Children's Hospital, Helsinki University Hospital HUS and University of Helsinki, Stenbäckinkatu 11 FI-00290 , Helsinki, Finland.
Eur J Pediatr. 2024 Jan;183(1):313-322. doi: 10.1007/s00431-023-05255-y. Epub 2023 Oct 25.
Vedolizumab (VDZ) is used off-label in pediatric inflammatory bowel disease (PIBD). There are less data on drug levels to achieve and maintain remission in children. We aimed to study vedolizumab (VDZ) trough levels in a pediatric population in a real-life setting. We traced 50 patients with PIBD receiving VDZ treatment at our hospital, reviewed their treatment protocol, trough levels, and antidrug antibodies, and compared those to fecal calprotectin (FC) levels and achievement of corticosteroid-free maintenance therapy (CF). VDZ trough level was available from 198 samples during a median follow- up of 12.6 months. Proceeding to maintenance therapy was associated with a decline in FC but not with VDZ trough levels that were comparable between patients with FC < 100 μg/g (remission), 100-1000 μg/g, or > 1000 μg/g at 3 months (mean levels of 36.8, 28.6, and 27 μg/mL, respectively p = 0.188). At 3 months, patients achieving CF (41%) and those on corticosteroids had comparable VDZ trough levels (33 vs. 27.5 μg/mL, respectively). At 6 months, the trough level was similar in groups with FC < 100 μg/g or FC > 1000 μg/g (31.5 and 27.6 μg/mL, p = 0.859). Treatment intensification did not improve the achieved CF at 12 months. None developed drug antibodies nor discontinued the therapy for an adverse event. Conclusion: VDZ was a well-tolerated and safe biologic treatment. A positive response on gut inflammation after induction predicted proceeding to maintenance therapy whereas trough levels did not. A VDZ trough level associated with clinical remission or continuing with VDZ treatment could not be determined. What is Known: • In pediatric inflammatory bowel disease, vedolizumab is still in off-label use. • The results on the relationship between drug levels of vedolizumab and clinical remission in pediatric patients are contradictory. What is New: • This real-life setting in pediatric-onset inflammatory bowel disease showed no benefit of therapy enhancement during a median follow-up of one year. • Trough levels of vedolizumab were not associated with therapy outcomes.
维得利珠单抗(VDZ)在儿科炎症性肠病(PIBD)中的应用属于超说明书用药。目前,关于儿童实现和维持缓解所需的药物水平的数据较少。我们旨在研究真实环境中儿科人群的维得利珠单抗(VDZ)谷浓度。我们追踪了在我院接受 VDZ 治疗的 50 名 PIBD 患者,回顾了他们的治疗方案、谷浓度和抗药物抗体,并将其与粪便钙卫蛋白(FC)水平和实现无皮质类固醇维持治疗(CF)进行了比较。在中位随访 12.6 个月期间,我们获得了 198 个样本的 VDZ 谷浓度。进入维持治疗与 FC 下降相关,但与 VDZ 谷浓度无关,在 3 个月时,FC<100μg/g(缓解)、100-1000μg/g 和>1000μg/g 的患者之间 VDZ 谷浓度相当(分别为 36.8、28.6 和 27μg/mL,p=0.188)。在 3 个月时,实现 CF(41%)的患者和使用皮质类固醇的患者 VDZ 谷浓度相当(分别为 33 和 27.5μg/mL)。在 6 个月时,FC<100μg/g 或 FC>1000μg/g 组的谷浓度相似(分别为 31.5 和 27.6μg/mL,p=0.859)。在 12 个月时,治疗强化并未改善实现的 CF。没有患者出现药物抗体,也没有因不良反应而停止治疗。结论:VDZ 是一种耐受良好且安全的生物治疗药物。诱导后肠道炎症的阳性反应预测进入维持治疗,而谷浓度则不然。未能确定与临床缓解相关的 VDZ 谷浓度或继续 VDZ 治疗。已知:•在儿科炎症性肠病中,维得利珠单抗仍属于超说明书用药。•关于儿科患者中维得利珠单抗的药物水平与临床缓解之间的关系,结果存在争议。新内容:•本研究真实反映了儿科发病的炎症性肠病,在中位随访一年期间,没有发现治疗增强的益处。•维得利珠单抗的谷浓度与治疗结果无关。