Atopic dermatitis (AD) is an inflammatory, chronically recurrent skin disease that is more likely to occur in people with a family history of allergies (1). Recent studies reported that Timothy, birch and house dust mite were the main allergens in AD patients, whereby molecular components including Phl p 1 (Timothy), Bet v 1 (Birch), Alt a 1 (Alternaria) play a significant role in the atopic march (2, 3). AD usually occurs in early childhood but can develop at any age (4). The incidence rate of AD has increased globally over the years (5). Guo et al. (6) found a prevalence of AD in Chinese children aged 1–7 years of 12.94%, higher than in previous reports. From a pathological point of view, AD manifests as thickening of the epidermis, infiltration of dendritic cells and T lymphocytes, and increases in inflammatory mediators (7, 8). The number of inflammatory factors, such as IL-4, IL-13, and IL-31, produced by Th2 cells is significantly increased in the skin of patients with AD, suggesting that AD is mainly driven by type 2 inflammation (9, 10). These data indicate that targeted therapy for Th2 inflammation may help to alleviate AD.

Dupilumab is a fully human anti-IL-4 receptor α (IL-4α) monoclonal antibody that blocks signaling mediated by IL-4 and IL-13 (11, 12) and the first biological agent used for AD. The results of clinical trials at 16 weeks and 52 weeks in patients with moderate to severe AD showed that dupilumab significantly improved the disease in the extension of visible lesions, itch intensity, pain and impact of skin disease on daily activities, work and social life by inhibiting inflammatory cell and the type 2 inflammatory response (13–15). Accumulating evidence supports the conclusions that the eczema area and severity index (EASI), SCORing Atopic Dermatitis (SCORAD), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) were the most widely used tools to evaluate treatments in AD. Treatment points in AD with dupilumab focus on clinician-reported disease severity, patient-reported symptoms, and impact on quality of life and long-term control. Recent studies supported that after dupilumab treatment, patients who achieved clinical improvement in at least one of primary (EASI 75) or secondary (NRS peak pruritus improvement ≥4 or DLQI improvement ≥4) endpoints were considered to have experienced good therapeutic effects (16–18). Additionally, dupilumab has an acceptable safety profile, and does not require laboratory monitoring during the working period (19).

There are limited data from Asia about existing real-world uses of dupilumab. Thus, for the purpose of researching the effectiveness and safety of dupilumab in the real world in China, we report actual data for dupilumab in the treatment of AD.

All patients with AD treated with dupilumab from the Department of Dermatology, Xiangya Hospital, Central South University between August 2020 and November 2021 were included, and all the data were collected from patient medical records and questionnaires. AD was diagnosed by two dermatologists independently according to the revised Hanifin and Rajka criteria (20). This research was approved by the Medical Ethics Committee of Xiangya Hospital, Central South University and conducted in accordance with research ethics (Ethical approval number: 201904112).

Patients (body weight more than 30 kg) were subcutaneously injected with 600 mg dupilumab for the initial dose and 300 mg dupilumab for the maintenance dose. For children with body weights less than 30 kg, the first dose and maintenance dose were 300 mg once every 3 weeks. Usually, the interval time between the two subcutaneous injections in adults was 2 weeks and adjusted according to the SCORAD after 16 weeks of treatment. Due to economic and distance reasons, the interval of medication was 3 or 4 weeks for 14 patients (12.07%). According to the evaluation of dermatologists, after the patient’s condition was significantly improved, whereby EASI improved by more than 50% from baseline or DLQI, NRS, and POEM scores improved by at least 4 points from baseline, the interval was extended from 2 weeks to 3 or 4 weeks. Three patients (23.08%) received dupilumab continuously up to 16 weeks were not treated with the classical 2-week interval during the whole treatment process. After a course of treatment or after the patient has reached the end point of treatment, it is changed to topical medication.

As indicative factors for AD, EASI, SCORAD, NRS, POEM, and DLQI were measured before treatment and at 2, 4, or 16 weeks after the first dose of dupilumab (21). In addition, serum IgE levels, serum C-reactive protein levels, lactate dehydrogenase (LDH) levels and eosinophil counts were measured, and electrocardiograms and chest radiography were used to help exclude potential comorbidities at enrollment.

Among the 116 patients with AD, 102 had significant improvement in clinical manifestations, even some patients were not treated with the classical 2-week interval. Based on the SCORAD and EASI scores at the 2nd, 4th, and 16th weeks, we found that the disease severity of the patients decreased significantly. According to the NRS, itching was basically controlled, and the DLQI score showed that the quality of life of patients had been greatly improved. In our study, among all patients, EASI 50, EASI 75, and EASI 90 were 46.00, 14.00, and 5.00%, respectively, at 2 weeks after the first subcutaneous dupilumab. At 16 weeks, EASI 50, EASI 75, and EASI 90 were 100.00, 84.62, and 30.77%, respectively. In a Korean cohort study, the proportions of EASI 50 and EASI 75 were 51.4 and 2.8% at 2 weeks after the first administration, respectively; 16 weeks later, EASI 50 was 92.7%, and EASI 75 was 63.6% (22). Real data from Italy showed EASI 50, EASI 75, and EASI 90 of 98.1, 81.5, and 50.8%, respectively, after 16 weeks (23). In the Netherlands, 85.7, 61.7, and 24.1% of patients achieved EASI 50, EASI 75, and EASI 90, respectively, after 16 weeks of treatment (24). EASI 50, EASI 75, and EASI 90 of the above countries are summarized in Figure 3. The therapeutic efficacy of dupilumab in our patients was better than that reported in other cohorts. The reason why treatment among our cohort is more effective than other populations may be that we had a larger proportion of patients who used combination drugs, including TCS and/or TCI. Compared with the Netherlands, the better curative effect in our cohort may be due to the higher disease severity in the Dutch cohort, in which 61% of patients failed to use ≥2 kinds of immunosuppressive drugs and with the mean baseline EASI (IQR) as 19.9 (13.6–28.3) higher than 19.5 (11.4–17.1) in our cohort. Our study only included a very small number of patients who had previously used immunosuppressive agents (11.21%) or systemic glucocorticoids (4.31%), although with serious condition.

In our study, older patients and those with a longer disease duration were found to have better efficacy with dupilumab. Similar to the results of an Italian real-world study in which elderly patients (≥65 years) with severe AD treated with dupilumab showed significant and persistent improvement in EASI, Pruritus-NRS, Sleep-NRS, and DLQI at 16 weeks and 52 weeks compared with baseline (25). Identifying this characteristic will lead to more informed drug choices in the future.

Eleven patients (9.48%) had a poor curative effect on dupilumab. After dupilumab treatment, one of their disease severity scores occurred an increase compared with baseline. Among them, 6 stopped taking dupilumab at 4 weeks. Eruption on the body was not alleviated and even tended to expand with exudation, and symptoms of itching also persisted. One patient was treated in combination with systemic antibiotics and then alleviated gradually. The characteristics of these eleven patients are summarized in Table 5 and representative photos of these patients are shown in Figure 4.

There may be two reasons for poor efficacy of dupilumab among the 11 patients in our cohort. (1) Secondary infection may be associated with poor efficacy, and AD is accompanied by an increased risk of secondary infection, defects of the skin barrier, inhibition of skin innate immunity by type 2 inflammation, Staphylococcus aureus colonization and skin ecological imbalance (26). (2) Although the immunophenotype of all populations is significantly associated with Th2 activation in the pathogenesis of AD, there are some differences. Activation of Th17/Th22 cells in Asian AD patients is stronger than that in American AD patients (27, 28). The poor efficacy of some patients may be because of the significantly high induction of Th17- and Th22-related cytokines.

We observed that treatment of head and face lesions is more difficult than that of trunk and limbs, which is consistent with real-world data reported in Japan (29). Patients with a rash similar to psoriasis (predominantly erythema and scales) also do not respond well to dupilumab, suggesting a possible abnormal Th1/Th17 inflammatory response in these patients.

In our patients, one patient with liver cirrhosis and seven patients with chronic renal failure on regular hemodialysis responded well to dupilumab without side effects, and after two doses, their EASI score decreased by more than 50%. Their skin lesions subsided, with mild tingling. Itching caused by chronic kidney disease-associated pruritus (CKD-aP) or jaundice related to liver cirrhosis may be one of the reasons. Potential pruritogens for CKD-aP include toxin deposition, peripheral neuropathy, Th1 cells, and interleukin, among others (30). Bile salt, histamine, serotonin, steroids and others are causes of jaundice pruritus (31). As dupilumab targets interleukin 4 (IL-4) receptor α, it did not completely relieve itching in these patients. The long-term effect remains to be seen and needs to expand the sample size.

Conjunctivitis is the most common adverse reaction. The occurrence of conjunctivitis in our study was 2.59%, and all of these patients had a history of conjunctivitis. In a real-life study in South Korea and Canada, the incidence of conjunctivitis was 4.95% (22) and 7.69% (32), which was similar to our results. In the United States, 27.27% of patients had adverse eye reactions, with conjunctivitis in 7.80%, though how many patients had symptoms of dry eyes and blurred vision was not assessed (33). In Italy, 12.15% of patients developed conjunctivitis, and the risk of conjunctivitis was associated with early onset of AD and eosinophilia (23). Conjunctivitis occurred with a higher ratio of 36–38.2% of patients in Japan and France (34, 35). A clinical trial showed that the occurrence of conjunctivitis is associated with a history of conjunctivitis and elevated baseline IgE or eosinophils and concluded that conjunctivitis is a comorbidity of AD (36). A total of 62.11% of patients in the United Kingdom developed ocular adverse reactions, including 13.68% with conjunctivitis, but the prevalence of pre-existing ocular diseases is unknown; 8.42% of patients developed orofacial herpes simplex, and 4 of them used a combination with immunosuppressive agents, which may be related to 45.26% of patients using immunosuppressive agents in their cohorts (37). In general, the reported rates of adverse reactions in other countries are higher than those in the Chinese population, especially for conjunctivitis (Figure 5), which may be related to racial differences or other unknown reasons.

Limitations of our study include the following three points: The first one is the small sample size due to the fact that dupilumab has only been on the market for more than 1 year. The second one is lack of a control group. The third point is not all patients have used dupilumab for 16 weeks because some of them already got a perfect response and transfer to other traditional treatments or some of them cannot afford it for a complete course of 16 weeks, since dupilumab was not covered by China’s medical insurance during the follow-up period. Further research should investigate on larger sample size and longer follow-up time.

This real-world study presents outcomes of a cohort of Chinese patients with AD who used dupilumab. The follow-up period was from the start of dupilumab to the end of 16 weeks. The patient characteristics were comparable with those reported in clinical trials and other real-world studies (14, 15, 38). Overall, SCORAD index, EASI, POEM, DLQI, and NRS scores decreased significantly after treatment. The curative efficacy of dupilumab at 4th weeks was related to the patient’s age and course of disease. To our knowledge, this is the first report of the therapeutic efficacy and side effects of dupilumab in controlling symptoms and signs of AD in a Chinese population, and our findings provide a practical basis for future research on dupilumab.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Xiangya Hospital, Central South University. Written informed consent to participate in this study was provided by the participants or their legal guardian/next of kin. Written informed consent was obtained from the individual(s) or their legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.

BZ and CP wrote the first draft of the report. LL, RL, and LZ revised and reviewed the manuscript. LL, RL, LZ, XC, and JL supervised the study. All authors contributed to interpretation of results and revised the final manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.