Zeynel Abidin AKAR, Ömer KARAKOYUN
Rheumatology Quarterly - 2026;4(1):39-46
Aim: Hepatitis B virus (HBV) infection is a major safety concern in patients with rheumatoid arthritis (RA) treated with biological disease-modifying antirheumatic drugs (bDMARDs). Long-term stability of HBV serological markers is essential for monitoring during therapy. Material and Methods: To evaluate 12-month changes in anti-HBs and anti-HBc IgG levels and to identify factors associated with anti-HBs decline in RA patients treated with TNF inhibitors (TNFi), rituximab, or abatacept. In this retrospective cohort study, 210 HBsAg-negative patients with rheumatoid arthritis (RA) were included and equally allocated into three treatment groups (n = 70 each): tumor necrosis factor inhibitors (TNFi), rituximab, and abatacept. Serum anti-HBs titers and anti-HBc IgG status were evaluated at baseline and after 12 months of treatment. Continuous variables were analyzed using one-way analysis of variance (ANOVA) or the Kruskal-Wallis test, as appropriate, while categorical variables were compared using the chi-square test. Multivariate logistic regression analysis was conducted to identify independent predictors of anti-HBs decline. Results: Baseline characteristics were comparable across all treatment groups (all p > 0.05). At 12 months, median anti-HBs titers declined in the rituximab group (from 99.4 to 86.3 mIU/mL; p = 0.008) and the TNFi group (from 108.6 to 101.3 mIU/mL; p = 0.042), while the reduction observed in the abatacept group did not reach statistical significance (from 106.7 to 98.4 mIU/mL; p = 0.063). Although a quantitative decline in anti-HBs titers was observed, no patient experienced a decrease below the protective threshold of 10 mIU/mL during follow-up. HBsAg seroconversion was observed in two patients (2.8%) receiving rituximab, whereas no cases were detected in the TNFi or abatacept groups. Anti-HBc IgG positivity remained stable throughout follow-up in all cohorts (all p > 0.40). In multivariate logistic regression analysis, rituximab use was identified as the only independent predictor of anti-HBs decline (OR 3.18, 95% CI 1.62-6.24; p = 0.001). Conclusion: Rituximab therapy was associated with a greater decline in anti-HBs titers and an increased frequency of HBsAg seroconversion compared with TNFi and abatacept in patients with RA. These findings highlight the importance of careful longitudinal HBV serological monitoring in patients receiving B-cell-depleting agents. Even among HBsAg-negative patients with baseline immunity, ongoing clinical vigilance appears warranted to support the safe use of biologic therapy.
