Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial

Abstract

Mycophenolate mofetil (MMF) has emerged as a new therapeutic option in steroid-dependent nephrotic syndrome (SDNS). We conducted a phase II Bayesian trial of MMF in children with SDNS. Phase II trials, usually single-arm studies, investigate the effect of new treatments. Standard Fleming's procedure relies on observed results (relapse rate during the trial), whereas Bayesian approach combines observed results with prior information (expected relapse rate according to prior studies and clinical experience). All patients were required to have received prior alkylating-agent treatment. Sixty-seven percent of them had also received levamisole. Patients received MMF (1,200 mg/m(2)/day) and prednisone according to a defined schedule [reduction of alternate-day (e.o.d) dose to 50% of pre-MMF dose at 3 months, 25% at 6 months]. Twenty-four children (median age 6.0 years, 2.8-14.4) entered the study and 23 completed it. Bayesian analysis showed that adding four patients would not change significance of results, allowing stopping inclusions. Four patients relapsed during the first 6 months (estimated probability 17.6%, 95% credibility interval: 5.4-35.0%) and two at months 8 and 11.5. In the 19 patients free of relapse during the first 6 months, median (Q1-Q3) prednisone maintenance dose decreased from 25 (10-44) to 9 (7.5-11.2) mg/m(2) e.o.d (p < 0.001) and cumulative dose from 459 (382-689) to 264 (196-306) mg/m(2)/month (p < 0.001) before and on MMF respectively. Pre-MMF patient characteristics and MMF pharmacokinetics did not differ between patients with or without relapse. MMF reduces relapse rate and steroid dose in children with SDNS and should be proposed before cyclosporine and cyclophosphamide.

Clinical practice guideline for pediatric idiopathic nephrotic syndrome 2013: medical therapy

“…Mycophenolate mofetil is well tolerated compared with other immunosuppressive agents, and its efficacy as a first-line treatment for frequently-relapsing and steroid-dependent nephrotic syndrome has been suggested [103][104][105]. The guideline by the Children's Nephrotic Syndrome Consensus Conference (CNSCC) (US) and the KDIGO guideline describe a 1-year administration of mycophenolate mofetil as an option for immunosuppressive therapy in patients with frequentlyrelapsing and steroid-dependent nephrotic syndrome.…”

“…Reported side effects of mycophenolate mofetil include gastrointestinal symptoms (diarrhea, abdominal pain) [92-95, 97, 103, 105], myelosuppression (leukocytopenia, anemia, thrombocytopenia) [93,100,105], and infection (herpes, varicella) [93, 100, 104] but can generally be reversed with dose reduction.…”

Mycophenolate Mofetil versus Cyclosporin A in Children with Frequently Relapsing Nephrotic Syndrome

“…Several small studies with limited statistical power have shown that MMF has steroid-sparing effects and reduces relapse rates in patients with FR-SSNS, albeit with varying efficacy. [11][12][13][14][15][16][17][18] We studied efficacy and safety of MMF in patients with FR-SSNS in comparison with CsA in a prospective randomized multicenter open-label crossover trial.…”

Mycophenolate-Associated Alopecia in an Adolescent Girl Mycophenolate and Alopecia

“…Although they have benefi cial effects, CsA has a signifi cant risk of nephrotoxicity along with cosmetic effects and CsA-dependency, while CYC may cause gonadotoxicity and malignancy (13). Recently, MMF has emerged as an immunosuppressive agent devoid of nephrotoxicity and gonadal toxicity, which is benefi cial in managing children with FRNS (3,4,9), SRNS (1,2,13,14), SDNS (5,7,12,15) and CsADNS (6,7). However, it has compromising side effects including GI disturbances, anemia, leukopenia, predisposition to infection and malignancies, which may lead to dose reduction or even medication withdrawal (2,5).…”