Comparative assessment of the efficacy and safety of mycophenolate mofetil versus cyclosporine A in children with steroid dependent nephrotic syndrome

Objectives: Rituximab (RTX), a possible alternative treatment option, is recognized as a new therapeutic hope for the treatment of steroid-dependent nephrotic syndrome (SDNS) in children. However, the efficacy and safety of RTX in the treatment of childhood SDNS are still controversial. The objective of this study was to evaluate the efficacy and safety of RTX treatment in children with SDNS.Study Design: Six randomized controlled trials (RCTs) and one retrospective comparative control study data from studies, performed before January 2021 were collected, from PubMed, Cochrane Library, Embase, and Web of Science. The studies evaluating the efficacy and safety of RTX in childhood SDNS were included.Results: Six RCTs and one retrospective comparative control study were included in our analysis. Compared with the control group, the RTX treatment group achieved a higher complete remission rate (OR = 5.21; 95% CI, 3.18–8.54; p < 0.00001), and we found significant differences between the two groups on serum albumin level (MD = 0.88; 95% CI, 0.43–1.33; p = 0.0001) and estimated glomerular filtration rate (MD = 6.43; 95% CI, 2.68–10.19; p = 0.0008). However, RTX treatment did not significantly lower serum creatinine levels nor did it significantly reduce the occurrence of proteinuria. In addition, we found no advantages with RTX on treatment safety.Conclusions: RTX has shown satisfactory characteristics in terms of efficacy and may be a promising treatment method for SDNS in children. However, the long-term effects have not been fully evaluated and should be further studied through randomized clinical trials.

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Mycophenolate Mofetil after Rituximab for Childhood-onset Complicated Frequently-relapsing or Steroid-dependent Nephrotic Syndrome

Journal of the American Society of Nephrology ◽

10.1681/asn.2021050643 ◽

2021 ◽

pp. ASN.2021050643

Author(s):

Kazumoto Iijima ◽

Mayumi Sako ◽

Mari Oba ◽

Seiji Tanaka ◽

Riku Hamada ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Mycophenolate Mofetil ◽

Treatment Failure ◽

Treatment Period ◽

Immunosuppressive Agents ◽

Steroid Resistance ◽

Rank Test ◽

Childhood Onset ◽

Steroid Dependent ◽

Steroid Dependent Nephrotic Syndrome

Background. Rituximab is the standard therapy for childhood-onset complicated frequently-relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS following peripheral B cell recovery. Methods. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). Thirty-nine patients (per group) were treated with rituximab, followed by either MMF or placebo until Day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until Day 505 for the last enrolled patient). Results. TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median: 784.0 vs. 472.5 days, hazard ratio (HR): 0.593, 95% confidence interval (CI): 0.336-1.049, log-rank test: P=0.0694). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR: 0.202, 95% CI: 0.081-0.503). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups. Conclusions. Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.

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