Long‑term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis in a Real‑world Setting: An Interim Analysis Through 48 Weeks of Observation

Background Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate- severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. Methods This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. Results One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physicianreported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. Conclusion This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change

TCRγ-Chain Gene Rearrangement by PCR-Based GeneScan: Diagnostic Accuracy Improvement and Clonal Heterogeneity Analysis in Multiple Cutaneous T-Cell Lymphoma Samples

Cutaneous T-cell lymphomas are a heterogeneous group of lymphomas where the tumor population emerges within a multiple subclone pattern (“clonal heterogeneity”). PCR analysis has been shown to be useful in the diagnosis of mycosis fungoides (MF) and Sézary Syndrome (SS). Focusing the attention on clonal heterogeneity, the efficacy of the multiplex/heteroduplex (HD) PCR and the GeneScan (GS) capillary electrophoresis analysis was compared in the early diagnosis of MF/SS, using a multiple sample approach. Indeed, GS demonstrated TCRγ gene rearrangement (GR) in all the 57 SS (100%) and in 123/146 (84%) of the MF samples, whereas the multiplex/HD PCR was less sensitive. An increase in clonality was observed in connection with both a worsening of the cutaneous disease (79% T1/T2; 100% T3/T4) and an increase in the histopathological score (HS<5, 76%; HS≥5, 94%). Clonal heterogeneity with adjunctive reproducible skin TCRγ-GRs was also observed. “Clonal instability,” with different GRs, was present in a small percentage of patients. Therefore, it can be concluded that GS analysis in TCRγ-GR is able to improve diagnosis in MF/SS patients and the multiple sample approach is helpful for a correct interpretation of clonal patterns in skin lesions, especially in early-stage MF and in SS skin/blood samples

Impact on health-related quality of life and symptoms of anxiety and depression after 32 weeks of Dupilumab treatment for moderate-to-severe atopic dermatitis

Dupilumab is the first biological agent approved for treatment of moderate‐to‐severe atopic dermatitis (AD). Evidence of Dupilumab effectiveness on psychological outcomes beyond 16 weeks of treatment from real‐life settings is lacking. To evaluate the effectiveness of Dupilumab treatment up to 32 weeks, focusing health‐related quality of life and psychological outcome of patients with moderate‐to‐severe AD. An observational prospective cohort study was conducted in a real‐life setting at an Italian tertiary centre. Assessment of outcome measures was carried out at baseline, after 16 and 32 weeks of treatment. A total of 171 patients were included. EASI‐75 and EASI‐90 were achieved in 85% and 60% of the participants, respectively, after 16 weeks, and in 89.6% and 69.8% after 32 weeks of treatment. Significant improvements (p < 0.001; r = 0.57–0.95) were found after 16 weeks for each outcome considered, including clinician and patient‐reported measures of AD severity and scales of health‐related quality of life and psychological morbidity, and maintained up to 32 weeks. Further analysis revealed that patients' quality of life was more associated with the subjective perception of disease severity rather than objective measures and suggested a possible different response to treatment based on the age of AD onset. Dupilumab was confirmed to be rapid, effective and safe in patients with moderate‐to‐severe AD. Its positive impact on psychological outcomes up to 32 weeks was ascertained here, adding new evidence on the need to consider subjective factors affecting patients' perception of disease severity in evaluating the response to treatment