Tumor Necrosis Factor-Alpha (+489 G/A) Polymorphism Can Predict the Response to Adalimumab in Chinese Han Patients With Ankylosing Spondylitis

Hong-Jin Liang; Xiao-Min Jiang; Feng-Cai Shen; Jian-Hua Peng; Dan-Min Wang; Shu-Xin Huang; Zhi-Duo Hou; Ling Lin

doi:10.7759/cureus.42704

Tumor Necrosis Factor-Alpha (+489 G/A) Polymorphism Can Predict the Response to Adalimumab in Chinese Han Patients With Ankylosing Spondylitis

Cureus. 2023 Jul 30;15(7):e42704. doi: 10.7759/cureus.42704. eCollection 2023 Jul.

Authors

Hong-Jin Liang¹, Xiao-Min Jiang¹, Feng-Cai Shen¹, Jian-Hua Peng¹, Dan-Min Wang¹, Shu-Xin Huang¹, Zhi-Duo Hou^{1

2}, Ling Lin^{1

2}

Affiliations

¹ Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, CHN.
² Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, CHN.

Abstract

Background: Studies investigating the association between single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and the efficacy of adalimumab (ADA) in ankylosing spondylitis (AS) therapy have reported conflicting results. We aimed to investigate the value of SNP typing of TNFα in predicting the efficacy of ADA in AS.

Materials and methods: Eighty patients with active AS who received ADA treatment were followed up for 24 weeks. Six known SNPs of TNFα (+489G/A, -238G/A, -308G/A, -857C/T, -863C/A, and -1031C/T) were subjected to the SNaPshot SNP typing method, which has been proven to be a reliable, efficient, and cost-effective method for detecting SNPs. The relationship between each SNP genotype and the therapeutic efficacy of ADA was analyzed.

Results: At the end of the 24-week follow-up, 58.8% of the patients with AS achieved Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR), 67.5% of the patients achieved the criteria of an ASAS40 response (40% improvement on indices), and 53.8% of the patients achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement (MI). The univariate analysis showed that patients with AS carrying the TNFα +489 A allele were more likely to achieve ASAS-PR, ASAS40 response criteria, and ASDAS-MI after ADA treatment. In the multivariate regression analysis, the TNFα +489 A allele was an independent factor influencing the efficacy of ADA in treating AS (ASAS-PR odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.01-7.01; ASAS40 OR = 4.56, 95% CI = 1.39-15.00; ASDAS-MI OR = 3.31, 95% CI = 1.02-10.69).

Conclusions: The patients carrying the TNFα +489 A allele may be more likely to experience better therapeutic efficacy and achieve the treatment target (ASAS-PR, ASAS40 response, or ASDAS-MI) after receiving ADA treatment. Detection of TNFα +489 G/A may predict the therapeutic efficacy of ADA, which can be used in clinical practice to tailor treatment for individual patients with AS. Further studies with larger sample sizes and longer follow-up periods with imaging evaluation are needed to verify our findings.

Keywords: adalimumab; adalimumab (humira); ankylosing spondylitis; biological therapy; single nucleotide polymorphism; tumor necrosis factor-alpha; tumour necrosis factor-α (tnf-α).

Grants and funding

This study was supported by grants from the Medical Scientific Research Foundation of Guangdong Province (A2018104), the Science and Technology Planning Project of Shantou City ((2017)85, (2022)88), and the Shantou University Medical College Clinical Research Enhancement Initiative (2014110109). The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript.