Department of Gastroenterology and Hepatology, Amsterdam UMC, Location AMC , Amsterdam, The Netherlands.
Projections Research Inc., Phoenixville, PA, USA.
Scand J Gastroenterol. 2021 Feb;56(2):145-154. doi: 10.1080/00365521.2020.1856405. Epub 2020 Dec 8.
Loss of response (LOR) to infliximab (IFX) remains a challenge in the management of inflammatory bowel diseases (IBD). Proactive dosing strategies to achieve and maintain predefined IFX trough levels (TL) may prevent LOR. We aimed to investigate the efficacy of dashboard driven IFX dosing compared to standard dosing in a prospective trial in IBD patients.
In this multicentre 1:1 'PRECISION' trial, we randomized IBD patients in clinical remission (Harvey Bradshaw Index ≤4 for Crohn's disease (CD) or a partial Mayo score ≤2 for ulcerative colitis (UC)) receiving IFX maintenance treatment. The precision group (PG) received IFX dosing guided by a Bayesian pharmacokinetic model, aiming to achieve and maintain a TL of 3 µg/ml by treatment (de)escalation as indicated by the dashboard. Patients in the control group (CG) continued treatment without dose adaptations. The primary endpoint was the proportion of patients in sustained clinical remission after 1 year.
Eighty patients were enrolled (66 CD, 14 UC), and the median [interquartile range] age was 37 years [27-51]). After one year, 28/32 (88%) of patients in the PG were in sustained clinical remission versus 25/39 (64%) in the CG ( = .017). PG patients had lower median faecal calprotectin levels after 1 year ( = .031), whereas no significant differences in median CRP levels were found.
We demonstrated that the use of a Bayesian dashboard for IFX dosing in maintenance treatment for IBD reduced the incidence of LOR compared to standard dosing. Precision dosing also resulted in lower FCP levels.
CLINICALTRIALS.GOV NUMBER: NCT02453776.
英夫利昔单抗（IFX）治疗应答丧失仍然是炎症性肠病（IBD）管理中的一个挑战。积极的剂量策略，以实现和维持预定的 IFX 谷浓度（TL），可能预防治疗应答丧失。我们旨在研究在 IBD 患者的前瞻性试验中，仪表盘驱动的 IFX 剂量与标准剂量相比的疗效。
在这项多中心 1:1 的“精准”试验中，我们随机分配处于临床缓解期（克罗恩病（CD）为 Harvey Bradshaw 指数≤4，溃疡性结肠炎（UC）为部分 Mayo 评分≤2）并接受 IFX 维持治疗的 IBD 患者。精准组（PG）接受贝叶斯药代动力学模型指导的 IFX 剂量，通过治疗（增减）根据仪表盘指示，旨在达到并维持 3μg/ml 的 TL。对照组（CG）患者继续接受治疗而不进行剂量调整。主要终点是 1 年后持续临床缓解的患者比例。
共纳入 80 例患者（66 例 CD，14 例 UC），中位[四分位间距]年龄为 37 岁[27-51]）。1 年后，PG 中 28/32（88%）例患者持续临床缓解，CG 中 25/39（64%）例患者持续临床缓解（ = .017）。PG 患者在 1 年后粪便钙卫蛋白水平中位数较低（ = .031），而 CRP 水平中位数无显著差异。
我们证明，在 IBD 的维持治疗中，与标准剂量相比，使用贝叶斯仪表盘进行 IFX 剂量可降低治疗应答丧失的发生率。精准剂量还导致粪便 calprotectin 水平降低。
NCT02453776。
