英夫利昔单抗和阿达木单抗的免疫原性
前沿进展丨英夫利昔单抗和阿达木单抗的免疫原性高于其他生物制剂
目的：对炎性疾病中使用生物制剂的免疫原性及其对药物疗效／安全性的潜在影响进行系统评价。
方法：于2016年11月进行文献检索，确定生物制剂／生物仿制药治疗类风湿关节炎，银屑病关节炎，幼年特发性关节炎，强直性脊柱炎，影像学阴性的中轴性脊柱关节炎，银屑病，克罗恩病，和溃疡性结肠炎的对照性和观察性研究。
结果：在>21,000篇文献中，共纳入443篇文献。抗药抗体（ADAb）的阳性率在不同疾病应用生物制剂治疗患者中的差异较大(由于免疫分析方法的异质性较大，无法直接进行比较)；ADAb阳性率最高的是英夫利昔单抗(0-83%)，阿达木单抗(0-54%)，英夫利昔单抗生物仿制药CT-P13 (21-52%)，最低的是secukinumab (0-1%)，ustekinumab (1-11%)，依那西普(0-13%), 和格利木单抗(0-19%)。除针对阿巴昔普和依那西普的ADAb之外，大部分ADAbs 是中和性抗体。与ADAb阴性的患者相比，ADAb阳性的患者对阿达木单抗(RA, PsA, JIA, AS, Ps), 格利木单抗 (RA), 英夫利昔单抗(RA, PsA, AS, Ps), 利妥昔单抗 (RA), ustekinumab (Ps)，和CT-P13 (RA, AS)的临床反应率更低。英夫利昔单抗 CT-P13治疗后ADAb阳性的患者输液相关反应更高。免疫抑制剂／抗增殖药物的使用可以减少各种疾病应用生物制剂的免疫原性。
结论：基于文献报道结果，不同的生物制剂／生物仿制药的免疫原性差异较大，英夫利昔单抗和阿达木单抗的ADAb阳性率最高。生物制剂／生物仿制药治疗患者ADAb的产生可能会增加药物疗效不佳的风险，在制定治疗方案的过程中要考虑到这些药物的免疫原性。
附原文：
OBJECTIVE: A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety.
METHODS: Literature searches were conducted through November 2016 to identify controlled and observational studies of biologics/biosimilars administered for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), psoriasis (Ps), Crohn's disease, and ulcerative colitis.
RESULTS: Of >21,000 screened publications, 443 were included. Anti-drug antibody (ADAb) rates varied widely among biologics across diseases (and are not directly comparable because of immunoassay heterogeneity); the highest overall rates were reported with infliximab (0-83%), adalimumab (0-54%), and infliximab biosimilar CT-P13 (21-52%), and the lowest with secukinumab (0-1%), ustekinumab (1-11%), etanercept (0-13%), and golimumab (0-19%). Most ADAbs were neutralizing, except those to abatacept and etanercept. ADAb+ versus ADAb- patients had lower rates of clinical response to adalimumab (RA, PsA, JIA, AS, Ps), golimumab (RA), infliximab (RA, PsA, AS, Ps), rituximab (RA), ustekinumab (Ps), and CT-P13 (RA, AS). Higher rates of infusion-related reactions were reported in infliximab- and CT-P13-treated ADAb+ patients. Background immunosuppressives/anti-proliferatives reduced biologic immunogenicity across diseases.
CONCLUSION: Based on reviewed reports, biologic/biosimilar immunogenicity differs among agents, with the highest rates observed with infliximab and adalimumab. As ADAb formation in biologic-/biosimilar-treated patients may increase the risk of lost response, the immunogenicity of these agents is an important (albeit not the only) consideration in the treatment decision-making process.
引自：
Strand V, Balsa A, Al-Saleh J, et al. Immunogenicity of Biologics in ChronicInflammatory Diseases: A Systematic Review. BioDrugs. 2017 Jun 13. doi: 10.1007/s40259-017-0231-8.[Epub ahead of print]
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