Toshiyuki Takahashi1, Takayuki Okamoto2, Yasuyuki Sato1, Takeshi Yamazaki1, Asako Hayashi1, Hayato Aoyagi3, Michihiko Ueno4, Norio Kobayashi5, Kimiaki Uetake6, Masanori Nakanishi7, Tadashi Ariga1. 1. Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo, Hokkaido, 060-8638, Japan. 2. Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo, Hokkaido, 060-8638, Japan. okamon@med.hokudai.ac.jp. 3. Department of Pediatrics, Obihiro Kyokai Hospital, Obihiro, Japan. 4. Department of Pediatrics, Nikko Memorial Hospital, Muroran, Japan. 5. Department of Pediatrics, Oji General Hospital, Tomakomai, Japan. 6. Department of Pediatrics, Obihiro Kosei Hospital, Obihiro, Japan. 7. Department of Pediatrics, Kushiro Red Cross Hospital, Kushiro, Japan.
Abstract
BACKGROUND: Rituximab (RTX) is effective in maintaining remission in patients with nephrotic syndrome (NS), but a standard protocol of RTX administration has not been established. METHODS: This study was a 2-year multicenter observational study, in which consistent treatments and evaluations were performed. We enrolled pediatric patients with refractory NS between January 2015 and December 2015. RTX infusion was performed four times at 6-month intervals, followed by mizoribine pulse therapy with early discontinuation of calcineurin inhibitor (CNI). Primary endpoints were the relapse-free survival rate and the number of relapses after RTX administration. Secondary endpoints were changes in side effects associated with long-term steroid administration. RESULTS: Twenty-two patients were analyzed. The relapse-free survival rate at 1 year and 2 years was 50 and 46%, respectively. Twenty-one patients accomplished our protocol and the frequency of relapse was reduced under the discontinuation of CNI. Although two patients were diagnosed with frequent relapse and/or steroid dependency during the observation period, the frequency of relapse decreased with each rituximab dose. Statistically significant improvements in all steroid complications were observed in the final examination, but no significant improvements were observed from 1 to 2 years after RTX administration. One patient had agranulocytosis, and three patients showed electrocardiographic abnormalities. CONCLUSIONS: Our protocol was useful and safe for refractory NS. However, RTX administration four times might have been excessive in patients who had no relapse by 1 year after the initial RTX administration. Further investigation of the most appropriate method of RTX administration is required.
BACKGROUND: Rituximab (RTX) is effective in maintaining remission in patients with nephrotic syndrome (NS), but a standard protocol of RTX administration has not been established. METHODS: This study was a 2-year multicenter observational study, in which consistent treatments and evaluations were performed. We enrolled pediatric patients with refractory NS between January 2015 and December 2015. RTX infusion was performed four times at 6-month intervals, followed by mizoribine pulse therapy with early discontinuation of calcineurin inhibitor (CNI). Primary endpoints were the relapse-free survival rate and the number of relapses after RTX administration. Secondary endpoints were changes in side effects associated with long-term steroid administration. RESULTS: Twenty-two patients were analyzed. The relapse-free survival rate at 1 year and 2 years was 50 and 46%, respectively. Twenty-one patients accomplished our protocol and the frequency of relapse was reduced under the discontinuation of CNI. Although two patients were diagnosed with frequent relapse and/or steroid dependency during the observation period, the frequency of relapse decreased with each rituximab dose. Statistically significant improvements in all steroid complications were observed in the final examination, but no significant improvements were observed from 1 to 2 years after RTX administration. One patient had agranulocytosis, and three patients showed electrocardiographic abnormalities. CONCLUSIONS: Our protocol was useful and safe for refractory NS. However, RTX administration four times might have been excessive in patients who had no relapse by 1 year after the initial RTX administration. Further investigation of the most appropriate method of RTX administration is required.
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