Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Alimentiv Inc, London, Ontario, Canada.
BMJ Open. 2022 Apr 1;12(4):e057656. doi: 10.1136/bmjopen-2021-057656.
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.
初步数据表明，与经验性剂量递增和/或反应性治疗药物监测相比，积极主动的治疗药物监测（TDM）与更好的结果相关，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，在诱导期早期，即疾病活动度和药物清除率最高时，尚未有关于积极主动的 TDM 联合 PK 仪表板开始使用的数据，以评估其在中度至重度活动 CD 患者中的效用。本随机、对照、多中心、开放标签试验的目的是评估与标准治疗（SOC）相比，在中度至重度活动 CD 患者中使用积极主动的 TDM 联合 PK 仪表板驱动的英夫利昔单抗给药与 SOC 治疗的疗效和安全性。
符合条件的青少年和成年（年龄≥16-80 岁）中度至重度活动 CD 患者将按 1:1 随机分配接受英夫利昔单抗单药治疗，同时使用 PK 仪表板（iDose，Projections Research）或 SOC 英夫利昔单抗治疗，是否同时使用免疫调节剂（IMM）（硫唑嘌呤或甲氨蝶呤）由研究者自行决定。该研究的主要结局是从第 14 周到第 52 周，持续无皮质类固醇缓解且无需抢救治疗的患者比例。抢救治疗定义为除 iDose 预测的剂量外，任何英夫利昔单抗剂量的增加，无论是经验性的还是基于反应性 TDM 的剂量增加；第 2 周后添加 IMM；初始减量后重新开始使用皮质类固醇；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、反应的持久性以及 CD 相关手术和住院治疗。
该方案已获得贝斯以色列女执事医疗中心机构审查委员会（IRB#：2021P000391）的批准。结果将在同行评议的期刊上发表，并在科学会议上报告。
NCT04835506。
