Associations of genetic polymorphisms with clinical response to tocilizumab in Chinese rheumatoid arthritis patients

Wen Qin; Meng-Qiao Wang; Ting-Hui Wang; Dong-Mei Xiao; Xiu-Di Wu; Han Cen

doi:10.1016/j.intimp.2024.113769

Associations of genetic polymorphisms with clinical response to tocilizumab in Chinese rheumatoid arthritis patients

Int Immunopharmacol. 2024 Dec 22:146:113769. doi: 10.1016/j.intimp.2024.113769. Online ahead of print.

Authors

Wen Qin¹, Meng-Qiao Wang², Ting-Hui Wang¹, Dong-Mei Xiao¹, Xiu-Di Wu³, Han Cen⁴

Affiliations

¹ Department of Rheumatology and Immunology, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
² School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
³ Department of Rheumatology and Immunology, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China. Electronic address: awu1100@aliyun.com.
⁴ Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: cenhan@smu.edu.cn.

PMID: 39718059
DOI: 10.1016/j.intimp.2024.113769

Abstract

Objective: To examine the associations of single-nucleotide polymorphisms (SNPs) within interleukin-6 (IL6) and IL-6 receptor (IL6R) as well as several potential SNPs revealed in a genome-wide association study (GWAS) with clinical response to tocilizumab (TCZ) in Chinese rheumatoid arthritis (RA) patients.

Methods: A total of 23 SNPs were genotyped in 68 RA patients receiving intravenous TCZ, who were prospectively followed for 6 months to determine the clinical response based on several criteria, including clinical disease activity index (CDAI) low disease activity (LDA) and remission, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) LDA and remission, European League Against Rheumatism (EULAR) good response and change in DAS28-ESR (ΔDAS28-ESR).

Results: The patients were on average 51.16 (13.23) years, and 55 were female (80.88%) and 47 were bDMARD-naïve (69.12%). After adjusting potential confounding factors, IL6R rs35717427 and GALNT18 rs4910008 were significantly associated with CDAI LDA, and IL6R rs11265621, rs6690230 were significantly associated with EULAR good response, DAS28-ESR LDA and remission. In addition, IL6 2069840 was found to be significantly associated with DAS28-ESR remission, and rs10108210, CLEC2D rs1560011 and KCNMB1 rs703505 were found to be significantly associated with ΔDAS28-ESR.

Conclusion: Genetic polymorphisms hold the potential as predictive biomarkers for clinical response to TCZ, which might aid in individualized treatment with TCZ in Chinese patients with RA.

Keywords: clinical response; interleukin-6; polymorphism; rheumatoid arthritis; tocilizumab.