The Pennsylvania State University College of Medicine, Penn State University, 500 University Drive, Hershey, PA 17033, USA.
Allergy, Asthma & Immunology, the Pennsylvania State University, College of Medicine, Department of Medicine and Pediatrics, 500 University Drive, Hershey, PA 17033, USA.
Immunotherapy. 2019 Aug;11(11):937-944. doi: 10.2217/imt-2018-0197. Epub 2019 Jun 25.
Hereditary angioedema with C1 esterase inhibitor deficiency is a rare disorder characterized by unpredictable swelling of the face, larynx and gastrointestinal tract. Kallikreins are serine proteases that cleave kininogens to produce bradykinin leading to inflammation. A new prophylactic drug is lanadelumab (DX-2930, SHP-643), a recombinant, fully human IgG1 monoclonal antibody kallikrein inhibitor. Pharmacokinetics show a half-life of 14 days with a dose-dependent effect. Completed trials for lanadelumab include two Phase III studies with updated efficacy in preventing angioedema in hereditary angioedema patients. Ongoing data show the safety of the targeted therapy along with less frequent administration requirements. Information on long-term safety is still needed, as well as, further studies on the correlation of subcutaneous administered dosing requirements and severity of side effects.
遗传性血管性水肿伴 C1 酯酶抑制剂缺乏症是一种罕见的疾病，其特征为面部、喉部和胃肠道不可预测的肿胀。激肽释放酶是一种丝氨酸蛋白酶，可将激肽原裂解为产生缓激肽，导致炎症。一种新的预防性药物是拉那芦单抗（lanadelumab，DX-2930，SHP-643），一种重组、全人源 IgG1 单克隆抗体激肽释放酶抑制剂。药代动力学显示半衰期为 14 天，具有剂量依赖性。拉那芦单抗已完成的临床试验包括两项 III 期研究，更新了预防遗传性血管性水肿患者血管性水肿的疗效。正在进行的数据显示靶向治疗的安全性以及更频繁的给药要求。仍需要有关长期安全性的信息，以及关于皮下给药剂量要求与副作用严重程度相关性的进一步研究。
