目的 系统评价克立硼罗软膏治疗特应性皮炎(AD)的有效性和安全性。方法 检索Cochrane Library、Embase、PubMed、中国学术期刊全文数据库(CNKI)、万方数据知识服务平台(Wanfang Data)、维普中文期刊全文数据库(VIP)、中国生物医学文献服务系统(SinoMed)、中华医学期刊全文数据库(Yiigle),系统收集建库至2024年1月30日发表的克立硼罗软膏治疗特应性皮炎的临床随机对照试验(RCT)。由2名研究者独立筛选、提取信息,通过Review Manager 5.3软件进行Meta分析,所形成的证据体使用GRADE系统进行证据质量评估。结果 共纳入11项RCTs,包括2 789例AD患者。Meta分析显示:与安慰剂或空白治疗比较,克立硼罗软膏可提高研究者静态总体评分成功率[RR=1.52,95 % CI (1.28,1.80),P<0.000 01]和缓解率[RR=1.43,95 % CI (1.27,1.62),P<0.000 01],降低湿疹面积及严重程度指数(EASI)评分[MD=-2.44,95 % CI (-4.15,-0.73),P=0.005],缓解瘙痒,增加无复发维持时间,减少复发次数;与阳性对照相比,具有更高的疾病疗效愈显率[RR=1.80,95 % CI (1.33,2.43),P=0.000 1],可提高生活质量;与一线药物联合使用对比单独使用一线治疗药物,联合治疗组具有更高的疾病疗效愈显率[RR=1.23,95 % CI (1.03,1.48),P=0.02],较高的EASI评分变化值[MD=-2.11,95 % CI (-3.13,-1.10),P<0.000 1],可缓解瘙痒,提高生活质量。安全性方面,不良反应主要表现为给药部位的局部反应,如给药部位刺激、疼痛、瘙痒、变色、感觉异常等,多数为轻度、中度反应,预后较好。结论 克立硼罗软膏可缓解AD疾病严重程度,缓解瘙痒,提高生活质量,病情稳定后以小剂量长期维持治疗可减少AD复发;在儿童、成人群体中应用耐受性较好,临床使用时应关注给药部位的异常局部反应。

Objective To evaluate the efficacy and safety of Crisaborole Ointment in the treatment of atopic dermatitis. Methods Randomized controlled trials (RCT) on the treatment of atopic dermatitis with Crisaborole ointment published in databases of Cochrane Library, Embase, PubMed, CNKI, Wanfang Database, VIP, SinoMed and Yiigle were electronically searched from database establishment until January 30, 2024. Two researchers independently screened and extracted information, assessed bias risk using the ROB-2 tool, conducted Meta-analysis using Review Manager 5.3, and evaluated the quality of evidence using the GRADE system. Results A total of 11 RCTs were involved with 2 789 AD patients. Meta-analysis showed that compared to placebo treatment, Crisaborole Ointment increased the ISGA success rate[RR=1.52, 95 %CI (1.28, 1.80), P < 0.000 01] and relief rate[RR=1.43, 95 %CI (1.27, 1.62), P < 0.000 01], decreased EASI scores[MD=-2.44, 95 %CI (-4.15, -0.73), P=0.005], relieved itching, prolonged flare-free time, and reduced relapse frequency. Compared to positive controls, it demonstrated a higher disease efficacy cure rate[RR=1.80, 95 %CI (1.33, 2.43), P=0.000 1], improving quality of life. When compared to the use of positive drug, combination therapy had a higher disease efficacy cure rate[RR=1.23, 95 %CI (1.03, 1.48), P=0.02], higher EASI score change value[MD=-2.11, 95 %CI (-3.13, -1.10), P < 0.000 1], relieved itching, and improved quality of life. In terms of safety, adverse reactions were mainly local reactions at the administration site, such as irritation, pain, itching, discoloration, and abnormal sensations, mostly mild to moderate, with a good prognosis. Conclusion Crisaborole Ointment can alleviate the severity of AD, relieve itching, improve the quality of life, and long-term maintenance therapy with a low dose can reduce AD recurrence after the condition stabilizes. It is well-tolerated in both children and adults, but clinicians should pay attention to abnormal local reactions at the administration site during clinical use.

R969.3;R986

国家科技重大专项课题:儿童中药新药临床评价技术示范性平台建设(2020ZX09201-008)