克罗恩病患者英夫利昔单抗的血药浓度监测
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摘要
目的分析克罗恩病(CD)患者的英夫利昔单抗(IFX)血药浓度及抗英夫利昔单抗抗体(ATI)水平的监测结果,为IFX的临床合理应用提供参考。方法对北京大学深圳医院2018年1—12月共37例接受IFX治疗并监测的CD患者数据进行回顾性分析。结果共67例次监测结果显示IFX的平均谷浓度为(5.59±1.26)μg/ml,ATI阳性患者的IFX谷浓度水平明显低于ATI阴性患者(P=0.029),机体白蛋白(ALB)降低和C反应蛋白(CRP)升高均可导致IFX谷浓度偏低。结论 IFX血药浓度个体化差异大,易受较多因素影响,应定期规律监测IFX血药浓度和ATI情况,根据监测结果制订个体化治疗方案,提高药物疗效。
Objective To provide a basis for the rational use of infliximab(IFX) by analyzing the blood concentration of infliximab(IFX) and anti-infliximab antibody(ATI) in patients with Crohn's disease(CD). Methods A retrospective analysis was conducted on 37 patients with CD who underwent IFX treatment and were monitored from January to December 2018 in Peking University Shenzhen Hospital. Results The level of IFX in ATI-positive patients was significantly lower than that in ATI-negative patients(P=0.029), and decreased albumin(ALB) and elevated C-reactive protein(CRP) resulted in low IFX concentrations.Conclusion The individualized difference of blood concentration of IFX is large and susceptible to many factors. IFX blood concentration and ATI should be monitored regularly, and individualized treatment plans should be formulated according to the monitoring results to improve the efficacy of the drug.
Objective To provide a basis for the rational use of infliximab(IFX) by analyzing the blood concentration of infliximab(IFX) and anti-infliximab antibody(ATI) in patients with Crohn's disease(CD). Methods A retrospective analysis was conducted on 37 patients with CD who underwent IFX treatment and were monitored from January to December 2018 in Peking University Shenzhen Hospital. Results The level of IFX in ATI-positive patients was significantly lower than that in ATI-negative patients(P=0.029), and decreased albumin(ALB) and elevated C-reactive protein(CRP) resulted in low IFX concentrations.Conclusion The individualized difference of blood concentration of IFX is large and susceptible to many factors. IFX blood concentration and ATI should be monitored regularly, and individualized treatment plans should be formulated according to the monitoring results to improve the efficacy of the drug.
引文
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[15]陈禾凤,陈冰,杨婉花.克罗恩病治疗中英夫利西单抗药物监测的临床意义[J].中国医院药学杂志,2016,36(22):2030-2034.
[16]Nanda KS,Cheifetz AS,Moss AC.Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease(IBD):a meta-analysis[J].Am J Gastroenterol,2013,108(1):40-47;quiz 48.
[17]Strik AS,van den Brink GR,Ponsioen C,et al.Suppression of anti-drug antibodies to infliximab or adalimumab with the addition of an immunomodulator in patients with inflammatory bowel disease[J].Aliment Pharmacol Ther,2017,45(8):1128-1134.
[18]Tighe D,Hall B,Jeyarajah SK,et al.One-year clinical outcomes in an IBD cohort who have previously had anti-TNFa trough and antibody levels assessed[J].Inflamm Bowel Dis,2017,23(7):1154-1159.
[2]Huang H,Xu S,Huang F,et al.A Meta-Analysis of Efficacy and Safety of Infliximab for Prevention of Postoperative Recurrence in Patients with Crohn's Disease[J].Biomed Res Int,2018,2018:2615978.
[3]张群雄.英夫利昔单克隆抗体对克罗恩病伴不完全性肠梗阻患者的临床疗效评价[J].抗感染药学,2015,12(6):866-870.
[4]Vande CN,Khanna R,Levesque BG,et al.The relationship between infliximab concentrations,antibodies to infliximab and disease activity in Crohn's disease[J].Gut,2015,64(10):1539-1545.
[5]Vande CN,Gils A.Pharmacokinetics of anti-TNF monoclonal antibodies in inflammatory bowel disease:Adding value to current practice[J].J Clin Pharmacol,2015,55 Suppl 3:S39-50.
[6]Papamichael K,Chachu KA,Vajravelu RK,et al.Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab[J].Clin Gastroenterol Hepatol,2017,15(10):1580-1588.e3.
[7]中华医学会消化病学分会炎症性肠病学组.炎症性肠病诊断与治疗的共识意见(2018年,北京)[J].中华消化杂志,2018,38(5):292-311.
[8]Hibi T,Sakuraba A,Watanabe M,et al.Retrieval of serum infliximab level by shortening the maintenance infusion interval is correlated with clinical efficacy in Crohn's disease[J].Inflamm Bowel Dis,2012,18(8):1480-1487.
[9]Marits P,Landucci L,Sundin U,et al.Trough s-infliximab and antibodies towards infliximab in a cohort of 79 IBD patients with maintenance infliximab treatment[J].J Crohns Colitis,2014,8(8):881-889.
[10]Jürgens M,Mahachie John JM,Cleynen I,et al.Levels of C-reactive protein are associated with response to infliximab therapy in patients with Crohn's disease[J].Clin Gastroenterol Hepatol,2011,9(5):421-427.
[11]李冠炜,任建安.重视我国克罗恩病流行病学的研究[J].肠外与肠内营养,2017,24(3):135-137.
[12]余慧芬,唐李,李妍.克罗恩病非手术治疗的研究进展[J].医学与哲学(B),2018,39(20):43-45.
[13]Limketkai BN,Wolf A,Parian AM.Nutritional Interventions in the Patient with Inflammatory Bowel Disease[J].Gastroenterol Clin North Am,2018,47(1):155-177.
[14]Wong U,Cross RK.Primary and secondary nonresponse to infliximab:mechanisms and countermeasures[J].Expert Opin Drug Metab Toxicol,2017,13(10):1039-1046.
[15]陈禾凤,陈冰,杨婉花.克罗恩病治疗中英夫利西单抗药物监测的临床意义[J].中国医院药学杂志,2016,36(22):2030-2034.
[16]Nanda KS,Cheifetz AS,Moss AC.Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease(IBD):a meta-analysis[J].Am J Gastroenterol,2013,108(1):40-47;quiz 48.
[17]Strik AS,van den Brink GR,Ponsioen C,et al.Suppression of anti-drug antibodies to infliximab or adalimumab with the addition of an immunomodulator in patients with inflammatory bowel disease[J].Aliment Pharmacol Ther,2017,45(8):1128-1134.
[18]Tighe D,Hall B,Jeyarajah SK,et al.One-year clinical outcomes in an IBD cohort who have previously had anti-TNFa trough and antibody levels assessed[J].Inflamm Bowel Dis,2017,23(7):1154-1159.