Dupilumab better than MTX, cyclosporine for moderate/severe AD in children

The use of dupilumab in children with moderate-to-severe atopic dermatitis (AD) results in greater improvements in AD severity, better adherence, and fewer treatment-emergent adverse events (TEAEs) than methotrexate (MTX) or cyclosporine, as shown by 2-year interim results from the PEDISTAD study.

PEDISTAD is a real-world, prospective, observational, 10-year study of paediatric patients (aged <12 years) with inadequately controlled moderate-to-severe AD. Of the included children, 144 received dupilumab, 114 MTX, and 121 cyclosporine. The median treatment durations were 8.1, 13.0, and 10.7 months, respectively.

Dupilumab use led to numerically higher within-group improvements (p<0.05) than MTX and cyclosporine in Eczema Area and Severity Index (EASI: –12.4 vs –5.7 and –3.3), body surface area affected (–19.9 percent vs –11.8 percent and –8.8 percent), itching (night-time: –21 vs –0.4 and 0.1; daytime: –1.5 vs 0.1 and 0.2; ≥6 years), itching/scratching (–3.6 vs –1.4 and –0.2; <6 years), and Patient-Oriented Eczema Measure (POEM: –7.0 vs –4.7 and –1.5). [J Am Acad Dermatol 2025;92:242-251]

In addition, patients treated with dupilumab were less likely to discontinue treatment (8.3 percent vs 28.9 percent and 43.0 percent) and to experience AEs (18.1 percent vs 29.8 percent and 31.4 percent) than those who received MTX and cyclosporine.

“To put our results into context, the mean EASI score among children who received dupilumab improved from 20.9 to 8.6, close to mild AD,” the investigators said. “In the MTX and cyclosporine groups, mean EASI scores improved but remained well within the moderate band.” [Br J Dermatol 2015;172:1353-1357]

Moreover, the mean POEM scores in each treatment group improved from severe (17–24) to moderate (8–16), on average, and the biggest improvement was noted among patients treated with dupilumab. [Br J Dermatol 2013;169:1326-1332]

Safety and satisfaction

Treatment satisfaction was also greater with dupilumab, as indicated by the lower discontinuation rates in this group. Some patients stopped using MTX or cyclosporine due to well-controlled disease, but none of those on dupilumab discontinued for this reason.

“This could indicate that dupilumab is seen as a long-term treatment due to its acceptable safety profile, while MTX and cyclosporine tend to be discontinued once control has been achieved,” the investigators said. “Indeed, higher rates of cyclosporine discontinuation may be expected as cyclosporine is frequently prescribed as a short-term rescue medication that is intended to be discontinued.”

In terms of safety, fewer patients who received dupilumab reported one or more TEAE as opposed to those on MTX or cyclosporine. They were also less likely to withdraw from this study due to TEAEs.

“Overall, the safety of dupilumab was consistent with its known safety profile,” according to the investigators. [Lancet 2022;400:908-919; J Am Acad Dermatol 2020;83:1282-1293]

Dupilumab is approved for moderate-to-severe AD from age 6 months in the US and for moderate-to-severe AD from 12 years and severe AD from 6 months in Europe. [https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761055s042lbl.pdf; https://www.ema.europa.eu/en/medicines/human/EPAR/dupixent]