Giuseppe Lauletta

Lebrikizumab, a monoclonal antibody targeting interleukin-13, has demonstrated efficacy and safety in adults with moderate-to-severe atopic dermatitis (AD), but data for older patients remain limited. We conducted a retrospective multicentre study including 90 patients aged ≥ 60 years with moderate-to-severe AD treated with lebrikizumab across 23 Italian dermatology centres. Clinical outcomes were assessed at baseline and at weeks (W) 16, 24 and 52. Mean (SD) Eczema Area and Severity Index (EASI) decreased from 23.24 (7.93) at baseline to 6.33 (6.54) at W16, 3.57 (3.74) at W24 and 2.70 (4.83) at W52 (P < 0.0001). EASI 75 (75% improvement from baseline) was achieved by 58%, 82% and 87% of patients at W16, W24 and W52, respectively. Clinical responses were similar across age groups and independent of prior biologic or Janus kinase inhibitor exposure. Adverse events occurred in 8% of patients and were mainly mild. These findings support the effectiveness and safety of lebrikizumab in older patients with AD in real-world clinical practice.

Background: Difficult-to-treat anatomical areas in atopic dermatitis (AD), including the head and neck, hands, genital and intertriginous regions, are frequently associated with therapeutic refractoriness, persistent pruritus, and substantial functional and psychosocial burden. Real-world evidence (RWE) regarding the effectiveness of Janus kinase (JAK) inhibitors in these site-dominant phenotypes remains fragmented. This structured narrative review aimed to synthesize available RWE on abrocitinib, baricitinib, and upadacitinib in AD involving difficult-to-treat areas. Methods: A comprehensive search of PubMed, Ovid MEDLINE, Scopus, Embase, and the Cochrane Library was conducted up to 31 December 2025. Real-world observational studies reporting site-specific outcomes in patients with AD treated with JAK inhibitors were included. Primary randomized controlled trial efficacy analyses were excluded, while relevant post hoc regional analyses were considered. A total of 22 studies met eligibility criteria for qualitative synthesis. Results: Across heterogeneous real-world cohorts, JAK inhibitors demonstrated clinically meaningful improvement in difficult anatomical regions, particularly the head and neck and hands. Rapid pruritus reduction was a consistent and clinically relevant finding. Safety profiles were broadly aligned with clinical trial data. Conclusions: Real-world data support JAK inhibitors as effective options for anatomically complex AD phenotypes, warranting further standardized regional assessment.

Introduction: Alopecia areata (AA) is a chronic immune-mediated disorder characterized by non-scarring hair loss and a significant psychosocial burden. Ritlecitinib, a selective Janus kinase 3 (JAK3) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor, has recently emerged as a targeted systemic therapy for moderate-to-severe AA. While randomized clinical trials have demonstrated its efficacy, real-world evidence remains limited and heterogeneous. Methods: A structured narrative review was conducted to summarize current evidence on ritlecitinib in AA, with a focus on real-world outcomes. A comprehensive search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Library was performed up to March 2026 using predefined keywords. Eligible studies included real-world observational studies, case series, and post hoc analyses of randomized controlled trials reporting clinical outcomes. Two independent reviewers performed study selection. Results: A total of 14 studies were included. Clinical trial analyses suggested sustained efficacy over time, with progressive improvement in Severity of Alopecia Tool (SALT) scores up to 24 months. Real-world studies reported clinically meaningful hair regrowth across diverse populations, including severe, pediatric, and treatment-experienced patients. Response rates increased over time, with a proportion of patients achieving SALT ≤ 20 or ≥80% improvement. Lower baseline severity and shorter disease duration were reported in several studies as potential factors associated with a better response. Safety profiles were favorable, with predominantly mild adverse events. Discussion: Ritlecitinib shows consistent effectiveness and acceptable safety in both clinical trials and real-world settings. Treatment response appears progressive and heterogeneous, supporting the importance of early intervention and adequate treatment duration. Further large-scale and long-term real-world studies are needed to better define predictors of response and optimize patient selection.

Introduction: Real-world evidence on the long-term use of dupilumab in very young children with moderate-to-severe atopic dermatitis (AD) remains limited. Observational data are needed to complement clinical trial findings by describing treatment outcomes in routine clinical practice. Methods: This multicenter retrospective study included children aged 6 months to 5 years with moderate-to-severe AD treated with dupilumab through the Italian Named Patient Program. Clinical assessments were performed at baseline and at weeks (W) 16, 24, 36, and 52. Disease severity, quality of life, and symptom burden were evaluated using the Eczema Area and Severity Index (EASI), Children’s Dermatology Life Quality Index (c-DLQI), pruritus-numeric rating scale (P-NRS), and sleep-numeric rating scale (S-NRS). EASI-50/75/90 responder rates were calculated at each time point. Safety data were collected throughout treatment. Growth parameters were monitored between baseline and W52. Results: Forty-seven children were included. Dupilumab led to rapid and progressive improvement of AD severity, with mean EASI decreasing from 26.1 at baseline to 2.7 at W52 (−89.7%). Marked improvements were also observed in quality of life (−91.3% in c-DLQI), itch intensity (−82.5% in P-NRS), and sleep disturbance (−82.7% in S-NRS). At W52, EASI-75 and EASI-90 responses were achieved by 79.5% and 59.0% of evaluable patients, respectively. Dupilumab was well tolerated, with treatment-emergent adverse events occurring in 10.6% of patients, all mild or moderate and none leading to discontinuation. Weight- and height-for-age z -scores significantly increased over 52 weeks; no child newly developed values below −2 standard deviations, although 1 child remained below this threshold at W52. Percentile-based analyses yielded consistent results, confirming the absence of negative effects on growth. Conclusion: Dupilumab was effective and well tolerated over 52 weeks in children aged 6 months to 5 years with moderate-to-severe AD, providing sustained skin clearance, symptom relief, and quality-of-life improvement. These findings support dupilumab as a valuable long-term therapeutic option in very young children with uncontrolled AD in clinical practice.

Background: Head and neck dermatitis (HND) represents a challenging phenotype of atopic dermatitis (AD), often showing suboptimal response or paradoxical worsening during biologic therapy. Objective: To review the efficacy and safety of current systemic treatments for HND, with a focus on dupilumab, tralokinumab, lebrikizumab, and janus kinase (JAK) inhibitors. Methods: We conducted a narrative review of randomized controlled trials, post hoc analyses, and real-world studies assessing clinical outcomes in patients with moderate-to-severe AD involving the head and neck. Outcomes included Eczema Area and Severity Index (EASI) H&N subscore, erythema grade, patient-reported measures, and adverse events. Results: Dupilumab shows substantial efficacy for HND in both clinical trials and real-life studies; however, responses are often less pronounced than in other anatomical regions, and facial redness (FR) has emerged as a notable adverse event in up to 9% of patients. Tralokinumab and lebrikizumab demonstrate significant improvements in HND involvement, with low incidence of paradoxical reactions. JAK inhibitors, particularly upadacitinib, provide rapid and marked improvement in refractory cases and in patients developing FR during biologic therapy. Conclusions: Systemic therapy for HND should be individualized, balancing efficacy and tolerability. JAK inhibitors represent a valuable alternative in biologic-refractory phenotypes or in patients experiencing dupilumab-associated FR.

Background: Biologic therapies such as dupilumab and tralokinumab have greatly impacted the management of moderate-to-severe atopic dermatitis (AD). However, recent clinical observations have reported paradoxical adverse events, including psoriasis and seronegative spondyloarthropathy (SpA). Objectives: To assess the incidence, clinical characteristics and management of psoriasis and SpA in patients with AD treated with dupilumab or tralokinumab in a real-world setting. Methods: We conducted a multicentre retrospective observational study involving patients with AD receiving dupilumab or tralokinumab for ≥ 16 weeks between January 2019 and May 2025. Data were collected on patients developing psoriasis and/or SpA, including demographics, time to onset, severity, management strategies and treatment outcomes. Results: Psoriasis developed in 78 of 5899 patients (1.3%) receiving dupilumab and 16 of 769 (2.1%) on tralokinumab, with respective mean times to onset of 57.7 (SD 66.5) and 28.3 (28.9) weeks. SpA occurred in 17 patients (0.3%) on dupilumab and 1 (0.1%) on tralokinumab. Topical calcipotriol/betamethasone was the most frequent treatment for psoriasis, while systemic agents, including methotrexate and corticosteroids, were required in refractory cases. In addition, a proportion of patients required switching to alternative biologics due to poor disease control. For SpA, management often involved systemic corticosteroids, nonsteroidal anti-inflammatory drugs or methotrexate, and upadacitinib was introduced in 41% of cases of dupilumab requiring therapeutic escalation. Conclusions: Although rare, psoriasis and SpA are adverse events emerging during dupilumab or tralokinumab therapy in patients with AD. Close monitoring and prompt differential diagnosis are essential to optimize patient outcomes.

Cancer immunotherapy, particularly immune checkpoint inhibitors (ICI), has revolutionized oncology treatment by leveraging the immune system to recognize and eliminate cancer cells. However, despite its efficacy, immunotherapy may induce immune‐related adverse events (irAEs), including dermatological events, that can range from mild rashes to severe life‐threatening conditions such as toxic epidermal necrolysis. This paper aims to explore and analyse the preventive measures for cutaneous irAEs (cirAEs). By identifying risk factors, recognizing early signs and implementing preventive strategies, healthcare professionals can significantly mitigate the severity of irAEs, thereby improving patient outcomes and quality of life.

Background: Atopic dermatitis (AD) in elderly patients presents unique clinical challenges due to comorbidities, polypharmacy, and an increased risk of adverse events. Janus kinase inhibitors (JAKis) have emerged as effective oral treatments, but limited data are available for their use in older adults. Methods: A narrative review was conducted through a comprehensive search of PubMed/MEDLINE, Ovid, Scopus, Embase, Cochrane Library, Web of Science, and Google Scholar up to July 2025. Only English-language studies evaluating abrocitinib, baricitinib, or upadacitinib in elderly patients (≥65 years) with moderate-to-severe AD were included. Results: RCTs enrolled few elderly patients and lacked dedicated subgroup analyses. Abrocitinib showed similar efficacy in older and younger adults, but higher rates of adverse events, especially at the 200 mg dose. Real-world studies, mainly on upadacitinib, demonstrated rapid and sustained clinical improvements, including in difficult-to-treat areas. Safety outcomes were generally favorable; most adverse events were mild and manageable. Herpes zoster and hematological changes were more frequent in elderly patients, while serious cardiovascular events were rare. Conclusions: JAK inhibitors are effective therapeutic options for elderly patients with moderate-to-severe AD. Careful patient selection, dose tailoring, and close monitoring are essential. Further age-specific RCTs and long-term real-world data are needed to guide clinical practice.