RITUXIMAB IN GLOMERULAR DISEASES: A COHORT ANALYSIS AND A LITERATURE REVIEW

Abstract Background and Aims Glomerular diseases (GD) account for about 20% of chronic kidney disease causes. They are a heterogeneous group of diseases and current treatment is still inadequate. Rituximab (RTX) is a chimeric antibody which binds specifically to the B-cell surface antigen CD20 and has been applied in the treatment of different GD. The authors present the single center experience of the use of RTX for the treatment of GD as well as a literature review. Method We performed a retrospective analysis of all patients with biopsy-proven GD treated with RTX as first or second-line therapy between January 2010 and March 2020. The protocol used was RTX 375 mg/m2 once a week for 4 weeks. Infusions were preceded by adequate premedication. Results Nineteen patients with biopsy-proven GD received RTX therapy. Seven patients had membranous nephropathy (MN) (36.8%), 4 patients had focal segmental glomerulosclerosis (FSGS), 4 patients had lupus nephritis (LN) and 4 patients had vasculitis (25.0% each). Five patients (26.3%) received RTX as first-line therapy and 14 patients (73.7%) as second-line therapy, namely long-term prednisolone (Pd) (n=15, 78.9%), calcineurin inhibitors (CNI) (n=6, 31.6%), cyclophosphamide (Cp) (n=7, 36.8%), mycophenolate mofetil (MMF) (n=5, 26.3%) and methotrexate (MTX) (n=1, 5.3%). Serum creatinine at diagnosis was 1.5 ± 1.7mg/dL and the 24-h urine protein at diagnosis was 4.9 ± 4.5g. Mean follow-up time was 7.7 ± 7.2 years. In MN, 2 patients (28.6%) had CR, 2 patients (28.6%) had PR and 3 patients (42.9%) had no response. In FSGS, 2 patients (50.0%) presented CR, 1 patient (25.0%) had no response and the other one had renal deterioration. Two patients (50.0%) had a LN class IV with a CR after RTX, 1 patient with LN class IIIC/V had no response and 1 patient with LN class II had renal deterioration. In vasculitis, 3 patients (75.0%) presented CR and 1 patient had PR. Mean serum creatinine after RTX was 1.6 ± 1.4mg/dL and the mean 24-h urine protein was 1.9 ± 3.1g. Two patients (10.5%) presented infusion reactions and one patient had multiple respiratory infections. This patient had received previous immunosuppression with cyclophosphamide. Conclusions A total of 19 patients with biopsy-proven GD received RTX therapy and 12 patients (63.2%) presented a complete or partial remission suggesting the efficacy of RTX in different types of GD. In MN, our response rate was similar to studies such as GEMRITUX and MENTOR trial, which have shown remission in 60–70% of patients. In FSGS, 50% of patients had a stable and complete remission with RTX therapy similar with a meta-analysis of five studies with 51 patients with FSGS. Two patients had refractory LN class IV and both had complete remission (50% of patients with LN). This is in line with a systematic review of case reports and case series that reported sustained complete and partial response rates of 67% in LN class IV. In our cohort, patients with vasculitis received RTX as first-line therapy and complete remission was achieved in 75% of cases, which is in line with the results found in RITUXVAS and RAVE trial. Rituximab was safe and effective in achieving remission in different types of immune-mediated glomerular diseases.