Murakami⁶, Yuichi Maeda⁷, Sadao Jinno⁸, Iku Shirasugi⁸, Yonsu Son⁹, Hideki Amuro⁹, Masaki Katayama¹⁰, Ryota Hara¹¹, Kenichiro Hata¹², Ayaka Yoshikawa¹², Wataru Yamamoto¹³, Shotaro Tachibana¹⁴, Shinya Hayashi¹⁴, Yuki Etani², Masao Katsushima¹, Kazuo Fukumoto¹, Shinsuke Yamada¹, Motomu Hashimoto¹

Affiliations

¹ Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
² Department of Musculoskeletal Regenerative Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
³ Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
⁴ Center for Senile Degenerative Disorders (CSDD), Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
⁵ Department of Advanced Medicine for Rheumatic diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁶ Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto Japan.
⁷ Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University, Erlangen-Nürnberg (FAU), Germany.
⁸ Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.
⁹ First Department of Internal Medicine, Kansai Medical University, Hirakata, Japan.
¹⁰ Department of Rheumatology, Osaka Red Cross Hospital, Osaka, Japan.
¹¹ Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan.
¹² Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
¹³ Department of Health Information Management, Kurashiki Sweet Hospital, Kurashiki, Japan.
¹⁴ Department of Orthopaedic Surgery, Kobe University, Kobe, Japan.

PMID: 38724245
DOI: 10.1093/rheumatology/keae265

Abstract

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.

Keywords: Janus kinase inhibitors; anti-interleukin-6 receptor antibodies; difficult-to-treat rheumatoid arthritis; tumour necrosis factor inhibitors.