Study of Artificial Intelligence-based Personalized Rituximab Treatment Protocol in Membranous nephropathy

Membranous nephropathy

Clinical remission (complete or partial) according to KDIGO or French guidelines: - Complete: urine protein/creatinine ratio (UPCR) <0.3 g/g and serum albumin>30 g/L - Partial: UPCR <3.5 g/g with a decrease >50% from baseline (i.e., at first rituximab infusion) and serum albumin improvement or normalization

Complete clinical remission at month-12 according to KDIGO or French guidelines, Partial clinical remission at month-12 according to KDIGO or French guidelines, Immunological remission: If membranous nephropathy anti-PLA2R1 associated: anti-PLA2R1 depletion (i.e., PLA2R1 titer < 14 RU/mL by ELISA EUROIMMUN kit) at month-3, month-6, month-12 ✓ If membranous nephropathy anti-THSD7A associated: anti-THSD7A depletion (i.e., positive or negative immunofluorescence), Percentage of change in urine protein/creatinine ratio (UPCR) (g/g) and urine albumin/creatinine ratio (mg/g) from day-0 to month-3, month-6, month-9, month-12, Percentage of change in serum creatinine (μmol/L) and Glomerular Filtration Rate estimated by CKD-EPI formula (mL/min/1.73m²) from day-0 to month-3, month-6, month-9, month-12, Percentage of change in anti-PLA2R1 titer (RU/mL) by ELISA (EUROIMMUN Kit) from day-0 to month-3, month-6, month-9, month-12 (membranous nephropathy anti-PLA2R1 associated only), Serum anti-rituximab antibodies (ng/mL) at month-3, month-6, month-9, month-12, Percentage of patients with serum rituximab (μg/mL) >2 μg/mL 3 months after the last infusion, Serious adverse events, Modification of non-immunosuppressive anti-proteinuric treatment during study follow-up, Pharmacokinetics in all patients with serum creatinine and serum albumin levels, weight, anti- PLA2R1 and rituximab level at day-0, day-15, day-30, day-45, month-3, month-6, Clinicians' satisfaction with the iRITUX algorithm and its value in helping them decide on the dose of rituximab to use to treat their patients will be assessed with a close-ended question., Predictive rate (%) of the algorithm for rituximab underdosing (i.e. serum level <2 mg/ml at month-3) in the control group (i.e. patients treated according to the standard-of-care strategy)., Cytokine levels in pg/mL (IFN-γ, IFN-α, IL-12p70, IL-17A, IL-4, IL-5, IL-10, IL-1, IL-6) at day- 0 and month-6.

France