Dupilumab mends skin barrier in children with AD, but with caveat

Use of dupilumab results in normalization of stratum corneum (SC) lipids, which is responsible for skin barrier function, in children with atopic dermatitis (AD) within 1 to 2 months of treatment, according to a study presented at AAAAI 2024.

“These beneficial changes persisted for at least 3 months after the end of treatment,” said the researchers led by Irina Bronova, National Jewish Health, Denver, Colorado, US.

However, another study cautioned against using dupilumab, which was found to potentially lead to the development of some serious cancers. [AAAAI 2024, abstract AB30]

In the PELISTAD open-label study, 23 paediatric patients aged 6‒11 years with moderate-to-severe AD received dupilumab for 16 weeks and were followed up for 3 months. A matched healthy control (HC; n=18) group was also followed up for 28 weeks.

The investigators obtained SC skin tape stripping (STS) and assessed STS samples serially for changes in lipid profile using mass spectrometry.

Lesional SC of children with AD at baseline had elevated levels of N(C18S)-Ceramides (mean Fold Change [mFC] 3.314; p=0.00224), decreased levels of esterified omega-hydroxy fatty acid containing ceramides (EO[C18S]S-Ceramides, mFC 0.48; p=0.00424), and increased ratio of N(C18S)-Ceramides-to-EO(C18S)-Ceramides (mFC 6.35; p<0.0001) compared with HC. [AAAAI 2024, abstract AB5]

Dupilumab treatment led to significant improvements in lipid components: N(C18)S-Ceramides, within 4 weeks (p=0.00125); EO(C18S)-Ceramides, within 8 weeks (p=0.00233); and N(C18S)-Ceramide-to-EO(C18S)-Ceramide ratio, within 2 weeks (p=0.0074). The normalized levels of SC lipids in lesional skin persisted for up to 3 months after the end of treatment.

“Dysregulation of SC barrier lipids in nonlesional skin was less pronounced than that of lesional skin, but their normalization followed similar pattern as lesional skin dynamics,” Bronova and colleagues said.

Cancer development

On the other hand, a literature review also presented at AAAAI 2024 found several multicentre and single-institutional studies showing “sporadic occurrence of serious malignancies in association with dupilumab use.” [AAAAI 2024, abstract AB30]

In a single institution, three patients who were using dupilumab for fungal sinusitis, asthma, and eczema developed rapidly progressive and aggressive cancers, such as glioblastoma multiforme, fatal pancreatic cancer, and advanced sinonasal cancer. More than 30 cases of cutaneous T-cell lymphoma related to dupilumab treatment were recorded as well.

Other haematological malignancies reported included anaplastic lymphoma, Sezary syndrome, and Hodgkin’s lymphoma. Cases of solid tumours such as sinonasal, pancreatic, lung, testicular, and prostate cancers were also found in the literature.

The link between dupilumab use and certain malignancies may have been driven on a molecular level by defects in interleukin (IL)-4 mediated surveillance, according to the researchers headed by Chase Rupprecht, Geisel School of Medicine at Dartmouth-Hitchcock Medical Center, US. Close monitoring is recommended since many symptoms are similar to the primary condition for which dupilumab is used.

“There is ever present danger of missed or delayed diagnosis of evolving cancer,” Rupprecht and colleagues said. “New onset headache, weight loss, or anorexia should suggest tumour development.”