目的：對炎性疾病中使用生物制劑的免疫原性及其對藥物療效／安全性的潛在影響進行系統(tǒng)評價,。
方法：于2016年11月進行文獻檢索，確定生物制劑／生物仿制藥治療類風濕關節(jié)炎,，銀屑病關節(jié)炎,，幼年特發(fā)性關節(jié)炎，強直性脊柱炎,，影像學陰性的中軸性脊柱關節(jié)炎,，銀屑病，克羅恩病,，和潰瘍性結腸炎的對照性和觀察性研究,。
結果：在>21,000篇文獻中，共納入443篇文獻,?？顾幙贵w（ADAb）的陽性率在不同疾病應用生物制劑治療患者中的差異較大(由于免疫分析方法的異質性較大，無法直接進行比較),；ADAb陽性率最高的是英夫利昔單抗(0-83%),，阿達木單抗(0-54%)，英夫利昔單抗生物仿制藥CT-P13 (21-52%),，最低的是secukinumab (0-1%),，ustekinumab (1-11%)，依那西普(0-13%), 和格利木單抗(0-19%),。除針對阿巴昔普和依那西普的ADAb之外,，大部分ADAbs 是中和性抗體。與ADAb陰性的患者相比,，ADAb陽性的患者對阿達木單抗(RA, PsA, JIA, AS, Ps), 格利木單抗 (RA), 英夫利昔單抗(RA, PsA, AS, Ps), 利妥昔單抗 (RA), ustekinumab (Ps),，和CT-P13 (RA, AS)的臨床反應率更低。英夫利昔單抗 CT-P13治療后ADAb陽性的患者輸液相關反應更高,。免疫抑制劑／抗增殖藥物的使用可以減少各種疾病應用生物制劑的免疫原性,。
結論：基于文獻報道結果，不同的生物制劑／生物仿制藥的免疫原性差異較大,，英夫利昔單抗和阿達木單抗的ADAb陽性率最高,。生物制劑／生物仿制藥治療患者ADAb的產生可能會增加藥物療效不佳的風險,，在制定治療方案的過程中要考慮到這些藥物的免疫原性。
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]
