<p>Rituximab maintains remission of complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS) by depleting peripheral B cells, but most patients eventually experience relapses after B cell recovery. We performed a multicenter, double-blind, randomized, placebo-controlled trial to assess rituximab’s efficacy and safety for childhood-onset uncomplicated FRNS/SDNS (without prior treatment with glucocorticoid-sparing immunosuppressive agents) with a follow-up study to assess rituximab’s long-term effect after B cell recovery. Patients were randomly assigned to receive either rituximab (375&#xa0;mg/m<sup>2</sup>, maximum 500&#xa0;mg, once weekly for 2&#xa0;weeks) or placebo. The primary endpoint was the relapse-free period. Of 43 randomized patients, 40 received the intervention (18 rituximab, 22 placebo). The relapse-free period during the 1-year trial was significantly longer in the rituximab vs. placebo groups (median: 285 vs. 81&#xa0;days; <i>p</i> &lt; 0.001). Infusion reactions were more frequent in the rituximab group (<i>p</i> &lt; 0.001), with no difference in adverse events incidence between the groups. Interestingly, the follow-up study demonstrated markedly higher 3-year cumulative relapse-free survival probability without further treatments in the rituximab vs. placebo groups (38% vs. 9%). A mini-systematic review with meta-analyses supported the findings. Rituximab is effective and well-tolerated, potentially leading to long-term remission with substantially high rates after B cell recovery for childhood-onset uncomplicated FRNS/SDNS.</p><p><i>Trial registration</i> JSKDC10, Clinical Trials Registry ID: jRCT1091220380; JSKDC10 follow-up study, Clinical Trials Registry ID: jRCT1050230024</p>

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Rituximab-induced long-term remission in childhood-onset, uncomplicated, frequently relapsing or steroid-dependent nephrotic syndrome: a randomized, placebo-controlled trial and a follow-up study

  • Kazumoto Iijima,
  • Mayumi Sako,
  • Tomoko Horinouchi,
  • Tomoyuki Sakai,
  • Tomohiko Yamamura,
  • Riku Hamada,
  • Yasufumi Ohtsuka,
  • Seiji Tanaka,
  • Koichi Kamei,
  • Ryojiro Tanaka,
  • Yuji Kano,
  • Takuo Kubota,
  • Yuko Shima,
  • Tamaki Morohashi,
  • Aya Inaba,
  • Shuichiro Fujinaga,
  • Masafumi Oka,
  • Hiroshi Kaito,
  • Akihide Konishi,
  • China Nagano,
  • Koichi Nakanishi,
  • Kenji Ishikura,
  • Shuichi Ito,
  • Hidefumi Nakamura,
  • Gian Marco Ghiggeri,
  • Rintaro Mori,
  • Takashi Omori,
  • Kandai Nozu,
  • Nana Sakakibara,
  • Atsushi Kondo,
  • Hideaki Kitakado,
  • Chika Ueda,
  • Toshihiro Sawai,
  • Kazuna Yamamoto,
  • Satoko Ichioka,
  • Toshiki Masuda,
  • Hiroshi Hataya,
  • Ryoko Harada,
  • Chikako Terano,
  • Naoaki Mikami,
  • Tomohiro Inoguchi,
  • Kouki Tomari,
  • Keiji Akamine,
  • Shoichiro Shirane,
  • Taishi Nada,
  • Toru Kanamori,
  • Chikako Kamae,
  • Yosuke Inaguma,
  • Yuhi Takagi,
  • Toru Uchimura,
  • Kandai Nozu,
  • Mayumi Sako,
  • Motoshi Hattori,
  • Nao Tsuchida,
  • Mari Oba

摘要

Rituximab maintains remission of complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS) by depleting peripheral B cells, but most patients eventually experience relapses after B cell recovery. We performed a multicenter, double-blind, randomized, placebo-controlled trial to assess rituximab’s efficacy and safety for childhood-onset uncomplicated FRNS/SDNS (without prior treatment with glucocorticoid-sparing immunosuppressive agents) with a follow-up study to assess rituximab’s long-term effect after B cell recovery. Patients were randomly assigned to receive either rituximab (375 mg/m2, maximum 500 mg, once weekly for 2 weeks) or placebo. The primary endpoint was the relapse-free period. Of 43 randomized patients, 40 received the intervention (18 rituximab, 22 placebo). The relapse-free period during the 1-year trial was significantly longer in the rituximab vs. placebo groups (median: 285 vs. 81 days; p < 0.001). Infusion reactions were more frequent in the rituximab group (p < 0.001), with no difference in adverse events incidence between the groups. Interestingly, the follow-up study demonstrated markedly higher 3-year cumulative relapse-free survival probability without further treatments in the rituximab vs. placebo groups (38% vs. 9%). A mini-systematic review with meta-analyses supported the findings. Rituximab is effective and well-tolerated, potentially leading to long-term remission with substantially high rates after B cell recovery for childhood-onset uncomplicated FRNS/SDNS.

Trial registration JSKDC10, Clinical Trials Registry ID: jRCT1091220380; JSKDC10 follow-up study, Clinical Trials Registry ID: jRCT1050230024