Rituximab with low-dose glucocorticoids for treating refractory membranous nephropathy: a prospective single-center...

Rituximab (RTX) is the first-line treatment for primary membranous nephropathy (pMN), yet approximately one-third of patients exhibit refractory disease. Evidence supporting RTX combined with low-dose glucocorticoids for refractory pMN remains limited. This study aimed to evaluate the efficacy and safety of this combination regimen in a rituximab-naïve refractory cohort.

Thirty-six adults with refractory pMN received rituximab plus low-dose glucocorticoids (prednisone equivalent). The primary endpoint was clinical remission at 24 months, analyzed in both the intention-to-treat (ITT, n = 36) and per-protocol (PP, n = 22) populations. Sensitivity analyses included a worst-case scenario (assuming all dropouts were non-remitters).

Thirty-five patients had evaluable 12-month outcomes, and 26 of them achieved remission (74.3%, with 25.7% achieving complete remission and 48.6% partial remission). By 24 months, the remission rate was 95.5% (21/22) in the per-protocol analysis and 91.67% in the intention-to-treat analysis, compared with 58.3% (21/36) in the worst-case scenario. We found no statistically significant difference in cumulative remission rates between serum PLA2R-positive and PLA2R-negative groups, or between renal tissue PLA2R-positive and PLA2R-negative groups. All 25 patients positive for anti-PLA2R antibodies showed a decreasing antibody trend after treatment, and 80.0% (20/25) achieved complete antibody clearance (antibody titer <20 RU/mL). Adverse events occurred in 37.1% (13/35) of patients, with 11.4% (4/35) of patients developing serious infections. No serious malignant events or fatal events were reported during the study.

In this cohort of patients with refractory pMN, rituximab combined with low-dose glucocorticoids achieved high short-term remission rates, and no safety signals were observed that would preclude further investigation. However, given the uncontrolled study design, repeated RTX dosing, and residual confounding from prior immunosuppression, we cannot draw definitive conclusions on whether adding glucocorticoids offers incremental benefit compared with rituximab monotherapy. The high remission rates observed in this study may also be attributable to repeated rituximab exposure and residual effects of prior immunosuppression. Furthermore, this empirical combination regimen was not designed to test whether glucocorticoids have a direct additive or synergistic effect. Larger randomized controlled trials are therefore warranted to confirm these findings.