American Journal of Clinical Dermatology最新文献

Background

Tralokinumab, a first-in-class and second biologic approved for treating moderate-to-severe atopic dermatitis in adolescents and adults, has demonstrated consistent efficacy and safety across multiple clinical trials.

Objective

We aimed to assess the real-world effectiveness and safety of tralokinumab by performing a systematic review and meta-analysis on the real-world evidence of tralokinumab.

Methods

We systematically searched PubMed and EMBASE from inception until 28 July, 2024 for observational studies describing the effectiveness and safety of tralokinumab for the treatment of atopic dermatitis. The primary outcome was the proportion of patients achieving a ≥75% improvement in the Eczema Area and Severity Index (EASI-75) after 16 weeks and secondary outcomes included the proportion of patients achieving EASI-50 and EASI-90 and the proportion of patients experiencing adverse events.

Results

Nineteen unique studies encompassing 911 bio-naïve and bio-experienced patients with atopic dermatitis treated with tralokinumab were included. After 16 weeks of treatment, 82%, 59% and 26% of patients achieved EASI-50, EASI-75 and EASI-90, respectively, and the proportion of patients developing conjunctivitis was 3.2%.

Conclusions

Tralokinumab demonstrates strong effectiveness and good tolerability in real-world settings, with a high proportion of patients achieving a clinical response and adverse events being observed only infrequently.

Background

Atopic dermatitis (AD) is a chronic inflammatory skin condition that significantly impairs the quality of life. Recent advancements in systemic therapies, such as Janus kinase (JAK) inhibitors, offer very effective new treatment options. However, concerns regarding potential adverse events, including cardiovascular and thromboembolic risk, have emerged from clinical studies and call for further real-life investigations. This has highlighted the need to establish specific risk categories, such as tobacco smokers.

Objective

This study aims to evaluate the safety and effectiveness of upadacitinib, a JAK1 inhibitor, in patients who smoke with moderate-to-severe AD over a 2-year treatment period, comparing outcomes with patients who do not smoke.

Patients and Methods

A retrospective multicenter study was conducted across 12 dermatology departments in Italy, including 375 patients treated with upadacitinib. The presence and intensity of smoking habits as well as effectiveness scores and safety data were collected.

Results

Patients who smoke accounted for 36.8% of the sample. Two thromboembolic events in patients who do not smoke were recorded in the 2-year (median follow up of 52.6 weeks) observation period. The most common adverse event was acneiform eruption (12.4% of patients after 104 weeks). No significant differences related to safety emerged regarding the presence or absence of a smoking habit. Drug survival was very high with no differences between the two cohorts (83.5% after 104 weeks for patients who smoke).

Conclusions

This study suggests that upadacitinib is a safe and effective treatment for moderate-to-severe AD in presence of tobacco smoke, with no significant differences in safety or effectiveness compared with patients who do not smoke.

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.