Association between anti-rituximab antibodies and treatment efficacy of rituximab in membranous nephropathy

BACKGROUND AND HYPOTHESIS: Rituximab (RTX) is a first-line therapy targeting B cells; however, 30%-40% of patients exhibit treatment resistance or relapse. Studies have shown that anti-rituximab antibodies (ARA) may lead to RTX resistance through mechanisms such as drug neutralization. The objective of this study is to explore the relationship between the emergence of ARA and the clinical efficacy of initial RTX treatment in adult MN. METHODS: Patients with MN who received RTX therapy were included in this study. Clinical data and laboratory results of the patients were collected, and ARA levels in serum samples were measured using a commercial ELISA kit. The impact of ARA on the clinical outcomes of MN patients treated with RTX was analyzed. RESULTS: Among 58 patients with membranous nephropathy who received initial RTX treatment, 11 patients (19.0%) tested positive for ARA. ARA were identified after a median of 9.3 months (IQR 8.2-11.1) following the last RTX injection. Among the patients who received initial RTX treatment and were monitored for over 6 months, ARA-positive patients (n = 11) exhibited a higher relapse rate (80.0% vs. 24.1%, P = 0.029) than ARA-negative patients (n = 41), which was also confirmed by Kaplan-Meier analysis (log-rank test, P = 0.027). At 6 months post-initial RTX, ARA-positive patients demonstrated higher B cell levels (p = 0.021). Four RTX-resistant and ARA-positive patients achieved clinical remission with obinutuzumab, with a median remission time of 4.8 months (IQR 3.0-6.8). CONCLUSION: This study confirms that adult patients with MN who are ARA positive have a higher relapse rate after initial RTX treatment. Patients who are RTX-resistant and ARA positive can achieve rapid clinical remission after receiving obinutuzumab treatment.