American Journal of Clinical Dermatology最新文献

Innovations in biologics are transforming the treatment of psoriatic diseases. The ability to target specific levels of immune activation provides a distinct advantage. Interleukin (IL)-17 inhibitors fall into this class of biologics, and they are effectively used to treat a spectrum of psoriatic diseases, such as psoriasis vulgaris and psoriatic arthritis. In recent years, anti-IL-17 agents have been the focus of therapeutic development, with various formulations and routes of administration. In this manuscript, we review pipeline anti-IL-17 therapies for psoriatic diseases identified through a search of ClinicalTrials.gov (January 2019–December 2024) and other databases. Key agents under investigation include netakimab, vunakizumab, xeligekimab, gumokimab, HB0017, CJM 112, JS005, 608, LZM012, ZL-1102, izokibep, sonelokimab, DC-806, DC-853, and LEO 153339. Both preclinical and clinical trial data for each agent are summarized, with an emphasis on their efficacy, adverse effects, immunogenicity, and future outlooks.

Background

The effectiveness of Janus kinase (JAK) inhibitors in treating atopic dermatitis (AD) is well established. However, little is known about whether disease control can be maintained with longer dosing intervals, especially in older patients who are at higher risk of adverse events from JAK inhibitors. The treat-to-target (T2T) consensus was established to guide systemic treatment in adults with AD, aiming to achieve disease control promptly and sustain it in the long term.

Objective

The aim of this study was to evaluate the efficacy and safety of extended JAK inhibitor dosing intervals based on the T2T consensus in older adults.

Methods

A prospective observational cohort study was conducted from July 2022 to February 2024. Fifty-eight elderly patients (aged ≥ 65 years) were included in the study and received upadacitinib with gradually longer dosing intervals. The primary outcome was the proportion of patients maintaining different treatment dosing intervals at the end of the follow-up, as well as the assessment of six scales at every visit.

Results

Among the 58 patients (median [IQR] age, 70 [68–77] years) included in the study, 86.2% completed the 1-year follow-up. By the last visit, among those who completed the follow-up, 26.0% maintained a dosing interval of every 3 days, and 72.0% maintained a dosing interval of every 2 days. The overall incidence of adverse events (AEs) was 29.3% among all patients, with the most common AE reported being herpes virus infection (13.8%).

Conclusions

The dose reduction regimen guided by the T2T consensus was well tolerated in elderly patients with moderate-to-severe AD. Prolonging dosing intervals offers potential benefits for both patients and socioeconomic outcomes.

Atopic dermatitis (AD) is a T helper 2-mediated chronic inflammatory skin disease that affects children and adults. Patients with AD are prone to recurrent infections of the skin and other organs, which can severely worsen the disease course. This review summarises the current evidence on the aetiology, pathogenesis, treatment and prevention of infections in patients with AD. PubMed was searched for English-language research articles, systematic reviews, meta-analyses and guidelines published until February 2023 using the key term “atopic dermatitis” and terms relevant to infections. Patients with AD have an increased risk of bacterial, viral and fungal infections of the skin, mainly due to impaired barrier function, altered immune response and frequent scratching. The most common pathogens are Staphylococcus aureus and herpes simplex virus, which can cause impetigo, folliculitis, abscesses, eczema herpeticum and other complications. They also appear to increase susceptibility to systemic infections, including respiratory and urinary tract infections and sepsis. Certain systemic treatments for AD, such as mycophenolate mofetil and Janus kinase inhibitors, increase the risk of viral infections. Prevention and treatment of recurrent infections in patients with AD require a multifaceted approach that includes topical and systemic antimicrobials, skin care and effective control of AD symptoms (to break the itch–scratch cycle). Preventing and limiting the development of infections are important considerations in choosing an AD treatment.

The unique immunomodulatory properties of hydroxychloroquine (HCQ) have attracted considerable interest beyond its use for malaria and rheumatological diseases, including a variety of dermatological conditions. Over recent years, especially after the coronavirus disease 2019 (COVID-19) pandemic, the prescription of HCQ has also significantly expanded, sometimes inappropriately, thus posing additional challenges on its optimal use, due to emerging safety issues. In this review, we provide dermatologists with the latest advancements on selected clinically relevant toxicities, namely retinopathy, pro-arrhythmia, cutaneous reactions, and neuropsychiatric effects. It is hoped this update can assist dermatologists to identify high-risk patients for tailored monitoring, screening, and risk minimization strategies, thus supporting safer HCQ prescribing.

Morbilliform eruptions, which are a clinical reaction pattern characterized by erythematous macules and papules coalescing into patches that cover most of the skin surface, are one of the most common cutaneous findings in the inpatient setting. In the hospital setting, most causes are benign and due to low-risk drug exanthems; however, morbilliform eruptions may also be a sign of high-risk diseases, including Stevens–Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, acute generalized exanthematous pustulosis, and graft-versus-host disease. Proper identification of the etiology and risk stratification of a morbilliform eruption is critical to ensure proper management and optimize patient outcomes. In this review, we discuss the key features that differentiate high-risk from low-risk morbilliform eruptions, as well as specific characteristics that differentiate the different high-risk eruptions. Additionally, we offer a clinical algorithm that may be applied in the management of a patient who presents with a morbilliform rash.

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.