Obinutuzumab is Effective for the Treatment of Refractory Membranous Nephropathy

Sethi, Supreet; Kumar, Sanjeev; Lim, Kathlyn; Jordan, Stanley C.

doi:10.1016/j.ekir.2020.06.030

Cited by 52 publications

(32 citation statements)

References 9 publications

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“…In 2 recent case series with rituximab refractory pMN, obinutuzumab has been shown to be effective. 7 , 8 However, the reason for treatment resistance was not analyzed (i.e. underdosing or antidrug antibodies), and therefore repeating rituximab injections could have been sufficient and cost effective.…”

Section: Introductionmentioning

confidence: 99%

Analysis and Management of Rituximab Resistance in PLA2R1-Associated Membranous Nephropathy

Teisseyre

Boyer‐Suavet

Crémoni

et al. 2021

Kidney International Reports

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Section: Introductionmentioning

confidence: 99%

Analysis and Management of Rituximab Resistance in PLA2R1-Associated Membranous Nephropathy

Teisseyre

Boyer‐Suavet

Crémoni

et al. 2021

Kidney International Reports

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“…Some patients with pMN may develop anti-rituximab antibodies that may decrease the effectiveness of the treatment (16). In these cases obinutuzumab and ofatumumab have been shown to be effective (17)(18)(19)(20). Other patients are undertreated because of the highly variable bioavailability of rituximab in nephrotic patients (21).…”

Section: Introductionmentioning

confidence: 99%

Rituximab Immunomonitoring Predicts Remission in Membranous Nephropathy

et al. 2021

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Primary membranous nephropathy (pMN) is an autoimmune kidney disease and a common cause of nephrotic syndrome in adults. Rituximab is becoming a first line therapy for patients with persistent nephrotic syndrome with proven safety and efficacy, achieving remission in 60%–80% of cases. For the remaining 20%–40% of patients there is an urgent need to identify early biomarkers of resistance to rituximab to adapt therapeutic management. In nephrotic patients, rituximab is found in the blood more transiently than in other autoimmune diseases without proteinuria, due to rituximab wasting in the urine. However, rituximab immunomonitoring is not routinely performed. We evaluated the predictive value of serum rituximab levels in patients with pMN three months after rituximab injection (month-3) on clinical remission rates six months (month-6) and 12 months (month-12) after injection and investigated predictive factors for serum rituximab levels at month-3. Sixty-eight patients treated with rituximab between July 2015 and January 2020 from two French nephrology centers were included. We identified residual rituximab levels at month-3 as a novel early predictor of remission at month-6 (p <0.0001) and month-12 (p = 0.001). Reduced likelihood of remission in patients with undetectable rituximab at month-3 was associated with lower serum albumin and higher anti-PLA2R1 titers at baseline and with lower serum albumin, higher proteinuria, higher CD19+ counts and higher anti-PLA2R1 titers during follow-up. In multivariate analysis, high baseline proteinuria and undetectable rituximab levels at month-3 were independent risk factors for treatment failure at month-6 and high baseline weight and undetectable rituximab levels at month-3 were independent risk factors for treatment failure at month-12. We identified serum albumin at baseline as a predictive factor for serum rituximab levels at month-3. Patients with serum albumin below 22.5 g/L at baseline had an 8.66-fold higher risk of having undetectable rituximab levels at month-3. Therefore, rituximab immunomonitoring in pMN patients treated with rituximab would allow the detection of patients at risk of treatment failure as early as month-3. Studies are needed to assess whether patients with low residual rituximab levels at month-3 may benefit from an early additional course of rituximab.

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“…Primary membranous nephropathy (PMN) is the most common cause of nephrotic syndrome in adults, accounting for 20-40% of all cases. It is an autoimmune disease with an incidence rate of 1.2 per 100,000 persons per year, and a male to female ratio of 2:1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. The discovery of autoantibodies to phospholipase A2 receptor (PLA2R) by Beck and Salant in 2009 revolutionized our understanding of the pathophysiology of this unique disease [2].…”

Section: Introductionmentioning

confidence: 99%

“…PLA2R, a normal molecule in the podocyte structure, serves as the target antigen for PLA2R antibodies, causing an immunological response that results in the clinical signs of proteinuria and hypoalbuminemia [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Furthermore, the identification of this antigen and antibody has had a significant impact on the treatment approach.…”

Section: Introductionmentioning

confidence: 99%

“…The purpose of this review is to illustrate the changing landscape of PMN therapy post-MEN-TOR, highlighting alternative therapies including rituximab and other agents that have been used more recently instead of the tried and tested cyclical regimen consisting of corticosteroids, alkylating agents, and calcineurin inhibitors. Alkylating agents and calcineurin inhibitors have significant adverse effects, including gonadal toxicity, bone marrow suppression, oncogenic effects, and nephrotoxicity [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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A Review of Therapy for Primary Membranous Nephropathy Post-MENTOR

Srinivasa

2021

World J Nephrol Urol

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Primary membranous nephropathy (PMN) is the most common cause of nephrotic syndrome in adults worldwide. Recent evidence confirms an autoimmune pathogenesis highlighted by the discovery of the phospholipase A2 receptor (PLA2R) antigen. PLA2R serves as both a marker and a guide for treatment. Traditional treatments, including alkylating agents and calcineurin inhibitors, have been associated with adverse risk profiles. Consequently, alternative therapies have been developed. Rituximab is a promising addition to the therapeutic armamentarium of PMN. However, there are few head-to-head trials comparing rituximab with cyclophosphamide. In this clinical review, the results of the MENTOR, STARMEN, and RI-CYCLO trials are discussed and evaluated. Based on the results of these trials, a more personalized treatment approach is needed.

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Obinutuzumab is Effective for the Treatment of Refractory Membranous Nephropathy

Cited by 52 publications

References 9 publications

Analysis and Management of Rituximab Resistance in PLA2R1-Associated Membranous Nephropathy

Analysis and Management of Rituximab Resistance in PLA2R1-Associated Membranous Nephropathy

Rituximab Immunomonitoring Predicts Remission in Membranous Nephropathy

A Review of Therapy for Primary Membranous Nephropathy Post-MENTOR

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