Inflammatory bowel disease (IBD) is a chronic systemic immune-mediated disorder. The disease is triggered and perpetuated by a complex interplay between genetic predisposition, dysregulated immune responses, and environmental factors. Pediatric IBD is considered to be more aggressive compared with adult-onset IBD, and commonly requires more intensive pharmacological and surgical treatments. Although the use of targeted therapy, such as biologic therapy and small molecule therapy, is on the rise, there are children with IBD who are refractory to all current therapeutic options. For them, a combination of biologic agents or a biologic agent with small molecules as dual-targeted therapy (DTT) may be a possible therapeutic option. The main indications for DTT are high inflammatory burden and refractoriness to standard therapy, extra-intestinal manifestations of IBD, adverse effects of therapy, and co-existing immune-mediated inflammatory disorders. Several combination therapies were described for pediatric refractory IBD. The main ones were anti-tumor necrosis factor (TNF) agents and vedolizumab (VDZ), anti-TNF and ustekinumab (UST), VDZ and UST, and biologic agents with tofacitinib. DTT exhibits high efficacy, with high rates of clinical response and remission as well as biomarker remission. The data on endoscopic and radiologic remission are scarce. Most of the adverse effects reported under DTT were mild; however, the serious ones that had been observed mandate a profoundly cautious approach when considering it. Triple immunosuppressive therapy and combinations of biologics with emergent therapies such as selective Janus kinase inhibitors, sphingosine-1-phosphate receptor modulators, and anti-interleukin-23 agents, are potential future regimens for children with IBD who are refractory to current therapeutic options. This review provides an update of publications on these issues.

炎症性肠病（IBD）是一种慢性全身性免疫介导疾病。该疾病是由遗传倾向、免疫反应失调和环境因素之间复杂的相互作用引发和延续的。与成人发病的 IBD 相比，儿童 IBD 被认为更具侵袭性，通常需要更强化的药物和手术治疗。尽管生物治疗和小分子治疗等靶向治疗的使用正在增加，但仍有一些 IBD 儿童对所有现有治疗方案均无效。对于他们来说，生物制剂或生物制剂与小分子的组合作为双靶向治疗（DTT）可能是一种可能的治疗选择。DTT 的主要适应症是高炎症负荷和标准治疗无效、IBD 的肠外表现、治疗的不良反应以及共存的免疫介导的炎症性疾病。描述了几种治疗儿科难治性 IBD 的联合疗法。主要有抗肿瘤坏死因子（TNF）药物和维多珠单抗（VDZ）、抗TNF药物和乌特克单抗（UST）、VDZ和UST，以及生物制剂和托法替布。DTT 具有很高的疗效，具有很高的临床反应率和缓解率以及生物标志物缓解率。内镜和放射学缓解的数据很少。DTT 报告的大多数不良反应都是轻微的；然而，所观察到的严重问题要求在考虑时采取极其谨慎的态度。三重免疫抑制疗法以及生物制剂与选择性 Janus 激酶抑制剂、1-磷酸鞘氨醇受体调节剂和抗白细胞介素 23 药物等紧急疗法的组合，是目前治疗方案难以治愈的 IBD 儿童的未来潜在治疗方案。这篇评论提供了有关这些问题的出版物的更新。