#5710 CHARACTERIZATION OF RESPONSE TO TREATMENT WITH RITUXIMAB IN PATIENTS WITH PRIMARY GLOMERULOPATIES

Abstract

Abstract Background and Aims Rituximab (RTX) is an anti-CD20 monoclonal antibody used in renal diseases with glomerular involvement, which usually present with proteinuria. The doses used in this pathologies are extrapolated from other diseases such as rheumatoid arthritis, but the optimal regimen in this population has not been well defined. Objective To describe the behaviuor of RITUXIMAB in patients with primary glomerulopathies in whom its use is indicated. Method Descriptive low-intervention single-center clinical trial approved by the Spanish Medicines Agency (NEFRTX, EUDRACT 2020-000484-23. Patients treated with rituximab were included according to medical criteria, prior approval by the Pharmacy Commission. The regimen used was 1g every 15 days, or only 1gr dose with premedication according to clinical practice guidelines. 24-hour blood and urine samples were collected on days 1 (post-rituximab), 7, 15 (pre and post-rituximab), 28, and 45. Serum rituximab was determined using ELISA (Lisa-Traker®-Rituximab, Theraradiag®). Clinical and pharmacokinetic data analyzes were performed considering a single compartment model by non-linear regression with Winnolin® to obtain clearance (Cl), half-life (t1/2), maximum concentration (Cmax) and volume of distribution (Vd). Some quantitative results are expressed as mean ± standard deviation. Linear regression was used to establish correlations. Results The results of 5 patients were analyzed, 2 women and 3 men, with a mean age of 68.8 ± 17.02 years of 72 years and a diagnosis of membranous GN (3), ANCA MPO GN (1), focal and segmental GN (1). Renal function CKD EPI: GFR between 45- 60 ml/min N = 2 GFR >60 ml/min N = 3. According to clinical practice guidelines, patients received 1g doses, 2/5 patients received a second dose on day 15. The evaluation parameters were: proteinuria, CD 19+ lymphocyte depletion, Antibodies titers and histological characteristics as appropriate. levels of rituximab in urine samples after the rituximab administration (15, 30, 180, 365 days after) were determinate. All the patients presented proteinuria, with a mean of 11±14.6 g in 24 h urine. Mean Rituximab clearance was 0.676±0.431 ml/h/kg, distribution volume was 222.35±140.52 mL/Kg and Cmax 69.66±26.14 mcg/mL and t1/2 269.66± 229.71 h (11 days approximately). There is a correlation between proteinuria and rituximab half-life (p = 0.077), as well as between proteinuria and clearance creatinine (p = 0.975) suggesting that half life of rituximab is lower if proteinuria increases (Fig. 1). All presented lymphocyte depletion of CD 19 at 45 days. However, those with more proteinuria >2.5 g (N = 3) in those 45 days, after 6 months of exposure to RTX, progressive repopulation of CD19 was observed, which persisted in the year of follow-up. Conclusion In patients with high proteinuria, rituximab has a t1/2 lower than the 21–28 days described in the data sheet, which may suggest that patients with nephrotic syndrome may require higher doses to ensure the effectiveness of treatment with rituximab. Repopulation of CD19 in 45 days could be a reliable indicator of non response in patients with nephrotic proteinuria.