Dupilumab therapy in children aged 2–12 years with uncontrolled moderate‐to‐severe atopic dermatitis: A Chinese real‐world study

Dupilumab is an interleukin-4 receptor α monoclonal antibody approved for moderate-to-severe atopic dermatitis (AD) in patients aged >6 years with inadequate response to topical AD medication(s) in China.1-3 Recently, a Phase 3 clinical trial regarding dupilumab in children aged 6 months to 6 years with AD demonstrated significant efficacy and safety profiles4 but real-world data is scanty, especially in Asian populations. We conducted a retrospective real-world "off-label" observational study to evaluate the effectiveness and safety of dupilumab in patients with AD younger than 6 years and compared the data with those aged 6–12 years. Demographic and clinical characteristics of the patients were collected and analysed. Also, the disease severity scores (Investigator's Global Assessment [IGA], Eczema Area and Severity Index [EASI], Scoring Atopic Dermatitis [SCORAD] and Children's Dermatology Life Quality Index [CDLQI]/Infants' Dermatitis Quality of Life Index [IDQoL])4, 5 at Weeks 4, 8, 12 and 16 were recorded. Adverse events (AE) and laboratory parameters were also evaluated. One hundred and twenty paediatric patients with moderate-to-severe AD (IGA score 3–4) were diagnosed according to revised Hanifin and Rajka diagnostic criteria6 and treated with dupilumab in Xiangya hospital from April 2021 to January 2023. They were divided into two groups by age: 2 to <6 years (n = 50) and 6–12 years (n = 70). An informed consent was signed by the parent or a legal guardian. This study was approved by the Ethics Review Committee (ethical approval number: 2021030471). For children aged 2 to <6 years, the initial subcutaneous dose is 300 mg, followed by 300 mg every 4 weeks; for children aged 6–12 years, the initial subcutaneous dose is 600 mg for patients weighing 15 kg to less than 30 kg, followed by 300 mg every 4 weeks; for patients weighing 30 kg to less than 60 kg, the initial subcutaneous dose is 400 mg, followed by 200 mg every 2 weeks during a 16-week treatment period. Topical therapies including topical corticosteroids and/or topical calcineurin inhibitors were allowed in combination with dupilumab. Demographics and clinical characteristics of the two groups were shown in Table 1. There was no statistical difference in gender and baseline disease severity scores between the two groups (p > 0.05). From baseline to Week 16, increasing improvements were observed in IGA, EASI, SCORAD, CDLQI (IDQoL) (Figure 1a,b). Patients aged 2 to <6 years treated with dupilumab had higher percentage of EASI-50 and EASI-75 (78.79% vs. 44.00%, 45.45% vs. 16.00%; respectively) at Week 4, when compared with patients aged 6–12 years (p < 0.05, Figure 1b). With continuous dupilumab treatment till Week 16, however, the therapeutic efficacy was comparable between the two groups, with similar EASI-75, EASI-90 and IGA0/1 (75.00% vs. 75.51%, 46.88% vs. 48.98%, 78.13% vs. 79.59%; respectively) (Figure 1a,b). Erythemato-desquamative pattern was the most common clinical phenotype in both groups (Table 1). Also, patients aged 2 to <6 years with head and neck dermatitis as the main clinical phenotype had higher EASI-50 (90.91%) than those aged 6–12 years (50.00%) at Week 4 after dupilumab treatment (p < 0.05). No AE was observed in the 2 to <6 years group, which may be partly due to the limited sample size of this study. Additionally, children in that age range may have difficulty expressing discomfort. Two patients (2.86%) in the 6–12 years group developed conjunctivitis during the treatment, which may be associated with their previous history of conjunctivitis.5, 7 To conclude, our real-life cohort data demonstrated that dupilumab has a significant effectiveness and a tolerable safety profile in children aged 2–12 years with uncontrolled moderate-to-severe AD. It seemed that the effectiveness of dupilumab was better in the first 4 weeks in patients aged 2 to <6 years when compared with that in patients aged 6–12 years but the treatment response was comparable at Week 16. The loading dose/body weight was significantly higher in the 2 to <6 years group than that in the 6–12 years group (16.58 ± 3.07 vs. 13.01 ± 5.93 mg/kg, respectively; p = 0.0016), which may explain the difference in efficacy between the two group at Week 4. Compared to the efficacy in Phase III clinical trials aged 6 months to younger than 6 years,4 higher percentage of EASI-75 and EASI-90 at Week 16 were shown in our study (75% vs. 53%, 47% vs. 25%; respectively), which may be related to the differences in race, prior medication history, sample size, etc. This study has some limitations. The first limitation of this study is the hospital-based, single-centre study, which may have selective bias. The second is the lack of patients aged 6 months to 2 years, and the third is the short period of follow-up. Therefore, further studies with multi-center and large samples are needed to provide more data and evidence for the rational application of dupilumab in paediatric AD patients. None. This work was supported by the funding supported by Grant No. 81974476, 82173424, 81673065, 81830096, 81773341 by the National Natural Science Foundation of China. This study also was supported by the Program of Introducing Talents of Discipline to Universities ("111" Project, No. B20017). The authors declare no conflicts of interest. This study was approved by the Ethics Review Committee of Xiangya hospital (ethical approval number: 2021030471). The patients/patients' legal guardian in this manuscript have given written informed consent to publication of their case details.