Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes

Chan, Eugene Yu-hin; Webb, Hazel; Yu, Eden S. H.; Ghiggeri, Gian Marco; Kemper, Markus J.; Lap-tak, Alison; Yamamura, Takehira; Sinha, Aditi; Bagga, Arvind; Hogan, Julien; Dossier, Claire; Vivarelli, Marina; Liu, Isaac Desheng; Kamei, Koichi; Ishikura, Kenji; Saini, Priya; Tullus, Kjell

doi:10.1016/j.kint.2019.09.033

Cited by 79 publications

(75 citation statements)

References 37 publications

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“…The most interesting finding of this trial is reflected by long-term remission of 8/15 patients after 4 years of single rituximab application. This number is distinctly higher than that reported in children with multidrug dependence [12] and challenges the finding in Japanese patients, who experienced a high rate of relapses within the first year after a single dose of rituximab [13]. Another trial from the same group compared a rituximab biosimilar versus low-dose MMF in children with SDNS [14].…”

contrasting

confidence: 57%

Commentary on “Pediatric Idiopathic Steroid-sensitive Nephrotic Syndrome Diagnosis and Therapy - Short version of the updated German Best Practice Guideline (S2e)”

et al. 2021

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contrasting

confidence: 57%

Commentary on “Pediatric Idiopathic Steroid-sensitive Nephrotic Syndrome Diagnosis and Therapy - Short version of the updated German Best Practice Guideline (S2e)”

et al. 2021

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“…The long term follow up of our RITURNS trial also revealed better relapse free survival with maintenance MMF therapy following rituximab induction, with a relatively benign side effect profile [14]. A recent retrospective multicenter study revealed that children receiving low-dose rituximab without maintenance immunosuppression had the shortest relapse-free survival, and both the cumulative rituximab dose and maintenance immunosuppression had important effects on treatment outcomes [29].…”

Section: Discussionmentioning

confidence: 97%

Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome

et al. 2020

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Background Approximately 30% of children with idiopathic nephrotic syndrome develop a complicated course with frequent relapses or steroid dependency. Rituximab, a B cell depleting monoclonal antibody, is a safe and effective alternative to steroids or other immunosuppressants for achieving and maintaining remission in this population at short term. Despite the good initial response relapses inevitably occur after regeneration of B lymphocytes, necessitating either repeat courses of rituximab or addition of another steroid-sparing immunosuppressant. Methods This is a prospective, single-center, open-label, two-parallel-arm randomized controlled phase III study among children with steroid dependent nephrotic syndrome who are maintained in remission with oral steroids. One hundred children will be randomized to either Rituximab and maintenance Mycophenolate mofetil (A) or repeated courses of prophylactic Rituximab only (B). In arm A, mycophenolate mofetil (1200 mg/m2 per day) will be started 3 months after Rituximab administration. In arm B, Rituximab infusions will be administered at 0, 8 and 16 months if B cell count normalize at the given time points. Prednisolone will be discontinued in both groups 2 weeks following first course of rituximab. Primary aim is to evaluate the difference in 24-month relapse-free survival. Main secondary endpoints are cumulative prednisolone dose, frequency of relapses and changes in anthropometry. Circulating B lymphocyte populations will be studied as biomarkers or predictors of rituximab responsiveness and adverse events will be analysed. Discussion The study will provide evidence as to the comparative safety and efficacy of two alternative steroid-sparing therapeutic options in children suffering from steroid dependent nephrotic syndrome. The two-year study design will address the long-term results obtained with the alternative treatment protocols. Trial registration This trial was prospectively registered to the Clinicaltrial.gov (NCT03899103 dated 02/04/2019; https://clinicaltrials.gov/) and Clinical Trials Registry of India (CTRI/2019/04/018517 dated 09/04/2019).

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“…In a recently published multicenter large cohort evaluating 511 children with complicated SDNS or FRNS, low (375 mg/m2), medium (750 mg/m 2 ), and high (1125-1500 mg/m 2 ) doses of RTX were compared with or without maintenance immunosuppression. The authors concluded that children who received low-dose RTX without maintenance immunosuppression had the shortest relapse-free survival (23).…”

Section: Discussionmentioning

confidence: 99%

“…Since RTX was first used in idiopathic NS, many different protocols (including single dose, 2 doses and 4 doses) and different dosing practices (such as 100 mg/m 2 , 375 mg/m 2 , 750 mg/m 2 , 1500 mg/m 2 ) have been reported (23). This heterogeneity leads to difficulties in assessing the ability of different regimens.…”

Section: Discussionmentioning

confidence: 99%

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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Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes

Cited by 79 publications

References 37 publications

Commentary on “Pediatric Idiopathic Steroid-sensitive Nephrotic Syndrome Diagnosis and Therapy - Short version of the updated German Best Practice Guideline (S2e)”

Commentary on “Pediatric Idiopathic Steroid-sensitive Nephrotic Syndrome Diagnosis and Therapy - Short version of the updated German Best Practice Guideline (S2e)”

Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome

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

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