American Journal of Clinical Dermatology最新文献

Individualized neoantigen-directed therapy represents a groundbreaking approach in melanoma treatment that leverages the patient’s own immune system to target cancer cells. This innovative strategy involves the identification of unique immunogenic neoantigens (mutated proteins specific to an individual’s tumor) and the development of therapeutic vaccines that either consist of peptide sequences or RNA encoding these neoantigens. The goal of these therapies is to induce neoantigen-specific immune responses, enabling the immune system to recognize and destroy cancer cells presenting the targeted neoantigens. This individualized approach is particularly advantageous given the genetic heterogeneity of melanoma, which exhibits distinct mutations among different patients. In contrast to traditional therapies, neoantigen-directed therapy offers a tailored treatment that potentially reduces off-target side effects and enhances therapeutic efficacy. Recent advances in neoantigen prediction and vaccine development have facilitated clinical trials exploring the combination of neoantigen vaccines with immune checkpoint inhibitors. These trials have shown promising clinical outcomes, underscoring the potential of this personalized approach. This review provides an overview of the rationale behind neoantigen-directed therapies and summarizes the current state of knowledge regarding personalized neoantigen vaccines in melanoma treatment.

Background

Family history (FH) of psoriasis has been implicated as a risk factor for developing psoriasis. However, whether FH also carries information on clinical presentation and treatment response to biological agents in patients with psoriasis remains unclear.

Objective

This prospective, multicenter observational study aimed to analyze the clinical presentation and efficacy differences between patients with psoriasis with and without a FH.

Patients and Methods

The SPEECH registry is an observational, multicenter, and prospective registry that has been collecting data on psoriasis treatment since November 2022. This study included adult patients diagnosed with moderate-to-severe plaque psoriasis initiating treatment with biologics, including guselkumab, secukinumab, ixekizumab, ustekinumab, and adalimumab. FH of psoriasis was identified through patient self-report in which a positive FH was defined as a first-degree relative having psoriasis. The primary outcome measures include 75% improvement in Psoriasis Area and Severity Index (PASI75) and the Physician’s Global Assessment score of cleared/minimal (PGA 0/1) after 3 months of treatment. Logistic regression was employed to determine the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the achievement of response in selected outcomes for patients with a FH compared with those without a FH.

Results

The study included a total of 859 patients, of whom 22.9% had a FH of psoriasis. Patients with psoriasis who had a FH experienced an earlier onset of the disease and more severe anxiety symptoms than those without a FH. After 3 months of treatment, patients with psoriasis with a FH exhibited a higher likelihood of achieving PASI75 (aOR 1.60 [95% CI 1.02, 2.51]) and PGA 0/1 (aOR 1.54 [95% CI 1.03, 2.31]). Notably, these differences persisted after 6 months of treatment, confirming the sustained effectiveness of biologic treatments in patients with a positive FH. Further mediation analysis uncovered a significant indirect effect of FH on the treatment response to biologics through age of onset (p = 0.028), and the proportion mediated was 20.5%.

Conclusion

FH of psoriasis may affect the clinical course of patients and enhance their treatment response to biologics, highlighting the importance of FH assessment in optimizing treatment outcome and guiding clinical decision of biologic selection. Future studies on biologic treatment responses in psoriasis should consider family history as a significant confounding factor.

Chinese Clinical Trial Registry

ChiCTR2000036186.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that can significantly affect quality of life. Presence, severity, and therapeutic response of AD are traditionally reported through clinical assessments including the Eczema Area and Severity Index or Investigator’s Global Assessment. These clinical rating scales are visual assessments used in clinical trials to denotate AD severity. Alternatively, biomarkers open the potential to further enhance diagnosis of AD, assess disease status and severity, and potentially enable tailored treatment options for patients. Biomarkers can be classified according to their clinical use, clinical presentation, and underlying/endogenous molecular mechanisms. Specifically, interleukin (IL)-13, which has been shown to be a key biomarker in AD pathogenesis, can be used for prediction of AD development and to monitor clinical severity/response to treatment. Treatment with tralokinumab, a human monoclonal antibody that binds directly to—and subsequently blocks signaling of—IL-13, has been shown to reduce inflammation, re-balance the skin microbiome, and improve the skin barrier in patients with AD. In this review, key AD-related biomarkers, the role of IL-13 in driving AD pathogenesis, and the impact of IL-13 inhibition by tralokinumab on other AD-related biomarkers are discussed.

Pityriasis rosea (PR) is a prevalent dermatological condition characterized by a distinctive herald patch, followed by secondary eruptions, often forming a “Christmas tree” pattern on the trunk. Despite its recognizable clinical presentation, the etiology of PR remains uncertain, with hypotheses pointing to both infectious and noninfectious origins. Human herpesviruses (HHV) 6 and 7 have been implicated, with evidence suggesting viral reactivation as a potential trigger. Epidemiologically, PR affects children, adolescents, and young adults, with a higher incidence in females. The condition is observed globally, with varying incidence rates and seasonal variations, suggesting an infectious component. While PR is generally benign and self-limiting, it can cause significant discomfort owing to pruritus, and atypical presentations and recurrences complicate diagnosis and management. This review evaluates the current understanding of PR’s pathogenesis, highlighting both infectious and noninfectious hypotheses, including viral reactivation and immune response mechanisms. It also examines treatment options, such as antivirals and phototherapy, which have shown varying degrees of effectiveness. Further research is needed to clarify etiological factors and to explore the efficacy and safety of various treatment modalities. Understanding these aspects is crucial for improving patient outcomes and developing targeted therapies, especially for atypical or recurrent cases.

Background

Ruxolitinib cream has demonstrated anti-inflammatory and antipruritic activity and was well tolerated in a phase 3 study in patients aged 2–11 years with mild to moderate atopic dermatitis (AD).

Objective

This study examined the safety, tolerability, pharmacokinetics, efficacy, and quality of life (QoL) with ruxolitinib cream under maximum-use conditions and with longer-term use.

Methods

Eligible patients were aged 2–11 years with moderate to severe AD [Investigator’s Global Assessment (IGA) score 3–4], and ≥ 35% affected body surface area (BSA). Patients applied 1.5% ruxolitinib cream twice daily to all baseline-identified lesions during the 4-week maximum-use period, then to active lesions only up to week 52 (patients with ≤ 20% affected BSA from week 8). Safety was assessed by frequency and severity of adverse events. Pharmacokinetic parameters were assessed as secondary endpoints, and efficacy and QoL were exploratory endpoints.

Results

Overall, 29 patients (median age 5 years) were enrolled. Treatment-emergent adverse events were reported in 9/29 patients (31.0%); there were no adverse events of special interest (i.e., no serious infections, malignancies, major adverse cardiovascular events, or thromboses) during the study period. Mean steady-state plasma concentration during the maximum-use period was below the known half-maximal inhibitory concentration of Janus kinase–mediated myelosuppression in adults. Reductions in affected BSA and IGA observed at week 4 were sustained with as-needed use through 52 weeks. Improvements in patient-reported outcomes and QoL measures were consistent with efficacy results.

Conclusion

These results support the safety of ruxolitinib cream in children (2–11 years) with AD, including those with extensive disease, and are consistent with previous efficacy findings.

ClinicalTrials.gov Identifier

NCT05034822, first registered 30 August 2021.

Melanoma, a highly aggressive form of skin cancer, has seen significant advancements in treatment through the introduction of immunotherapy. However, the variability in patient responses underscores the need for reliable biomarkers to guide treatment decisions. This article reviews key biomarkers in melanoma immunotherapy, such as PD-L1 expression, tumor mutational burden (TMB), and gene expression profiles (GEPs). It also explores emerging biomarkers, including LAG-3 expression, immune cell phenotyping in tissue and blood, gut microbiota, and circulating tumor DNA (ctDNA). Notably, ctDNA may offer valuable insights into the efficacy of T cell-engaging bispecific molecules, such as tebentafusp. The review provides a comprehensive overview of the evolving landscape of melanoma biomarkers, their role in personalizing treatment, and future research directions, including neoadjuvant immune checkpoint inhibition.