Longitudinal Anti-HBs Monitoring and Seroprotection Patterns in Rituximab-Treated Patients with Pemphigus Vulgaris: A Retrospective Cohort Study

Rituximab induces prolonged B-cell depletion and may alter protective antibody levels, but longitudinal antibody to hepatitis B surface antigen (anti-HBs) patterns in pemphigus vulgaris remain poorly characterized. This study evaluated anti-HBs levels and seroprotection after rituximab and explored associated factors. Methods: This retrospective cohort included 84 patients with pemphigus vulgaris treated with rituximab between 2010 and 2026 who had baseline and post-treatment anti-HBs measurements. Longitudinal changes in log-transformed anti-HBs levels were analyzed using a linear mixed-effects model with categorical time and a patient-specific random intercept. The probability of anti-HBs < 10 IU/L was assessed using a binomial generalized estimating equation model. Paired Wilcoxon signed-rank tests were performed as sensitivity analyses. Results: The median baseline anti-HBs level was 49.7 IU/L, and 34 patients (40.5%) had levels < 10 IU/L. Time was associated with longitudinal anti-HBs levels overall (p = 0.002). Compared with baseline, model-estimated levels were lower at month 6 (geometric mean ratio [GMR] 0.61, 95% CI 0.42–0.88), month 9 (GMR 0.64, 95% CI 0.45–0.89), and month 18 (GMR 0.50, 95% CI 0.32–0.78). Time was not significantly associated with the odds of anti-HBs < 10 IU/L (global p = 0.490). Positivity for antibody to hepatitis B core antigen (anti-HBc) IgG was associated with higher longitudinal anti-HBs levels (adjusted GMR 13.24, 95% CI 5.32–32.95; p < 0.001). No clinically or biochemically evident hepatitis B virus (HBV) reactivation was documented, although HBV DNA was not routinely monitored. Conclusions: Quantitative anti-HBs levels varied significantly during follow-up; whereas, the probability of crossing below the conventional seroprotection threshold did not increase significantly. These findings support HBV serological assessment and cautious interpretation of serial anti-HBs measurements in rituximab-treated patients with pemphigus vulgaris.