A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome

Abstract

Results. The primary analysis was conducted on 99 mizori-A multicenter trial of mizoribine compared with placebo in bine-and 98 placebo-treated patients. The relapse rate was children with frequently relapsing nephrotic syndrome.lower in the mizoribine group than in the placebo group (0.0055 Background. The use of corticosteroids or cytotoxic/immuvs. 0.0067; ratio 0.81, 95% CI, 0.61 to 1.05, P ϭ 0.12). The nosuppressive agents such as cyclophosphamide, chlorambucil, hazard ratio of the cumulative remission rate between the two and cyclosporine for the treatment of frequently relapsing negroups was 0.79 (95% CI, 0.57 to 1.08). In the subgroups conphrotic syndrome (FRNS) is limited because of their adverse sisting of patients 10 years old or younger, the relapse rate effects. This study was conducted to evaluate the efficacy and ratio between the mizoribine subgroup (54 patients) and the safety of mizoribine, a relatively new immunosuppressive drug placebo subgroup (57 patients) was 0.66 (95% CI, 0.44 to 0.94, developed in Japan, in children with FRNS.P ϭ 0.017). The hazard ratio of the cumulative remission rate Methods. A double-blind, placebo-controlled, multicenter between the two subgroups was 0.56 (95% CI, 0.37 to 0.85, trial was carried out in children, from 2 to 19 years old, with P ϭ 0.007). Hyperuricemia was the most common adverse FRNS. At relapse, patients were treated with prednisolone. event with mizoribine (16%), but was transient. According to a dynamic allocation, mizoribine or a placebo Conclusions. Compared with the placebo, mizoribine significantly decreased the relapse rate and prolonged the remission was concurrently administered to each patient. Prednisolone period in the subgroup consisting of patients 10 years old or was gradually tapered and discontinued within 12 weeks. The younger. This drug may be useful in young children with FRNS test drug was maintained for 48 weeks. The primary end point who generally relapse more frequently than older children. was the relapse rate (the total number of relapses/the total treatment days for all patients). Analyses were performed according to the intention-to-treat principle.

Two-Year Follow-Up of a Prospective Clinical Trial of Cyclosporine for Frequently Relapsing Nephrotic Syndrome in Children

“…To note, however, four of five children who were excluded from analysis due to relapse during tapering were steroid dependent; inclusion of these children would have strengthened the association between steroid dependency and risk. In six patients (three each in group A and B), mizoribine, an agent in the same antimetabolite class as mycophenolate mofetil whose efficacy is mild and limited to patients aged #10 years (21), was administered during follow-up to prevent regression to FRNS (data not shown). On inclusion in Poisson analyses, administration of mizoribine was positively associated with relapse.…”

“…First, although protocols for the administration of immunosuppressants and prednisolone after treatment with cyclosporine were provided, treatment was at the discretion of the physician in charge. Immunosuppressants were occasionally started before criteria for the diagnosis of FRNS or SDNS had been met, and mizoribine to prevent relapse was sometimes started very early, even before the first relapse, owing to its low incidence of adverse events (21). Second, several data points were missing, including some measurements of height and serum creatinine, particularly among stable children.…”

Population Pharmacokinetics of Higher-Dose Mizoribine in Healthy Male Volunteers

“…1,15,16) However, the relationship between the therapeutic effect and serum concentration of mizoribine is unclear, and the optimal dose of the drug for autoimmune diseases as well as organ transplantation is still unkown. 15) Because the serum mizoribine concentration can be easily measured by an HPLC method, monitoring the serum mizoribine concentration in the patients may be useful to assess the relationship between the drug exposure (AUC and/or C max ) and response.…”

Mycophenolate Mofetil in Children with Frequently Relapsing Nephrotic Syndrome

“…Preliminary data from a series of pediatric (1)(2)(3)(4)(5)(6)(7)(8) and adult (9 -11) studies suggest that mycophenolate mofetil (MMF) may represent a less toxic alternative for patients with FRNS. Other recent studies have reported that mizoribine (12)(13)(14)(15)(16)(17) or levamisole (18) also may be options to consider in such patients.…”