调节细胞内铁代谢
新出现以铁调素-膜铁转运蛋白轴为靶点的慢性病贫血新疗法。其中包括铁调素直接拮抗剂、铁调素生成抑制剂、红富铁激素类似物及能增强膜铁转运蛋白对铁调素耐受作用的药物。[59]Sun CC, Vaja V, Babitt JL, et al. Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation. Am J Hematol. 2012 Apr;87(4):392-400.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653431/http://www.ncbi.nlm.nih.gov/pubmed/22290531?tool=bestpractice.com 维生素 D 在体外和体内均对铁调素有抑制作用,[60]Bacchetta J, Zaritsky JJ, Lisse TS, et al. Vitamin D as a new regulator of iron metabolism: vitamin D suppresses hepcidin in vitro and in vivo. Nephrol Dial Transplant. 2012;27(suppl 2):ii28-30. 且维生素 D 缺乏可引起老年患者中的炎症性贫血患病率升高。[61]Perlstein TS, Pande R, Berliner N, et al. Prevalence of 25-hydroxyvitamin D deficiency in subgroups of elderly persons with anemia: association with anemia of inflammation. Blood. 2011 Mar 10;117(10):2800-6.http://bloodjournal.hematologylibrary.org/content/117/10/2800.longhttp://www.ncbi.nlm.nih.gov/pubmed/21239700?tool=bestpractice.com 补充维生素D可降低接受血液透析的维生素D缺乏患者的红细胞生成素需求。[62]Kumar VA, Kujubu DA, Sim JJ, et al. Vitamin D supplementation and recombinant human erythropoietin utilization in vitamin D-deficient hemodialysis patients. J Nephrol. 2011 Jan-Feb;24(1):98-105.http://www.ncbi.nlm.nih.gov/pubmed/20563998?tool=bestpractice.com 白介素-6 (IL-6) 是最重要的一种促炎性细胞因子,可引起细胞内铁代谢的改变。 Castleman 病患者使用托珠单抗(tocilizuma,一种抗 IL-6 受体抗体)可降低铁调素水平,改善该疾病状态下的炎症性贫血。[63]Song SN, Tomosugi N, Kawabata H, et al. Down-regulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman disease. Blood. 2010 Nov 4;116(18):3627-34.http://bloodjournal.hematologylibrary.org/content/116/18/3627.longhttp://www.ncbi.nlm.nih.gov/pubmed/20644113?tool=bestpractice.com 但是,有证据表明,使用 IL-6 抑制剂可增加感染性并发症的风险。[64]Lang VR, Englbrecht M, Rech J, et al. Risk of infections in rheumatoid arthritis patients treated with tocilizumab. Rheumatology (Oxford). 2012 May;51(5):852-7.https://academic.oup.com/rheumatology/article/51/5/852/1804905http://www.ncbi.nlm.nih.gov/pubmed/21865281?tool=bestpractice.com
新型依泊汀衍生物(生物类似物)
许多新的依泊汀类药物已经被研制出来或正在研究中,[65]Schmid H, Schiffl H, Lederer SR. New strategies for managing anemia of chronic kidney disease. Cardiovasc Hematol Agents Med Chem. 2012 Dec;10(4):339-51.http://www.ncbi.nlm.nih.gov/pubmed/22642238?tool=bestpractice.com 其中包括倍他依泊汀、依泊汀-δ、依泊汀-ζ、依泊汀-θ、依泊汀-κ、以及依泊汀-ω。这些依泊汀是利用不同克隆基因或细胞系生成的,其糖基化模式可能不同,但具有相同的人促红细胞生成素 165 个氨基酸序列。长效持续性促红细胞生成素受体激活剂甲氧基聚乙二醇促红细胞生成素-β 亦已面市。其中很多药物显示出与生物学参照制剂(第一种获许可的依泊汀)相似的疗效和安全性,[66]Kamioner D. Erythropoietin biosimilars currently available in hematology-oncology. Target Oncol. 2012 Mar;7(suppl 1):S25-8.http://www.ncbi.nlm.nih.gov/pubmed/22252675?tool=bestpractice.com[67]Locatelli F, Del Vecchio L. An expert opinion on the current treatment of anemia in patients with kidney disease. Expert Opin Pharmacother. 2012 Mar;13(4):495-503.http://www.ncbi.nlm.nih.gov/pubmed/22296648?tool=bestpractice.com[68]Debeljak N, Sytkowski AJ. Erythropoietin and erythropoiesis stimulating agents. Drug Test Anal. 2012 Nov;4(11):805-12.http://www.ncbi.nlm.nih.gov/pubmed/22508651?tool=bestpractice.com[69]Gertz B, Kes P, Essaian A, et al. Epoetin theta: efficacy and safety of subcutaneous administration in anemic pre-dialysis patients in the maintenance phase in comparison to epoetin beta. Curr Med Res Opin. 2012 Jul;28(7):1101-10.http://informahealthcare.com/doi/full/10.1185/03007995.2012.688736http://www.ncbi.nlm.nih.gov/pubmed/22533679?tool=bestpractice.com 尽管目前还未有在肿瘤性贫血中经确认的数据。