Nishimura Jun-Ichi
Osaka University Graduate School of Medicine, Department of Hematology and Oncology.
Rinsho Ketsueki. 2023;64(6):466-473. doi: 10.11406/rinketsu.64.466.
The anti-C5 antibody eculizumab was approved in 2007 as the first anti-complement agent for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). While eculizumab's indication has been expanded to include other diseases, the development of new anti-complement agents has been aggressively pursued for various diseases. In PNH, the anti-C5 recycling antibody ravulizumab, which is an improved version of eculizumab, has been developed, with an extended dosing interval of 2 to 8 weeks, vastly improving convenience. The treatment of PNH with terminal complement inhibitors such as eculizumab and ravulizumab presents a new challenge-extravascular hemolysis. To address this issue, the proximal complement inhibitor, a C3 inhibitor called pegcetacoplan, was approved in the United States of America. Furthermore, the amplification loop inhibitors-a factor B inhibitor iptacopan, and a factor D inhibitor danicopan-are being developed. Recently, the anti-C1s antibody sutimlimab was approved for the treatment of cold agglutinin disease, a type of autoimmune hemolytic anemia. This article discusses novel anti-complement therapies for hemolytic anemia.
抗C5抗体依库珠单抗于2007年获批，成为首个用于治疗阵发性夜间血红蛋白尿（PNH）的抗补体药物。虽然依库珠单抗的适应证已扩大到其他疾病，但针对各种疾病，新型抗补体药物的研发一直在积极推进。在PNH治疗中，已研发出抗C5再循环抗体ravulizumab，它是依库珠单抗的改进版本，给药间隔延长至2至8周，极大地提高了便利性。使用依库珠单抗和ravulizumab等末端补体抑制剂治疗PNH带来了一个新挑战——血管外溶血。为解决这一问题，近端补体抑制剂，一种名为培克珠单抗的C3抑制剂，在美国获批。此外，补体放大环抑制剂——一种因子B抑制剂iptacopan和一种因子D抑制剂danicopan也在研发中。最近，抗C1s抗体苏替利单抗获批用于治疗冷凝集素病，这是一种自身免疫性溶血性贫血。本文讨论了溶血性贫血的新型抗补体疗法。
