Abstract: 【Abstract】 Objective To evaluate the efficacy and safety of dupilumab in the treatment of moderate-to-severe atopic dermatitis （AD） in infants aged 6 months to 2 years. Methods A prospective cohort study was conducted. Children aged 6 months to 2 years with moderate-to-severe AD were enrolled from the Department of Dermatology, Children′s Hospital of Chongqing Medical University between July 2022 and March 2023. Children weighing 5 to < 15 kg received subcutaneous injections of dupilumab at a dose of 200 mg every 4 weeks, while those weighing 15 to < 30 kg received subcutaneous injections of dupilumab at a dose of 300 mg every 4 weeks. Three age-matched healthy children were recruited as controls at the same time. Clinical assessments were performed at weeks 0, 2, 4, 8, 12, and 16 by using the parameters scoring AD （SCORAD）, eczema area and severity index （EASI）, investigator′s global assessment （IGA）, body surface area （BSA） involvement, patient-oriented eczema measure （POEM）, pruritus numerical rating scale （NRS）, sleep NRS, and infants′ dermatitis quality of life （IDQoL） index. The primary efficacy endpoint was the proportion of patients achieving an IGA score of 0 or 1 （IGA0/1） at week 16, and the key secondary efficacy endpoint was the proportion of patients achieving at least 75% improvement from baseline in EASI （EASI75） at week 16. In addition, serum immunoglobulin （Ig） E, IgG, IgM, and IgA levels and peripheral blood eosinophil counts were measured at weeks 0, 4, and 16. Peripheral blood T helper （Th） cell subsets were analyzed in 10 AD patients and 3 healthy children at baseline by flow cytometry, and 6 AD patients underwent repeat testing at week 16. Adverse reactions were recorded throughout treatment. Changes in clinical scores over time after dupilumab treatment were analyzed using repeated-measures analysis of variance, and changes in serum total IgE levels were analyzed using generalized estimating equations. Results A total of 12 children with AD were enrolled, including 8 males and 4 females, aged 1.5 ± 0.3 years, and the baseline SCORAD was 64.8 ± 9.9 points. Compared with baseline, SCORAD, EASI, IGA, BSA, POEM, pruritus/sleep NRS, and IDQoL scores were all significantly reduced at week 2 （all P < 0.05）, and continued to decrease at weeks 4, 8, 12, and 16. At week 16, the IGA scores decreased from 3.9 ± 0.3 points at baseline to 1.7 ± 0.9 points, with 9 patients achieving IGA0/1; the EASI scores decreased from 28.1 ± 12.4 points at baseline to 4.9 ± 5.4 points, with 9 patients achieving EASI75. Compared with baseline, serum total IgE levels were significantly reduced at weeks 4 and 16 （Wald χ2 = 11.51, P = 0.003）. At baseline, the proportion of Th2 cells among total CD3?CD4? T cells in patients was significantly higher than that in healthy controls （6.3% ± 1.3% vs. 4.3% ± 0.8%, t = 2.45, P = 0.032）; at week 16, the proportion of Th2 cells in patients （5.3% ± 2.0%） was significantly lower than that at baseline （t = 5.56, P = 0.003）. The proportion of Th1/17 cells increased from 2.2% ± 1.5% at baseline to 3.9% ± 2.1% at week 16 （t = 3.51, P = 0.007）, whereas the proportions of Th1 and Th17 cell subsets showed no statistical significance compared with baseline （both P > 0.05）. One patient experienced an injection-site reaction and another developed fever, but no treatment-related serious adverse reactions were observed. Conclusions Dupilumab demonstrated favorable efficacy and safety in infants aged 6 months to 2 years with moderate-to-severe AD. In addition, dupilumab could decrease the proportion of Th2 cell subsets and serum levels of total IgE.

Key words: Dermatitis, atopic, Moderate-to-severe, Dupilumab, Therapy, Infant, Treatment outcome, Drug-related side effects and adverse reactions