Observational 24‐week study to assess clinical response to upadacitinib posttrial in patients with moderate‐to‐severe atopic dermatitis

BackgroundThe oral anti-janus kinase 1 inhibitor upadacitinib has shown a good efficacy-safety profile in the treatment of moderate-to-severe atopic dermatitis (AD) in clinical trials; however, few data from real clinical practice have been published so far.ObjectivesTo evaluate the efficacy and safety of upadactinib in clinical practice.MethodsAn observational and multicentric study was conducted. Inclusion criteria consisted of patients who had previously received upadacitinib in the clinical trial M19-850 and continued treatment with upadacitinib (15 mg or 30 mg) under daily clinical practice conditions for 12 months. Demographic data, characteristics of AD, treatment response and adverse events were recorded. Preliminary results at 24-week follow-up are herein presented.ResultsA total of 26 patients (61.54% males, mean age: 35.58 years) were included in the study; of these, 92.31% received upadacitinib 30 mg at baseline. At 24 weeks, mean values of Eczema Area and Severity Index and body surface area were 2.26 and 2.37%, respectively, 82.35% of the patients reached the Investigator's Global Assessment 0/1 and the mean value of peak pruritus numerical rating scale was 1.74. Adverse events were present in 19.23% of the cases, causing one definitive treatment interruption (due to herpes zoster) and two temporary treatment discontinuations (due to temporary elevation of creatine kinase).ConclusionsThese data support the maintenance of the efficacy of upadacitinib at 24-week posttrial follow-up, with no unexpected safety concerns. More real-world data are needed to confirm these results

Caracterización histológica de los melanomas con mutaciones en el promotor de TERT

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 08-03-2024Junto con las mutaciones en los genes BRAF y NRAS, las mutaciones en el promotor de TERT (pTERT) son las mutaciones somáticas más frecuentes en el melanoma maligno (MM). (1)Estas últimas han mostrado recientemente una relevancia importante ya que condicionan una mayor agresividad del MM, lo que se traduce en una peor supervivencia, sobre todo si se asocian a mutaciones en BRAF o NRAS. (2–5)Adicionalmente, ciertos hallazgos histológicos característicos del MM como son la ulceración, el índice mitótico o un mayor índice de Breslow, permiten predecir un peor pronóstico. Además, se ha descrito que los MM de rápido crecimiento, con un comportamiento más agresivo, muestran casi el doble de mutaciones en el pTERT que los de lento crecimiento. (6)Existen ciertos hallazgos histopatológicos en relación con mutaciones concretas como es en el caso de BRAF. Así, los MM con mutaciones en BRAF tienen un predominio de celularidad epitelioide con formación de nidos, pigmentación intensa y extensión pagetoide. Sin embargo, en el caso de NRAS, no se han hallado datos tan característicos. (7) Por último, se desconoce si los MM con mutación en el pTERT presentan de una forma similar a aquellos con mutación en BRAF rasgos histológicos característicos...Along with mutations in the BRAF and NRAS genes, those in the promoter of the TERT gene(pTERT) are the most frequent somatic mutations in malignant melanoma (MM). (1)The latter have recently shown an important relevance since they condition a greater aggressivenessof the MM, which translates into worse survival, especially if they are associated with mutations inBRAF or NRAS. (2–5)Additionally, certain histological findings characteristic of MM, such as ulceration, the mitoticindex or a higher Breslow index, allow a worse prognosis to be predicted.Furthermore, it has been described that fast-growing MM, with a more aggressive behavior, showalmost twice as many mutations in pTERT than slow-growing ones.(6)There are histopathological findings in relation to specific mutations, such as in the case ofBRAF. Thus, MM with BRAF mutations have a predominance of epithelioid cellularity with nestformation, intense pigmentation, and pagetoid extension. However, in the case of NRAS, suchcharacteristic data have not been found. (7) Finally, it is unknown whether MM with a pTERTmutation present characteristic histological features like those with a BRAF mutation...Fac. de MedicinaTRUEunpu