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ABSTRACT Introduction and Objectives Materials and Methods Results Conclusion Tralokinumab—a biological that specifically targets interleukin‐13—is one of the newer advanced systemic treatments for patients with moderate‐to‐severe atopic dermatitis (AD). Although safety and efficacy have been shown in phase‐III clinical trials, daily practice data are needed. Therefore, the aim of this study was to evaluate 28‐week safety and effectiveness, serum proteins and total IgE levels in adult AD patients treated with tralokinumab in daily practice.Data of all adult AD patients who started treatment with tralokinumab and participated in the BioDay registry were collected at baseline, and after 4,16 and 28 weeks of treatment. Clinical efficacy was evaluated by clinical outcome measures, such as the Eczema Area and Severity Index (EASI) as well as patient‐reported outcome measures, such as the numerical rating scale (NRS) for pruritus. Adverse events were evaluated. In a subgroup of patients, 18 proteins as well as total IgE levels were measured in serum.A total of 84 patients were included, of whom 39 were dupilumab‐naïve (D‐naïve) and 45 were dupilumab non‐naïve (D‐non‐naïve) patients. All primary outcomes significantly improved during 28 weeks of tralokinumab treatment and the probability of achieving EASI ≤ 7 and NRS‐pruritis ≤ 4 was 75.8% (56.9–88.2) and 51.4% (28.0–74.2), respectively. The disease severity‐associated proteins TARC/CCL17 and PARC/CCL18 decreased during treatment, and total IgE levels significantly decreased in the D‐naïve patients. The most reported adverse events were eye disorders (n = 24, 28.6%). A total of 23 patients (27.4%) discontinued treatment due to adverse events and/or ineffectiveness, with hair loss being the most common adverse event leading to treatment discontinuation (n = 6).Tralokinumab is an effective treatment for moderate‐to‐severe AD in adult patients, in both dupilumab‐naïve patients and patients who previously failed on dupilumab treatment. The clinical effect is supported by the biological data. [ABSTRACT FROM AUTHOR]

Background: Injection site reaction (ISR) is a local phenomenon defined as a constellation of symptoms, including swelling, erythema, pruritus, and pain around the site of injection. Objective: ISR is reported as a frequent adverse event after subcutaneous injection (SCI) of several biologics. Methods: We performed an observational real-life study to compare dupilumab and tralokinumab as regards ISR, analysing frequency, duration and intensity of symptoms related to SCI. From January 2023 to June 2023, we enrolled adult patients affected by moderate to severe AD and being on dupilumab or tralokinumab treatment. A 12 items questionnaire was administered to all enrolled patients. Results and conclusions: Three hundred and ninety-two patients were included. ISR was a frequent occurrence in both the treatment groups, with tralokinumab causing ISR more frequently than dupilumab. However, the reactions were generally mild and no patient stopped therapy. [ABSTRACT FROM AUTHOR]

Background: Tralokinumab is a fully human IgG4 monoclonal antibody targeting IL-13, used for treating atopic dermatitis. This study analyzed tralokinumab-related adverse drug events by mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database to provide a safety reference for clinical application. Methods: Adverse drug event reports from Q1 2022 to Q2 2024 were extracted from the FAERS database. After standardizing the data, various signal detection methods were used for analysis, including ROR, PRR, BCPNN, and MGPS. Results: A total of 1,820 reports of adverse events (AEs) with tralokinumab as the primary suspected drug were identified. 70 preferred terms (PTs) met the criteria across four signal detection methods, involving 11 system organ classes (SOCs). These included known adverse reactions like conjunctivitis and injection site reactions, and signals not previously reported in clinical trials, such as eye pruritus, dry eye, eye swelling, pneumonia pneumococcal, and cutaneous T-cell lymphoma. Most AEs occurred within one month of initiating tralokinumab treatment. Conclusions: Based on the FAERS database, this study comprehensively and systematically analyzed AE signals in tralokinumab treatment. The results enhance the understanding of tralokinumab's safety and serve as valuable references for reducing the risk of adverse reactions during clinical use. [ABSTRACT FROM AUTHOR]

Luca Potestio,1,&ast; Cataldo Patruno,2,&ast; Stefano Dastoli,2 Claudio Brescia,1 Maddalena Napolitano1 1Section of Dermatology Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 2Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy&ast;These authors contributed equally to this workCorrespondence: Luca Potestio, Section of Dermatology Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 081 7462457 ; Fax +39 081 7462442, Email potestioluca@gmail.comIntroduction: Even if mild forms of atopic dermatitis (AD) are usually well controlled with topical prescription drugs and emollients, the management of severe forms of the disease may be challenging, especially in special populations (SPs). These patients include groups of disadvantaged people (elderly, patients with disabilities and serious medical conditions) who are usually excluded from clinical trials. As a consequence, most of the data about the efficacy and safety of a drug in these patients derives from post-marketing experiences. In this context, the aim of our study was to retrospectively investigate the effectiveness and safety of tralokinumab in the management of AD in SPs.Methods: A 24-weeks retrospective, dual-center study was performed enrolling patients with a diagnosis of moderate-to-severe AD undergoing treatment with tralokinumab at labelled dosage. Disease severity was assessed using Eczema Area Severity Index (EASI), Pruritus–Numerical Rating Scale (P-NRS), and Dermatology Life Quality Index (DLQI) score at baseline and after 4 weeks (W4), W16, and W24. Adverse events (AEs) were monitored at the same timepoints. Statistical significance of clinical improvement (EASI, P-NRS, DLQI) at week 4, week 16, and week 24 as compared with baseline was evaluated by using Student’s t-test, considering significant a p-value < 0.05.Results: Our study enrolling 27 SPs patients showed a significant improvement in EASI and P-NRS since week 4, continuing to improve up to week 24. Similarly, DLQI significantly decreases at each timepoint as compared with baseline. Finally, no AEs were reported during the study period. Of interest, our cohort included oncologic patients, a patient with a history of severe infection, as well as subjects affected by severe neurological, psychiatric, pulmonary, and/or cardiovascular disease.Discussion: Our experience showed that tralokinumab is effective and safe in elderly patients and subjects affected by severe comorbidities.Keywords: atopic dermatitis, special populations, treatment, tralokinumab, biologics

Background: Tralokinumab, a humanized monoclonal antibody targeting interleukin-13, has been primarily used for the treatment of moderate-tosevere atopic dermatitis. Given its extensive use in clinical practice, understanding its safety profile in the real-world setting is crucial. Methods: This study utilized disproportionality analysis to evaluate the safety of tralokinumab in clinical practice by analyzing all adverse event reports since 2021 in the FDA Adverse Event Reporting System database that identified tralokinumab as the primary suspected drug. Reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network were used for disproportionality analyses of adverse events related to tralokinumab. Additionally, the Weibull distribution was employed to model the risk of adverse events over time. Results: Adverse reactions documented on the drug label, such as injection site reactions, conjunctivitis, and upper respiratory infections, displayed positive signals. Additionally, potential adverse reactions not mentioned on the label were also identified, including dizziness, headache, nausea, vomiting, hair loss, and acne. The importance of adverse event monitoring, particularly in the first month after treatment initiation, was emphasized. Conclusion: This study has provided preliminary safety data on the real-world application of tralokinumab, confirming some known adverse reactions and revealing additional potential risks. The findings offer critical safety information for clinicians prescribing tralokinumab to treat atopic dermatitis. [ABSTRACT FROM AUTHOR]

Introduction and aim: Atopic dermatitis (AD) is a chronic inflammatory skin disease. It is characterised by periods of exacerbation and remission of symptoms such as pruritus, dry skin and eczematous lesions with characteristic morphology. The aim of this study is to present the current state of knowledge on new treatments for atopic dermatitis. Review methods: The review was based on publicly available PubMed and Google Scholar databases from 2020 to 2024 using the following phrases: atopic dermatitis, treatment of atopic dermatitis, diagnosis of atopic dermatitis, epidemiology, biological treatment of atopic dermatitis, JAK inhibitors, stem cells, dermatitis. Brief description of the state of the art: Atopic dermatitis is a disease whose mechanism of origin is incompletely understood.It involves interactions between genotype, environment, and the immune system, and is largely related to the T-cell response. The main symptom is pruritus and dry skin leading to lichenification or exfoliation of the epidermis, which characterise the chronic form. Diagnosis is confirmed by clinical criteria such as skin lesions characteristic of AD, a family predisposition to allergic disease and a full history and skin tests. Treatment focuses on managing the symptoms associated with the disease and improving the patient's quality of life using mainly corticosteroids, calcineurin inhibitors and antihistamines. Recent studies show positive effects of treatment with biologic drugs, JAK inhibitors, stem cells and provide great hope towards the development of treatments for atopic dermatitis. Summary: The authors emphasise the need for further research towards the development of promising, innovative treatments for atopic dermatitis in order to significantly improve patients' quality of life.

Background Genital involvement in atopic dermatitis(AD) can have a significant impact on the patient’s quality of life. However, inspection of genital areas is not usually conducted during routine examination and patients may be reluctant to inform the clinician or show this area.Objective to evaluate the efficacy of tralokinumab in AD patients with genital involvement.Methods Adult patients with moderate/severe AD and genital involvement receiving tralokinumab have been analyzed. Primary endpoints were EASI, DLQI, PP-NRS, genital-IGA (g-IGA) and genital itching (GI) at week 16.Results out of 48 patients with moderate/severe AD under treatment with tralokinumab, 12 patients (25%) showed a genital involvement. Seven patients reported itching in the genital area (58%), while none reported a positive history of genital infections. Median scores at T0 were EASI 17.5, PP-NRS 8 and DLQI 14. After 16 weeks of treatment, we observed a median EASI of 3, a median PP-NRS of 1 and a median DLQI of 1. Finally, concerning the genital response, after 16 weeks of treatment, we observed a statistically significant decrease in mean GI and g-IGA scores.Conclusion despite the small size of our sample, tralokinumab can be considered as a valid treatment option for AD with genital involvement.

Background: Genital involvement in atopic dermatitis(AD) can have a significant impact on the patient's quality of life. However, inspection of genital areas is not usually conducted during routine examination and patients may be reluctant to inform the clinician or show this area. Objective: to evaluate the efficacy of tralokinumab in AD patients with genital involvement. Methods: Adult patients with moderate/severe AD and genital involvement receiving tralokinumab have been analyzed. Primary endpoints were EASI, DLQI, PP-NRS, genital-IGA (g-IGA) and genital itching (GI) at week 16. Results: out of 48 patients with moderate/severe AD under treatment with tralokinumab, 12 patients (25%) showed a genital involvement. Seven patients reported itching in the genital area (58%), while none reported a positive history of genital infections. Median scores at T0 were EASI 17.5, PP-NRS 8 and DLQI 14. After 16 weeks of treatment, we observed a median EASI of 3, a median PP-NRS of 1 and a median DLQI of 1. Finally, concerning the genital response, after 16 weeks of treatment, we observed a statistically significant decrease in mean GI and g-IGA scores. Conclusion: despite the small size of our sample, tralokinumab can be considered as a valid treatment option for AD with genital involvement. [ABSTRACT FROM AUTHOR]

Background: Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)‐13, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2‐year impacts of IL‐13 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate‐to‐severe AD. Methods: Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long‐term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein expression was assessed by immunohistochemistry and immunoassay. Results: Tralokinumab improved the transcriptomic profile of lesional skin by Week 4. Mean improvements in the expression of genes dysregulated in AD were 39% at Week 16 and 85% at 2 years with tralokinumab, with 15% worsening at Week 16 with placebo. At Week 16, tralokinumab significantly decreased type 2 serum biomarkers (CCL17/TARC, periostin, and IgE), reduced epidermal thickness versus placebo, and increased loricrin coverage versus baseline. Two years of tralokinumab treatment significantly reduced expression of genes in the Th2 (IL4R, IL31, CCL17, and CCL26), Th1 (IFNG), and Th17/Th22 (IL22, S100A7, S100A8, and S100A9) pathways as well as increased expression of epidermal differentiation and barrier genes (CLDN1 and LOR). Tralokinumab also shifted atherosclerosis signaling pathway genes (SELE, IL‐37, and S100A8) toward non‐lesional expression. Conclusion: Tralokinumab treatment improved epidermal pathology, reduced systemic markers of type 2 inflammation, and shifted expression of key AD biomarkers in skin towards non‐lesional levels, further highlighting the key role of IL‐13 in the pathogenesis of AD. Clinical Trial Registration: NCT03131648, NCT03587805. [ABSTRACT FROM AUTHOR]

Background/Objectives: The evaluation of the efficacy and safety of new molecules for atopic dermatitis (AD) in real clinical practice is very important to obtain information that clinical trials (EECC) lack. The pattern of AD in the head and neck (H&N) continues to be a challenge in treatment today, despite the new molecules, and real‐life data on the use of tralokinumab is still missing. This is the first daily practice study of tralokinumab treatment in patients with H&N AD pattern. The objective is to evaluate the efficacy and safety of tralokinumab in the short term (16 weeks) in patients with AD with H&N pattern, for the first time. Methods: A multicentre prospective observational study was conducted, including patients with moderate‐severe AD and H&N pattern who started tralokinumab treatment in four hospitals in Andalusia. Values of severity and quality of life scales, as well as patient‐reported outcomes (PROs), were collected at baseline and at Weeks 4 and 16. Safety events were also recorded. Results: Twelve patients were included. An improvement was observed in all efficacy and quality of life parameters evaluated at 16 weeks with respect to the baseline. No serious adverse events were recorded. Conclusions: In real clinical practice, tralokinumab is demonstrated to be an effective and safe treatment for patients with AD and H&N pattern at short term. [ABSTRACT FROM AUTHOR]

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Abstract Introduction Tralokinumab and dupilumab are biological agents licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients who are candidates for systemic treatment. However, no head-to-head studies of their efficacy have been conducted. This study indirectly compared the efficacy of tralokinumab and dupilumab, both in combination with topical corticosteroids (TCS), at week 32. Methods An unanchored matching-adjusted indirect comparison was conducted using individual patient data (IPD) from the ECZTRA 3 tralokinumab trial and aggregate data from the LIBERTY AD CHRONOS dupilumab trial. IPD were selected by applying inclusion criteria from LIBERTY AD CHRONOS and weighting to match summary baseline characteristics—age, sex, race, body mass index, disease duration, Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and SCORing Atopic Dermatitis index—of patients treated with dupilumab. Week 32 outcomes of interest were 50%, 75% or 90% improvements in EASI (EASI-50, EASI-75 and EASI-90), IGA scores of 0 or 1 (IGA 0/1), ≥ 4-point improvement in worst daily pruritus numerical rating scale (NRS) score, and mean improvements in DLQI and the Patient Oriented Eczema Measure (POEM). Results After matching, tralokinumab and dupilumab, both in combination with TCS, showed similar efficacy across clinical response endpoints at week 32 (IGA 0/1, tralokinumab 49.9% vs dupilumab 39.3%; EASI-50, 78.9% vs 77.5%; EASI-75, 71.5% vs 71.9%; EASI-90, 53.3% vs 56.2%). The mean change from baseline in DLQI was statistically significantly larger in the matched tralokinumab plus TCS population than in the dupilumab plus TCS arm (− 12.1 vs − 10.4, p = 0.005). Changes in POEM and worst daily pruritus NRS were similar in the two groups. Conclusion The results of this analysis demonstrate that, in combination with TCS, tralokinumab and dupilumab have similar efficacy in the treatment of moderate-to-severe AD at 32 weeks of therapy.

Abstract Atopic dermatitis (AD) is an inflammatory chronic recurrent skin condition that causes recurrent, itching eczematous lesions with a great impact on the quality of life of patients. We describe a case series of five adult patients with severe AD (Eczema Area Severity Index [EASI] ≥24) treated with tralokinumab. Tralokinumab is a monoclonal antibody that specifically binds IL‐13 with high affinity, blocking the interaction of IL‐13 with its specific receptors and neutralising its biological activity. Tralokinumab was recently approved for the treatment of moderate‐to‐severe AD in adults. In these patients, several conventional topical and systemic treatments (such as UV‐B phototherapy, systemic cyclosporine and dupilumab) had been previously tried. Three patients reported severe conjunctivitis during the previous treatment with dupilumab and one patient had not a good clinical response to dupilumab, as this treatment was stopped. Therefore, treatment with tralokinumab as a subcutaneous injection at an initial dose of 600 mg followed by 300 mg administered every other week was started. The severity of AD was assessed at baseline, Week 12 and Week 20 using several clinical scores (EASI, SCOring Atopic Dermatitis, Itch score, Dermatology Life Quality Index). All patients achieved clinical remission with a significant clinical improvement of itching and eczema in all body areas, assessed with several clinical scores; furthermore, no adverse events were reported during the observation period. During the treatment with tralokinumab, one patient was also infected by the SARS‐CoV‐2 virus, reporting mild clinical symptoms of the upper respiratory tract. These symptoms spontaneously resolved in 2 days with no medications. Although additional real‐world data are certainly required about the efficacy and safety of tralokinumab, the prospects of new drugs for the long‐term treatment of moderate‐to‐severe AD represent a great opportunity for these patients, which had very few therapeutic options until now.

The article explores the association between atopic dermatitis burden, sociodemographic index, and the utilization of biologics like dupilumab and tralokinumab across 50 countries from 2017 to 2022. It highlights disparities in biologic utilization based on countries' economic status, with high-cost barriers limiting access in low-middle and middle-SDI countries. The study suggests that measures to reduce costs and improve access to biologics, such as biosimilars, are needed to address these disparities and improve outcomes in resource-limited settings. [Extracted from the article]

Introduction/Background Clinical trials of up to 52 weeks showed that tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, was efficacious and well-tolerated as monotherapy and combination with TCS. Objectives Here, we evaluate the long-term safety of tralokinumab in an integrated analysis of seven phase 3 parent trials (PTs) (NCT03131648, NCT03160885, NCT03363854, NCT03562377, NCT03526861, NCT03761537, NCT04587453), and the ongoing, up to 5-year extension study (ECZTEND; NCT03587805). Methods Two datasets were analyzed: placebo-controlled (initial 16-week period of the PTs), and all-tralokinumab combining PTs with ECZTEND including patients from first dose until end of tralokinumab exposure or data cut-off (April 30th, 2022). In the all-tralokinumab dataset, periods on placebo were disregarded. Treatment-emergent adverse events (AEs) were recorded. AEs of special interest (AESIs) were predefined. Proportions of patients with events and incidence rates (IR) per 100 patient-years of exposure (PYE) were calculated. PYE was defined as time until first event or exposure end, whichever came first, and incidence was defined as first event. Results 2693 patients (≥12 years) received tralokinumab for up to 238.5 weeks (≈4.5 years) with a median exposure time of 76.5 weeks in the all-tralokinumab dataset. Median age at baseline was 33.0 years (min-max; 12-92). 10.4% of patients were 12-17 years. 2307 patients experienced an AE (IR=202.0), most (97.3%) of which were mild-to-moderate. Serious AEs (SAEs) were reported in 226 patients (IR=4.5); SAEs were considered possibly or probably related by the investigator in 50 patients (IR=0.9). No preferred term level SAEs were reported with an IR≥0.1. Discontinuation of treatment due to AEs was low (IR=2.8). AEs leading to drug withdrawal with an IR>0.1 were dermatitis atopic (IR=0.5) and injection site reaction (ISR) (IR=0.2). Frequently reported AEs in the all-tralokinumab dataset were consistent with the placebo-controlled dataset, including nasopharyngitis (IR=18.4), upper respiratory tract infection (IR=6.9), conjunctivitis (IR=5.0), ISR (IR=3.6), conjunctivitis allergic (IR=2.7), and injection site pain (IR=1.5). AESIs, including eye disorders, skin infections requiring systemic treatment, eczema herpeticum, and malignancies, were observed in the all-tralokinumab dataset at rates similar to or lower than the placebo-controlled dataset. Conclusion Long-term use of tralokinumab, for up to 4.5 years, was well-tolerated, and the pattern of AEs was consistent with the initial placebo-controlled treatment period with no new safety signals identified. [ABSTRACT FROM AUTHOR]

Introduction: Tralokinumab and dupilumab are biological agents licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients who are candidates for systemic treatment. However, no head-to-head studies of their efficacy have been conducted. This study indirectly compared the efficacy of tralokinumab and dupilumab, both in combination with topical corticosteroids (TCS), at week 32. Methods: An unanchored matching-adjusted indirect comparison was conducted using individual patient data (IPD) from the ECZTRA 3 tralokinumab trial and aggregate data from the LIBERTY AD CHRONOS dupilumab trial. IPD were selected by applying inclusion criteria from LIBERTY AD CHRONOS and weighting to match summary baseline characteristics—age, sex, race, body mass index, disease duration, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and SCORing Atopic Dermatitis index—of patients treated with dupilumab. Week 32 outcomes of interest were 50%, 75% or 90% improvements in EASI (EASI-50, EASI-75 and EASI-90), IGA scores of 0 or 1 (IGA 0/1), ≥ 4-point improvement in worst daily pruritus numerical rating scale (NRS) score, and mean improvements in DLQI and the Patient Oriented Eczema Measure (POEM). Results: After matching, tralokinumab and dupilumab, both in combination with TCS, showed similar efficacy across clinical response endpoints at week 32 (IGA 0/1, tralokinumab 49.9% vs dupilumab 39.3%; EASI-50, 78.9% vs 77.5%; EASI-75, 71.5% vs 71.9%; EASI-90, 53.3% vs 56.2%). The mean change from baseline in DLQI was statistically significantly larger in the matched tralokinumab plus TCS population than in the dupilumab plus TCS arm (− 12.1 vs − 10.4, p = 0.005). Changes in POEM and worst daily pruritus NRS were similar in the two groups. Conclusion: The results of this analysis demonstrate that, in combination with TCS, tralokinumab and dupilumab have similar efficacy in the treatment of moderate-to-severe AD at 32 weeks of therapy. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, intensely pruritic disease associated with significant patient burden. Recent advancements in AD pathogenesis have expanded its therapeutics pipeline. Tralokinumab is a fully human monoclonal antibody that binds specifically Interleukin (IL)-13, inhibiting the downstream IL-13 signaling. Phase 3 clinical trials and some real-world studies showed that tralokinumab, as monotherapy or in combination with topical corticosteroids, is efficacious and safe in adult patients with moderate-to-severe AD. Similar results were reported in a phase 3 trial in adolescents (aged ≥12 years). We review the role of IL-13 in AD and discuss the value of tralokinumab for treating moderate-to-severe AD, comparing efficacy and safety results derived from clinical trials and real-life data. The role of IL-13 in AD supports a targeted therapeutic approach. Tralokinumab has proven efficacious and well-tolerated in a large proportion of patients confirming its value for treating moderate-to-severe AD from age 12 years onwards; it quickly improves itching and can maintain a high-level of response over time; it can be administered with flexible dosing schedules. Future studies will further clarify the role of IL-13 pathway and which patients would be best suited to tralokinumab, shifting AD treatment into an era of precision medicine. [ABSTRACT FROM AUTHOR]

The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL. [ABSTRACT FROM AUTHOR]

Introduction: The advent of biotechnological drugs has significantly changed the management of atopic dermatitis (AD) and the approach to the moderate-to-severe form of this chronic relapsing disease. Objectives: The aim of our review is to summarize the current literature on anti-interleukin (IL)-13 in atopic dermatitis. Methods: A literature search was organized and a systematic review was performed to summarize the most recent evidence supporting the efficacy and safety of tralokinumab. Results: Tralokinumab (anti-IL-13) 300 mg every 2 weeks subcutaneously has proven effective in several clinical trials in adults and adolescents with moderate to severe atopic dermatitis inadequately controlled with other topical or systemic therapies. Tralokinumab was found to be significantly superior in terms of efficacy in reducing IGA, EASI-75, NRS pruritus, and DLQI scale numbers. During follow-up, tralokinumab was well tolerated with limited severity of adverse events. Conclusion: Tralokinumab leads to statistically significant improvements in disease severity and outcome scores. It represents an effective treatment option for adults with moderate to severe AD, but further large-scale studies are needed to verify long-term superiority over other treatments.

Atopic dermatitis (AD) is a chronic, inflammatory, intensely pruritic skin disorder associated with significant patient burden. Interleukin (IL)‐13 is a cytokine that acts as a driver of immune dysregulation, skin‐barrier dysfunction, and microbiome dysbiosis that characterizes AD, and is consistently overexpressed in AD skin. Tralokinumab is a fully human immunoglobulin (Ig) G4 monoclonal antibody that binds specifically to IL‐13 with high affinity, thereby inhibiting subsequent downstream IL‐13 signaling. Three pivotal phase 3 clinical trials demonstrated that tralokinumab 300 mg every other week, as monotherapy or in combination with topical corticosteroids as needed, provides significant improvements in signs and symptoms of moderate‐to‐severe AD, as measured by Investigator's Global Assessment 0/1 (clear/almost clear) and Eczema Area and Severity Index‐75 at Week 16. Improvements were observed soon after tralokinumab initiation and were maintained over 52 weeks of therapy. Tralokinumab significantly improved patient‐reported outcomes such as itch and sleep, and demonstrated a safety profile comparable with placebo; conjunctivitis during tralokinumab therapy was generally mild. Similar results were observed in a phase 3 adolescent trial. The role of IL‐13 in the pathophysiology of AD justifies a targeted approach and a wealth of clinical data supports tralokinumab as a new therapeutic option for people with moderate‐to‐severe AD. [ABSTRACT FROM AUTHOR]

The article discusses the efficacy of dupilumab in patients with atopic dermatitis who did not respond to tralokinumab treatment. A study involving 15 patients showed that switching to dupilumab led to significant improvements in AD severity scores. The results suggest that dupilumab could be a valuable alternative for patients who fail tralokinumab, emphasizing the need for further research to establish guidelines for treatment switching. [Extracted from the article]

The article discusses injection-site reactions (ISR) associated with the subcutaneous injection of tralokinumab, a medication used for atopic dermatitis. A case study of a 17-year-old male with severe atopic dermatitis showed improvement with tralokinumab treatment but experienced pruritic and painful ISR. Skin tests and a skin biopsy were performed to understand the pathophysiology of these reactions. The study highlights the importance of patient education in reducing the frequency and intensity of ISR. [Extracted from the article]

The article discusses a case of tralokinumab-related facial redness in a 28-year-old female with severe atopic dermatitis. The patient experienced intense erythema and desquamation on her face after initially responding well to tralokinumab treatment. Treatment was switched to abrocitinib, leading to complete remission after 3 weeks. The pathogenesis of this "red face" side effect is not yet fully understood, and further research is needed to improve management for patients with severe atopic dermatitis. [Extracted from the article]

Background Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus). Objectives To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib). Data sources Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review. Methods A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources. Results Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost. Conclusions The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations. Future work and limitations The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective. Study registration This study is registered as PROSPERO CRD42021266219. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in Health Technology Assessment; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information. Plain language summary Atopic dermatitis is one of the most common skin conditions in children but can also develop in adulthood. People with atopic dermatitis have dry, red (inflamed) skin that is also extremely itchy (pruritus). There is no cure for atopic dermatitis. Therapy starts with topical treatments that are applied to the skin, such as emollients. Severe forms of atopic dermatitis are often treated with systemic treatments, which are drugs that are provided as tablets or an injection. Ciclosporin A is often the first systemic therapy given. If atopic dermatitis does not get better with ciclosporin A, options available in the National Health Service are dupilumab and baricitinib. New therapies that have been evaluated in clinical trials for atopic dermatitis but have not been assessed for use in the National Health Service are abrocitinib, tralokinumab and upadacitinib. The aim of this project is to review the medical benefits, risks and value for money for the National Health Service of abrocitinib, tralokinumab and upadacitinib for the treatment of moderate-to-severe atopic dermatitis in a multiple technology appraisal. Our review found that: For children aged between 12 and 18 years, abrocitinib and a low dose of upadacitinib (15 mg) are good value for money for the National Health Service. For adults who need a first systemic treatment, upadacitinib is unlikely to be good value for money for the National Health Service. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, upadacitinib 15 mg and tralokinumab could be good value for money for the National Health Service if they are used on their own. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, but need to take it with steroid cream, abrocitinib 100 mg, upadacitinib 15 mg and tralokinumab could all be good value for money for the National Health Service. Scientific summary Background Atopic dermatitis (AD), often referred to as atopic eczema, is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, AD typically manifests before the age of 5 years, but can develop at any age. AD is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus). As many as 1 in 5 children and 1 in 10 adults in the UK are estimated to have AD, with about 18% of cases of childhood AD categorised as moderate and 2% as severe. Of adults with AD, it has been reported that 5% of cases are severe. Of the people who need treatment for AD, 7% are estimated to have moderate-to-severe disease. Atopic dermatitis is currently uncurable, and the goal of treatment is to improve symptoms and achieve long-term disease control. Those with moderate-to-severe AD that only partially responds to treatment, and those presenting with severe disease, are referred to secondary care for a more specialised therapy, where phototherapy [predominantly ultraviolet B (UVB)] is frequently the first treatment option. If phototherapy is unsuccessful, subsequent treatment typically constitutes systemic treatments. Systemic treatment options available within the NHS for the management of AD in line with their marketing authorisations are ciclosporin A (CsA) in the first-line setting, and baricitinib and dupilumab as subsequent therapies. The three interventions for which an evaluation of the clinical and cost effectiveness in the treatment of moderate-to-severe AD form the basis of this report are abrocitinib, tralokinumab and upadacitinib. The clinical and cost effectiveness of these treatments at their recommended dose or doses versus treatment options available in the NHS for moderate-to-severe AD was evaluated in the positions in the treatment pathway proposed by the sponsoring company. The proposed positions are: Abrocitinib: second-line systemic therapy for adolescents second-line systemic therapy for adults. Tralokinumab: second-line systemic therapy for adults. Upadacitinib: adolescents first-line systemic therapy for adults second-line systemic therapy for adults. Objectives The research objectives of the multiple technology appraisal (MTA) are to appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe AD in the UK clinical setting compared to systemic immunosuppressants (first-line CsA or second-line dupilumab and baricitinib). Methods Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) up to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence submissions provided by companies. Clinical studies and economic evaluations were included based on pre-specified inclusion criteria. Screening of title and abstracts to identify potentially relevant studies and evaluation of full-text publications were done independently by two reviewers. Data from included studies were extracted into a standardised data extraction form by one reviewer and validated by a second. Quality of included studies was assessed independently by two reviewers using standard checklists. Extracted data and quality assessment for each study were presented in structured tables. Where sufficient comparable data were available for an outcome measure, network meta-analysis (NMA) was performed using a Bayesian Markov Chain Monte Carlo simulation. The primary outcome of the review of clinical effectiveness was Eczema Area and Severity Index (EASI) 50 + Dermatology Life Quality Index (DLQI) ≥ 4 and EASI 75 was explored as a scenario. Treatment effects were analysed as odds ratios (ORs). A de novo hybrid economic model was developed to assess the cost effectiveness of the three new drugs, comprising a short-term (1 year) decision tree component, to capture the treatment induction phase and treatment response assessments, followed by a long-term (lifetime), three-state Markov model. In consultation with clinical experts, the Evidence Assessment Group (EAG) selected baseline characteristics for the model from the upadacitinib trials, which were considered representative of the eligible patient population in England. Estimates of treatment response, based on the composite outcome of EASI 50 + DLQI ≥ 4 from the NMA of clinical effectiveness data, were used in the short-term model. Conditional discontinuation data (defined as people whose condition responded to treatment at week 16 but withdrew from treatment for any reason at week 52) were used to estimate week-52 outcomes as well as long-term treatment discontinuation. Conditional discontinuation data were provided by the companies. Where there was a paucity of data, the EAG adopted a drug class approach to fill the gaps, where upadacitinib was used to inform Janus kinase inhibitors and tralokinumab was used to inform monoclonal antibodies. Additionally, in the long-term model treatment, waning assumptions were applied to all treatments as patients may lose response to treatment over time and these were informed by assumptions accepted in the NICE technology assessment of dupilumab for treating moderate to severe atopic dermatitis (TA534). Rates of adverse events and flare (based on the use of rescue medication) associated with each treatment were obtained from the companies, and where data gaps existed, a similar drug class approach was adopted for the missing data. Utilities based on drug class were obtained from key trials of upadacitinib and tralokinumab. Costs were obtained from standard UK sources. Probabilistic, one-way and scenario analyses were carried out to assess parameter uncertainty. Results The EAG identified 23 studies of relevance to the MTA. Most of the studies included in the assessment of clinical effectiveness were considered to be well-conducted and well-designed Phase III randomised controlled trials (RCTs), and, as such, are at an overall low risk of bias. However, the identified studies predominantly included mixed populations of people with moderate-to-severe AD, with some studies comprising both adolescents and adults, as well as a combination of people receiving systemic therapy as a first-line or second-line regimen. Thus, data informing the NMAs for the populations and outcomes of interest to the MTA are predominantly derived from post hoc subgroups. There were considerable amounts of uncertainty, and the vast majority of results were not statistically significant. However, there were consistent trends across the outcomes (EASI 50 + ΔDLQI ≥ 4 and EASI 75), interventions (combination therapy or monotherapy) and populations (adults in the first- or second-line setting and adolescents). Treatment with abrocitinib 200 mg leads to a better response, assessed as either EASI 50 + ΔDLQI ≥ 4 or EASI 75, than dupilumab, whereas there was less of a difference in the effectiveness between dupilumab and abrocitinib 100 mg with some comparisons showing a benefit in favour of dupilumab and others favouring abrocitinib 100 mg. Both doses of abrocitinib were more effective than baricitinib 4 mg (EASI 75 for adults in the second-line setting) and in the adolescent population, both doses of abrocitinib were more effective than dupilumab (EASI 75). Although significantly better than placebo, tralokinumab treatment was numerically, but not statistically significantly, less effective than treatment with either dupilumab or baricitinib 4 mg (response assessed as either EASI 50 + ΔDLQI ≥ 4 or EASI 75). Similar to abrocitinib, treatment with upadacitinib 30 mg led to a better response (assessed as either EASI 50 + ΔDLQI ≥ 4 or EASI 75) than dupilumab, whereas there was less of a difference in the effectiveness between dupilumab and upadacitinib 15 mg with some comparisons showing a benefit in favour of dupilumab and others favouring upadacitinib 15 mg. Both doses of upadacitinib were more effective than baricitinib 4 mg (EASI 75 for adults in the second-line setting). In the adolescent population, upadacitinib 15 mg was more effective than dupilumab (EASI 75). The National Institute for Health and Care Excellence (NICE) typically considers interventions a cost-effective use of the NHS resources if the incremental cost-effectiveness ratio (ICER) sits within a £20,000–30,000 threshold. The decision rule is reversed if an intervention is less costly and less effective (south-west quadrant), such that if the ICER is >£20,000–30,000 threshold, it can be considered a cost-effective use of NHS resources. For the adolescent population analyses, both doses of abrocitinib and upadacitinib 15 mg were less costly and more effective than dupilumab, resulting in dominant probabilistic ICERs. For the adult second-line monotherapy population, upadacitinib 15 mg is less costly and more effective than dupilumab (dominant) and tralokinumab was less costly and less effective than dupilumab (south-west quadrant ICER of £409,271). For the adult second-line combination therapy population, compared with dupilumab, abrocitinib 100 mg, upadacitinib 15 mg and tralokinumab were associated with south-west quadrant probabilistic ICERs of £58,920, £204,598 and £285,653, respectively. Compared with dupilumab, the following were not considered a cost-effective use of NHS resources with ICERs above £30,000 threshold commonly used by NICE: upadacitinib 15/30 mg (adult first-line combination therapy), abrocitinib 100/200 mg and upadacitinib 30 mg (adult second-line monotherapy), and abrocitinib 200 mg and upadacitinib 30 mg (adult second-line combination therapy). The key drivers of cost effectiveness were week-16 response probabilities and conditional discontinuation probabilities (used to inform the week-52 response and annual discontinuation), which are as expected, as these are the key effectiveness estimates in the model. In particular, the NMA for week-16 response was associated with substantial uncertainty, especially for abrocitinib, due to small numbers informing the network. Key scenarios that had a substantial impact on the cost-effectiveness results were reducing the time horizon in the adult analyses to 5 years and 18 years of age for the adolescent analyses, as well as using data from TA534 and an alternative NMA where censoring for rescue therapy was included. The EAG cautions the interpretation of the cost-effectiveness results presented in the MTA report as they are based on list prices for abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib, but all have confidential patient access scheme (PAS) in place. Conclusions The population which is most likely to be important for decision-making is the adult second-line systemic treatment subgroup, in particular, the combination treatment analyses, as all three new drugs have a proposed position in this part of the treatment pathway. Furthermore, clinical experts advising the EAG considered combination therapy is more widely using in clinical practice in England. For this population, composite outcome data were available for each new treatment under consideration, as well as for one of the relevant comparators, dupilumab (which is approved for use by NICE at this step in the treatment pathway). Baricitinib, in combination with topical corticosteroid (TCS), is also a relevant comparator in the adult second-line systemic treatment population. However, composite outcome data for baricitinib were not made available to the EAG for inclusion in the clinical effectiveness analysis. Instead, the EAG obtained EASI 75 data for baricitinib and included this in the adult second-line systemic combination treatment NMA. As such, a scenario looking at the cost effectiveness of each of the three new drugs compared with baricitinib was explored to support decision-making. As the adult first-line systemic treatment and adolescent populations are also relevant for decision-making, the EAG was able to produce base-case cost-effectiveness results for the new drugs using the EASI 75 outcome, as the composite outcome was unavailable. However, RCT data for CsA were not available for the comparison with upadacitinib in the first-line setting, but observational data were identified that could be used in the NMA. Though the EAG notes that even though observational data for CsA are the best available evidence, it is associated with the bias inherent in observational studies and the results should be interpreted with caution. Additionally, for the adult first-line systemic treatment population, outcome data were only available for combination therapy, but the EAG’s clinical experts considered it to be more relevant for clinical practice. Thus, the EAG considered missing monotherapy data are unlikely to be critical for decision-making for the adult first-line systemic treatment subgroup. Analyses of the adolescent population were limited to assessing monotherapy, as combination data for dupilumab were unavailable to inform the NMA. Thus, the adolescent monotherapy analyses may potentially underestimate the relative effectiveness of the treatments when used in combination with TCS in clinical practice, as combination treatment results typically demonstrate higher treatment effectiveness. The summary of product characteristics for both abrocitinib and upadacitinib takes into consideration circumstances, where moving to the lower or higher dose of each drug may be beneficial and this is likely to happen in clinical practice. However, analyses exploring increasing or decreasing dose for abrocitinib and upadacitinib were not possible as efficacy data based on titrating dose are unavailable. Nonetheless, the EAG considers that clinical and cost-effectiveness results for abrocitinib and upadacitinib by low and high dose are useful to facilitate consideration of the impact of dose titration for each drug. The robustness of the clinical and cost-effectiveness analyses is limited by the use of post hoc subgroups; while the use of subgroups increases the comparability and applicability of the analyses, it introduces bias and uncertainty to the results generated by the NMAs. In particular, the sample size of the second-line systemic therapy subgroup in the abrocitinib trials was very small as the majority of patients in the abrocitinib trials were eligible for first-line rather than second-line systemic therapy. This research assesses the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib as alternative therapies for treating moderate-to-severe AD compared to standard practice with systemic immunosuppressants. At the different steps in the treatment pathway assessed, new options were identified that represent a cost-effective use of scarce NHS resources. Study registration This study is registered as PROSPERO CRD42021266219. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award reference: 135138) and is published in full in Health Technology Assessment; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.

Purpose: Although psoriasis and atopic dermatitis (AD) were for decades considered to be opposing diseases, it is now known that these skin conditions can coexist or even overlap in the same individual. Especially when using modern drugs with targeted IL inhibition, the balance between Th1 and Th2 immunity can be disturbed. In line with it, numerous clinical cases of AD have been induced by antipsoriatic biologics (e.g., TNF-alpha, IL-23, or IL-17 inhibitors), and IL-4-/IL-13 inhibition by dupilumab also resulted in paradoxical psoriasis in patients with AD. Materials and methods: Herein, we describe a case of psoriasis vulgaris in a patient with intrinsic AD after systemic treatment with the anti-IL-13 antibody tralokinumab. Results: We present a 36-years-old male patient with a severe course of an intrinsic atopic dermatitis and dyshidrotic hand eczema. He responded well to the therapy with tralokinumab. However, about 7 months after the start of anti-IL-13 treatment the patient developed psoriasiform lesions. The drug was then discontinued. Currently, the patient is receiving topical therapy with topical corticosteroids and calcineurin inhibitors with stable course of psoriasis and AD. Conclusions: This case suggests, that not only a dual IL-4-/IL-13-blockade, but also a selective IL-13-inhibition is able to skew immune responses toward IL-17 cytokine pathway-related disease. However, no clinical scores exist to predict the development of paradoxical psoriasis in patients with AD during therapy with biologics.

This is the English version of the Japanese guidance for biologics in treating atopic dermatitis (AD). The signaling pathway mediated by interleukin (IL)‐4 and IL‐13 contributes to type 2 inflammatory responses and plays an important role in the pathogenesis of AD. IL‐31 is a cytokine mainly produced by activated T cells and is known to be involved in the pruritus of AD. Biologics for AD have been approved, including dupilumab, an anti‐IL‐4 receptor α antibody that was approved for expanded use in AD in 2018. In 2022, nemolizumab, an anti‐IL‐31 receptor α antibody, was approved for pruritus of AD, and tralokinumab, an anti‐IL‐13 antibody, was approved for AD. Physicians who intend to use these drugs should sufficiently understand and comply with the contents of the guidelines prepared by the Japanese Ministry of Health, Labour, and Welfare to promote the optimal use of the drugs. In treatment with biologics, it is important to consider disease factors (activity and severity), treatment factors (dosage and administration as well as the efficacy and safety), and patients' background characteristics (age and comorbidities) and share this information with patients when choosing treatment options. This guidance was developed for board‐certified dermatologists who specialize in treating AD, and for promoting the proper use of biologics, taking into account the variety of factors in individual patients. [ABSTRACT FROM AUTHOR]

Eva Moennig, Stephan Traidl Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School (MHH), Hannover, GermanyCorrespondence: Eva Moennig, Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School (MHH), Carl-Neuberg-Str.1, Hannover, 30625, Germany, Email moennig.eva@mh-hannover.deAbstract: Atopic dermatitis (AD) is a common inflammatory skin disease, which negatively impacts the individual’s quality of life (QoL). In particular, moderate-to-severe AD is frequently difficult to treat. We report a case involving a 40-year-old male who has suffered from AD since early childhood and who also had co-morbid seasonal allergic rhinitis. In June 2021, we initiated treatment with the fully human IgG4 monoclonal antibody tralokinumab that specifically targets IL-13 and the patient has been followed for 38 weeks. During this time period, he received a booster vaccination for COVID-19 (week 18) and developed the disease in April 2022 (both with minimal impact). Tralokinumab treatment reduced AD symptoms, was well tolerated and improved QoL scores, and the patient reported that he was very satisfied with the treatment.Keywords: atopic dermatitis, COVID-19, systemic therapy, tralokinumab

Respected Madam, Atopic dermatitis (AD) is a prevalent inflammatory skin condition that affects people of all ages and can cause significant distress based on the severity of the condition. Researchers have examined focussed therapies that rely on a better understanding of the underlying pathophysiology of AD. While some therapies that target specific molecules, such as IL-13, IL-31, and OX40 (CD134), have been assessed, there is still much to be done regarding narrow-acting agents which act on a single molecule only.1 Tralokinumab, targeting interleukin-13 in patients with moderate-to-severe atopic dermatitis, was found to be an effective treatment hence beneficial in enhancing health-related quality of life (QoL) in adults.2 Paller et al. recently conducted a clinical trial focussing on adolescents (aged 12-17) with moderate to severe atopic dermatitis, finding that tralokinumab was both effective and safe, showcasing its potential as a treatment option for the said age group.3 Tralokinumab is a fully human monoclonal immunoglobulin G4 antibody that binds with remarkable affinity to the IL-13 cytokine, blocking its interaction with the IL-13 receptor and thus preventing downstream signalling and its ensuing inflammatory effects.4 Atopic dermatitis can be treated with the use of Janus Kinase inhibitors; however, these treatments have shown to result in unexpected adverse effects (AEs) due to the interaction of unintended pathways as well as the target ones; the most common being acne.5 Dupilumab, another therapeutic agent for atopic dermatitis, has been observed to cause conjunctivitis in adolescent patients. The study revealed that Tralokinumab (150mg/300mg) demonstrated to be an effectual treatment for atopic dermatitis, as the primary and secondary endpoints of the trial between Tralokinumab and placebo were statistically significant (p

Background: The heterogeneous (endo)phenotypes of atopic dermatitis (AD) require precision medicine. Currently, systemic therapy is recommended to patients with an Eczema Area and Severity Index (EASI) ≥ 16. Previous studies have demonstrated an improved treatment response to the anti‐interleukin (IL)‐13 antibody tralokinumab in AD subgroups with elevated levels of the IL‐13‐related biomarkers dipeptidyl‐peptidase (DPP)‐4 and periostin. Methods: Herein, 373 AD patients aged ≥12 years were stratified by IL‐13high, periostinhigh and DPP‐4high endotypes using cross‐sectional data from the ProRaD cohort Bonn. "High" was defined as >80th quantile of 47 non‐atopic controls. We analyzed endotype‐phenotype associations using machine‐learning gradient boosting compared to logistic regression. Results: Atopic dermatitis severity and eosinophils correlated with IL‐13 and periostin levels. Correlations of IL‐13 with EASI were stronger in patients with increased (rs = 0.482) than with normal (rs = 0.342) periostin levels. We identified eosinophilia >6% and an EASI range of 5.5–17 dependent on the biomarker combination to be associated with increasing probabilities of biomarkerhigh endotypes. Also patients with mild‐to‐low‐moderate severity (EASI < 16) featured increased biomarkers (IL‐13high: 41%, periostinhigh: 48.4%, DPP‐4high: 22.3%). Herthoge sign (adjusted Odds Ratio (aOR) = 1.89, 95% Confidence Interval (CI) [1.14–3.14]) and maternal allergic rhinitis (aOR = 2.79–4.47) increased the probability of an IL‐13high‐endotype, "dirty neck" (aOR = 2.83 [1.32–6.07]), orbital darkening (aOR = 2.43 [1.08–5.50]), keratosis pilaris (aOR = 2.21 [1.1–4.42]) and perleche (aOR = 3.44 [1.72–6.86]) of a DPP‐4high‐endotype. Conclusions: A substantial proportion of patients with EASI < 16 featured high biomarker levels suggesting systemic impact of skin inflammation already below the current cut‐off for systemic therapy. Our findings facilitate the identification of patients with distinct endotypes potentially linked to response to IL‐13‐targeted therapy. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most common, relapsing, chronic inflammatory skin disease, being regarded as a global health issue. Recent studies have shown that Th2 cell-mediated type 2 immunity plays a central role in AD. The type 2 inflammatory cytokines such as IL-4, IL-13, IL-22, IL-31, IL-17 and IL-5 mediate the pathogenesis of AD. A variety of antibody drugs targeting these cytokines have been developed to treat AD in clinics. Notably, several antibody drugs have exhibited high efficacy in treating atopic dermatitis in previous studies, demonstrating that they could be therapeutic methods for AD patients. Herein, we reviewed the clinical trials of antibody drugs in the treatment of AD, which provides a useful guideline for clinicians to treat patients with AD in clinics.

Atopic dermatitis (AD) is a chronic inflammatory disease with a heterogeneous pathogenesis correlated with dysregulation of the immune system and a prevalence of the T2-mediated immune pathway. Recent understanding of the pathogenesis of AD has allowed the development of new drugs targeting different mechanisms and cytokines that have changed the treatment approach. The aim of this review is to update knowledge on the standard of care and recent advancements in the control of skin inflammation. In light of recent guidelines, we report on the clinical efficacy of novel treatments, with special attention to situations where biologics and small molecules are involved.

Dyshidrotic palmoplantar eczema or pompholyx is considered to be a part of the spectrum of atopic dermatitis with a significant impact on the quality of life and limited treatment options. Tralokinumab is a new fully human monoclonal antibody which neutralizes interleukin 13, a chief cytokine in itch pathogenesis and skin barrier defects. Tralokinumab is FDA‐approved for the treatment of atopic dermatitis in adults and EMA‐approved for the treatment of atopic dermatitis in adults and adolescents. We, hereby, report a 40‐year‐old female with severe dyshidrotic palmoplantar eczema who was successfully treated with tralokinumab. To the best of our knowledge, this is the first report of the efficacious use of tralokinumab in dyshidrotic eczema. [ABSTRACT FROM AUTHOR]

Introduction/Background Tralokinumab is a high-affinity monoclonal antibody that specifically targets IL-13, a driver of inflammation in atopic dermatitis (AD). The ECZTRA 1, 2, 3, and 6 trials demonstrated that tralokinumab is efficacious and safe in adults and adolescents; however, real-world evidence on tralokinumab use is limited. Objectives To assess the change from baseline in clinician-assessed and patient-reported outcomes (PROs) among US adults with AD following 6 months of persistent tralokinumab use after treatment initiation in the CorEvitas AD registry. Methods The CorEvitas AD Registry is a prospective, non-interventional registry launched in July 2020 for adult AD patients under the care of a licensed dermatologist or qualified dermatology practitioner. This analysis includes US patients enrolled in the CorEvitas AD registry who initiated tralokinumab between February 1, 2022 and May 31, 2023, had baseline data, and were persistent on tralokinumab at the 6-month follow-up (defined as a visit occurring 5 to 9 months from tralokinumab initiation). Baseline data were summarized using descriptive statistics and stratified by advanced systemic therapy (AST) experience (defined as any previous history of dupilumab, abrocitinib, or upadacitinib). Outcome measures collected included: validated Investigator's Global Assessment for atopic dermatitis (vIGA-ADTM), ≥50%/≥75% improvement in Eczema Area and Severity Index (EASI) (EASI-50/75), ≥4-point improvement in Dermatology Life Quality Index (DLQI), ≥3-point improvement in mean weekly pruritis numerical rating scale, and mean change in Work Productivity and Activity Impairment (WPAI). Results Among the 60 patients in this analysis, the mean age was 49.1 years and mean AD duration was 15.0 years. The majority of patients were female (34/60, 56.7%), White (51/60, 85.0%), worked full-time (38/60, 63.3%), and AST-naïve (44/60, 73.3%). At baseline, the majority of patients had moderate-to-severe AD based on EASI (EASI≥ 7, 40/60, 67%) and vIGA-ADTM (vIGA-ADTM 3: 50/60, 83.3%; vIGA-ADTM 4: 4/60, 6.7%). Disease severity was lower in AST-experienced patients, all of whom were dupilumab-experienced. A notable proportion of patients experienced improvements in clinician-assessed endpoints and PROs from baseline to 6 months: vIGA-ADTM ≤1 from 6.7% (4/60) to 55.0% (33/60), EASI ≤7 from 33.3% (20/60) to 85.0% (51/60), and DLQI ≤5 from 38.3% (23/60) to 66.7% (40/60). Among patients with EASI ≥7.1 at baseline, 85.0% (34/40) achieved EASI-50 (AST-naïve: 90.9%, 30/33; AST-experienced: 57.1%, 4/7) and 77.5% (31/40) achieved EASI-75 (AST-naïve: 84.8%, 28/33; AST-experienced: 42.9%, 3/7) at the 6-month follow-up. In patients with vIGA-ADTM of 3 or 4 at baseline, 79.6% (43/54) achieved EASI-50 (AST-naïve: 83.3%, 35/42; AST-experienced: 66.7%, 8/12) and 66.7% (36/54) achieved EASI-75 (AST-naïve: 76.2%, 32/42; AST-experienced: 33.3%, 4/12) at follow-up. Among patients with baseline DLQI ≥4, 71.4% (30/42) achieved ≥4-point improvement at follow-up (AST-naïve: 78.1%, 25/32; AST-experienced: 50.0%, 5/10). Of patients with baseline mean weekly pruritus NRS ≥3, 69.8% (37/53) achieved ≥3-point improvement at follow-up (AST-naïve: 70.0%, 28/40; AST-experienced: 69.2%, 9/13). Among the 40 patients employed at both baseline and follow-up visit, improvements were reported in WPAI. Percent impairment at work due to AD decreased by 14.8% (95% CI: -25.6%; -3.9%) and percent overall work impairment due to AD decreased by 15.7% (95% CI: -26.4%; -5.0%). For all 60 patients, non-work activity impairment due to AD decreased by 14.5% (95% CI: -23.9%; -5.1%). Conclusions In this real-world study, patients with AD experienced notable improvements in both clinician-assessed and patient-reported outcomes after 6-months of persistent tralokinumab treatment, regardless of prior AST therapy use. All 16 AST-experienced patients had prior use of dupilumab. These findings support the therapeutic potential of tralokinumab for AD patients, highlighting the need for future studies with longer follow-up period and larger sample size. [ABSTRACT FROM AUTHOR]

Introduction/Background Tralokinumab is a high-affinity monoclonal antibody that specifically targets interleukin (IL)-13, a key driver of atopic dermatitis (AD). In clinical trials, tralokinumab demonstrated efficacy and a favorable safety profile for the treatment of moderate-to-severe AD in adults and adolescents. However, data on patients in the real-world setting and persistence to treatment is currently limited. Objectives To describe the baseline characteristics and persistence at 6 months of treatment in US adult patients with AD initiating tralokinumab in the CorEvitas AD registry. Methods The CorEvitas Atopic Dermatitis Registry is a prospective, non-interventional registry launched in July 2020 for adult AD patients under the care of a licensed dermatologist or qualified dermatology practitioner. Data are collected from both patients and providers approximately every 6 months during routine clinical encounters. This analysis included U.S. patients enrolled in the CorEvitas AD registry who initiated tralokinumab between February 1, 2022 (the commercial launch date) and May 31, 2023 and had baseline data. Baseline demographics and clinical characteristics were summarized using descriptive statistics and stratified by advanced systemic therapy (AST) experience, defined as any previous history of dupilumab, abrocitinib, or upadacitinib for AD treatment. A 6-month follow-up visit was defined as a visit occurring 5 to 9 months following tralokinumab initiation. Results Among 259 included patients in this study the mean age was 50.8 years. The majority of patients were female (156/259, 60.2%), White (202/259, 78.0%), worked full-time (143/259, 55.2%), had private health insurance (201/259, 77.6%), and were concomitantly on topical therapy (203/259, 78.4%). Most patients had moderate-to-severe disease, with mean Eczema Area and Severity Index (EASI) of 14.2. Approximately half of patients reported AD involvement of head (face: 121/259, 46.7%; scalp: 80/259, 30.9%; neck: 93/259, 35.9%) and hands (dorsal: 150/259, 57.9%; palmar: 130/259, 50.2%). Patients reported high symptomatic disease burden, demonstrated by mean peak pruritus in past 24 hours numerical rating scale (NRS) of 6.2, and moderate impact on quality of life, as demonstrated by mean Dermatology Life Quality Index (DLQI) of 9.8. At tralokinumab initiation, 87 patients (33.6%) were AST-experienced, of whom 95.4% (83/87) had used dupilumab. Among AST-naïve patients, 80.8% (139/172) had used super potent topical steroids, 36.0% (62/172) topical calcineurin inhibitors, and 10.5% (18/172) topical PDE4 inhibitors. Overall, socio-demographic characteristics were similar between AST-naïve and AST-experienced groups, while AST-naïve patients had higher disease severity at initiation, including mean BSA (29.4% vs. 16.9%) and mean EASI (16.9 vs. 8.8). Among patients with a 6-month follow-up visit (n=81), 74.1% (60/81) remained persistent on tralokinumab. Baseline characteristics of patients with 6-month follow-up, and of persistent patients, were similar to the total population. Among persistent patients, 73.3% (44/60) were AST-Naïve and 26.7% (16/60) were AST-experienced, all of whom were dupilumab-experienced. Mean EASI among persistent patients improved from 13.8 at baseline to 3.3 at 6 months. Of the 21 patients who discontinued tralokinumab, 52.4% (11/21) were AST-experienced at initiation, and 42.9% (9/21) switched to another systemic therapy following tralokinumab. Reasons for discontinuation included lack of efficacy (AST-naïve: 30.0%, 3/10; AST-experienced: 45.5%, 5/11), safety (AST-naïve: 30.0%, 3/10; AST-experienced: 9.1%, 1/11), insurance (AST-naïve: 10.0%, 1/10; AST-experienced: 9.1%, 1/11), and other (AST-naïve: 30.0%, 3/10; AST-experienced: 36.4%, 4/11). Conclusions In this US real-world study, adult AD patients initiating tralokinumab were both AST-naïve and AST-experienced with a high burden of disease. Approximately three-quarters of patients were persistent with tralokinumab treatment at 6 months. Further real-world evidence studies on tralokinumab persistence with longer follow-up period are warranted. [ABSTRACT FROM AUTHOR]

Introduction/Background Tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD) pathogenesis. Numerous clinical studies have established that tralokinumab is an efficacious treatment for patients with moderate-to-severe AD, along with having a favorable safety profile. However, there is a lack of evidence on tralokinumab use in routine clinical practice, where patient management may differ from that defined by clinical trial protocols. Objectives TRACE is a global, real-world study that aims to better understand the effectiveness, safety, and clinical use of tralokinumab in patients with AD in daily practice. Methods TRACE is a global, observational, prospective, single-cohort study of tralokinumab-treated adults with moderate-to-severe AD. Overall, 11 countries across Europe, North America and the Middle East are participating. The primary objective of TRACE is to assess changes in clinical signs and symptoms of AD in patients treated with tralokinumab according to the nationally approved labels. Secondary objectives include safety, quality of life, patient-reported outcomes and treatment adherence. For this interim analysis, the objective was to report the baseline characteristics of the first 100 US patients. Results Overall, 55% of the first 100 US patients initiated on tralokinumab in the TRACE study were female; the majority (54%) were White, followed by 18% Black or African American and 12% Asian. Mean (standard deviation [SD]) age was 46.4 years (18.2) and body mass index was 28.6 kg/m2 (7.7). Patients had a mean disease duration of 13.9 years (SD 16.5), with 46% being biologic-naïve and 54% biologic-experienced. Most patients (88%) had moderate-to-severe AD, with a mean Investigator's Global Assessment score of 3.2 (SD 0.8); mean Eczema Area and Severity Index was 15.4 (SD 7.9). A heavy symptomatic burden of disease was evident, with a mean eczema-related sleep numerical rating scale (NRS) of 4.2 (SD 3.3) and mean worst daily pruritus NRS of 6.1 (SD 2.6). Patients also reported a substantial impact of AD on quality of life; mean Dermatology Life Quality Index was 13.2 (SD 8.5). Almost one quarter (24%) of patients reported ≥1 atopic comorbidity, with asthma (12%), cardiovascular disease (8%) and autoimmune disease (6%) being the most frequent; 3% of patients had psychiatric illness. Conclusions Initial findings showed that tralokinumab is being prescribed as a first-line biologic treatment option in the US in accordance with the label. Treated patients had a heavy burden of disease with considerable impact on quality of life. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a chronic, inflammatory disease that can affect multiple regions of the body, but can be particularly burdensome on exposed areas of skin, such as the head and neck (H&N).Tralokinumab, a high-affinity monoclonal antibody that specifically neutralizes interleukin-13, is approved in multiple countries for adults with moderate-to-severe AD. Phase 3 trials showed tralokinumab provided significant improvements in AD severity and was well-tolerated up to 52 weeks of treatment. The ongoing open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses the safety and efficacy of tralokinumab after the completion of parent trials (PT). Objective To assess tralokinumab efficacy in the H&N region. Methods This post hoc analysis included adult patients with moderate-to-severe AD initially randomized to tralokinumab 300mg Q2W in the phase 3 PTs ECZTRA 1 (NCT03131648) or ECZTRA 2 (NCT03160885). Patients on active tralokinumab treatment were followed for up to 52 weeks in PTs and for up to 152 weeks in ECZTEND as of data cutoff April 30, 2022. Patients re-randomized to placebo at Week (Wk) 16 were not included beyond that timepoint. For this analysis, overall EASI and H&N regional EASI (H&N EASI) were evaluated. H&N EASI (0-7.2) was calculated based on the severity of erythema, induration/papulation, excoriation, lichenification and area of involvement. All data were analyzed and presented as observed. Results At baseline, 87.8% (1047/1192) of patients had H&N involvement (H&N EASI>1), and 49.9% (591/1192) of patients exhibited severe AD (IGA 4). Baseline median H&N EASI for the pooled PTs was 3.0 (IQR 1.8; 4.5). In the pooled PTs, 48.2% (542/1125) and 71.2% (558/784) of patients achieved H&N EASI≤1, at Wk16 and Wk52, respectively. After 3 years additional treatment (Wk152 in ECZTEND), the proportion of patients with H&N EASI≤1 was 87.2% (232/266) and the median H&N EASI was 0.2 (IQR 0.0; 0.5). In the subgroup of patients (n=301) with severe AD (IGA 4) and high H&N involvement (H&N EASI≥4), median H&N EASI improved from 5.4 at baseline to 2.4 and 0.8 at Wk16 and Wk52, respectively, and 0.4 at Wk152. Improvements in H&N region were comparable to overall EASI improvement. Conclusions Tralokinumab provided sustained improvements in the H&N regions in patients with moderate-to-severe AD for up to 4 years. Sustained improvements were also seen in patients with severe disease and substantial H&N involvement at baseline. [ABSTRACT FROM AUTHOR]

Introduction/Background To ensure minimal residual disease and to prevent relapses, recently published consensus reports have defined optimal long-term treatment targets for atopic dermatitis (AD).1,2 Tralokinumab, a monoclonal antibody specifically neutralizing interleukin-13, is approved for the treatment of moderate-to-severe AD. ECZTEND (NCT03587805) is an ongoing open-label, 5-year extension trial investigating the long-term safety and efficacy of tralokinumab 300 mg every other week (Q2W) plus optional topical corticosteroids (TCS). Objectives To determine the proportion of patients treated for up to 4 years with tralokinumab in AD clinical trials who: 1) exhibit stable improvement, with no or minimal fluctuations, in lesion extent and severity long-term (ie, response in ≥80% of attended visits), and 2) exhibit a stable long-term composite response (ie, up to 4 years of tralokinumab treatment and response in ≥80% of attended trial visits) in signs and symptoms of AD, and quality of life based on recent treat-to-target recommendations (EASI ≤7 and either DLQI ≤5 or Itch NRS ≤4). Methods This post hoc analysis included 347 patients who were continuously treated with tralokinumab for 52 weeks in the identically designed phase 3 monotherapy trials ECZTRA 1&2 and subsequently for up to 152 weeks in ECZTEND as of the April 30, 2022 data cutoff. Stability of long-term response, with no or minimal fluctuations, was defined as meeting the target endpoints at ≥80% of attended visits between Weeks 16-152 in ECZTEND. Endpoints analyzed were EASI ≤7, EASI ≤2, and a composite long-term treatment target: EASI ≤7 and either DLQI ≤5 or worst weekly pruritus NRS ≤4. Results A stable EASI ≤7 response (at ≥80% of attended visits) was observed in 70.2% (233/332) of tralokinumab-treated patients over Weeks 16-152 of ECZTEND. A stable EASI ≤2 response was observed in 34.0% (113/332) of patients, and a long-term optimal composite target, EASI ≤7 and either DLQI ≤5 or Itch NRS ≤4, was observed in 60.5% (201/332) of patients. Conclusions High proportions of clinical trial patients maintained stable responses, with no or minimal fluctuations in efficacy, with continued tralokinumab 300 mg Q2W plus optional TCS for up to 4 years of treatment. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is characterized by microbial dysbiosis, immune dysregulation, and an impaired skin barrier. Microbial dysbiosis in AD involves a reduction in diversity primarily driven by an increased abundance of Staphylococcus aureus. Tralokinumab, an approved treatment for adults with moderate-to-severe AD, improves the skin barrier and immune abnormalities by specifically targeting the interleukin 13 cytokine, but its impact on the skin microbiome is unknown. To investigate how tralokinumab affects the skin microbiome by examining the lesional skin of adults with moderate-to-severe AD from the phase 3 ECZTRA 1 trial (NCT03131648). Microbiome profiling, S aureus abundance, and biomarker data were assessed in a subset of ECZTRA 1 participants (S aureus abundance at baseline and week 16; microbiome profiling at baseline, and week 8/16; and serum sampling before dose and week 4/8/16/28/52). Tralokinumab treatment led to increased microbial diversity, reduced S aureus abundance, and increased abundance of the commensal coagulase-negative Staphylococci. Limitations include a lack of S aureus abundance data at week 8, sampling site variation between participants, and possible influence from concomitant systemic antiinfectives. Our findings indicate specific targeting of the interleukin 13 cytokine with tralokinumab can directly and/or indirectly improve microbial dysbiosis seen in AD skin. [ABSTRACT FROM AUTHOR]

Objective: To review pharmacokinetics, efficacy, and safety of tralokinumab in treatment of atopic dermatitis (AD). Data Sources: Literature review was conducted using MEDLINE (PubMed), EMBASE, and ClinicalTrials.gov for articles published between January 2010 and May 2022. Study selection and data extraction: Articles in English discussing tralokinumab in AD were included. Data synthesis: In one phase 2 trial, more subjects treated with tralokinumab 150 and 300 mg achieved an Investigator's Global Assessment (IGA) of 0/1 with minimum ≥2 point IGA reduction (23%), versus placebo (11.8%, P = 0.10). During 2 phase 3 trials, more subjects treated with tralokinumab achieved IGA success (ECZTRA 1: 15.8% and ECZTRA 2: 22.2%), versus placebo (7.1% and 10.9%, respectively; P = 0.002 and P < 0.001). During one phase 3 trial, in conjunction with topical corticosteroids (TCS), more subjects treated with tralokinumab 300 mg achieved IGA success (ECZTRA 3: 38.9%), versus placebo (26.2%, P = 0.015). During another phase 3 trial in subjects with resistance or contraindication to oral cyclosporine, more subjects treated with tralokinumab 300 mg achieved an Eczema Area Severity Index 75 (64.2%), versus placebo (50.5%, P = 0.018). Relevance to patient care and clinical practice: Tralokinumab is efficacious for moderate-to-severe AD, as monotherapy, in conjunction with TCS, and resistance or contraindication to cyclosporine. Although IL-4 and IL-13 are both implicated in AD's pathogenesis, IL-13 is overexpressed, and head-to-head trials are needed to assess efficacy of tralokinumab, versus dupilumab. Compared with upadacitinib and abrocitinib, tralokinumab is not associated with black-box warnings. Conclusions: Tralokinumab is an efficacious and safe systemic treatment for moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common chronic inflammatory skin condition that has a significant impact on a patient's quality of life and requires ongoing management. Conventional topical and systemic therapies do not target specific components of AD pathogenesis and, therefore, have limited efficacy and may be associated with long-term toxicity. Thus, AD management is challenging, with a significant proportion of patients not achieving clear skin or a reduction in pruritus. There remains a large unmet need for effective therapeutic strategies with favorable safety profiles that can be used long-term in patients with refractory AD. The emergence of targeted biological and small molecule therapies has effectively broadened available treatment options for moderate-to-severe AD. Most recently, interleukin 13 (IL-13) inhibitors were shown to be efficacious and well-tolerated, with tralokinumab already approved for use in this patient population. It is important for dermatologists to be aware of the evidence behind this emerging class of biologic agents to guide treatment choices and improve outcomes in patients with AD. The main objective of this paper is to review the current literature regarding the efficacy and safety of current and emerging anti-IL-13 monoclonal antibodies, including tralokinumab, lebrikizumab, cendakimab, and eblasakimab, for the treatment of moderate-to-severe AD. [ABSTRACT FROM AUTHOR]