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炎症性肠病患儿生物药物的抗药物抗体管理。

Management of Anti-drug Antibodies to Biologic Medications in Children With Inflammatory Bowel Disease.

机构信息

Division of Pediatric Gastroenterology, Emory University School of Medicine Atlanta, Children's Healthcare of Atlanta, Atlanta, GA.

出版信息

J Pediatr Gastroenterol Nutr. 2019 Nov;69(5):551-556. doi: 10.1097/MPG.0000000000002440.

Abstract

BACKGROUND

Treatment of pediatric inflammatory bowel disease (IBD) with monoclonal anti- tumor necrosis factor-alpha (TNFα) can result in immunogenicity and formation of anti-drug antibodies (ADAs). ADAs are associated with loss of clinical response and worsening disease progression. Data examining treatment interventions to overcome ADA in pediatric patients with IBD are lacking.

RESULTS

Medical records were reviewed from 234 children and adolescents with IBD treated with infliximab or adalimumab who underwent therapeutic drug monitoring (626 tests). All patients who had detectable antibodies were further analyzed. A total 58 patients (24.8%) developed ADA while being treated with infliximab or adalimumab. The incidence of antibody development was 12.9 per 100 person-years of anti-TNF treatment. Twenty-eight patients underwent dose optimization and 54% had undetectable ADA on follow-up monitoring. The mean duration of antibody suppression was 16.8 ± 10.9 months in those who were successfully suppressed with optimization. Patients who switched to a second anti-TNF medication were not more likely to develop antibodies to the second agent.

CONCLUSIONS

With limited therapies for IBD and the chronicity of the disease, we advocate salvage of the current anti-TNF through dose optimization in pediatric patients with antibody level <10 U/mL.

摘要

背景

在儿科炎症性肠病(IBD)的治疗中,使用单克隆抗肿瘤坏死因子-α(TNFα)药物可能导致免疫原性和抗药物抗体(ADA)的形成。ADA 与临床应答丧失和疾病恶化有关。目前缺乏针对 ADA 的治疗干预措施的数据,用于儿科 IBD 患者。

结果

对接受英夫利昔单抗或阿达木单抗治疗的 234 名 IBD 儿童和青少年的病历进行了回顾,共进行了 626 次治疗药物监测(TDM)测试。所有检测到抗体的患者均进行了进一步分析。共有 58 名(24.8%)患者在接受英夫利昔单抗或阿达木单抗治疗时发生 ADA。抗体产生的发生率为每 100 人年抗 TNF 治疗 12.9 例。28 名患者进行了剂量优化,54%的患者在随访监测中 ADA 检测不到。在成功抑制 ADA 的患者中,平均抑制抗体持续时间为 16.8±10.9 个月。与转换为第二种抗 TNF 药物的患者相比,第二种药物产生抗体的可能性并没有增加。

结论

鉴于 IBD 的治疗方法有限且疾病具有慢性特征,我们提倡在 ADA 水平<10U/mL 的儿科患者中,通过剂量优化来挽救当前的抗 TNF 治疗。

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