Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UCSF Benioff Children's Hospital, Oakland, California.
Pediatric Gastroenterology, Phoenix Children's Hospital, Phoenix, Arizona.
Clin Gastroenterol Hepatol. 2024 Oct;22(10):2075-2083.e1. doi: 10.1016/j.cgh.2024.03.043. Epub 2024 May 8.
BACKGROUND & AIMS: Biologic therapies may effectively treat Crohn's disease (CD), and pediatric patients who discontinue multiple biologics risk exhausting treatment options. The frequency and context of biologic discontinuation have not been well-characterized. We aimed to determine patterns of biologic use, discontinuation, and evaluation in pediatric patients with CD.
Pediatric patients with CD at 7 U.S. centers (2010-2020) were identified. Prospective ImproveCareNow registry data were supplemented with medical record abstraction. Biologics included monoclonal antibody and small molecule medications. Therapeutic drug monitoring (TDM) was considered induction if <14 weeks after biologic start, proactive if later during quiescent disease, and reactive during active disease.
Of 823 patients included (median age, 13.0 years; 40% female), 86% started biologics (78% infliximab, 21% adalimumab, <1% others). Twenty-six percent used concomitant immunomodulators for ≥12 months. Most (85%) measured TDM including 47% induction, 69% proactive, and 24% reactive. Twenty-nine percent discontinued their first biologic after median 793 days because of inefficacy (34%), anti-drug antibodies (8%), adverse events (8%), or non-adherence (12%). If inefficacy, 86% underwent pre-discontinuation evaluation. If infliximab or adalimumab inefficacy and TDM was done, 62% had levels <10 μg/mL. Proactive TDM and concomitant immunomodulators were associated with 60% and 32% reduced biologic discontinuation.
Most children with CD are treated with biologics; 25%-37% discontinue biologics, resulting in 1 in 12 using >2 biologics during pediatric care. Half of patients discontinued biologics without trial of high-dose therapy and 14% without any evaluation. Concomitant immunomodulator use and proactive TDM decreased risk of biologic discontinuation. Strategies are needed to preserve biologic efficacy and prevent biologic discontinuation.
生物制剂可能有效治疗克罗恩病（CD），而停止使用多种生物制剂的儿科患者可能会耗尽治疗选择。生物制剂停药的频率和情况尚未得到很好的描述。我们旨在确定儿科 CD 患者使用、停药和评估生物制剂的模式。
在美国 7 家中心（2010-2020 年）确定患有 CD 的儿科患者。前瞻性 ImproveCareNow 登记数据补充了病历摘录。生物制剂包括单克隆抗体和小分子药物。治疗药物监测（TDM）如果在生物制剂开始后 <14 周，则被认为是诱导，如果在疾病静止期后，则被认为是主动，如果在疾病活动期，则被认为是反应性。
纳入 823 例患者（中位年龄 13.0 岁；40%为女性），86%开始使用生物制剂（78%英夫利昔单抗，21%阿达木单抗，<1%其他）。26%使用免疫调节剂 ≥12 个月。大多数（85%）进行了 TDM 测量，包括 47%诱导、69%主动和 24%反应性。29%在中位 793 天后因疗效不佳（34%）、抗药物抗体（8%）、不良事件（8%）或不依从（12%）而停用首种生物制剂。如果疗效不佳，86%进行了停药前评估。如果英夫利昔单抗或阿达木单抗无效且进行了 TDM，则 62%的患者水平<10μg/mL。主动 TDM 和同时使用免疫调节剂与 60%和 32%的生物制剂停药减少相关。
大多数 CD 患儿接受生物制剂治疗；25%-37%的患儿停止使用生物制剂，导致 12 例患儿中有 1 例在儿科治疗期间使用>2 种生物制剂。一半的患者在没有高剂量治疗试验的情况下停止使用生物制剂，14%的患者没有进行任何评估。同时使用免疫调节剂和主动 TDM 降低了生物制剂停药的风险。需要制定策略来维持生物制剂的疗效并防止生物制剂停药。
