主动监测英夫利昔单抗水平在儿科克罗恩病中的应用。
Utility of proactive infliximab levels in paediatric Crohn's disease.
机构信息
Department of Gastroenterology, Hepatology and Liver Transplant, Lady Cilento Children's Hospital, South Brisbane, Queensland, Australia.
Discipline of Paediatrics and Child Health, University of Queensland, Brisbane, Queensland, Australia.
出版信息
Arch Dis Child. 2019 Mar;104(3):251-255. doi: 10.1136/archdischild-2018-315100. Epub 2018 Jun 27.
OBJECTIVE
Infliximab (IFX) has an established role in Crohn's disease (CD), with serum trough levels of IFX (TLI) increasingly used to optimise dosing. We report the utility of routine, proactive TLI in children on combination therapy with immunosuppression (IS) from a single paediatric centre.
METHODS
This is a retrospective chart review of all children with CD receiving IFX therapy conducted betweenJanuary 2014-May 2017. Clinical phenotype, duration of therapy, TLI (µg/mL), drug antibodies, type of IS, biomarkers and changes in management were recorded.
RESULTS
60 children (8-17 years; median 14.1 years) had 206 TLIs recorded. 56/60 (93%) were on IS, with 5/60 (8%) developing antidrug antibodies (ADAs). 63/206 TLIs were recorded duringan episode of relapse (median 3.0 µg/mL) vs 143/206 TLIs recorded in remission (median 5.2 µg/mL). For children with TLI <3 µg/mL, 31/63 (49%) were in relapse vs 30/143 (21%) in remission. For children with TLI >7 µg/mL, 7/63 (11%) were in relapse vs 46/143 (32%) in remission. Change in management resulted from 43/206 (21%) TLIs in 31/60 (52%) children: 21 dose escalations, 12 de-escalations and 10 changed to adalimumab. Of 31 postinduction TLIs, 15/17 (88%) children with TLI >7 µg/mL achieved clinical and biochemical remission for the duration of therapy (median 14 months), while 4/5 (80%) children with TLI <3 µg/mL required early dose escalation. Combination therapy with thiopurines (TP) (median TLI 4.9 µg/mL) versus methotrexate (MTX) (median TLI 5.2 µg/mL) achieved comparable levels with no difference in relapse frequency.
CONCLUSIONS
Routine, proactive TLIs guide optimal management in children with CD. Postinduction and during maintenance, levels <3 µg/mL were associated with relapse and levels >7 µg/mL with sustained remission. Combination IS with TP and MTX appears to offer comparable TLI and ADA rates.
目的
英夫利昔单抗（IFX）在克罗恩病（CD）中具有既定的作用，IFX 的血清谷浓度（TLI）越来越多地用于优化剂量。我们报告了来自单一儿科中心的接受免疫抑制（IS）联合治疗的儿童常规、主动 TLI 的实用性。
方法
这是一项对 2014 年 1 月至 2017 年 5 月期间接受 IFX 治疗的所有 CD 儿童的回顾性图表审查。记录临床表型、治疗持续时间、TLI（µg/mL）、药物抗体、IS 类型、生物标志物和管理变化。
结果
60 名儿童（8-17 岁；中位数 14.1 岁）共记录了 206 个 TLI。60 名儿童中有 56/60（93%）正在接受 IS 治疗，其中 5/60（8%）产生了抗药物抗体（ADAs）。63/206 个 TLI 是在复发期间（中位数 3.0 µg/mL）记录的，而 143/206 个 TLI 是在缓解期间（中位数 5.2 µg/mL）记录的。对于 TLI <3 µg/mL 的儿童，31/63（49%）处于复发状态，而 30/143（21%）处于缓解状态。对于 TLI >7 µg/mL 的儿童，63/63（11%）处于复发状态，而 46/143（32%）处于缓解状态。由于 31/60（52%）名儿童中的 43/206（21%）个 TLI 导致了管理方式的改变：21 个剂量升级，12 个剂量降级，10 个改为阿达木单抗。在 31 个诱导后 TLI 中，15/17（88%）TLI >7 µg/mL 的儿童在治疗期间（中位数 14 个月）达到了临床和生化缓解，而 4/5（80%）TLI <3 µg/mL 的儿童需要早期剂量升级。与甲氨蝶呤（MTX）（中位数 TLI 5.2 µg/mL）相比，联合使用硫嘌呤（TP）（中位数 TLI 4.9 µg/mL）的组合 IS 实现了可比的水平，复发频率无差异。
结论
常规、主动 TLI 指导 CD 儿童的最佳管理。诱导后和维持期间，TLI <3 µg/mL 与复发相关，而 TLI >7 µg/mL 与持续缓解相关。TP 和 MTX 的联合 IS 似乎提供了可比的 TLI 和 ADA 率。
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