Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome

Abstract

ObjectiveRituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution.MethodsWe conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells.ResultsSixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1–4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups.ConclusionsUse of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose.Electronic supplementary materialThe online version of this article (10.1007/s00467-018-4172-3) contains supplementary material, which is available to authorized users.

Treatment response to cyclophosphamide, rituximab, and bortezomib in chronic immune-mediated sensorimotor neuropathies: a retrospective cohort study

“…Dosing of RTX is discussed frequently, and some studies show that lower dosing of RTX depending on CD19 depletion results in similar effectiveness with fewer side effects like infections. 30 – 32 …”

Rituximab Use in the Management of Childhood Nephrotic Syndrome

“…Four weekly doses of rituximab may improve the chances of response by compensating for the amount of medication lost in the urine in some children with NS (90). However, several studies have demonstrated no significant difference in the response rate in children between 1 and 2 doses vs. Three to Four doses (37, 91, 92). Takahashi reported on the efficacy of a single rituximab infusion given routinely, regardless of proteinuria, every 6 months for 2 years in children with SRNS.…”

“…In addition to variability in the number of rituximab doses administered, there have also been different rituximab doses used for the management of INS, with most studies have used 375 mg/m 2 (35, 55, 70, 94). 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).…”

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

“…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.…”