Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth-Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA, 02215, USA.
Department of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA.
Dig Dis Sci. 2018 Nov;63(11):3067-3073. doi: 10.1007/s10620-018-5202-5. Epub 2018 Jul 13.
A treat-to-target therapeutic approach is emerging as the new standard of care for treating inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC).
We aimed to investigate the association of serum adalimumab concentrations during maintenance therapy with biochemical, endoscopic, and histologic remission in IBD.
This retrospective multicenter study included consecutive IBD patients on adalimumab maintenance therapy who had a C-reactive protein (CRP) within 1 week and/or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between July 2013 and December 2016. Biochemical remission was defined as a normal CRP (≤ 5 mg/L). Endoscopic remission was defined as the absence of any ulceration/erosion or a Rutgeerts score of ≤ i1 for patients with an ileocolonic resection for CD and a Mayo endoscopic score of ≤ 1 for UC. Histologic remission was defined as the absence of any sign of active inflammation. Adalimumab concentrations were measured using the homogeneous mobility shift assay.
Ninety-one CRP levels and 72 colonoscopies from 98 IBD patients [CD: n = 72 (73%)] were evaluated. Based on receiver operating characteristic analyses, we identified an adalimumab concentration threshold of 11.8, 12, and 12.2 μg/mL in CD and 10.5, 16.2, and 16.2 μg/mL in UC to stratify patients with or without biochemical, endoscopic, or histologic remission, respectively. Adalimumab concentrations ≥ 12 μg/mL (OR 8; 95% CI 2-31.9; p = 0.003) and ≥ 12.2 μg/mL (OR 9.6; 95% CI 1.7-56.1; p = 0.012) were independently associated with endoscopic and histologic remission in CD, respectively.
This study demonstrates that higher maintenance adalimumab concentrations are associated with objective therapeutic outcomes in IBD.
靶向治疗方法作为治疗炎症性肠病（IBD）、克罗恩病（CD）和溃疡性结肠炎（UC）的新标准正在出现。
我们旨在研究维持治疗期间血清阿达木单抗浓度与 IBD 患者的生化、内镜和组织学缓解之间的关系。
本回顾性多中心研究纳入了 2013 年 7 月至 2016 年 12 月期间接受阿达木单抗维持治疗且在治疗药物监测的 1 周内和/或 12 周内有 C 反应蛋白（CRP）和/或内镜评估的连续 IBD 患者。生化缓解定义为正常 CRP（≤5mg/L）。内镜缓解定义为无任何溃疡/糜烂或 CD 患者经回肠结肠切除术的 Rutgeerts 评分≤i1 和 UC 的 Mayo 内镜评分≤1。组织学缓解定义为无任何活动炎症迹象。阿达木单抗浓度采用均相迁移率分析法测定。
评估了 98 例 IBD 患者[CD：n=72（73%）]的 91 个 CRP 水平和 72 次结肠镜检查结果。基于受试者工作特征分析，我们确定了 11.8、12 和 12.2μg/mL 作为 CD 患者实现生化、内镜或组织学缓解的阿达木单抗浓度阈值，分别为 10.5、16.2 和 16.2μg/mL 在 UC 中。阿达木单抗浓度≥12μg/mL（比值比 8；95%置信区间 2-31.9；p=0.003）和≥12.2μg/mL（比值比 9.6；95%置信区间 1.7-56.1；p=0.012）分别与 CD 患者的内镜和组织学缓解独立相关。
本研究表明，较高的维持阿达木单抗浓度与 IBD 的客观治疗结果相关。
