Rituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery.

We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient).

TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P=0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups.

Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.

利妥昔单抗是儿童期发病并发频繁复发或类固醇依赖性肾病综合征 (FRNS/SDNS) 的标准疗法。然而，大多数患者在外周 B 细胞恢复后再次出现 FRNS/SDNS。

我们进行了一项多中心、随机、双盲、安慰剂对照试验，以检验利妥昔单抗后给予吗替麦考酚酯 (MMF) 是否可以预防治疗失败（FRNS、SDNS、类固醇耐药或使用免疫抑制剂或利妥昔单抗）。总共有 39 名患者（每组）接受利妥昔单抗治疗，随后接受 MMF 或安慰剂治疗，直至第 505 天（治疗期）。主要结果是整个治疗和随访期间的治疗失败时间 (TTF)（直到最后一名入组患者的第 505 天）。

与接受利妥昔单抗单药治疗的患者相比，利妥昔单抗后给予 MMF 的患者的 TTF 在临床上但无统计学意义（中位数，784.0 与 472.5 天，风险比 [HR]，0.59；95% 置信区间 [95% CI]，0.34 至 1.05，对数秩检验：P =0.07）。由于 MMF 组中的大多数患者在停用 MMF 后出现治疗失败，我们进行了事后分析分析仅限于治疗期，发现利妥昔单抗后的 MMF 延长了 TTF 并将治疗失败的风险降低了 80%（HR，0.20；95% CI，0.08 至 0.50）。此外，利妥昔单抗后的 MMF 使治疗期间的复发率和每日类固醇剂量分别降低了 74% 和 57%。两组不良事件的发生频率和严重程度相似。

利妥昔单抗后给予 MMF 可充分预防治疗失败的发生并且耐受性良好，尽管 MMF 停药后预防复发的作用消失。