Existing studies on rituximab (RTX) and cyclophos- phamide (CTX) in membranous nephropathy

The gap

Evidence profile

Sourced from the discussion and future work of the source papers, classified as general, drawn from work published between 2025 and 2026, spanning 3 journals. Those papers have been cited 5 times in total.

Supporting evidence — 3 representative gaps

• Rituximab vs. cyclophosphamide in treatment-naive IMN: efficacy and renal protection in early renal impairment (2026) · Clinical and Experimental Nephrology · doi

  Existing studies on rituximab (RTX) and cyclophos- phamide (CTX) in membranous nephropathy (MN) have long faced a key limitation: most cohorts include refractory patients or those with prior immunosuppressive exposure, which may mask the true efficacy of initial therapies. [16] summarized that RTX has become a first-line option for moderate-to-high- risk MN, but noted that "data on treatment-naive patients, especially those with impaired renal function, remain scarce.

  generaldiscussion
  Keywords: patients existing rituximab cyclophos phamide membranous nephropathy long faced limitation cohorts include refractory prior immunosuppressive
• From ANCA-mediated vascular injury to coronary microvascular and myocardial involvement in granulomatosis with polyangiitis: an immunocardiology perspective (2026) · Rheumatology International · doi

  For newly diagnosed or relapsing GPA with organ- or life- threatening manifestations, remission induction with gluco- corticoids combined with rituximab or cyclophosphamide is recommended [5, 39]. Rituximab is generally favored in relapsing GPA and may also be preferred when avoidance of further cyclophosphamide exposure is clinically important, including in patients with concerns regarding cumulative toxicity or fertility [5, 39]. In selected patients with rapidly progressive glomerulonephritis, plasma exchange may be considered after individualized assessment of renal progno- sis, disease severity, and treatment-related risks [6, 39]. For GPA without organ- or life-threatening manifesta- tions, rituximab combined with glucocorticoids is rec- ommended by the current EULAR framework, while methotrexate or mycophenolate mofetil may be consid- ered in selected patients when rituximab is inappropriate or unavailable [39]. Randomized trials have shown that methotrexate can induce remission in selected patients with non-severe AAV but may be associated with a greater subse- quent relapse burden than cyclophosphamide-based strate- gies [59, 60]. Mycophenolate mofetil has also demonstrated remission-induction efficacy in selected AAV populations, although higher relapse rates or less consistent disease control have been reported in some studies [61, 62]. These data support individualized treatment selection rather than assuming therapeutic equivalence across disease pheno- types and severity categories. 1 3Rheumatology International(2026)46:247  247 Page 14 of 20 Following remission, prevention of relapse represents a distinct therapeutic objective. Rituximab is the preferred maintenance option for GPA/MPA in the EULAR rec- ommendations [39]. In patients with relapsing AAV, the RITAZAREM trial demonstrated superior prevention of relapse with repeated rituximab compared with azathioprine [63]. Azathioprine or methotrexate remain alternatives in selected patients according to clinical circumstances [39]. Complement-targeted therapy requires particular cau- tion in the current evidence context. Earlier phase II studies, including CLASSIC, provided evidence that pharmacologi- cal inhibition of the C5a receptor with avacopan was fea- sible when added to standard immunosuppressive treatment [7]. The 2022 EULAR update incorporated avacopan as a glucocorticoid-sparing option on the basis of the evidence available at that time [39]. However, the pivotal ADVO- CATE publication was formally retracted in June 2026 after undisclosed post-unblinding readjudication of primary end- point assessments in nine participants [64]. Accordingly, previous efficacy conclusions derived from ADVOCATE and the therapeutic positioning of avacopan should now be interpreted cautiously and reassessed as guideline and reg

  generalfuture work
  Keywords: rituximab patients selected remission relapse relapsing cyclophosphamide disease treatment eular methotrexate therapeutic evidence avacopan organ
• The Use of Rituximab in Glomerulonephritis: What Is the Evidence? (2025) · Biomedicines · cited 5× · doi

  Despite its widespread use in various forms of glomerulonephritis, the optimal dosing and redosing schedule of rituximab is unclear. In this regard, prospective trials are neces- sary to establish the optimal dosage, treatment duration, and redosing strategy (fixed vs. biomarker-guided) for rituximab and other biologics. In the same light, more research is needed to search for biomarkers that can accurately predict treatment response or relapse, guide redosing, and enable personalized therapy. We believe establishing a long-term safety registry for rituximab users over an extended period will help clinicians and researchers to understand its safety in long-term use. Finally, future trials comparing the efficacy and safety of rituximab versus next-generation agents will provide information on how we can best use these drugs in practice. Funding: This research was funded by (1) Shenzhen Clinical Research Center for Rare Diseases (LCYSSQ20220823091402005); (2) Sanming Project of Medicine in Shenzhen (No. SZSM202311022); (3) Translational Medicine Research Center of HKU-Shenzhen Hospital. Institutional Review Board Statement: The study has received approval from the Research Ethics Committee/Institutional Review Board of The University of Hong Kong-Shenzhen Hospital (HKU- SZH IRB 2025200) date 28 August 2025. Biomedicines 2025, 13, 2157 9 of 12 Informed Consent Statement: Not applicable. Data Availability Statement: The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author(s). Conflicts of Interest: The authors declare no competing interests.

  generalfuture work
  Keywords: rituximab shenzhen redosing safety statement optimal trials treatment long term center medicine hospital institutional review

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