背景:婴儿发作的炎症性肠病(IO-IBD)的治疗通常具有挑战性,因为它具有侵袭性的疾病过程和标准疗法的失败,需要生物制剂。继发性反应丧失通常是由抗药物抗体的产生引起的,IBD患者接受生物治疗的一个众所周知的问题。我们介绍了1例IO-IBD治疗药物监测(TDM)指导的大剂量抗肿瘤坏死因子治疗,其中剂量递增监测被用作克服抗药物抗体的策略.
方法:一个5个月大的男孩,从生命的第10天开始就有持续性便血史,以及复发性肛周脓肿和生长障碍。低白蛋白血症,贫血,和升高的炎症标志物也存在。内镜评估显示跳跃性病变伴深绞痛溃疡,炎性肛门狭窄,和有持续性脓肿的深裂缝。诊断为IO-IBD克罗恩样。患者最初接受口服类固醇和瘘管切开术治疗。肛周脓肿愈合后,阿达木单抗(ADA)的同时使用类固醇逐渐减量。在良好的波谷水平下实现了无临床和生化类固醇的缓解。3个月后,发现ADA(ATA)的抗体具有无法检测的波谷水平;因此,我们优化了治疗方案,首先每周给药10mg,然后每周给药20mg(2.8mg/kg/剂)。大剂量治疗2个月后,ATA消失了,伴随高谷水平和稳定的临床和生化疾病缓解。
结论:TDM指导的高剂量ADA治疗作为单一疗法克服了ATA产生。这种策略可以替代联合治疗,特别是在非常年轻的病人。
BACKGROUND: Treatment of infantile-onset inflammatory bowel disease (IO-IBD) is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics. Secondary loss of response is frequently caused by the production of anti-drug antibodies, a well-known problem in IBD patients on biologic treatment. We present a
case of IO-IBD treated with therapeutic drug monitoring (TDM)-guided high-dose anti-tumor necrosis factor therapy, in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.
METHODS: A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life, as well as relapsing perianal abscess and growth failure. Hypoalbuminemia, anemia, and elevated inflammatory markers were also present. Endoscopic assessment revealed skip lesions with deep colic ulcerations, inflammatory anal sub-stenosis, and deep fissures with persistent abscess. A diagnosis of IO-IBD Crohn-like was made. The patient was initially treated with oral steroids and fistulotomy. After the perianal abscess healed, adalimumab (ADA) was administered with concomitant gradual tapering of steroids. Clinical and biochemical steroid-free remission was achieved with good trough levels. After 3 mo, antibodies to ADA (ATA) were found with undetectable trough levels; therefore, we optimized the therapy schedule, first administering 10 mg weekly and subsequently up to 20 mg weekly (2.8 mg/kg/dose). After 2 mo of high-dose treatment, ATA disappeared, with concomitant high trough levels and stable clinical and biochemical remission of the disease.
CONCLUSIONS: TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production. This strategy could be a good alternative to combination therapy, especially in very young patients.