临床回顾:炎症性肠病抗体类药物抗药抗体的发生率、预防和处理
翻译及点医院夏璐
来源丨医学界消化频道(CCCF—IBD学习驿站出品)
Incidence,PreventionandManagementofAnti-DrugAntibodiesAgainstTherapeuticAntibodiesinInflammatoryBowelDisease:APracticalOverview
PieterHindryckx,GregorNovak,NielsVandeCasteele,ReenaKhanna,DebbyLaukens,JairathVipul,BrianG.Feagan
摘要
生物治疗是炎症性肠病治疗策略的重大变革,但是与其他蛋白质类药物相似,单抗类制剂有免疫原性,其疗效和安全性受多种药物及患者因素的影响。文献报道中IBD生物制剂的抗药性抗体(ADAs)发生率极不一致,不仅与与药物致敏性有关,还与检测方法及检测时间点有关,而形成ADAs的药物致敏性则与输液反应的增加、药物清除的加速及对药物失应答(LOR)密切相关。
近期关于治疗性抗体药动学研究的进展引发了关于新治疗的思考,即如何减少免疫原性并促进药物的利用度。预防ADA的措施包括规律性、有计划地使用药物,维持稳定的药物谷浓度,合并使用免疫抑制剂等。药物浓度不足且ADAs水平低下者可通过调节剂量来解决。
Abstract
Theintroductionofbiologictherapyhasrevolutionizedthetreatmentofinflammatoryboweldisease(IBD).However,likealltherapeuticproteins,monoclonalantibodieshaveimmunogenicpotentialwhichisinfluencedbymultipledrug-andpatient-relatedfactors.Thereportedincidenceof
anti-drugantibodies(ADAs)towardsbiologicdrugsinIBDvariesgreatlyintheliteratureanddependsnotonlyondifferencesinsensitizationbutalsoontheassaymethodologyandthetimepointofmeasurement.SensitizationwithformationofADAsisassociatedwithanincreasedriskofinfusionreactions,accelerateddrugclearance,andalossofresponse(LOR)todrug.Recently,agreaterunderstandingofthepharmacokineticsoftherapeuticantibodieshasledtothedevelopmentof
newstrategiestoreduceimmunogenicityandmoreefficientuseofthesedrugs.Thesepreventivestrategiesincluderegularscheduleddosingwithmaintenanceofstabletherapeutictroughdrugconcentrations,andco-administrationofanimmunosuppressive.Sub-therapeuticdrugconcentrationswithlowlevelsofADAscangenerallybeover北京最专业看白癜风医院云南治疗白癜风
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