Comparative effects of biological and targeted synthetic DMARDs on incident chronic kidney disease in patients with rheumatoid arthritis

Nozomi Nishimura; Akira Onishi; Wataru Yamamoto; Koji Nagai; Hideyuki Shiba; Yasutaka Okita; Yonsu Son; Hideki Amuro; Takaichi Okano; Yo Ueda; Ryota Hara; Masaki Katayama; Shinsuke Yamada; Motomu Hashimoto; Yuichi Maeda; Hideo Onizawa; Takayuki Fujii; Koichi Murata; Kosaku Murakami; Masao Tanaka; Shuichi Matsuda; Akio Morinobu

doi:10.1093/rheumatology/keae603

Comparative effects of biological and targeted synthetic DMARDs on incident chronic kidney disease in patients with rheumatoid arthritis

Rheumatology (Oxford). 2024 Oct 30:keae603. doi: 10.1093/rheumatology/keae603. Online ahead of print.

Authors

Nozomi Nishimura¹, Akira Onishi², Wataru Yamamoto³, Koji Nagai⁴, Hideyuki Shiba⁴, Yasutaka Okita⁵, Yonsu Son⁶, Hideki Amuro⁶, Takaichi Okano^{7

8}, Yo Ueda⁸, Ryota Hara⁹, Masaki Katayama¹⁰, Shinsuke Yamada¹¹, Motomu Hashimoto¹¹, Yuichi Maeda¹², Hideo Onizawa¹³, Takayuki Fujii^{2

14}, Koichi Murata^{2

14}, Kosaku Murakami¹⁵, Masao Tanaka², Shuichi Matsuda¹⁴, Akio Morinobu¹

Affiliations

¹ Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
² Department of Advanced Medicine for Rheumatic diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
³ Department of Health Information Management, Kurashiki Sweet Hospital, Okayama, Japan.
⁴ Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Osaka, Japan.
⁵ Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁶ First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
⁷ Department of Clinical Laboratory, Kobe University Hospital, Kobe, Japan.
⁸ Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.
⁹ Department of Orthopedic Surgery, Nara Medical University, Nara, Japan.
¹⁰ Department of Rheumatology, Osaka Red Cross Hospital, Osaka, Japan.
¹¹ Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
¹² Friedrich-Alexander Universität Erlangen-Nürnberg, Nürnberg, Germany.
¹³ Department of Immunology, Shiga General Hospital, Shiga, Japan.
¹⁴ Department of Orthopaedic surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹⁵ Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

PMID: 39475445
DOI: 10.1093/rheumatology/keae603

Abstract

Objectives: The impact of individual biological/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) on kidney function in patients with rheumatoid arthritis (RA) remains unclear. This study aimed to determine the comparative effects of b/tsDMARDs on chronic kidney disease (CKD) incidence in patients with RA.

Methods: This multicentre cohort study included patients with RA who had baseline estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m2 and started a tumor necrosis factor inhibitor (TNFi), cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig), interleukin-6 receptor inhibitor (IL-6Ri), or Janus kinase inhibitor (JAKi) in Japan. Multiple propensity score-based inverse probability weighting (IPW) was used to adjust confounders. The incidence of CKD was compared among b/tsDMARDs using IPW mixed-effect Cox proportional hazards models and linear mixed-effect models with IPW examined trajectories of eGFR.

Results: Among 2187 patients with 3068 treatment courses and up to 11 years of follow-up, CKD occurred in 275 cases. Compared with the CTLA4-Ig group, the TNFi group had a significantly lower CKD incidence (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.46-0.97, p= 0.04), whereas the JAKi group had a significantly higher incidence (HR 2.16, 95% CI 1.23-3.79, p= 0.01). The trajectory of eGFR was significantly greater in the JAKi group than in the CTLA4-Ig group (CTLA4-Ig: -1.28 mL/min/1.73 m2/year, JAKi: -2.29 mL/min/1.73 m2/year, p< 0.001).

Conclusions: TNFi use was associated with reduced CKD incidence, whereas JAKi showed a less protective association for kidney function in patients with RA.

Keywords: Rheumatoid arthritis; biological DMARD; chronic kidney disease; targeted synthetic DMARD.