Efficacy of remission-induction regimens for ANCA-associated vasculitis.
Efficacy of remission-induction regimens for ANCA-associated vasculitis.
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DOI：
10.1056/nejmoa1213277
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发表时间：
2013-08-01
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通讯作者：
RAVE-ITN Research Group
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作者：
Specks U;Merkel PA;Seo P;Spiera R;Langford CA;Hoffman GS;Kallenberg CG;St Clair EW;Fessler BJ;Ding L;Viviano L;Tchao NK;Phippard DJ;Asare AL;Lim N;Ikle D;Jepson B;Brunetta P;Allen NB;Fervenza FC;Geetha D;Keogh K;Kissin EY;Monach PA;Peikert T;Stegeman C;Ytterberg SR;Mueller M;Sejismundo LP;Mieras K;Stone JH;RAVE-ITN Research Group
对于严重（威胁器官的）抗中性粒细胞胞浆抗体（ANCA）相关性血管炎患者，单疗程利妥昔单抗与传统免疫抑制（环磷酰胺随后硫唑嘌呤）相比的 18 个月疗效尚不清楚。在一项多中心、随机、双盲、双模拟、非劣效性试验中，我们比较了利妥昔单抗（每平方米体表面积 375 mg，每周一次，持续 4 周），随后与安慰剂联合环磷酰胺给药 3 至 6 个月，随后联合硫唑嘌呤给药 12 至 15 个月。主要结局指标是 6 个月时疾病完全缓解，且缓解持续 18 个月。共有 197 名患者入组。正如之前报道的，利妥昔单抗组中有 64% 的患者在 6 个月内完全缓解，而环磷酰胺-硫唑嘌呤组中有 53% 的患者得到完全缓解。在 12 个月和 18 个月时，利妥昔单抗组中分别有 48% 和 39% 的患者保持完全缓解，而对照组分别为 39% 和 33%。利妥昔单抗满足预先指定的非劣效性标准（P<0.001，非劣效性界限为 20%）。各组之间在任何疗效指标上均无显着差异，包括完全缓解的持续时间以及复发的频率或严重程度。在 101 名基线时患有疾病复发的患者中，利妥昔单抗在 6 个月 (P = 0.01) 和 12 个月 (P = 0.009) 时优于传统免疫抑制，但在 18 个月 (P = 0.06) 时则不然，此时利妥昔单抗组中的大多数患者已重建 B 细胞。不良事件的组间差异无显着性。在患有严重 ANCA 相关血管炎的患者中，单疗程利妥昔单抗与连续常规免疫抑制治疗在 18 个月的疗程中诱导和维持缓解一样有效。 （由国家过敏和传染病研究所等资助；RAVE ClinicalTrials.gov 编号，NCT00104299。）
The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is unknown. In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months. A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide–azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P = 0.01) and at 12 months (P = 0.009) but not at 18 months (P = 0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, NCT00104299.)