*Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France; †Department of Gastroenterology, Hospices Civils de Lyon, and INSERM U1111, Lyon, France; ‡Department of Statistics, University of Lyon, Lyon, France; §Department of Gastroenterology, University Hospital of Nancy, Nancy, France; and ‖Department of Immunology, CIC1408, GIMAP EA3064, University Hospital of Saint Etienne, Saint Etienne, France.
Inflamm Bowel Dis. 2017 Nov;23(11):2048-2053. doi: 10.1097/MIB.0000000000001223.
Several studies have reported a strong correlation between infliximab (IFX) trough levels (trough levels of infliximab [TLI]) and clinical remission (CR). We aimed to determine threshold values of TLI associated with the occurrence of CR, with or without normal inflammatory biomarkers, including serum C-reactive protein (CRP) and fecal calprotectin (fCal).
We included prospectively all consecutive patients with inflammatory bowel disease under IFX therapy (5 mg/kg every 8 wk) for at least 6 months. Disease activity (using the Crohn's Disease Activity Index or Mayo score) was recorded, and TLI, CRP, and fCal were measured before IFX infusion.
Two hundred thirteen patients (131 Crohn's disease) were included. The median TLIs were higher in patients who achieved CR compared with those in patients who did not (2.6 versus 1.2 μg/mL, P < 0.01). The median TLI were higher in patients achieving CR with CRP normalization or CR with fCal <250 μg/g in comparison with patients with persistent elevated CRP or fCal (3.5 versus 1.6 μg/mL, P < 0.01 and 4.9 versus 1.8 μg/mL, P < 0.001, respectively). Finally, the median TLIs were higher in patients achieving CR with normal CRP and fCal <50 μg/g in comparison with patients without strictly normal biomarkers (5.9 versus 2.1 μg/mL, P < 0.001). The more the expected level of response to IFX was stringent, the more the median TLI and optimal thresholds were high.
Threshold values of TLI differ according to therapeutic outcomes expected in patients with inflammatory bowel disease under maintenance therapy with IFX.
几项研究报告称,英夫利昔单抗(IFX)谷浓度(英夫利昔单抗谷浓度[TLI])与临床缓解(CR)之间存在很强的相关性。我们旨在确定与 CR 发生相关的 TLI 阈值,无论是否存在正常的炎症生物标志物,包括血清 C 反应蛋白(CRP)和粪便钙卫蛋白(fCal)。
我们前瞻性地纳入了所有接受 IFX 治疗(5mg/kg,每 8 周 1 次)至少 6 个月的炎症性肠病连续患者。记录疾病活动度(使用克罗恩病活动指数或 Mayo 评分),并在 IFX 输注前测量 TLI、CRP 和 fCal。
共纳入 213 例(131 例克罗恩病)患者。与未达到 CR 的患者相比,达到 CR 的患者 TLI 中位数更高(2.6 与 1.2μg/ml,P<0.01)。与 CRP 持续升高或 fCal>250μg/g 的患者相比,CRP 正常或 fCal<250μg/g 时达到 CR 的患者 TLI 中位数更高(3.5 与 1.6μg/ml,P<0.01 和 4.9 与 1.8μg/ml,P<0.001)。最后,与未达到严格正常生物标志物的患者相比,CRP 和 fCal 正常且<50μg/g 时达到 CR 的患者 TLI 中位数更高(5.9 与 2.1μg/ml,P<0.001)。IFX 预期疗效越严格,TLI 的中位数和最佳阈值越高。
在接受 IFX 维持治疗的炎症性肠病患者中,根据治疗预期疗效,TLI 的阈值值不同。