Impact of TNF-alpha -308 G/A polymorphism on response to TNF inhibitors in Tunisian patients with inflammatory rheumatic diseases

OBJECTIVES: To evaluate the impact of the TNF-α promoter SNP -308G/A on therapeutic response, serum drug levels, and immunogenicity of TNF inhibitors in chronic inflammatory rheumatic diseases. METHODS: ). Genotyping for SNP -308 was performed via PCR-RFLP. Therapeutic response was assessed at 6 months using delta DAS28 and EULAR response in RA and delta BASDAI, BASDAI20 and BASDAI50 responses in SpA patients. RESULTS: In RA, the heterozygous G/A genotype was significantly associated with a greater reduction in median DAS28 compared to G/G (p=0.039) and a higher proportion of good EULAR responders (p=0.154). In SpA, G/A carriers showed larger decreases in BASDAI scores though differences were not statistically significant. Across both diseases, the G/A genotype was associated with significantly higher median serum drug levels (p=0.032). No association was observed between SNP -308G/A and ADA positivity. CONCLUSIONS: The TNF-α -308G/A polymorphism may be a predictive marker of TNF inhibitor efficacy in RA, potentially influencing serum drug levels while immunogenicity appears unaffected. Larger prospective studies are needed to confirm these findings and explore additional determinants of TNF inhibitor response.