TNFRSF11A Exon 5 Variants in Early RA: Associations with Disease Activity and Biologic Treatment Response—A Prospective Cohort Study

Introduction: This study aimed to investigate the impact of polymorphisms in exon 5 of the TNFRSF11A gene on disease activity and treatment outcomes in newly diagnosed rheumatoid arthritis (RA). Methods In this prospective cohort, 57 newly diagnosed RA patients (2019 ACR/EULAR criteria) underwent genotyping for TNFRSF11A exon 5 polymorphisms by PCR and direct sequencing. Clinical and laboratory evaluations—including DAS28-CRP, CDAI, SDAI, ESR, and CRP—were performed at baseline and after six months of methotrexate (MTX). Treatment responses and initiation of biological agents were recorded. Results TNFRSF11A exon 5 polymorphisms were detected in 18% of patients. Both variant-positive and variant-negative groups showed significant improvements in disease activity indices after treatment (p < 0.05). Although not statistically significant, variant-positive patients tended to have lower baseline CRP levels, reduced post-treatment disease activity, fewer tender/swollen joints, and lower rates of biological agent initiation. A higher proportion of seronegative RA was observed in the variant-positive group. Conclusion No statistically significant associations were found between TNFRSF11A exon 5 polymorphisms and clinical outcomes. However, observed trends suggest that larger cohorts are warranted to clarify the potential prognostic value of these variants.