SAT-398 LOW DOSE OF RITUXIMAB IS CLINICALLY AND COST EFFECTIVE IN PRIMARY MEMBRANOUS NEPHROPATHY

Abstract

B cells are thought to be involved in the pathogenesis of Primary Membranous nephropathy(IMN) and therapies targeting B cells may have a role. Though cyclophosphamide based therapies were traditionally used, targeting B cells with Rituximab and thereby depleting antibody production has been suggested as an alternative and possibly more effective therapy1. Most of the studies have extrapolated the dose used in treating B cell lymphoproliferative diseases in a four weekly dose of 375mg/m2. There have even been suggestions that mega doses may be more effective by preventing epitope spreading2. At the same time, clinical efficacy with a single dose has also been reported3. We studied the role of a single low dose of 100mg Rituximab in decreasing CD19 B cells, proteinuria, renal functions and antiphospholipid 2 receptor antibody titres (Anti PLA2R) in IMN. A single centre, prospective observational study was conducted at a tertiary care centre in South India over a six month period. Biopsy proven cases of IMN with proteinuria >8g/day and eGFR >30ml/min/m2 who did not receive previous therapy with cyclophosphamide or calcineurin inhibitors received Inj. Rituximab 100 mg as monotherapy after informed consent along with Angiotensin 11 receptor blockers, statins and diuretics. Dose of antihypertensive drugs were targeted to keep blood pressure <140/90 mmHg. CD 19 counts were measured at baseline, at 4 weeks,12 weeks and 24weeks following Rituximab. Anti PLA2R titres were also measured at baseline and if elevated, periodically. Other baseline parameters like serum albumin, total cholesterol and proteinuria were also recorded at baseline and at intervals mentioned above. Five patients including 3 males with a mean age of 55+/-2 years were studied. Mean serum creatinine at baseline was 1.3+/-0.6 mg/dl. Baseline 24 hour proteinuria was 10.2+/-1.8g.Four patients were PLA2R negative and one was positive. Following 100mg of rituximab, CD19 counts were suppressed in all patients at 1 month. Four patients attained partial remission by 3 months and were in complete remission by 6months. One patient had transient decrease in proteinuria and Anti PLA2R titres but relapsed by 2nd month and thereafter failed to respond. At the end of 24 weeks significant reduction in proteinuria along with normal serum albumin and total cholesterol were observed in 4 patients. Among those who responded, proteinuria at the end of 24 weeks came down to an average of 1.08+/-0.5g/day(p<0.005). There were a limited number of minor side-effects. Though initial cluster of differentiation 19 (CD19)+ B cell were depleted in all patients at 4 weeks(count <1%), repopulation of CD19+ B cells occurred in 4 patients by 3 months. Clinical remission could be achieved at the end of 24 weeks in 4 of our patients. Lack of response in one patient despite initial fall in PLA2R titres and CD19 count could be explained due to PLA2R epitope spreading. A single dose of 100mg Rituximab was sufficient to suppress the CD 19 count to less than 1% at 4 weeks. Targetting further doses depending on whether repopulation of CD19 Bcells occur and Anti PLA2R titres become elevated could limit the cumulative dose of rituximab, be cost effective and decrease toxicity. These observations may need to be confirmed by larger, preferably multicentre trials.