Efficacy and safety of rituximab in childhood-onset, difficult-to-treat nephrotic syndrome: A multicenter open-label trial in Korea - PubMed (original) (raw)

Randomized Controlled Trial

. 2018 Nov;97(46):e13157.

doi: 10.1097/MD.0000000000013157.

Seong Heon Kim 2, Kyoung Hee Han 3, Hyun Jin Choi 4, Heeyeon Cho 5, Jung Won Lee 6, Jae Il Shin 7, Min Hyun Cho 8, Joo Hoon Lee 9, Young Seo Park 9, Il-Soo Ha 4, Hae Il Cheong 4, Su Young Kim 2, Seung Joo Lee 6, Hee Gyung Kang 4

Affiliations

Randomized Controlled Trial

Efficacy and safety of rituximab in childhood-onset, difficult-to-treat nephrotic syndrome: A multicenter open-label trial in Korea

Yo Han Ahn et al. Medicine (Baltimore). 2018 Nov.

Abstract

Background: The anti-CD20 monoclonal antibody rituximab (RTX) has been proposed as a rescue therapy for difficult-to-treat nephrotic syndrome (NS). We conducted a clinical trial to evaluate the efficacy and safety of RTX in children with difficult-to-treat NS dependent on or resistant to steroids and calcineurin inhibitors (CNIs).

Methods: A multicenter open-label trial was performed at 8 major pediatric nephrology centers in Korea. The investigation consisted of a randomized controlled trial for steroid- and CNI-dependent NS (DDNS; randomization into the RTX group and the control group, at a ratio of 2:1) and a single-arm study of steroid and CNI-resistant NS (DRNS). DDNS patients in the RTX group and DRNS patients received a single dose of intravenous RTX (375 mg/m of body surface area) for B-cell depletion. A second RTX dose was administered at week 2 if the first dose failed to achieve depletion of CD19(+) cells. The primary endpoint was rate of maintaining remission at 6 months after treatment for DDNS and rate of remission achievement for DRNS.

Results: Sixty-one children with DDNS were enrolled while in remission and randomized to the control group (21 patients) or the RTX group (40 patients). At 6 months after treatment, the remission rates were 74.3% in the RTX group and 31.3% in the control group (P = .003). The mean duration of remission maintenance was significantly higher in the RTX group than in the control group (9.0 vs 2.9 months, P = .004). Of the 23 patients with DRNS enrolled in the single-arm study and treated with RTX, 9 (39.1%) achieved partial or complete remission within 6 months. Depletion of B cells occurred in all patients with RTX therapy. Thirty patients (50.8% of 59 patients analyzed) experienced mild and transient infusion reaction during RTX administration, and most adverse events were mild.

Conclusions: RTX administration was safe and effective in patients with difficult-to-treat NS. One or 2 doses of RTX may be sufficient to deplete B cells and achieve better control of pediatric NS.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1

Figure 1

Study design. (A) Randomized controlled trial of drug-dependent nephrotic syndrome. (B) Single-arm study of drug-resistant nephrotic syndrome.

Figure 2

Figure 2

Flowchart of patient enrollment, evaluation, and follow-up. (A) Randomized controlled trial of drug-dependent nephrotic syndrome. (B) Single-arm study of drug-resistant nephrotic syndrome.

Figure 3

Figure 3

Survival analysis. (A) Kaplan–Meier analysis for relapse-free survival in the randomized controlled trial of drug-dependent nephrotic syndrome. (B) Cumulative remission rate in single-arm study of drug-resistant nephrotic syndrome.

Figure 4

Figure 4

CD19 B-cell counts after rituximab therapy. (A) Randomized controlled trial of drug-dependent nephrotic syndrome. (B) Single-arm study of drug-resistant nephrotic syndrome.

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