P0341RITUXIMAB IN THE TREATMENT OF PRIMARY MEMBRANOUS NEPHROPATHY - A COMPARATIVE STUDY OF THREE REGIMEN
Authors: Kohli Harbir Singh , Ramachandran Raja , Rathi Manish , Minz Ranjana , Nada Duseja Ritambhra 
Published: June 2020

Abstract

Background and Aims
Different rituximab dosing schedules have been used to manage primary membranous nephropathy (PMN). Better response rate and toxicity needs to be balanced to arrive at correct dose. The dosing schedules in PMN as of now are an on the lines of the management of lymphoma or rheumatoid arthritis. In the current study, we report the 1-year outcome of patients treated with three dosing schedules of rituximab in PMN.

Method
The current report is a study of patient of PMN treated with three different dosing schedules of rituximab treatment. The study included PMN patients with nephrotic syndrome (proteinuria&gt;3.5 g/day and serum albumin of &lt; 3.5 g/dL). Patients with secondary membranous nephropathy and a history of prior exposure of immunosuppressive therapy in the last three months were excluded from the study. The three dosing schedules of rituximab were 1 g (on day 0,15) (regimen 1), 375 mg/m2 (weekly for four weeks) (regimen 2) or CD19 targeted rituximab therapy (375 mg/m2 as the initial dose and additional dose 100 mg, when the CD19 cell count was&gt; 5/ul or &gt;1%, done every month for 12 months) (regimen 3). Serum PLA2R autoantibodies were done before rituximab therapy and at six months of therapy initiation. Primary outcomes: Remission at the end of 12 months of therapy initiation. Secondary outcome: Complete remission (CR) and partial remission (PR), remission with different treatment schedules and adverse events. Definition: CR: reduction of proteinuria to &lt;0.5 g/d and with creatinine clearance of &gt;60 ml/min/1.73m2 and serum albumin &gt; 3.5 g/dl. PR: reduction of proteinuria to 0.5–3.5 g/day and stable serum creatinine. A p-value of &lt;0.05 was considered significant.

Results
The study included 87 patients of PMN. The mean age of the patients was 33.36±15.38 (range 15-61) years. Thirty-two (36.4%) and 56 (63.6%) patients received rituximab as the first-line therapy and for relapsing/resistant disease, respectively. Forty, 15 and 33 patients received regimen 1, 2 and 3, respectively. The median proteinuria, serum albumin and creatinine at the baseline before rituximab therapy was 5.90 (IQR 4.20,9.75) gm, 2.50 (IQR 2.15,3.25) g/dl and 0.88 (IQR 0.77,1.09) mg/dl, respectively. At the end of 12 months of follow-up, 55 (56.8%) patients received remission. Nineteen (21.6%) and 32 (36.3%) patients achieved CR and PR, respectively. In regimen 1, 12 (30%) and 13 (32.5%) patients achieved CR and PR, respectively. In regimen 2, 2 (13.3%) and 5 (33.3%) patients achieved CR and PR, respectively. In regimen 3, 5 (15.6%) and 14 (43.7%) patients achieved CR and PR, respectively. One patient in the CD19 targeted therapy (regimen 3) was lost to follow-up after the 1st dose; all but one patient in the received regimen three as a second-line treatment. There was a significant association of anti-PLA2R to clinical response (p&lt;0.05). There was no difference in the response rate among the three groups (p&gt;0.05). A total of 7 (7.9%) patients had severe adverse events, there was no difference in the 3 regimens. (p&gt;0.05) The cumulative dose in regimen 3 was significantly less as compared to regimen 1 & 2 (p&lt;0.01)

Conclusion
Rituximab induces remission in two-thirds of the patients with PMN. There is no significant difference in the remission rates between different rituximab regimens. CD19 targeted therapy is equally effective with lower cumulative dose.