Abstract: 【Abstract】 Objective To evaluate the efficacy and tolerability of crisaborole 2% ointment in the treatment of childhood atopic dermatitis （AD） at the early stage, and to compare the efficacy of every-other-day （Qod） regimen versus twice-a-week （Biw） regimen against recurrence in the remission stage of AD. Methods A multicenter, randomized, open-label clinical trial was conducted. Totally, 150 children with mild to moderate AD aged 2 - < 18 years were enrolled from 6 hospitals （including Beijing Children′s Hospital, Capital Medical University, etc）, and randomly divided into the Qod group （76 cases） and the Biw group （74 cases）. In the acute stage of AD, both groups were treated with topical crisaborole 2% ointment on skin lesions twice a day for 2 - 4 weeks, as well as with emollients throughout the whole body. The improvement of early clinical symptoms was evaluated, and the occurrence of adverse reactions was recorded in the follow up. Once the investigator′s static global assessment （ISGA） scores decreased to 1 point or less, the patient would be enrolled into the remission stage. In the remission stage of AD, patients in the Qod group and Biw group were treated with crisaborole ointment every other day and twice a week respectively; the recurrence rate of AD in the remission stage was evaluated, as well as the severity of skin lesions, itching, life quality, and the occurrence of adverse reactions at weeks 4, 8, and 12. Statistical analysis was carried out with SPSS 23.0 software by using t test for comparisons of normally distributed continuous data between two groups, Mann-Whitney U test for non-normally distributed data, chi-square test for enumeration data, and Kaplan-Meier method for analysis of survival rates. Results A total of 142 patients were enrolled in the modified intention-to-treat population, including 71 in the Qod group and 71 in the Biw group. In the acute stage of AD, the improvement of itching and skin lesions self-reported by the children or their family members occurred on days 1.9 （1.0, 3.0） and 2.0 （1.0, 4.1） after the application of crisaborole ointment, respectively. At the end of treatment in the acute stage, 89 children （62.7%） achieved ISGA 0/1 and successfully transferred into the remission stage. The follow-up in the remission stage was completed in 83 patients （44 in the Qod group and 39 in the Biw group）. In addition, recurrence occurred in 19 （43.2%） and 12 （30.8%） patients in the Qod group and Biw group respectively, and there was no significant difference in the recurrence rate between the two groups （χ2 = 1.36, P = 0.243）; the average time to recurrence was 64.25 （95% CI: 53.33 - 75.17） days and 75.78 （95% CI: 65.46 - 86.10） days in the Qod group and Biw group respectively. Among the patients who were in the remission stage and had not yet experienced relapse at weeks 4, 8, and 12, there were no significant differences in the eczema area and severity index （EASI） scores, ISGA scores, pruritus numerical rating scale （NRS） scores, or quality-of-life scores between the two groups （all P > 0.05） at any time points, except for the ISGA scores at week 12 （Biw group: 0 ［0, 1］ point vs. Qod group: 1 ［0, 1］ point; Z = -2.31, P = 0.021）. A total of 146 patients were enrolled in the safety set. During the study period, 70 adverse events occurred in 65 patients, with an incidence rate of 44.5%, and all were mild or moderate adverse events; 55 （37.7%） patients experienced discomfort at the medication site, which mainly referred to pain （45 cases, 30.8%） and mostly occurred in the tender and skinfold areas. Conclusions Crisaborole 2% ointment could effectively relieve clinical symptoms in children with mild to moderate AD in the early stage, and intermittent treatment could continuously relieve clinical symptoms in the remission stage. The common adverse reaction was discomfort at the application site in the early stage of AD. There was no significant difference in the impact on AD recurrence in the remission stage between the Qod regimen and Biw regimen.

Key words: Dermatitis, atopic, Child, Randomized controlled trial, Early stage, Remission stage, Crisaborole