Efficacy of body weight vs body surface area-based prednisolone regimen in nephrotic syndrome.

BACKGROUND: Prednisolone dosing regimen based on body surface area (BSA) or body weight (BW) in managing uncomplicated nephrotic syndrome (NS) has been a matter of controversy. METHODS: In this parallel-arm randomized clinical trial, 60 children with uncomplicated NS in relapse were randomized to receive either of two regimens. Children of BW cohort received prednisolone (2 mg/kg/day) till remission (or 6 weeks for first episode); followed by 1.5 mg/kg on alternate days for 4 weeks (or 6 weeks for first episode). Children randomized for BSA cohort received prednisolone (60 mg/m2/day) till remission (or 6 week for first episode); followed by 40 mg/m2 on alternate days for 4 weeks (or 6 weeks for first episode). The primary endpoint was 6-month relapse-free survival in the intention-to-treat population (clinical trial registry of India CTRI/2015/03/005655). RESULTS: The 6-month relapse-free survival rates were similar for both BSA cohort 73.33% (22/30) and BW cohort 70% (21/30) (p = 1, OR 0.19, 95% CI 0.07-0.52). Requirement of cumulative steroid to achieve initial remission (96.1 ± 57.8 vs 63.58 ± 40.2 mg/kg, p = 0.014) and over 6-month study period (104.34 ± 50.82 vs 73.88 ± 42.95 mg/kg, p = 0.015) were significantly higher in BSA cohort in comparison to BW cohort. However, time taken in achieving remission during enrolment episode in both BSA and BW groups was comparable (7 ± 1.7 vs 6.9 ± 1.4 days, p = 0.81). While both treatments were well tolerated, the number of adverse events was one and half times as common in the BSA group than BW group (37 vs. 22 events). CONCLUSIONS: In treating children with uncomplicated NS, both BSA and BW regimens were equally effective in achieving initial remission and maintaining disease remission. Due to fewer adverse events and lesser cumulative steroid exposure with BW based regimen, it may be considered as better option over BSA regimen. CLINICAL TRIAL REGISTRY NAME: Clinical Trial Registry of India (CTRI/2015/03/005655).

Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome: A Randomized Clinical Trial.

Importance: Calcineurin inhibitors are an established first-line corticosteroid-sparing therapy for patients with corticosteroid-dependent nephrotic syndrome (CDNS), whereas B-lymphocyte-depleting therapy is mostly used as a rescue for calcineurin inhibitor-resistant cases. The positive efficacy and safety profile of rituximab raises the question of whether it could be used as a first-line alternative to calcineurin inhibitor therapy. Objective: To compare the efficacy of rituximab and tacrolimus in maintaining relapse-free survival among children with CDNS. Design, Setting, and Participants: A parallel-arm, open-label, randomized clinical trial was performed from May 8, 2015, to September 20, 2016, with 1-year follow-up in a single-center, tertiary care unit. A total of 176 consecutive children aged 3 to 16 years with CDNS not previously treated with corticosteroid-sparing agents were screened for eligibility. Interventions: The children received either tacrolimus (along with tapering alternate-day prednisolone) for 12 months or a single course of rituximab (2 infusions of 375 mg/m2). Main Outcomes and Measures: Twelve-month relapse-free survival in the intention-to-treat population. Results: Of the 176 children screened for eligibility, 120 were randomized and all but 3 patients completed 1 year of follow-up. The groups were comparable, with mean (SD) age of 7.2 (2.8) years, 32 boys (53.3%) in each group, mean (SD) disease duration of 2.5 (1.5) years and 2.3 (1.7) in the tacrolimus and rituximab groups, respectively, disease duration less than 1 year among 15 children (25.0%) in each group, median (interquartile range) of 4 (3-5) relapses in each group, and mean (SD) cumulative prednisolone dose of 246 (48) mg/kg and 239 (52) mg/kg in the prestudy year in the tacrolimus and rituximab groups, respectively. Rituximab therapy was associated with a higher 12-month relapse-free survival rate than tacrolimus (54 [90.0%] vs 38 [63.3%] children; P < .001; odds ratio, 5.21; 95% CI, 1.93-14.07). Among the patients who experienced relapse, median time to first relapse was 40 weeks in the rituximab group and 29 weeks in the tacrolimus group. Only 2 patients in the rituximab group had more than 1 relapse during the study period compared with 10 patients in the tacrolimus group. The cumulative corticosteroid dose during the 12-month study period was lower with rituximab compared with tacrolimus (mean [SD], 25.8 [27.8] vs 86.3 [58.0] mg/kg). Although both treatments were well tolerated, mild to moderate infections were twice as common in the tacrolimus group (26 [43.3%] vs 13 [21.7%] events). Conclusions and Relevance: In children with CDNS, rituximab appears to be more effective than tacrolimus in maintaining disease remission and minimizing corticosteroid exposure and, given its good tolerability and lack of nephrotoxic effects, may be considered as first-line corticosteroid-sparing therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02438982; Clinical Trial Registry of India: CTRI/2014/01/004355.