血清C-反应蛋白、白蛋白及腹部超声弹性成像技术对活动期克罗恩病患者抗肿瘤坏死因子-α单克隆抗体治疗疗效的预测价值

Predictive value of CRP,albumin and abdominal ultrasound elastography technology on efficacy of anti-tumor necrosis factor-αmonoclonal antibodies in patients with active Crohn′s disease

目的本研究旨在评估活动期克罗恩病患者治疗前血清C-反应蛋白(CRP)、白蛋白、经腹超声下肠壁厚度及出现狭窄肠段的肠壁弹性成像弹性模量SD值对治疗疗效的预测价值。方法前瞻性纳入2018年1月至2021年6月期间首次使用英夫利昔单抗或阿达木单抗治疗活动期克罗恩病的所有患者。根据治疗后不同疗效将其分为原发性失应答组(PNR组)、继发性失应答组(SLOR组)与临床缓解组(REM)。治疗前均接受血清白蛋白、CRP的检测及完善经腹超声下肠壁厚度的测量,若出现肠道狭窄,则完善超声弹性成像测量狭窄肠段肠壁弹性模量SD值,并随访至2021年6月。结果观察期间共纳入45例活动期克罗恩病患者,其中8例(18%)患者治疗前出现肠道狭窄。43例(96%)患者接受英夫利昔单抗一线治疗,2例(4%)患者使用阿达木单抗一线治疗。观察14周均出现临床应答,无原发性无应答者,38例(84.4%)患者显示持续临床缓解,7例(15.6%)患者出现继发性失应答,发生继发性失应答的时间为(11.4±7.4)月。REM组CRP水平与SLOR组差异无统计学意义,血清白蛋白浓度、肠壁厚度及狭窄肠段SD值差异有统计学意义,其中REM组血清白蛋白浓度明显高于SLOR组[(38.1±5.2)g/L vs.(31.1±4.6)g/L],超声下肠壁厚度明显低于SLOR组[(5.8±1.9)mm vs.(8.2±1.5)mm],治疗前肠道狭窄的患者中弹性模量SD值也低于继发性失应答组[(7.6±1.2)vs.(9.9±2.0)],且治疗前低白蛋白血症、肠壁厚度≥8 mm及狭窄肠段弹性模量SD值≥9与治疗后较早失去反应相关(P<0.05)。结论活动期克罗恩病患者治疗前血清白蛋白浓度、肠壁厚度、出现狭窄部位肠壁弹性模量SD值与抗肿瘤坏死因子α治疗疗效相关,而治疗前血清CRP水平与治疗疗效无关,且治疗前低白蛋白血症、经腹超声下肠壁厚度≥8 mm及狭窄肠段弹性模量SD值≥9与抗肿瘤坏死因子α治疗较早失应答风险密切相关。

Objective The purpose of this research is to evaluate the predictive value of serum CRP,albumin,bowel wall thickness under transabdominal ultrasound,and intestinal wall elasticity modulus SD value of intestinal stenosis before treatment in patients with active Crohn’s disease.Methods Prospectively,all patients treated for the first time with either infliximab or adalimumab for active Crohn’s disease between January 2018 and June 2021 were included.All patients were tested for serum albumin,CRP,bowel wall thickness under transabdominal ultrasound and intestinal wall elastic modulus SD value of intestinal stenosis and were followed up until June 2021.Results A total of 45 active Crohn’s disease patients were included in the study.Forty-three patients(96%)received first-line treatment with infliximab,and 2 patients(4%)received first-line treatment with adalimumab,of which 8 patients had intestinal stenosis before treatment.Clinical responses occurred in all 14 weeks of observation;there were no primary non-responders;38 patients(84.4%)showed sustained clinical remission,and 7 patients(15.6%)developed a secondary loss of response.Meantime to develop secondary loss of response was(11.4±7.4)months.There was no statistical difference between the CRP level in the sustained clinical remission group and the secondary failure group,while the serum albumin concentration,intestinal wall thickness,and SD value of stenotic intestine were statistically different.The serum albumin concentration in the sustained clinical remission group was significantly higher than that in the secondary failure group[(38.1±5.2)g/L vs.(31.1±4.6)g/L];the thickness of the bowel wall under ultrasound was significantly lower than that in the secondary loss of response group[(5.8±1.9)mm vs.(8.2±1.5)mm],and the SD value of patients with sustained clinical response was also lower[(7.6±1.2)vs.(9.9±2.0)].Hypoalbuminemia,bowel wall thickness≥8 mm,and SD value≥9 were related to early loss of response.Conclusion Serum albumin concentration,bowel wall thickness and elastic modulus SD value before treatment in patients with active Crohn’s disease are related to the therapeutic effect of anti-tumor necrosis factor-a monoclonal antibody,while the serum CRP level has nothing to do with the therapeutic effect.Hypoalbuminemia,bowel wall thickness≥8 mm under transabdominal ultrasound and elastic modulus SD value≥9 are closely associated with a higher risk for early loss of response to the anti TNF-αmonoclonal antibody treatment.