Background The efficacy and safety of upadacitinib in atopic dermatitis (AD) have been defined in clinical trials, but no real-world data are currently available. We aimed to assess the safety and effectiveness of upadacitinib in a real-world AD patient cohort that mostly included patients who failed the available systemic therapies, including dupilumab. Methods Prospective cohort study collecting data on upadacitinib-treated AD adult patients completing at least 16 weeks of therapy. Results Forty-three patients showed rapid and marked response to upadacitinib with significant reduction of all disease severity scores since the first follow-up visit. At week 16, Eczema Area and Severity Index (EASI) 75, EASI 90, and EASI 100 response was observed in 97.5%, 82.1%, and 69.2% of patients, respectively. EASI 90 response reflected the achievement of a clear or almost clear condition (POEM 0-2), self-evaluated by 79.5% of patients. Patients’ quality of life improved as suggested by the achievement of DLQI 0/1 by 38.5% of patients at week 4, and by 76.9% at week 16. Conclusion Elevated effectiveness and favorable safety of upadacitinib were confirmed in patients unresponsive to dupilumab, who were not included in upadacitinib trials.

Scalp is a frequent localization of psoriasis that has a massive impact on patient's quality of life. Managing this psoriasis' manifestation is often challenging, thus biologic drugs are widely used as a treatment option in refractory scalp psoriasis. The aim of our study is to retrospectively compare the efficacy of anti‐interleukin (IL) 23 drugs (guselkumab, tildrakizumab, risankizumab) and anti‐IL17 or anti‐IL17RA biologics (secukinumab, ixekizumab, and brodalumab) in real‐life patients affected by scalp psoriasis. One hundred twenty‐seven patients with a clinical diagnosis of scalp psoriasis and a baseline scalp Physician Global Assessment ≥3 were enrolled; 65 patients were treated with anti‐IL23 and anti‐IL62 with anti‐IL17 or anti‐IL17RA. Statistical analysis trough χ2 test was performed in order to evaluate the percentage of response among the two groups of patients. Responders' percentage of patients under anti‐IL23 was 41.5%, 75.4%, 88.1%, 87.5%, 93.7%, and 100% at Week 4, 16, 48, 96, and 144, respectively. In the group on anti‐IL17 was 62.9%, 90.3%, 91.2%, 97.3%, 96.9%, and 95.2% at Week 4, 16, 48, 96, and 144, respectively. Both anti‐IL17 and anti‐IL23 appeared to be effective on scalp psoriasis; in particular patients treated with anti‐IL17 drugs reached a faster significant reduction of the lesions; on the other hand, anti‐IL23 monoclonal antibodies were slightly superior in maintaining the clinical improvement through the follow‐up.

a b s t r a c t TP53 belongs to a small gene family that includes, in mammals, two additional paralogs, TP63 and TP73. The p63 and p73 proteins are structurally and functionally similar to p53 and their activity as transcription factors is regulated by a wide repertoire of shared and unique post-translational modifications and interactions with regulatory cofactors. p63 and p73 have important functions in embryonic development and differentiation but are also involved in tumor suppression. The biology of p63 and p73 is complex since both TP63 and TP73 genes are transcribed into a variety of different isoforms that give rise to proteins with antagonistic properties, the TA-isoforms that act as tumorsuppressors and DN-isoforms that behave as proto-oncogenes. The p53 family as a whole behaves as a signaling ''network'' that integrates developmental, metabolic and stress signals to control cell metabolism, differentiation, longevity, proliferation and death. Despite the progress of our knowledge, the unresolved puzzle of complexity, redundancy and hierarchy in the p53 family continues to represent a formidable challenge.