Successful response of upadacitinib in different clinical phenotypes of atopic dermatitis

Adult atopic dermatitis (AD), specifically late-onset phenotypes, is characterized by a notable degree of clinical heterogeneity in terms of morphologic and topographic characteristics.1-4 Alongside the classic flexural AD presentation, adult patients can manifest other less common phenotypes, including prurigo nodularis-like, nummular eczema and generalized/erythrodermic,2 that may exhibit variations in immune and skin barrier proteins with potential influence on topical and systemic therapies' efficacy.5 Upadacitinib, a JAK 1 inhibitor indicated for treatment of patients aged ≥12 years with moderate-to-severe AD, has shown good short- and long-term efficacy and a favourable safety profile both in randomized clinical trials and real-world studies.6-8 However, the effectiveness of upadacitinib in distinct AD clinical phenotypes has not been investigated. We performed a multicentre retrospective study on adult patients with moderate/severe AD treated with upadacitinib recruited from October 2020 to September 2022 at seven Italian university hospitals. The objective of our study was to characterize the effectiveness of upadacitinib in the most prevalent clinical AD phenotypes, including flexural, prurigo nodularis-like, nummular eczema and erythrodermic, with a view towards identifying clinical predictors of treatment response. A total of 245 adult patients, 105 women and 140 men with a mean age of 35.9 years (SD ±13.9), with moderate-to-severe AD were included in the study. Table 1 illustrates patients' demographic and clinical characteristics. A significant reduction of mean Eczema Area and Severity Index (EASI) score (from 22.1 ± 13.3 to 2.6 ± 4.4, p < 0.0001) as well as an improvement of Worst Pruritus (WP)-Numeric Rating Scale (NRS) and Dermatology Life Quality Index (DLQI) were observed at week 16 and were then maintained throughout the 52 weeks of treatment (Table 1). By week 16, 84.2%, 65.2% and 40.8% of patients achieved EASI75, 90 and 100, respectively, with sustaining response throughout 12 months of treatment. In addition, at week 16, a significant improvement (≥4 point) of WP-NRS, NRS-sleep and DLQI 0/1 were recorded for 74.8%, 78.2% and 53.3% of patients, respectively, with slight improvement thereafter (Table 1, p < 0.0001 for each time point from baseline). Disease phenotype did not affect the likelihood of achieving a good or optimal clinical response as evidenced by a similar proportion of patients reaching EASI75/90/100 throughout the study period among each phenotype (Table 2). We also sought to identify clinical variables influencing the likelihood of achieving a minimal disease activity (MDA) after 16 weeks of treatment, as defined by a recent international consensus (EASI90 plus absolute WP-NRS ≤ 1).9 The multivariable analysis highlighted that the erythrodermic AD phenotype was associated with a 78% reduced likelihood of achieving MDA at week 16 (OR = 0.22, 95% CI = 0.08–0.63, p = 0.005), regardless of the age at treatment initiation and disease severity (EASI) at baseline (Prob > chi2 = 0.030, Number of observations = 154), underlying the challenge of attaining such an optimal outcome in this severely debilitating phenotype. Recently, a multicentre real-world experience including 221 moderate/severe AD patients, described a good and comparable clinical response of dupilumab in six different clinical phenotypes after 16 and 52 weeks of treatment, thus supporting the central role of IL-4 and IL-13 across different clinical phenotypes.10 It should be noted, however, that the aforementioned study is limited by the absence of a comprehensive efficacy analysis including more stringent end points such as EASI 90/100 and MDA. 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 AD patients across different clinical phenotypes, with no notable differences in the extent of clinical response. We recognise the retrospective nature of the study as a limitation, along with the relatively small number of non-classic AD phenotype included in the analysis. No funding sources supported this study. Outside of the submitted work, the authors declare the following conflicts of interest: Niccolò Gori served as advisory board member and received honoraria for lectures for AbbVie, Sanofi and Leo-Pharma. Andrea Chiricozzi has served as advisory board member and consultant and has received fees and speaker's honoraria or has participated in clinical trials for AbbVie, Almirall, Boehringer-Ingelheim, Bristol Myers Squibb, Leo Pharma, Lilly, Janssen, Novartis, Pfizer and Sanofi Genzyme. Angelo Valerio Marzano reports consultancy/advisory boards disease-relevant honoraria from AbbVie, Amgen, Boehringer-Ingelheim, Bristol Myers Squibb, Incyte, Leopharma, Novartis, Pfizer, Sanofi and UCB. Giampiero Girolomoni has received personal fees from AbbVie, Almirall, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli-Lilly, Leo Pharma, Merck Serono, Novartis, Pfizer, Pierre Fabre, Samsung Bioepis and Sanofi. Silvia Mariel Ferrucci served as advisory board member, principal investigator in clinical trials and speaker for Almirall, AbbVie, Amgen, Leo Pharma, Galderma, Elli Lilly, Novartis, Pfizer and Sanofi. Maria Concetta Fargnoli has served on advisory boards, received honoraria for lectures and/or research grants from AMGEN, Almirall, AbbVie, Boehringer-Ingelheim, BMS, Galderma, Kyowa Kyrin, Incyte, LEO Pharma, Pierre Fabre, UCB, Lilly, Pfizer, Janssen, MSD, Novartis, Sanofi, Regeneron and Sun Pharma. Marco Galluzzo has acted as a speaker and/or consultant for AbbVie, Almirall, Eli-Lilly, Janssen-Cilag, LeoPharma, Novartis and Sanofi outside the submitted work. Maria Esposito has served as speaker/consultant for AbbVie, Amgen, Almirall, Eli Lilly, Janssen, Leopharma, Novartis, Pfizer, Sanofi and UCB. Ketty Peris has served on advisory board and received honoraria for lectures from Abbvie, Almirall, Lilly, Galderma, Leo Pharma, Pierre Fabre, Philogen, Novartis, Sanofi, Sun Pharma and Janssen. The other authors have no competing interests to declare. Approval of this study was obtained by the Local Ethics Committee—Comitato Etico Territoriale (CET) Lazio Area 3, Prot. ID: 5909. The patients included in this study have given written informed consent to publication of their case details. Enquiries related to the data generated or analysed during this study can be directed to the corresponding author.