阿达木单抗治疗克罗恩病的有效性和安全性

Efficacy and safety of adalimumab in the treatment of Crohn′s disease

目的评估阿达木单抗(ADA)治疗克罗恩病的有效性和安全性,并分析ADA疗效的预测因素。方法连续纳入2020年1至12月于同济大学附属第十人民医院消化内科接受ADA治疗的49例克罗恩病患者,收集治疗前的临床资料;ADA治疗12周期间,每2周进行1次临床随访,每4周进行1次实验室检查,并于ADA治疗第12周时复查肠镜。评估患者在ADA治疗2、4、6周的主要症状改善情况;ADA治疗12周时临床应答(克罗恩病活动指数较基线下降≥70分)、临床缓解(克罗恩病活动指数评分<150分)、内镜应答(克罗恩病简化内镜评分较基线下降>50%)、内镜下缓解(克罗恩病简化内镜评分≤2分或Rutgeerts评分≤1分)情况,合并肛瘘患者的肛瘘闭合情况;治疗期间不良反应的发生情况。分析ADA治疗12周时克罗恩病患者临床缓解的预测因素。统计学方法采用Mann-WhitneyU检验、二元logistic回归分析。结果49例克罗恩病患者在ADA治疗2、4、6周的主要症状改善率分别为75.5%(37/49)、95.9%(47/49)、98.0%(48/49),主要症状改善时间为14.0 d(7.0 d,17.0 d);ADA治疗12周时,临床缓解率为55.1%(27/49),临床应答率为73.5%(36/49),内镜下缓解率为43.3%(13/30),内镜应答率为55.6%(15/27),肛瘘闭合率为7/18,总体不良反应发生率为24.5%(12/49);临床缓解组(27例)患者的基线粪钙防卫蛋白水平低于疾病活动组(22例)患者[111.0μg/g(26.3μg/g,125.6μg/g)比540.5μg/g(420.2μg/g,866.9μg/g)],差异有统计学意义(Z=-4.44,P<0.001)。二元logistic回归分析结果提示,基线粪钙防卫蛋白水平是ADA治疗12周时克罗恩病患者临床缓解的独立预测因素(OR值=1.08,95%置信区间1.02~1.14,P=0.013)。当基线粪钙防卫蛋白为172.39 g/g时,其预测ADA治疗12周时克罗恩病患者临床缓解的灵敏度为81.48%,特异度为90.91%,受试者操作特征曲线曲线下面积为0.87(P<0.001)。结论ADA治疗克罗恩病安全、有效,基线粪钙防卫蛋白水平是ADA治疗12周时克罗恩病患者临床缓解的独立预测因素。

Objective To evaluate the efficacy and safety of adalimumab(ADA)in the treatment of Crohn′s disease(CD),and to analyze the predictive factors of ADA efficacy.Methods From January 2020 to December 2020,49 CD patients treated with ADA at the Department of Gastroenterology,Tenth People′s Hospital of Tongji University of Shanghai were enrolled.The clinical data before treatment were collected.During 12 weeks of ADA treatment,the patients were followed up every 2 weeks,the laboratory examinations were conducted every 4 weeks,and colonoscopy examination was rechecked at the 12th week.The improvement of the main symptoms of patients was assessed at 2nd,4th,and 6th week during ADA treatment.At the 12th week after ADA treatment,the clinical response(Crohn′s disease activity index(CDAI)score decreased≥70 points from baseline),clinical remission(CDAI score<150 points),endoscopic response(simple endoscopic score for Crohn′s disease(SES-CD)decreased>50%from baseline)and endoscopic remission(SES-CD≤2 points or Rutgeerts score≤1 point),closure of anal fistula of CD patients complicated with anal fistula and occurrence of adverse reactions during treatment were recorded.The predictive factors of clinical remission of CD patients after ADA treatment for 12 weeks were analyzed.The Mann-Whitney U test and binary logistic regression analysis were used for statistical analysis.Results The main symptom improved rates of 49 CD patients received ADA treatment at 2nd,4th and 6th week were 75.5%(37/49),95.9%(47/49)and 98.0%(48/49),respectively,and the main symptom improved time was 14.0 d(7.0 d,17.0 d).After ADA treatment for 12 weeks,the clinical remission rate was 55.1%(27/49),the clinical response rate was 73.5%(36/49),the endoscopic remission rate was 43.3%(13/30),the endoscopic response rate was 55.6%(15/27),the anal fistula closure rate was 7/18,and the overall incidence of adverse reactions was 24.5%(12/49).The baseline of fecal calprotectin(FC)level of patients in the clinical remission group(27 cases)was lower than that of the patients in the active disease group(22 cases)(111.0μg/g,26.3μg/g to 125.6μg/g vs.540.5μg/g,420.2μg/g to 866.9μg/g),and the difference was statistically significant(Z=-4.44,P<0.001).The results of binary logistic regression analysis showed that baseline FC level was an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks(OR=1.08,95%confidence interval 1.02 to 1.14,P=0.013).When the baseline FC cut-off value was 172.39 g/g,the sensitivity and specificity of it in predicting clinical remission in CD patients treated with ADA for 12 weeks were 81.48%and 90.91%,and the area under the receiver operator characteristic curve was 0.87(P<0.001).Conclusions ADA is safe and effective in the treatment of CD.The baseline FC level is an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks.