Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome

Hogan, Julien; Dossier, Claire; Kwon, Thérèsa; Macher, Marie‐Alice; Maisin, Anne; Couderc, Anne; Niel, Olivier; Baudouin, Véronique; Deschênes, Georges

doi:10.1007/s00467-018-4052-x

Cited by 41 publications

(46 citation statements)

References 34 publications

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“…A few studies have been reported with a rituximab dose of 750 mg/m 2 , but this dose has not clearly been associated with a better response rate than the standard dose of 375 mg/m 2 (37, 95). However, using a lower dose of rituximab (100 mg/m 2 ) has been associated with a shorter duration of B cell depletion, and thus appears to increase the risk of earlier relapse (96).…”

Section: Factors That May Affect the Clinical Response Of Rituximab Imentioning

confidence: 99%

“…They found that there was a good correlation between the rituximab dose and the median time to B cell reconstitution (2.5 vs. 5.0 vs. 6.6 months in Groups 1, 2, and 3, respectively). One-year relapse-free survival rates associated with these treatments were also 50, 59, and 72%, respectively (96). These results suggest direct correlations both between dosing regimens and time to B cell reconstitution, and also between time to B cell reconstitution and relapse-free survival.…”

Section: Biomarkers Of Response To Rituximabmentioning

confidence: 99%

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Rituximab Use in the Management of Childhood Nephrotic Syndrome

2019

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Childhood nephrotic syndrome is a challenging and often persistent renal disorder, and its incidence varies between different ethnicities and regions. Corticosteroids have been the main treatment for decades and are effective in most children with idiopathic NS, although 10–15% of these children become steroid resistant. Furthermore, some initially steroid sensitive children follow a steroid dependent or frequently relapsing course and are therefore at increased risk for developing steroid toxicity. In such children, alternative immunosuppressive medications are used to induce and/or maintain remission of NS. One such drug, rituximab, is a monoclonal antibody directed against the B lymphocyte CD20 marker which induces depletion of B cells, and has shown promising results in the management of NS in children. In this review, we summarize recent studies on the efficacy and safety of rituximab in the different types of childhood nephrotic syndrome, the known and potential mechanisms of action of rituximab, its possible complications and side effects, and the available and potential biomarkers of rituximab activity.

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Section: Factors That May Affect the Clinical Response Of Rituximab Imentioning

confidence: 99%

Section: Biomarkers Of Response To Rituximabmentioning

confidence: 99%

Rituximab Use in the Management of Childhood Nephrotic Syndrome

2019

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“…15,16,28,42 Higher initial doses may not influence time for B cell reconstitution . 45,46 Though there were reports suggesting that a single dose of rituximab may be ineffective, 47 our observations suggest that additional doses of Rituximab spaced within 1 month of initial doses may not be necessary if there are no target B cells in circulation. Similar observations have been reported by others.…”

Section: Discussionmentioning

confidence: 66%

Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology

et al. 2020

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Background There is no consensus regarding dose and frequency of rituximab in Nephrology with extrapolation of dose used in treating lymphoproliferative disorders. There are no guidelines on targeting initial and subsequent doses based on CD19 + B cells. Methods 100 mg rituximab was given initially in 42 adults with steroid dependent (SDNS) and frequently relapsing nephrotic syndrome (FRNS), idiopathic membranous nephropathy (MN) and high immunologic risk kidney transplantation. Absolute and percentage CD19 B cells and clinical status were assessed at baseline, days 30, 90, 180 and 1 year. Subsequent doses of rituximab were based on CD19 B cell reconstitution and clinical response. Results CD19 B cell percentage decreased from 16.3+7.6 to 0.3±0.3 (P=<0.001), 1.9±1.7 (P=<0.001) and 4.0±4.5 (P=0.005) by 30, 90 and 180 days respectively. Suppression of CD 19 B cell count below 1% at day 30, 90 and 180 was 40/42 (95.2%), 18/42(42.9%) and 7/42(16.7%) respectively. Of 30 with SDNS and FRNS followed up for one year, 29(96.7%) went into remission at day 30. Remission was sustained in 23(76.6%) at day 180 and 21(70%) at 1 year. There was significant decrease [P <0.001] in the dose of steroids needed to maintain remission at 180 days following rituximab (0.27±0.02mg/Kg to 0.02±0.00mg/Kg). CD 19 B cell percentage at 90 days correlated with relapse (P=0.001, OR 1.422, 95% CI 1.246-2.574). Eighteen (60%) required an additional dose. Of five with MN, four achieved remission by 6 months which was sustained in three by 1 year. Of the 7 kidney transplant recipients, 2 had antibody mediated rejections though CD19 B cells were suppressed even at one year. Conclusions Low dose rituximab induces sustained depletion of CD19 B cells up to 90 days. Its role in preventing relapses in SDNS, FRNS, MN and rejection needs further studies.

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“…Currently, there is no consensus regarding the use of RTX with optimal initial and maintenance dose protocols. Although there is no strong evidence that lower doses increase the risk of earlier relapses or higher doses are more beneficial, the most preferred dose is 375 mg/m (29,30). In the present study, data were collected from 13 different centers retrospectively, with a dose of 375 mg/m 2 and different dose intervals (weekly or biweekly).…”

Section: Discussionmentioning

confidence: 98%

Rituximab treatment for difficult-to-treat nephrotic syndrome in children: a multicenter, retrospective study

et al. 2021

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Background/aim: This study aimed to evaluate the efficacy of rituximab in children with difficult-to-treat nephrotic syndrome, considering the type of disease (steroid-sensitive orresistant) and the dosing regimen. Materials and methods: This multicenter retrospective study enrolled children with difficultto-treat nephrotic syndrome on rituximab treatment from 13 centers. The patients were classified based on the steroid response and initial dose of rituximab as low (single dose of 375 mg/m 2) or high (2-4 doses of 375 mg/m 2). Clinical outcomes were compared. Results: Data from 42 children [20 steroid-sensitive (frequent relapsing / steroid-dependent) and 22 steroid-resistant nephrotic syndrome, aged 1.9-17.3 years] were analyzed. Eleven patients with steroid-sensitive nephrotic syndrome (55%) had a relapse following initial rituximab therapy, with the mean time to first relapse of 8.4±5.2 months. Complete remission was achieved in 41% and 36% of steroid-resistant patients, with the median remission time of 3.65 months. At Year 2, eight patients in steroid-sensitive group (40%) and four in steroidresistant group (18%) were drug-free. Total cumulative doses of rituximab were higher in steroid-resistant group (p=001). Relapse rates and time to first relapse in steroid-sensitive group or remission rates in steroid-resistant group did not differ between the low and high initial dose groups. Conclusions: The current study reveals that rituximab therapy may provide a lower relapse rate and prolonged relapse-free survival in the steroid-sensitive group, increased remission rates in the steroid-resistant group, and a significant number of drug-free patients in both groups. The optimal regimen for initial treatment and maintenance needs to be determined.

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Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome

Abstract: The initial dose of rituximab impacts time to B cell reconstitution and the probability of relapse. Risk of relapse is also associated with patient characteristics, suggesting that RTX regimen could be modified for each patient to balance efficacy, cost, and side effects.

Cited by 41 publications

References 34 publications

Rituximab Use in the Management of Childhood Nephrotic Syndrome

Rituximab Use in the Management of Childhood Nephrotic Syndrome

Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology

Rituximab treatment for difficult-to-treat nephrotic syndrome in children: a multicenter, retrospective study

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