Study Highlights Success of Upadacitinib for Atopic Dermatitis in Various Clinical Phenotypes

Upadacitinib is an efficacious and safe treatment for patients with moderate-to-severe atopic dermatitis across various clinical phenotypes, new findings suggest, although those with the erythrodermic phenotype do have a 78% decrease in the likelihood of minimal disease activity achievement.1

These findings were the result of recent research conducted to examine the effectiveness of this medication in distinct clinical phenotypes for those with atopic dermatitis, a topic which was noted as not having been widely evaluated. Niccolò Gori, from the dermatology department at Università Cattolica del Sacro Cuor in Rome, led a team of investigators for this analysis.

“Upadacitinib, a JAK 1 inhibitor indicated for treatment of patients aged ≥12 years with moderate-to-severe [atopic dermatitis], has shown good short- and long-term efficacy and a favourable safety profile both in randomized clinical trials and real-world studies,” Gori and colleagues wrote. “However, the effectiveness of upadacitinib in distinct [atopic dermatitis] clinical phenotypes has not been investigated.”1,2

Trial Design and Findings on Effectiveness in Different Phenotypes

The investigative team noted that although the most common atopic dermatitis phenotype is the classic flexural presentation, adults with the skin disease may also have less typical versions, such asnummular eczema, prurigo nodularis-like, and generalized or erythrodermic variants.

Given that there are these phenotypic differences, such distinctions may show a link with variations in patients’ immune responses and in skin barrier dysfunction. As a result, such differences could impact the efficacy of different forms of medications.

Therefore, the investigators sought to assess upadacitinib’s efficacy in different subtypes of atopic dermatitis, conducting a multicenter retrospective analysis across 7 Italian university hospitals. The research team determined their primary aim would be to evaluate treatment responses in the most prevalent clinical phenotypes—flexural, nummular eczema, prurigo nodularis-like, and erythrodermic atopic dermatitis.

In addition, the researchers also pointed to possible clinical predictors of success with treatment. The team decided to include adult patients reporting moderate-to-severe atopic dermatitis, specifically those who had been treated with upadacitinib in the timeframe between October 2020 - September 2022. They ended up including a total of 245 adults in their study, with 105 women and 140 men. The investigators highlighted that the average age of subjects was 35.9 years (SD ±13.9).

Overall, the researchers concluded that at the 16-week mark, significant decreases in participants' mean Eczema Area and Severity Index (EASI) scores were observed, with 22.1 ± 13.3 dipping to 2.6 ± 4.4 (P < .0001). They further highlighted that improvements took place in both subjects' Worst Pruritus (WP)-Numeric Rating Scale (NRS) scores and their Dermatology Life Quality Index (DLQI) scores.

Such benefits, the team noted, continued through 52 weeks of the medication. At the 16-week mark, the research team found that 84.2% of the study subjects achieved an EASI75 score, adding that at the same point, 65.2% and 40.8% reported achieving EASI90 and EASI100, respectively.

These response rates remained stable over the course of a year. Additionally, by the same 16-week time point, a substantial ≥4-point reduction was observed in participants' NRS-sleep, WP-NRS, and DLQI 0/1 for 78.2%, 74.8%, and 53.3% of those taking part, respectively. The investigators expressed that continued progress was also observed over time (P < .0001 for all time points from baseline).

Notably, the investigative team found that clinical phenotype did not appear to influence participants' likelihood of reporting a strong response to the drug, as similar proportions of subjects were shown across all phenotypes to have achieved EASI75, 90, and 100 throughout the study.

Despite these results, when the investigators assessed factors linked to achieving minimal disease activity (MDA)—a point they defined as EASI90 along with an absolute WP-NRS ≤ 1—by the 16-week mark, their multivariable analysis demonstrated that the erythrodermic phenotype was linked to subjects being 78% less likely of to report MDA (OR = 0.22, 95% CI = 0.08–0.63, P = .005).

Such a reduced response continued to take place, despite adjustments for age at the initiation of treatment and despite disease severity at baseline. This finding points to the challenges of achieving optimal disease control in this severe atopic dermatitis subtype.

Prior real-world research, including a study looking at 221 individuals reporting moderate-to-severe disease, have also shown comparable clinical responses to dupilumab across 6 distinct phenotypes of atopic dermatitis after both 16 and 52 weeks of medication use. Such data, the team noted, underscore the vital role of IL-4 and IL-13 in the skin condition's pathogenesis.

Despite the comparison, the researchers noted that this prior study lacked comprehensive evaluations of efficacy with stringent endpoints such as EASI90, EASI100, and MDA. Thus, comparability was limited for their current research.

“In conclusion, the present study confirms that upadacitinib, due to its broad cytokine inhibitory spectrum, can be an effective and safe option for the treatment of a significant proportion of [atopic dermatitis] patients across different clinical phenotypes, with no notable differences in the extent of clinical response,” they wrote. “We recognise the retrospective nature of the study as a limitation, along with the relatively small number of non-classic [atopic dermatitis] phenotype included in the analysis.”1

References

1. Gori, N., Quaglino, P., Chiricozzi, A., Marzano, A.V., Argenziano, G., Girolomoni, G., Bianchi, L., Fargnoli, M.C., Ortoncelli, M., Di Nardo, L., Ferrucci, S.M., Caccavale, S., Maurelli, M., Galluzzo, M., Esposito, M. and Peris, K. (2025), Successful response of upadacitinib in different clinical phenotypes of atopic dermatitis. J Eur Acad Dermatol Venereol. https://doi.org/10.1111/jdv.20568.
2. Chiricozzi A, Ortoncelli M, Schena D, Gori N, Ferrucci SM, Babino G, et al. Long-term effectiveness and safety of Upadacitinib for atopic dermatitis in a real-world setting: an interim analysis through 48 weeks of observation. Am J Clin Dermatol. 2023; 24(6): 953–961.