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 (375mg/m2 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.
Bibliographical noteFunding Information:
This research was supported by a grant (11172MFDS298) from Ministry of Food and Drug Safety in 2011-2012. The authors have no conflicts of interest to disclose. Supplemental Digital Content is available for this article. aDepartment of Pediatrics, Seoul National University Bundang Hospital, Seongnam, bDepartment of Pediatrics, Pusan National University Children’s Hospital, Yangsan, cDepartment of Pediatrics, Jeju National University School of Medicine, Jeju, dDepartment of Pediatrics, Seoul National University Children’s Hospital, Seoul, eDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, fDepartment of Pediatrics, Ewha Womans University School of Medicine, Seoul, gDepartment of Pediatrics, Yonsei University College of Medicine, Severance Children’s Hospital, Seoul, hDepartment of Pediatrics, Kyungpook National University, School of Medicine, Daegu, iDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea. ∗Correspondence: Hee Gyung Kang, Department of Pediatrics, Seoul National University College of Medicine and Seoul National University Children’s Hospital, 101 Deahangno, Jongno-gu, Seoul, 03080, Korea (e-mail: email@example.com).
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