Dupilumab delivers on its promise for Asians with atopic dermatitis

Singaporeans who have been treated with dupilumab in real-world clinical setting achieve improvements in the signs and symptoms of moderate-to-severe atopic dermatitis (AD), as shown in a retrospective study.

The body surface area (BSA) involved decreased over 4 months of dupilumab treatment, from a mean of 28.2 percent at baseline to 15.4 percent at month 1 (p<0.001) and 6.6 percent at month 4 (p<0.001). Likewise, the Eczema Area and Severity Index (EASI) scores dropped from a mean of 12.58 at baseline to 6.68 (p=0.007) and 6.46 (p=0.009) at months 1 and 4, respectively. [Singapore Med J 2024;doi:10.4103/singaporemedj.SMJ-2023-031]

Scoring Atopic Dermatitis (SCORAD) scores also showed a sustained decline, from a mean of 46.47 at baseline to 31.15 at month 1 and 24.0 at month 4. Meanwhile, the Dermatology Quality of Life Index (DLQI) scores initially remained unchanged at 1 month, from a mean of 15.43 at baseline to 13.80 (p=0.159) but decreased significantly to 9.46 at month 4 (p=0.014).

Notably, most patients (at least 75 percent) achieved clear improvements in all measured parameters (BSA, SCORAD, EASI, DLQI) within the first month of dupilumab treatment. These improvements were sustained and even increased over the next 3 months, with nearly all patients (between 92 percent and 100 percent) experiencing significant relief in signs and symptoms and having better quality of life.

By month 4, 73.7 percent and 31.6 percent of patients had achieved at least 50-percent (EASI-50) and 75-percent (EASI-75) improvement in skin status, respectively.

Multivariable analysis showed that azathioprine exposure before dupilumab therapy was associated with a decreased likelihood of BSA clearance at month 1 (p=0.019), as well as a 50-percent (p=0.0054) or 75-percent (p=0.0351) improvement in BSA scores at month 4. Moreover, patients with childhood-onset AD were more likely to achieve BSA improvements than those with adult-onset AD over 4 months of treatment (90.7 percent vs 9.3 percent).

Comparison with other cohorts

While dupilumab demonstrated effectiveness in treating moderate-to-severe AD in the current study cohort, “the extent of improvement was considerably low,” the investigators said.

For example, the EASI-75 of 31.6 percent was much lower relative to the 51.0 percent obtained in the pivotal SOLO trial, the 64.5 percent in a Chinese study, the 68.0 percent in an Indian study, and the 63.6 percent in a Korean study. [N Engl J Med 2016;375:2335-2348; J Eur Acad Dermatol Venereol 2022;36:1064-1073; Indian J Dermatol 2021;66:297-301; J Clin Med 2020;9:1982]

“Many external confounding factors in the real-world setting, such as treatment compliance of topicals and emollients, environmental factors, and types of AD, could have affected its treatment efficacy,” the investigators pointed out.

“We observed that patients who had previously tried azathioprine, a third-line oral immunosuppressant for AD, were less likely to have clinical improvement. This, together with the observation that many of our patients had previously failed other immunosuppressant therapies, suggests a higher eczema severity at baseline in our cohort,” they continued.

Nevertheless, AD recurrence in the Singaporean cohort was 30.8 percent, less frequent than the 56.7 percent reported in a long-term extension clinical trial. This difference, according to the investigators, could also be attributed to multiple external confounding environmental factors, as well as in a smaller sample size and a different healthcare setting. [Am J Clin Dermatol 2022;23:365-383]

Eye symptoms, head and neck dermatitis

In terms of safety, eye symptoms occurred in 42.0 percent of patients, while head and neck dermatitis occurred in 35.3 percent. Also, serum immunoglobulin E (IgE) and absolute eosinophil count showed a downward trend over 4 months of dupilumab treatment, with a transient increase in mean serum IgE at seen at month 1. There were no major adverse events reported.

The frequency of head and neck dermatitis in the current cohort was much higher than that reported in European adults in the existing literature (3 percent to 4 percent). This event has been linked to a preferential shift to Th1-, Th17- and Th22-dominated responses due to blocking of the Th2 pathway. [Br J Dermatol 2020;183:745-749; JAMA Dermatol 2019;155:1312-1315]

“Furthermore, sensitization to the human and/or fungal enzyme superoxide dismutase with overgrowth of Malassezia could have stimulated the Th17 pathway and induced a drug-induced photosensitivity reaction. Correspondingly, Asian AD cases also tend to have an enhanced Th17 cytokine profile, and such observations may explain the significantly larger proportion of patients in our study,” the investigators said.

The study included 51 patients (mean age 36.5 years, 70.6 percent men, 80.4 percent Chinese) with moderate-to-severe AD treated with dupilumab in real-world settings. Of the patients, 84.3 percent had classic AD with disease onset in childhood. The mean duration of eczema was 22.5 years, and 10 percent of patients had a previous history of eczema herpeticum as a complication of their AD.

“This study has provided local data on the effectiveness and adverse effects of dupilumab in a clinical cohort of adult AD. This is important for a better understanding of dupilumab as a treatment option for moderate-to-severe AD in Singapore and provides a basis for future clinical and cost-effective studies,” according to the investigators.

However, they acknowledged that their study was limited by its small sample size and retrospective nature. Also, Chinese and male patients were overrepresented in the cohort, which was likely influenced by the initial access to dupilumab as a relatively new treatment option.

“Further clinical investigations with a larger study population may be necessary to elucidate the associations and findings reported,” they said.