半夏泻心汤加减联合维得利珠单抗治疗克罗恩病寒热错杂证的临床疗效

Clinical Efficacy of Modified Banxia Xiexintang Combined with Vedolizumab in Treatment of Crohn's Disease with Syndrome of Cold and Heat in Complexity

目的:评价半夏泻心汤加减联合维得利珠单抗(VDZ)治疗活动期中重度克罗恩病(CD)寒热错杂证的临床疗效及对肠道菌群的影响。方法:将80例患者按随机数字表法分为对照组和观察组,每组各40例。对照组,采用VDZ治疗;观察组,在对照组治疗的基础给予半夏泻心汤加减,每日1剂;连续治疗14周,并随访至52周。于治疗前、治疗后、随访结束时评估CD活动指数(CDAI)评分、CD简化内镜评分(SES-CD)、炎症性肠病患者生活质量问卷(IBDQ)和寒热错杂证评分。评估治疗前后血红蛋白(HGB)、血细胞比容(HCT)、白蛋白(ALB)、C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-17(IL-17)和粪便钙卫蛋白(FC)。检测治疗前后肠道菌群。进行安全性评价。结果:与本组治疗前比较,治疗后两组患者CDAI、SES-CD和寒热错杂证评分下降(P<0.05),IBDQ评分升高(P<0.05);与本组治疗前比较,随访结束时两组CDAI、SES-CD和寒热错杂证评分升高(P<0.05),IBDQ评分下降(P<0.05)。与对照组治疗结束和随访结束时比较,观察组患者CDAI、SES-CD和寒热错杂证评分更低(P<0.05),IBDQ评分更高(P<0.05);治疗后和随访结束时,观察组临床缓解率(χ^(2)=4.381、3.962)和临床应答率(χ^(2)=5.541、4.306)均高于对照组,无应答率(χ^(2)=6.646、4.306)低于对照组(P<0.05),观察组内镜下缓解率(χ^(2)=4.072、3.985)和内镜应答率(χ^(2)=4.528、5.161)均高于对照组(P<0.05)。与本组治疗前比较,治疗后两组患者HGB、HCT和ALB升高(P<0.05),与对照组治疗后比较,观察组患者HGB、HCT和ALB升高更明显(P<0.05)。与本组治疗前比较,治疗后两组患者CRP、IL-6、TNF-α、IL-17和FC水平下降(P<0.05),与对照组治疗后比较,观察组患者CRP、IL-6、TNF-α、IL-17和FC降低更明显(P<0.05)。与本组治疗前比较,治疗后两组患者双歧杆菌、乳酸杆菌、普拉梭菌增加(P<0.05),变形菌、克雷伯菌、肠球菌下降(P<0.05),与对照组治疗后比较,观察组患者双歧杆菌、乳酸杆菌、普拉梭菌增加更明显(P<0.05),变形菌、克雷伯菌、肠球菌降低更明显(P<0.05)。研究期间未观察到使用半夏泻心汤加减相关不良反应。结论:半夏泻心汤加减联合VDZ治疗中重度活动期CD寒热错杂证患者,可起到增效作用,有着较好的近期和远期疗效,并可改善营养状态,调节肠道菌群,减轻炎性损伤,临床使用安全。

Objective:To evaluate the clinical efficacy of modified Banxia Xiexintang combined with vedolizumab(VDZ)in the treatment of active moderate to severe Crohn's disease(CD)with the syndrome of cold and heat in complexity and the effect of the therapy on intestinal flora.Method:Eighty patients were randomized based on the random number table method into a control group(40 cases)and an observation group(40 cases).The control group was treated with VDZ,and the observation group was treated with modified Banxia Xiexintang(1 bag per day)combined with VDZ.The treatment in both groups lasted for 14 weeks and the follow-up lasted until the 52th weeks.The CD activity index(CDAI),CD simplified endoscopic score(SES-CD),inflammatory bowel disease questionnaire(IBDQ)score,and syndrome score of cold and heat in complexity were assessed before treatment,after treatment,and at the end of follow-up.The levels of hemoglobin(HGB),hematocrit(HCT),albumin(ALB),C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-17(IL-17),and fecal calprotectin(FC)were measured before and after treatment.Intestinal flora was examined before and after treatment.The safety of the therapy was evaluated.Result:Compared with those before treatment,the scores of CDAI,SES-CD,and the syndrome of cold and heat in complexity decreased(P<0.05)and the IBDQ score increased after treatment(P<0.05).Compared with those before treatment,the scores of CDAI,SES-CD,and the syndrome of cold and heat in complexity increased(P<0.05)and the IBDQ score decreased(P<0.05)at the end of follow-up.After treatment and at the end of follow-up,the observation group had lower scores of CDAI,SES-CD,and syndrome of cold and heat(P<0.05)and higher IBDQ score(P<0.05)than the control group.Moreover,the observation group had higher clinical remission rate(χ^(2)=4.381,3.962)and response rate(χ^(2)=5.541,4.306)and lower non-response rat(eχ^(2)=6.646,4.306)than the control group at the two time points(P<0.05).The endoscopic remission rat(eχ^(2)=4.072,3.985)and response rate(χ^(2)=4.528,5.161)in the observation group were higher than those in the control group(P<0.05).After treatment,the HGB,HCT,and ALB levels in both groups elevated,and the observation group had higher levels than the control group(P<0.05).The treatment in both groups lowered the levels of CRP,IL-6,TNF-α,IL-17,and FC(P<0.05),and the observation group had lower levels of CRP,IL-6,TNF-α,IL-17,and FC than the control group after treatment(P<0.05).The relative abundance of Bifidobacterium,Lactobacillus,and Prevotella increased(P<0.05),while that of Proteus,Klebsiella,and Enterococcus decreased(P<0.05)in the two groups after treatment.Moreover,the changes in the relative abundance of these bacteria in the observation group were more obvious than those in the control group(P<0.05).No adverse reactions related to the modified Modified Banxia Xiexintang were observed during the study period.Conclusion:Modified Banxia Xiexintang combined with VDZ can play a synergistic role and has good short-term and long-term efficacy.This therapy can improve the nutritional status,regulate intestinal flora,and reduce inflammatory injury in the treatment of moderate to severe active CD patients with the syndrome of cold and heat in complexity without causing severe adverse reactions.