阿伐斯汀联合氯雷他定治疗慢性难治性荨麻疹的多中心随机对照研究

Acrivastine combined with loratadine in the treatment of chronic refractory urticaria:a multicenter,randomized controlled study

目的比较阿伐斯汀与阿伐斯汀联合氯雷他定治疗慢性难治性荨麻疹的疗效。方法2017年3月至2018年12月,于4家中心采用多中心、随机对照的临床研究,联合治疗组慢性难治性荨麻疹患者口服阿伐斯汀胶囊8 mg每日3次及氯雷他定片10 mg每日1次,阿伐斯汀组口服阿伐斯汀胶囊8 mg每日3次及安慰剂10 mg每日1次,治疗4周。分别于治疗前、治疗1、2、4周随访,采集临床指标及记录不良反应事件。根据瘙痒、风团的数目、风团大小、每次发作持续时间、每周发作次数评估症状积分,使用症状积分下降指数(SSRI)评价疗效。采用重复测量的方差分析和χ^2检验进行疗效和安全性评价。结果联合治疗组53例、阿伐斯汀组59例纳入疗效分析。治疗前,两组症状积分、瘙痒视觉模拟评分差异均无统计学意义。治疗2周,联合治疗组痊愈19例、显效10例,有效率54.72%;阿伐斯汀组痊愈15例,显效6例,有效率35.59%。治疗4周,联合治疗组痊愈23例,显效9例,有效率60.38%;阿伐斯汀组痊愈20例,显效2例,有效率37.29%。治疗2、4周,联合治疗组有效率均高于阿伐斯汀组(χ^2=4.13、5.96,均P<0.05)。两组各随访时间点的SSRI差异、组间SSRI差异均有统计学意义(F=8.62、4.38,均P<0.05)。多变量方差分析,治疗2、4周时,联合治疗组SSRI(0.63±0.05、0.68±0.05)高于阿伐斯汀组(0.47±0.05、0.51±0.05),差异均有统计学意义(均P<0.05)。联合治疗组发生药物相关性不良反应7例,阿伐斯汀组3例,主要表现为嗜睡、胃部不适、头痛、肝功能异常。结论阿伐斯汀治疗慢性难治性荨麻疹安全、有效;阿伐斯汀联合氯雷他定可以显著提高疗效。

Objective To evaluate the efficacy of acrivastine alone or in combination with loratadine in the treatment of chronic refractory urticaria.Methods From March 2017 to December 2018,a multicenter,randomized,controlled clinical study was conducted in 4 centers.Patients with chronic refractory urticaria were randomly divided into two groups,i.e.,combined treatment group receiving oral acrivastine capsules 8 mg thrice a day plus oral loratadine tablets 10 mg once a day,and acrivastine alone group receiving oral acrivastine capsules 8 mg thrice a day plus a placebo 10 mg once a day.The course of treatment was 4 weeks.Visits were scheduled at baseline and after 1,2 and 4 weeks of treatment.At the same time,clinical data were collected,and adverse events were recorded.Symptom scores were evaluated based on degree of itching,number and size of wheals,duration of each attack and number of attacks per week,and symptom score reduce index(SSRI)was used to evaluate the efficacy.Repeated measures analysis of variance and chi-square test were used to evaluate the efficacy and safety.Results Fifty-three patients in the combined treatment group and 59 in the acrivastine alone group were included in the efficacy analysis.Before treatment,there was no significant difference in symptom score or visual analogue score between the two groups.After 2 weeks of treatment,19 patients were cured and 10 achieved marked improvement in the combined treatment group,with a response rate of 54.72%;15 were cured and 6 achieved marked improvement in the acrivastine alone group,with a response rate of 35.59%.After 4 weeks of treatment,23 patients were cured and 9 achieved marked improvement in the combined treatment group,with a response rate of 60.38%;20 were cured and 2 achieved marked improvement in the acrivastine alone group,with a response rate of 37.29%.After 2 and 4 weeks of treatment,the response rates were significantly higher in the combined treatment group than in the acrivastine alone group(χ^2=4.13,5.96 respectively,both P<0.05).The SSRI significantly differed among different follow-up time points,as well as between the 2 groups(F=8.62,4.38 respectively,both P<0.05).Multivariate analysis of variance showed that SSRI was significantly higher in the combined treatment group(0.63±0.05,0.68±0.05,respectively)than in the acrivastine alone group(0.47±0.05,0.51±0.05,respectively)after 2 and 4 weeks of treatment(both P<0.05).Drug-related adverse reactions,including drowsiness,stomach upsets,headache and liver function abnormality,occurred in 7 patients in the combined treatment group,as well as in 3 in the acrivastine alone group.Conclusion Acrivastine is safe and effective for the treatment of chronic refractory urticaria,and acrivastine combined with loratadine can markedly improve the efficacy.