Atopic dermatitis (AD) is a chronic pruritic inflammatory dermatosis that occurs most frequently in children below 5 years of age. In Malaysia, the prevalence of AD among 5–7-year-old Kelantanese children was 13.7% and 9.9% among those 12–14 years of age.
Systemic agents such as prednisolone, cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil are used in the treatment of severe AD with variable success. Dupilumab is the first biologic that is approved by the Food and Drug Administration, United States, for the treatment of moderate-to-severe AD. It was approved for use in adults in March 2017, and for adolescents 2 years later. Since October 2021, the National Pharmaceutical Regulatory Agency in Malaysia has approved the use of dupilumab in children aged 6 years and older with moderate-to-severe AD.
A 5-year-4-month-old Malay boy has AD from 6 months of age, which worsened at the age of 3 years. He progressed to severe erythrodermic eczema with nodular prurigo and had multiple severe flares due to bacterial and viral infections. He had 3 flares that required systemic corticosteroids in the span of 5 months. At 3 years 10 months, he was commenced on oral azathioprine 25 mg daily (2 mg/kg/day) in addition to topical corticosteroids, emollients, and wet wrap therapy. Two weeks later, the azathioprine dose was escalated to 3 mg/kg/day and continued for a total of 4 months. Azathioprine was discontinued after 4 months as there was no clinical improvement [Figure 1] and he developed methicillin-resistant Staphylococcus aureus infection which was treated with co-trimoxazole and rifampicin. The skin biopsy done in January 2020 was consistent with nodular prurigo. He was commenced on oral methotrexate 0.5mg/kg/dose weekly and further worked up for immune deficiencies due to recalcitrant AD. Enzyme-linked immunosorbent assay test for HIV 1 and 2 was nonreactive. He had normal T-and B-cell enumeration, but immunoglobulin A level was extremely low (0.06g/L). Methotrexate was stopped due to concerns of possible primary immune deficiency. In view of hypertension and the possibility of primary immune deficiency, the parents were counseled for off-label use of dupilumab instead of cyclosporine [Figure 2 and Graph 1].
This 10-year-4-month-old Malay boy was diagnosed with AD at 4 years of age, which was initially localized to the flexures, but progressed to involve his face, scalp, and trunk by the age of 6 years [Figure 3]. Due to frequent flares despite being on optimized topical and systemic steroids, he was commenced on oral cyclosporine for a total of 2 years. Even with cyclosporine, he continued to have flares, requiring hospitalizations every 3–4 months due to infected eczema. At the age of 9 years, he was given regular subcutaneous dupilumab injections [Figure 4 and Graph 2].
This is a 5-year-10-month-old Malay girl with AD and toilet seat dermatitis since the age of 3 years. She was treated with emollients, topical corticosteroids, and topical calcineurin inhibitors [Figure 5]. She had recurrent infected eczema that required repeated courses of systemic antibiotics and even hospitalization in 2020. She was referred to our center for further management of AD, as her elder brother, patient 2, had remarkable improvement since commenced on dupilumab therapy [Figure 6 and Graph 3].
This is a 14-year-old Chinese boy who had atopic eczema since the age of 11 years. He was treated with emollients and topical corticosteroids, but he had recurrent flares since the age of 13 years [Figure 7]. His schooling and daily life were greatly affected by the severe itch. He was put on subcutaneous dupilumab of 300 mg every 4 weeks since the age of 13 years and 7 months [Figure 8 and Graph 4].
Dupilumab is a human monoclonal immunoglobulin G4 antibody that inhibits signaling of interleukin-4 (IL-4) and IL-13 by binding to the IL-4Ra subunit. The LIBERTY AD PEDS trial involved 367 children on topical corticosteroid aged between 6 and 12 years that were randomized into 3 groups, i.e., 2 weekly weight-based dupilumab regimens (100 mg for those <30kg; 400 mg loading followed by 200 mg 2 weekly for ≥30kg), 4 weekly dupilumab group (600 mg loading followed by 300 mg 4 weekly, regardless of the weight) and placebo group. At week-16, 67.2% of the patients on weight-based regimen achieved Eczema area and severity index (EASI)-75 while 69.7% for nonweight-based group and 26.8% for placebo (P < 0.0001).
In our cohort, most patients received lower doses of dupilumab due to financial limitations. However, we see comparable outcomes as previous studies. With our individualized dupilumab regimen, 75% of the patients achieved EASI-75 in <16 weeks with a median duration of 12 weeks (range = 8–56). The efficacy of dupilumab is also illustrated in our cohort as 75% attained EASI-50 by 8 weeks and 25% achieved EASI-50 by 4 weeks. Impressively, 50% achieved EASI-75 by week 12, 25% at week 16, and 25% at week 56 [Graph 5 and 6]. Patient 1 received dupilumab at a lower dose (100 mg 4 weekly without loading dose), yet achieved EASI-50 at week 4 and EASI-75 at week 8 of treatment. Patients 3 and 4 received the recommended dose without loading. Both reached EASI-50 at week 8 and EASI-75 at 12 weeks. Patient 2 attained EASI-50 at week 8, but had multiple eczema flares due to dermatophyte infections. He reached EASI-75 at week 56 when he was free of infection.
None of our patients developed conjunctivitis or upper respiratory tract infections during treatment with dupilumab. Reduction of daily peak pruritus score by at least 4 points was observed in 75% of patients at week 16 of treatment [Table 1].
Our case series is limited by a small sample size and its retrospective nature. Future studies of higher evidence levels are vital to further elucidate the dupilumab regimen in a resource-limited setting.
It is possible to achieve similar efficacy as the LIBERTY AD PEDS trial even without fixed-dose regimen of dupilumab. Furthermore, the limited resource does not impede the use of dupilumab, as a carefully tailored regimen according to the patients’ needs lead to better control of AD.
Declaration of consent
The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s)/guardian(s) of the patient. In the form, the parent(s)/guardian(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child/children will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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