Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos [IdISSC], Madrid, Spain.
Instituto de Investigación del Hospital Clínico San Carlos [IdISSC], Madrid, Spain.
Aliment Pharmacol Ther. 2022 Aug;56(4):614-624. doi: 10.1111/apt.16964. Epub 2022 May 4.
Optimal golimumab concentration thresholds for important outcomes during maintenance are lacking.
To investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC.
This multi-centre, cross-sectional study included patients with UC on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy.
Fifty-two patients were included. Median golimumab trough concentrations (μg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS ≤2 + faecal calprotectin <250 μg/g) (2.21 vs. 1.47, p = 0.041), endoscopic healing (Mayo endoscopic subscore 0) (2.52 vs. 1.47, p = 0.003), histologic remission (Geboes index ≤2.0) (2.33 vs. 1.50, p = 0.02) and disease clearance (clinical remission endoscopic healing + histologic remission) (2.52 vs. 1.70, p = 0.009), compared with those not meeting these criteria. Golimumab concentrations were significantly higher in patients who avoided golimumab dose escalation/discontinuation during follow-up (2.24 vs. 0.98, p = 0.012). Receiver-operating characteristic analyses identified golimumab thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.76], 2.29 [0.75], 1.79 [0.68], 2.29 [0.72] and 1.56 [0.71] μg/ml as associated with clinical remission, combined remission, endoscopic healing, histologic remission, disease clearance and long-term event-free persistence with golimumab, respectively.
Golimumab trough concentrations during maintenance are associated with favourable treatment outcomes including endoscopic healing, histologic remission and long-term persistence on golimumab. We identified the optimal golimumab thresholds most closely associated with key outcomes.
维持治疗中，理想的戈利木单抗浓度阈值对于重要结局仍不明确。
旨在探究接受戈利木单抗维持治疗的 UC 患者，戈利木单抗谷浓度与关键结局之间的关联，这些结局包括内镜和组织学缓解，以及长期无事件持续使用戈利木单抗。
这是一项多中心、横断面研究，纳入正在接受戈利木单抗维持治疗的 UC 患者，这些患者或是处于缓解期，或是处于发作期。安排结肠镜检查，并进行研究特定的直肠结肠活检，用于盲法中央组织学阅读。在接近结肠镜检查时采集戈利木单抗谷浓度样本。
共纳入 52 例患者。与未达到这些标准的患者相比，处于临床缓解（2.01 vs. 0.72，p=0.047）、联合临床-生物化学缓解（PMS ≤2+粪便钙卫蛋白<250μg/g）（2.21 vs. 1.47，p=0.041）、内镜愈合（Mayo 内镜下评分 0）（2.52 vs. 1.47，p=0.003）、组织学缓解（Geboes 指数≤2.0）（2.33 vs. 1.50，p=0.02）和疾病清除（临床缓解+内镜愈合+组织学缓解）（2.52 vs. 1.70，p=0.009）的患者，其戈利木单抗谷浓度（μg/ml）显著更高。与在随访期间避免戈利木单抗剂量升级/停药的患者相比（2.24 vs. 0.98，p=0.012），这些患者的戈利木单抗浓度也显著更高。受试者工作特征分析确定了与临床缓解、联合缓解、内镜愈合、组织学缓解、疾病清除和长期无事件持续使用戈利木单抗相关的戈利木单抗阈值 [曲线下面积] 分别为 0.85 [0.76]、1.90 [0.76]、2.29 [0.75]、1.79 [0.68]、2.29 [0.72] 和 1.56 [0.71]μg/ml。
维持治疗中的戈利木单抗谷浓度与包括内镜愈合、组织学缓解和长期持续使用戈利木单抗在内的有利治疗结局相关。我们确定了与关键结局最密切相关的最佳戈利木单抗阈值。
