乌司奴单抗一线治疗克罗恩病的短期疗效分析

Analysis of the short-term efficacy of ustekinumab as the first-line treatment for Crohn′s disease

目的评估乌司奴单抗(UST)一线治疗克罗恩病的短期疗效。方法纳入2020年10月1日至2023年3月1日苏州大学附属第一医院收治的以UST作为一线生物制剂治疗的64例克罗恩病患者。采用蒙特利尔分型对患者进行分类,分别以克罗恩病疾病活动指数(CDAI)和克罗恩病简化内镜评分(SES-CD)评估临床、内镜的应答和缓解情况。CDAI评分下降≥70分为临床应答,CDAI评分<150分为临床缓解;SES-CD评分下降≥50%为内镜应答,SES-CD评分≤2分为内镜缓解。观察克罗恩病患者用药第24和48周的临床应答率和临床缓解率,以及用药第48周的内镜应答率和内镜缓解率(内镜预后结果仅纳入21例患者)。统计学方法采用Mann-Whitney秩和检验。结果64例克罗恩病患者中,男47例,女17例;年龄为(33.5±13.7)岁。蒙特利尔分型为A1型(≤16岁)3例(4.7%),A2型(17~40岁)44例(68.8%),A3型(>40岁)17例(26.6%);L1型(回肠末端型)43例(67.2%),L2型(结肠型)10例(15.6%),L3型(回结肠型)8例(12.5%),L4型(上消化道型)1例(1.6%),L1+L4型2例(3.1%);B1型(非狭窄非穿透)23例(35.9%),B2型(狭窄型)34例(53.1%),B3型(穿透型)2例(3.1%),B2+B3型5例(7.8%);合并肛周病变者44例(68.8%)。56例以每8周1次的频率进行UST维持治疗的克罗恩病患者,用药第24和48周的CDAI评分均低于用药第0周[64.46分(30.61分,123.30分)、34.24分(15.77分,64.83分)比353.40分(290.40分,391.30分)],用药第48周的CDAI评分低于用药第24周,差异均有统计学意义(Z=-9.01、-9.13、-3.14,P<0.001、<0.001、=0.002);用药第24周的临床应答率为100.0%(56/56),临床缓解率为91.1%(51/56);用药第48周的临床应答率为100.0%(56/56),临床缓解率为98.2%(55/56);其中39例合并肛周病变患者中,用药第24周的肛周病变闭合率为87.2%(34/39),用药第48周的肛周病变闭合率达100.0%(39/39)。8例以每12周1次的频率进行UST维持治疗的克罗恩病患者,用药第24和48周的CDAI评分均低于用药第0周[100.40分(71.20分,171.30分)、38.49分(18.25分,143.50分)比268.00分(242.60分,364.90分)],差异均有统计学意义(Z=-3.26、-3.36,均P<0.001);用药第24周时7例达到临床应答,5例达到临床缓解;用药第48周时8例均达到临床应答,6例达到临床缓解;其中5例合并肛周病变患者中,用药第24周时3例肛周病变闭合,用药第48周时5例均肛周病变闭合。21例进行内镜复查的患者中,16例以每8周1次的频率进行UST维持治疗,用药第48周的SES-CD评分低于用药第0周[4.00分(3.00分,7.75分)比9.50分(7.25分,10.75分)],差异有统计学意义(Z=-3.43,P<0.001),其中9例达到内镜应答、2例达到内镜缓解;5例以每12周1次的频率进行UST维持治疗,用药第48周的SES-CD评分与用药第0周比较[4.00分(1.50分,6.50分)比7.00分(3.50分,10.00分)],差异无统计学意义(P>0.05),其中3例达到内镜应答、1例达到内镜缓解。结论以UST作为一线生物制剂治疗克罗恩病患者可在短期内即有临床疗效(应答或缓解),且UST维持治疗利于内镜缓解和肛周病变闭合。

Objective To evaluate the short-term efficacy of ustekinumab(UST)as the first-line treatment of Crohn′s disease(CD).Methods From October 1,2020 to March 1,2023,at the First Affiliated Hospital of Soochow University,64 CD patients treated with UST as first-line biologics were enrolled.The patients were classified using the Montreal classification.Clinical and endoscopic response and remission were assessed by Crohn′s disease activity index(CDAI)and simple endoscopic score for crohn′s disease(SES-CD),respectively.Clinical response was defined as a reduction in CDAI score≥70,and clinical remission was defined as a CDAI score<150;Endoscopic response was defined as≥50%reduction from baseline in SES-CD score,and endoscopic remission was defined as SES-CD score≤2.The clinical response rate and clinical remission rate at week 24 and week 48,as well as the endoscopic response rate and endoscopic remission rate at week 48 were observed in CD patients(only 21 patients with endoscopic prognostic results).Mann-Whitney rank sum test was used for statistical analysis.Results Among 64 CD patients,there were 47 males and 17 females,with an age of(33.5±13.7)years old.According to Montreal classification,there were 3 cases(4.7%)of type A1(≤16 years old),44 cases(68.8%)of type A2(17 to 40 years old),and 17 cases(26.6%)of type A3(>40 years old);43 cases(67.2%)of type L1(terminal ileum type),10 cases(15.6%)of type L2(colonic type),8 cases(12.5%)of type L3(ileocolonic type),1 case(1.6%)of type L4(upper gastrointestinal type),2 cases(3.1%)of type L1+L4;23 cases(35.9%)of type B1(non-stricturing,non-penetrating),34 cases(53.1%)of type B2(stricturing),2 cases(3.1%)of type B3(penetrating),5 cases(7.8%)of type B2+B3;44 cases(68.8%)complicated with perianal lesions.Among 56 CD patients with UST maintenance therapy once every 8 weeks,the CDAI scores at week 24 and 48 after treatment were both lower than that at week 0(64.46(30.61,123.30),34.24(15.77,64.83)vs.353.40(290.40,391.30)),and the CDAI score at week 48 after treatment was lower than that at week 24 after treatment,and the differences were statistically significant(Z=-9.01,-9.13,and-3.14;P<0.001,<0.001,and=0.002).The clinical response rate was 100.0%(56/56)and the clinical remission rate was 91.1%(51/56)at week 24;the clinical response rate was 100.0%(56/56)and the clinical remission rate was 98.2%(55/56)at week 48.Among 39 CD patients complicated with perianal lesions,the closure rate of anal lesions at week 24 was 87.2%(34/39)and at week 48 was 100.0%(39/39).Among 8 CD patients who received UST maintenance therapy once every 12 weeks,the CDAI scores at week 24 and 48 were both lower than that at week 0(100.40(71.20,171.30),38.49(18.25,143.50)vs.268.00(242.60,364.90)),and the differences were statistically significant(Z=-3.26 and-3.36;both P<0.001).At week 24,7 CD patients achieved clinical response and 5 CD patients achieved clinical remission.At week 48,8 CD patients achieved clinical response and 6 CD patients achieved clinical remission.Among 5 CD patients complicated with perianal lesions,3 CD patients achieved perianal closure at week 24 and all 5 CD patients achieved closure of perianal lesions at week 48.Among 21 CD patients who underwent endoscopic evaluation,16 CD patients received UST maintenance therapy once every 8 weeks,the SES-CD score at week 48 was lower than that at week 0(4.00(3.00,7.75)vs.9.50(7.25,10.75)),and the difference was statistically significant(Z=-3.43,P<0.001),among them,9 CD patients achieved endoscopic response and 2 CD patients achieved endoscopic remission;5 CD patients received UST maintenance therapy once every 12 weeks,there was no statistically significant difference in the SES-CD score at week 48 compared with that at week 0(4.00(1.50,6.50)vs.7.00(3.50,10.00))(P>0.05),among them,3 CD patients achieved endoscopic response and 1 CD patients achieved endoscopic remission.Conclusion UST as the first-line treatment for CD patients can achieve clinical efficacy(response or remission),and the maintenance therapy is beneficial for endoscopic remission and closure of perianal lesions.