DOP62 Immunogenicity to second anti-TNF therapy (IMSAT): Implications for sequencing of biologic therapy
DOP62 Immunogenicity to second anti-TNF therapy (IMSAT): Implications for sequencing of biologic therapy
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DOP62 对第二种抗 TNF 疗法 (ISAT) 的免疫原性：对生物疗法测序的影响
DOI：
10.1093/ecco-jcc/jjab073.101
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Chanchlani N
中科院分区：
文献类型：
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作者：
Chanchlani N
研究背景IBD患者抗肿瘤坏死因子（aTNF）治疗失败是常见的。国际指南建议，当aTNF药物水平达到治疗水平时，应换出该类药物，而当aTNF药物水平低于最佳水平并与抗体形成相关时，应在免疫调节剂类药物范围内换用。我们试图定义：1）第二aTNF的免疫原性的风险分层的免疫原性的第一aTNF和2）率的药物持久性的第二aTNF患者的药效学或免疫原性失败的第一aTNF drug.MethodsWe进行了一项回顾性队列研究，在32家英国医院。确定了2013年5月至2020年11月期间由我们的服务进行英夫利昔单抗和阿达木单抗治疗药物监测的870例患者（444例男性，630例（72%）克罗恩病）。使用IDKmonitor®药物耐受ELISA测定法测量药物和抗体水平。治疗失败包括原发性无应答、继发性应答丧失、药物不良反应和IBD相关手术，并通过病例记录审查确定。免疫原性失败定义为治疗失败，药物水平不佳（英夫利西单抗水平<2 mg/L，阿达木单抗水平<6 mg/L），抗体浓度≥ 10 Au/ml。药效学失败被定义为治疗失败，尽管足够的药物levels.ResultsPatients开发免疫原性阿达木单抗（第一）更有可能开发免疫原性英夫利西单抗（第二）（63% vs 40%，p = 0.004），对英夫利西单抗产生免疫原性的患者（第一次）更有可能对阿达木单抗产生免疫原性（第二次）（33% vs 19%，p = 0.002）（图1）。发生以下情况的患者：抗体和不可检测的药物、低药物水平或对英夫利昔单抗具有免疫原性的低药物水平（第一）更可能对阿达木单抗（第二）产生这些结果（所有p <0.001）。在免疫原性（但不是药效学）失败的患者中，在转换为第二种aTNF药物时开始使用免疫调节剂与整个或不是全部使用免疫调节剂治疗的患者的药物持续时间更长相关（图3）。在转换为第二种aTNF时开始使用免疫调节剂与免疫原性失败的药物持久性改善相关，但与药效学失败无关。然而，两组中50%的患者在第5年时仍接受第二次aTNF治疗，这表明无论治疗失败至首次aTNF的原因如何，类内转换可能是适当的。
BackgroundAnti-TNF (aTNF) treatment failure in patients with IBD is common. International guidelines recommend switching out of class when aTNF drug levels are therapeutic and within class with an immunomodulator when aTNF drug levels are suboptimal and associated with antibody development. We sought to define the: 1) risk of immunogenicity to a second aTNF stratified by immunogenicity to the first aTNF and 2) rates of drug persistence to a second aTNF in patients with pharmacodynamic or immunogenic failure of their first aTNF drug.MethodsWe performed a retrospective cohort study across 32 UK hospitals. 870 patients (444 male, 630 (72%) Crohn’s disease) who had both infliximab and adalimumab therapeutic drug monitoring performed by our service from May 2013 to November 2020 were identified. Drug and antibody levels were measured using the IDKmonitor® drug tolerant ELISA assays. Treatment failure included primary nonresponse, secondary loss of response, adverse drug reactions and IBD-related surgeries, and was identified by case note review. Immunogenic failure was defined as treatment failure with suboptimal drug levels (infliximab level <2 mg/L, adalimumab level <6 mg/L) with an antibody concentration ≥10 AU/ml. Pharmacodynamic failure was defined as treatment failure despite adequate drug levels.ResultsPatients who developed immunogenicity to adalimumab (first) were more likely to develop immunogenicity to infliximab (second) (63% vs 40%, p = 0.004), and patients who developed immunogenicity to infliximab (first) were more likely to develop immunogenicity to adalimumab (second) (33% vs 19%, p = 0.002) (Fig 1). Patients who developed: antibodies and undetectable drug, low drug levels, or low drug levels with immunogenicity to infliximab (first), were more likely to develop these outcomes to adalimumab (second) (all p<0.001).There was no difference in drug persistence to second aTNF in patients with pharmacodynamic and immunogenic treatment failure (Fig 2). In patients with immunogenic (but not pharmacodynamic) failure, commencing an immunomodulator at the time of switching to second aTNF drug was associated with longer drug persistence than in patients treated with an immunomodulator throughout or not all (Fig 3).ConclusionImmunogenicity to the first aTNF was associated with immunogenicity to the second aTNF, irrespective of drug sequence. Commencing an immunomodulator at the time of switching to second aTNF was associated with improved drug persistence in immunogenic, but not pharmacodynamic, failure. However, 50% of patients remained on second aTNF at 5 years in both groups, suggesting switching in-class may be appropriate irrespective of the cause of treatment failure to first aTNF.