Department of Pediatric and Adolescent Medicine, Akershus University Hospital, 1478, Lørenskog, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Paediatr Drugs. 2020 Aug;22(4):409-416. doi: 10.1007/s40272-020-00396-1.
Treatment with biological agents such as anti-tumor necrosis factors (TNFs) has become standard of care in moderate to severe pediatric inflammatory bowel disease (IBD). However, a significant proportion of patients experience loss of response to anti-TNFs, need treatment escalation, or develop side effects. There is no data in the literature regarding combination of biological agents in pediatric IBD.
At our hospital, which is a tertiary referral center, we have combined the anti-TNF infliximab with either vedolizumab or ustekinumab in patients with severe pediatric IBD. The indications for dual biological therapy were insufficient efficacy of infliximab or vedolizumab monotherapy, or side effects such as psoriasis due to anti-TNFs.
Eight patients (four boys) aged 14-17.5 years received a combination of infliximab and vedolizumab due to only a partial response to infliximab, four with Crohn's disease (CD) and four with ulcerative colitis (UC). Clinical remission was achieved in four patients (3 UC) and four had a colectomy (3 CD, 1 UC). Five CD patients (3 girls) aged 11-17 years, on maintenance therapy with infliximab, developed psoriasis resistant to topical treatment. A combination of infliximab and ustekinumab resulted in clinical remission of CD without skin symptoms. No serious adverse events occurred in any of the patients on combination therapy. Thirteen publications report on combining biologicals, all in adult IBD.
In pediatric IBD, combining biological agents seems to be safe and beneficial in selected patients. The safety should be addressed in long-term follow-up studies.
在中重度儿科炎症性肠病（IBD）中，使用抗肿瘤坏死因子（TNF）等生物制剂的治疗已成为标准治疗方法。然而，相当一部分患者对抗 TNF 的反应丧失，需要升级治疗或出现副作用。在儿科 IBD 中，关于联合使用生物制剂的文献尚无数据。
在我们的医院，这是一家三级转诊中心，我们在患有严重儿科 IBD 的患者中联合使用抗肿瘤坏死因子的英夫利昔单抗与维得利珠单抗或乌司奴单抗。双重生物治疗的适应证为英夫利昔单抗或维得利珠单抗单药治疗效果不佳，或因抗 TNF 而出现银屑病等副作用。
8 名（4 男）年龄 14-17.5 岁的患者因英夫利昔单抗治疗仅部分缓解而接受英夫利昔单抗联合维得利珠单抗治疗，其中 4 名患有克罗恩病（CD），4 名患有溃疡性结肠炎（UC）。4 名患者（3 例 UC）达到临床缓解，4 名患者进行结肠切除术（3 例 CD，1 例 UC）。5 名（3 名女孩）年龄 11-17 岁的 CD 患者在接受英夫利昔单抗维持治疗时出现对局部治疗有抗药性的银屑病。英夫利昔单抗联合乌司奴单抗治疗使 CD 患者的临床症状缓解，且无皮肤症状。联合治疗的患者均未发生严重不良事件。有 13 篇文献报告了联合使用生物制剂的情况，均在成人 IBD 中进行。
在儿科 IBD 中，联合使用生物制剂在选择的患者中似乎是安全且有益的。在长期随访研究中应注意安全性。
