Proactive infliximab optimisation using a pharmacokinetic dashboard versus standard of care in patients with Crohn's disease: study protocol for a randomised, controlled, multicentre, open-label study (the OPTIMIZE trial).
Proactive infliximab optimisation using a pharmacokinetic dashboard versus standard of care in patients with Crohn's disease: study protocol for a randomised, controlled, multicentre, open-label study (the OPTIMIZE trial).
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DOI：
10.1136/bmjopen-2021-057656
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发表时间：
2022-04-01
期刊：
影响因子：
2.9
通讯作者：
Cheifetz A
中科院分区：
文献类型：
--
作者：
Papamichael K;Jairath V;Zou G;Cohen B;Ritter T;Sands B;Siegel C;Valentine J;Smith M;Vande Casteele N;Dubinsky M;Cheifetz A
初步数据表明，与经验性剂量递增和/或反应性TDM相比，主动治疗药物监测（TDM）与更好的结局相关，并且药代动力学（PK）建模可以提高克罗恩病（CD）个体给药方案的精度。然而，没有关于在诱导期早期（疾病活动和药物清除率最高时）开始主动TDM联合PK仪表板的效用的数据。这项随机、对照、多中心、开放标签试验的目的是在中重度活动性CD患者中评价主动TDM联合PK仪表板驱动的英夫利西单抗给药与标准治疗（SOC）给药相比的疗效和安全性。符合条件的中重度活动性CD青少年和成人（年龄≥16-80岁）患者将按照1：1的比例随机分配接受英夫利西单药治疗联合使用PK仪表板（iDose，Projections Research）的主动TDM或SOC英夫利西单药治疗，根据研究者的判断，联合或不联合免疫调节剂（IMM）（硫嘌呤或甲氨蝶呤）。研究的主要结局是从第14周至第52周持续无皮质类固醇临床缓解且无需补救治疗的受试者比例。补救治疗定义为任何IFX剂量递增（iDose根据经验或基于反应性TDM预测的剂量除外）;第2周后添加IMM;初始减量后重新引入皮质类固醇;改用另一种生物制剂或需要CD相关手术。次要结局将包括疗效和安全性终点，如内镜和生物学缓解、缓解持久性和CD相关手术和住院治疗。该方案已获得Beth Israel Deaconess Medical Center机构审查委员会委员会的批准（IRB编号：2021 P000391）。研究结果将在同行评审的期刊上传播，并在科学会议上提出。NCT 04835506。
Preliminary data indicates that proactive therapeutic drug monitoring (TDM) is associated with better outcomes compared with empiric dose escalation and/or reactive TDM, and that pharmacokinetic (PK) modelling can improve the precision of individual dosing schedules in Crohn’s disease (CD). However, there are no data regarding the utility of a proactive TDM combined PK-dashboard starting early during the induction phase, when disease activity and drug clearance are greatest. The aim of this randomised, controlled, multicentre, open-label trial is to evaluate the efficacy and safety of a proactive TDM combined PK dashboard-driven infliximab dosing compared with standard of care (SOC) dosing in patients with moderately to severely active CD. Eligible adolescent and adult (aged ≥16–80 years) patients with moderately to severely active CD will be randomised 1:1 to receive either infliximab monotherapy with proactive TDM using a PK dashboard (iDose, Projections Research) or SOC infliximab therapy, with or without a concomitant immunomodulator (IMM) (thiopurine or methotrexate) at the discretion of the investigator. The primary outcome of the study is the proportion of subjects with sustained corticosteroid-free clinical remission and no need for rescue therapy from week 14 throughout week 52. Rescue therapy is defined as any IFX dose escalation other than what is forecasted by iDose either done empirically or based on reactive TDM; addition of an IMM after week 2; reintroduction of corticosteroids after initial tapering; switch to another biologic or need for CD-related surgery. The secondary outcomes will include both efficacy and safety end points, such as endoscopic and biological remission, durability of response and CD-related surgery and hospitalisation. The protocol has been approved by the Institutional Review Board Committee of the Beth Israel Deaconess Medical Center (IRB#:2021P000391). Results will be disseminated in peer-reviewed journals and presented at scientific meetings. NCT04835506.
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