Association between TNF-α polymorphisms and responsiveness to TNF-α blockers in ankylosing spondylitis and psoriatic arthritis: a meta-analysis

To investigate the association between tumor necrosis factor-alpha (TNF-α) polymorphisms and the responsiveness to anti-TNF-α therapy in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A comprehensive literature search of the PubMed/Medline, Embase, and Web of Science databases was performed to identify relevant published studies. Meta-analysis was performed to assess the relationship between specific TNF-α polymorphisms (-308 A/G, + 489 A/G, -238 A/G, -857 C/T, or -1031 C/T) and the responsiveness of patients with AS or PsA to anti-TNF-α therapy. The study was registered in PROSPERO (CRD42023472655). The analysis incorporated data from 11 comparison studies within 9 articles, involving 611 patients (453 responders and 158 non-responders). Meta-analysis revealed a significant association between the TNF-α -308 G allele and a positive response to TNF-α blockers (odds ratio [OR] 4.221 [95% confidence interval (CI) 1.691–10.54]; p = 0.002). Stratification according to ethnicity demonstrated this association in both the European and Asian populations. Disease-specific meta-analyses indicated an association between the TNF-α -308 G allele and a favorable response to TNF-α blockers in those with AS and PsA. However, the TNF-α + 489 GG genotype did not exhibit a consistent association with the response in PsA, although a single study suggested an association in AS. Furthermore, TNF-α -857 C and − 238 G alleles were associated with a positive response to TNF-α blockers in PsA. No association was found between the TNF-α -1037 TT genotype and response in PsA. Results of this meta-analysis provide evidence supporting a significant association between the TNF-α -308 G allele and an increased responsiveness to TNF-α blockers in AS and PsA. It also suggests that TNF-α -857 C and − 238 G alleles may influence TNF-α blocker responsiveness in PsA.