较高的药物水平和低剂量口服甲氨蝶呤 (LD-MTX) 联合治疗可能会减少儿童克罗恩病的抗肿瘤坏死因子 (TNF) 治疗失败。我们试图（1）评估 LD-MTX 联合治疗是否与较高的抗 TNF 水平相关，（2）评估抗 TNF 水平与随后治疗失败之间的关联，以及（3）探索联合治疗对维持治疗的影响治疗药物水平（英夫利昔单抗 > 5 µg/mL，阿达木单抗 > 7.5 µg/mL）患者的缓解率。我们对 COMBINE 试验进行了事后分析，该试验比较了抗 TNF 单一疗法与 LD-MTX 联合疗法。我们纳入了进入维持治疗并在随机分组后约 4 个月提供血清样本的参与者。在 112 名英夫利昔单抗和 41 名阿达木单抗起始药物中，联合治疗和单药治疗之间的中位药物水平相似（英夫利昔单抗：8.8 vs 7.5 μg/mL [P = .49] ]；阿达木单抗：11.1 vs 10.5 μg/mL [P = .11]）。治疗失败的患者中位药物水平较低（英夫利昔单抗：4.2 vs 9.6 μg/mL [P <0.01]；阿达木单抗：9.1 vs 12.3 μg/mL [P <0.01]）。在接受英夫利昔单抗治疗药物水平的患者中，我们观察到接受单一疗法或联合疗法的参与者之间的治疗失败没有差异。在接受阿达木单抗治疗的患者中，联合治疗组治疗失败减少的趋势并不具有统计学意义 (P = .14)。LD-MTX 组合与较高的药物水平无关，但较高的药物水平与降低的风险相关治疗失败。在具有治疗药物水平的患者中，我们观察到 LD-MTX 对接受英夫利昔单抗治疗的患者没有益处。添加接受阿达木单抗治疗的 LD-MTX 患者后，治疗失败的减少趋势并不显着，值得进一步研究。© 作者 2024。由牛津大学出版社代表克罗恩病出版

Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab).We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization.Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 μg/mL [P = .49]; adalimumab: 11.1 vs 10.5 μg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 μg/mL [P < .01]; adalimumab: 9.1 vs 12.3 μg/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14).LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation.© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.