Céspedes-Martínez Elena, Robles-Alonso Virginia, Serra-Ruiz Xavier, Herrera-De Guise Claudia, Mayorga-Ayala Luis, García-García Sonia, Larrosa-García María, Casellas Francesc, Borruel Natalia
Unitat d'Atenció Crohn Colitis (UACC), Gastroenterology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
Pharmacy Department, Vall d'Hebron University Hospital, Barcelona, Spain.
Crohns Colitis 360. 2025 Jun 27;7(3):otaf023. doi: 10.1093/crocol/otaf023. eCollection 2025 Jul.
Proactive therapeutic drug monitoring facilitates early dose optimization to prevent primary and secondary failure to antitumor necrosis factor (TNF). We aimed to investigate the impact of dashboard-guided induction dosing strategy on anti-TNF durability and immunogenicity.
We conducted a single-center cohort analysis of patients with Crohn's disease (CD) and Ulcerative colitis (UC) who initiated treatment with infliximab or adalimumab between January 2020 and March 2023. Induction was prospectively personalized using a pharmacokinetic model-guided dosing strategy, with drug measurements at week 2, 6, and 14, and the first dose adjustment occurred in week 4. Data were recorded retrospectively. We assessed treatment durability, pharmacokinetic outcomes, clinical remission (CR), and endoscopic remission (ER), at both weeks 24 and 56. Multivariate analysis and Kaplan-Meier curves were used to compare outcomes.
We enrolled 147 patients (92 CD /55 UC). Anti-TNF drug survival probability was 85.00% after a year. Seventy-seven percent of patients were prescribed an intensified dose in the first year, which was associated with improved drug durability. Only 1 patient out of 147 developed antibodies to adalimumab, none to infliximab. After 24 and 52 weeks of treatment 92.5% (136/147) and 72.78% (107/147) of patients achieved CR, respectively. ER was observed in 59.39% (79/133) of patients. The use of immunomodulators or carriage of HLA DQA1*05 variant was not associated with adverse treatment or pharmacokinetic outcomes.
Optimizing anti-TNF induction with a dashboard-guide dosing strategy proves to be a valuable approach to enhance treatment durability and clinical outcomes in inflammatory bowel disease patients. Immunogenicity appears to be mitigated by the model, which even mitigates the impact of immunomodulators and overcomes HLA DQA1*05 effect.
积极的治疗药物监测有助于早期剂量优化，以预防抗肿瘤坏死因子（TNF）治疗的原发性和继发性失败。我们旨在研究仪表盘引导的诱导给药策略对抗TNF药物持久性和免疫原性的影响。
我们对2020年1月至2023年3月期间开始使用英夫利昔单抗或阿达木单抗治疗的克罗恩病（CD）和溃疡性结肠炎（UC）患者进行了单中心队列分析。诱导治疗采用药代动力学模型引导的给药策略进行前瞻性个体化，在第2、6和14周进行药物测量，首次剂量调整在第4周进行。数据进行回顾性记录。我们在第24周和第56周评估了治疗持久性、药代动力学结果、临床缓解（CR）和内镜缓解（ER）。采用多变量分析和Kaplan-Meier曲线比较结果。
我们纳入了147例患者（92例CD/55例UC）。一年后抗TNF药物存活概率为85.00%。77%的患者在第一年接受了强化剂量，这与药物持久性改善相关。147例患者中只有1例产生了阿达木单抗抗体，英夫利昔单抗无一例产生抗体。治疗24周和52周后，分别有92.5%（136/147）和72.78%（107/147）的患者达到CR。59.39%（79/133）的患者观察到ER。免疫调节剂的使用或HLA DQA1*05变异的携带与不良治疗或药代动力学结果无关。
事实证明，采用仪表盘引导的给药策略优化抗TNF诱导治疗是提高炎症性肠病患者治疗持久性和临床结局的一种有价值的方法。该模型似乎减轻了免疫原性，甚至减轻了免疫调节剂的影响并克服了HLA DQA1*05的作用。
