Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.
Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.
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DOI：
10.1056/nejmoa0906393
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发表时间：
2010-08-05
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影响因子：
--
通讯作者：
Fan WT
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作者：
Cicardi M;Banerji A;Bracho F;Malbrán A;Rosenkranz B;Riedl M;Bork K;Lumry W;Aberer W;Bier H;Bas M;Greve J;Hoffmann TK;Farkas H;Reshef A;Ritchie B;Yang W;Grabbe J;Kivity S;Kreuz W;Levy RJ;Luger T;Obtulowicz K;Schmid-Grendelmeier P;Bull C;Sitkauskiene B;Smith WB;Toubi E;Werner S;Anné S;Björkander J;Bouillet L;Cillari E;Hurewitz D;Jacobson KW;Katelaris CH;Maurer M;Merk H;Bernstein JA;Feighery C;Floccard B;Gleich G;Hébert J;Kaatz M;Keith P;Kirkpatrick CH;Langton D;Martin L;Pichler C;Resnick D;Wombolt D;Fernández Romero DS;Zanichelli A;Arcoleo F;Knolle J;Kravec I;Dong L;Zimmermann J;Rosen K;Fan WT
遗传性血管性水肿的特征是皮肤、喉和胃肠道血管性水肿的反复发作。缓激肽是症状的关键介质。Icatibant是一种选择性缓激肽B2受体拮抗剂。在两项双盲、随机、多中心试验中，我们评估了艾替班特对表现为皮肤或腹部发作的遗传性血管性水肿患者的疗效。在血管性水肿皮下治疗（FAST）1试验中，患者接受艾替班特或安慰剂;在FAST-2中，患者接受艾替班特或口服氨甲环酸，剂量为3 g/天，持续2天。艾替班特皮下给药一次，剂量为30 mg。主要终点是症状临床显著缓解的中位时间。在FAST-1和FAST-2试验中，分别有56例和74例患者接受了随机化。在FAST-1试验中，达到主要终点的时间为2.5小时，而安慰剂为4.6小时（P = 0.14）;在FAST-2试验中，达到主要终点的时间为2.0小时，而氨甲环酸为12.0小时（P<0.001）。在FAST-1研究中，3名接受艾替班特治疗的患者和13名接受安慰剂治疗的患者需要接受急救药物治疗。在两项试验中，患者和研究者评估的至症状首次改善的中位时间均显著缩短。未报告与艾替班相关的严重不良事件。在遗传性血管性水肿急性发作的患者中，我们发现在一项试验中，与氨甲环酸相比，艾替班特具有显著获益，而在另一项试验中，与安慰剂相比，艾替班特在主要终点方面无显著获益。早期使用补救药物可能掩盖了安慰剂试验中艾替班特的获益。（由Jerini资助; ClinicalTrials.gov编号，NCT 00097695和NCT 00500656。
Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P = 0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)