Retrospective study of treatment effectiveness and remission predictors of obinutuzumab in primary membranous nephropathy

BACKGROUND: Rituximab is recommended as the first-line treatment for moderate- to high-risk primary membranous nephropathy (PMN). Obinutuzumab, a highly humanized anti-CD20 monoclonal antibody, has been shown to exhibit enhanced efficacy in laboratory studies. This study aimed to investigate the efficacy, side effects, and potential remission predictors of obinutuzumab in PMN treatment. METHODS: This retrospective cohort study included PMN patients who presented with nephrotic syndrome and who were treated with obinutuzumab (1 g on day 1 and day 28 in the majority of patients) between March 2022 and December 2023. Logistic regression, Kaplan-Meier curve analysis, and the log-rank test were used to assess treatment effectiveness and predictors of remission. Safety profiles were also recorded and analyzed. RESULTS: A total of 66 PMN patients, with a mean age of 50 ± 13 years, were enrolled, and 48 (72.7%) were male. The average follow-up duration was 18.1 ± 8.0 months. During the follow-up period, 60 patients (90.9%) achieved clinical remission, including 31 (47.0%) who achieved complete remission. The median time to the first recorded partial response (PR) was 4 (IQR 2 ~ 8) months. The anti-phospholipase A2 receptor antibody (aPLA2Rab) decrease rate during the first month of treatment was 88.3% (IQR 68.0%~95.7%). In total, 47/52 (90.4%) patients in the low aPLA2Rab group (aPLA2Rab < 150 RU/ml) and 13/14 (92.9%) in the high aPLA2Rab group (aPLA2Rab ≥ 150 RU/ml) achieved clinical remission. The remission rate of the low aPLA2Rab group did not significantly differ from that of the high aPLA2Rab group (HR = 1.656, 95% CI 0.895 ~ 3.065; P = 0.108). Decrease in aPLA2Rab at month-1 was associated with complete remission (OR = 1.033, 95% CI 1.003 ~ 1.063; P = 0.033) and had a predictive value for complete remission (AUC = 0.734, 95% CI 0.606 ~ 0.862; P = 0.002), and patients were more likely to achieve complete remission when the decrease rate exceeded 90.8%, with a sensitivity of 65.5% and a specificity of 75.8%. No serious adverse events were observed; the most common were mild infusion-related reactions (48.5%). CONCLUSION: Obinutuzumab rapidly and persistently reduces serum aPLA2Rab levels in PMN patients, leading to a favorable clinical remission rate. Decrease in aPLA2Rab at month-1 after treatment can predict clinical remission of PMN.