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

Teisseyre, Maxime; Boyer‐Suavet, Sonia; Crémoni, Marion; Brglez, Vesna; Esnault, Vincent; Seitz-Polski, Barbara

doi:10.1016/j.ekir.2021.01.022

Cited by 25 publications

(24 citation statements)

References 9 publications

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“…However, despite with a similar treatment regimen (21). In addition to urinary excretion of rituximab, internalization and destruction of rituximab by target B cells (27,28) and anti-rituximab antibodies (16,20) may also contribute to decreased residual rituximab levels. Here, we identified baseline serum albumin level as a predictive factor for residual serum rituximab levels at month 3.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, we have shown that residual rituximab levels at month-3 were significantly lower in patients with pMN compared to myasthenia gravis patients without proteinuria matched for age, gender and weight and treated with a similar treatment regimen ( 21 ). In addition to urinary excretion of rituximab, internalization and destruction of rituximab by target B cells ( 27 , 28 ) and anti-rituximab antibodies ( 16 , 20 ) may also contribute to decreased residual rituximab levels. Here, we identified baseline serum albumin level as a predictive factor for residual serum rituximab levels at month 3.…”

Section: Discussionmentioning

confidence: 99%

“…Our present results suggest that this regimen of rituximab may still be insufficient in patients with severe NS. It has recently been shown that reinfusion of rituximab can induce remission in patients considered refractory to rituximab ( 20 , 30 ). Therefore, the management of pMN patients treated with rituximab should be individually adjusted by rituximab immunomonitoring.…”

Section: Discussionmentioning

confidence: 99%

“…To conclude, in pMN patients treated with rituximab, rituximab immumonitoring at month-3 might be a useful biomarker to adapt therapeutic management in addition to CD19 + cell count monitoring, anti-rituximab antibodies monitoring ( 16 , 20 ), anti-PLA2R1 antibody titer ( 36 ) and PLA2R1 epitope spreading ( 37 ). Personalized management may increase the efficacy of rituximab in patients with severe NS and may dispense the use of cyclophosphamide.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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