0.03%他克莫司软膏长期间歇维持治疗儿童特应性皮炎的多中心随机对照临床研究

Objective To compare the efficacy and safety of the long-term intermittent maintenance treatment with tacrolimus 0.03% ointment versus traditional treatment in reducing relapses and prolonging the recurrence interval in children with moderate to severe atopic dermatitis (AD) . Methods A two-phase randomized, open-labelled, controlled clinical trial was conducted from September 2012 to November 2013. In the first phase, a total of 171 children aged 2 - 15 years with moderate to severe AD were enrolled from 7 hospitals in China, and received conventional treatment with tacrolimus 0.03% ointment twice a day for 2 - 6 weeks. At the end of the treatment, the patients who achieved an investigator′s global assessment (IGA) score ≤ 2 (n = 125) were randomly classified into 2 groups to receive the second-phase treatment: test group (n = 62) receiving intermittent maintenance treatment with tacrolimus 0.03% ointment twice a week (Monday and Thursday) , and control group (n = 63) receiving no treatment. If the patients in the 2 groups experienced relapse, they received conventional treatment with tacrolimus 0.03% ointment twice a day. The overall observation period was 6 months. The primary endpoint was the time to the first relapse, which was defined as the number of days from the end of the first-phase treatment to the first relapse. The secondary endpoints included the number of relapses at the second-phase trial, the disease severity at the time of relapse, the duration of relapse, the pruritus score at the time of relapse, the total amount of tacrolimus ointment used, the total response rate at the second-phase trial, and the incidence of adverse events. Results A total of 125 children with AD were enrolled into the second-phase trial, and 121 of them completed the follow-up. Among the 121 patients, the recurrence rate was significantly lower in the test group (25/60, 41.7%) than in the control group (46/61, 75.4%; χ2 = 14.20, P < 0.001) . The time to the first relapse was significantly longer in the test group (46.9 ± 37.7 d) than in the control group (28.8 ± 32.3 d; Z = 1 093.50, P = 0.020) . The total number of recurrence was 31 and 86 in the test group and control group respectively, and the mean number of recurrence in each patient was significantly lower in the test group (0.52 ± 0.68) than in the control group (1.41 ± 1.23, t = 4.96, P < 0.001) . There were no significant differences between the two groups regarding disease severity during relapse (eczema area and severity index: Z = 971.50, P = 0.39) , duration of relapse (Z = 747.00, P = 0.07) , and pruritus score during relapse (Z = 894.00, P = 0.95) . The therapeutic drug was tolerated well in all the children, and no tacrolimus-related serious adverse events occurred. Conclusion The intermittent maintenance treatment with tacrolimus 0.03% ointment twice a week for 6 months can effectively and safely prevent and reduce relapses, and prolong the recurrence interval in children with moderate to severe AD. Key words: Dermatitis, atopic; Child; Randomized controlled trial; Treatment outcome; Drug toxicity; Tacrolimus