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Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and a relapsing course, affecting approximately 25% of children and 4-7% of adults. This study evaluated the efficacy, safety, and quality-of-life impact of tralokinumab, a humanized monoclonal antibody targeting interleukin-13 (IL-13), in treating moderate-to-severe AD in a real-world setting, with a focus on different AD phenotypes., Methods: An observational cohort of 30 adults treated with tralokinumab for ≥ 16 weeks was analyzed. Clinical and demographic data were collected, and outcomes were assessed using the Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), and numeric rating scales (NRS) for pruritus and sleep disturbances., Results: By week 16, 60% achieved a 75% improvement in EASI (EASI75) and 31% reached a 90% improvement in EASI (EASI90), reflecting substantial clinical improvements. A ≥ 4-point reduction in pruritus NRS was observed in 63% of patients by week 16, increasing to 70% by week 32. Similarly, 75% achieved significant improvements in sleep disturbance NRS by week 16, with sustained effects through week 32. Subgroup analysis revealed superior clinical responses in patients with early-onset AD and atopic comorbidities. Lower total immunoglobulin E (IgE) levels at week 16 correlated with better outcomes, suggesting total IgE as a potential biomarker. By week 32, 70% of patients had a DLQI ≤ 5, indicating minimal quality-of-life impact. Additionally, 88% reached at least one therapeutic target, and 81% met composite endpoints combining clinician-assessed and patient-reported outcomes. The safety profile was consistent with clinical trials, with mild conjunctivitis and injection site reactions as the most common adverse events., Conclusion: These findings support tralokinumab as an effective and well-tolerated treatment, emphasizing the importance of phenotype-specific approaches in AD management., Competing Interests: Declarations. Conflicts of Interest: Ersilia Tolino, Luca Ambrosio, Nicoletta Bernardini, Ilaria Proietti, Nevena Skroza and Concetta Potenza have nothing to disclose. Ethical Approval: The study was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all subjects involved in the study., (© 2025. The Author(s).)

Atopic dermatitis is characterized by a complex epidermal barrier deficiency and exaggerated immune responses dominated by type 2 mechanisms with variable contributions of additional immune axes. IL-13 is overexpressed in atopic dermatitis skin and a key driver of both barrier dysfunction and inflammation. In this study, we prospectively studied the effects of IL-13 inhibition with tralokinumab on cutaneous transcriptome profiles using RNA sequencing of biopsies from 16 patients with moderate-to-severe atopic dermatitis obtained at baseline, week 2, and week 16. Tralokinumab therapy induced early and delayed expression changes and progressively shifted the transcriptomic profile of lesional toward nonlesional skin by modulating both genes associated with keratinocyte proliferation and differentiation, itch signaling, and downstream inflammatory responses. At week 16, 751 genes were still significantly dysregulated compared with those in healthy control skin, reinforcing the need for long-term immunomodulatory therapy of moderate-to-severe atopic dermatitis to achieve deep responses. The study was registered with ClinicalTrials.gov (NCT04556461)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: 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., Materials and Methods: 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., Results: 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)., Conclusion: 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., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Patients with atopic dermatitis (AD) may discontinue dupilumab owing to dupilumab-induced ocular adverse events (DOAEs) or dupilumab-induced facial redness (DFR)., Objective: To evaluate DOAE and DFR outcomes after switching to tralokinumab or Janus kinase inhibitor (JAKi)., Methods: This retrospective study included 106 patients discontinuing dupilumab because of DOAEs and/or DFR. The primary outcome was the proportion of patients with resolution of adverse events or improvement between dupilumab discontinuation (M0) and 3 to 6 months of tralokinumab or JAKi (M3-M6) treatment; the secondary outcome was the percentage of patients with controlled AD defined by Investigator's Global Assessment scores of 0/1 at M3 to M6., Results: Proportions of patients with DOAE (92% vs 72%; P = .0244) and DFR (85% vs 33%; P = .0006) resolution or improvement were higher with JAKi than with tralokinumab. Proportions of patients reaching an Investigator's Global Assessment score of 0/1 increased from M0-M3 through M6 (22% vs 42%; P = .0067) in the JAKi group and remained similar (32% vs 35%) in the tralokinumab group. However, 57% discontinued the new treatment after 8 months on average, mainly owing to lack of efficacy., Conclusions: Janus kinase inhibitor appears to be more efficient than tralokinumab in managing dupilumab-induced AE; however, both strategies may fail to control AD., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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.

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: 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.

Atopic dermatitis (AD) is a common chronic pruritic inflammatory skin disease that affects all ages and is recognized as a global health problem. Pathophysiology is complex with skin barrier abnormalities, immune dysregulation, and microbial dysbiosis all implicated. Markers of immune and inflammatory activation in the circulation provide a rationale for systemic therapy. Type 2 immune polarization is central, though other cytokine pathways including Th22 and Th17/IL-23 have been described, suggesting additional therapeutic targets in a subset of patients. Dupilumab and tralokinumab are monoclonal antibodies currently approved for moderate-to-severe AD with lebrikizumab and nemolizumab in late stages of development., Competing Interests: Disclosure M. Nevid has no conflicts to disclose. M. Boguniewicz has been involved in clinical research for Regeneron and Sanofi-Genzyme and served as a consultant for Amgen, Eli Lilly, LEO Pharma, Regeneron, and Sanofi-Genzyme., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is a common, chronic, and recurrent inflammatory skin condition that affects a considerable portion of the population, and is particularly prevalent among children. The development of AD is influenced by environmental and genetic factors, which cause epidermal barrier dysfunction, immune dysregulation, and dysbiosis. In immune dysregulation, there is excessive production of cytokines. Among the cytokines, interleukin (IL)-13 plays a major role in the pathogenesis of AD. Searching for new and more selective treatments for moderate-to-severe cases is important because of the considerable effect of AD on the quality of life. Tralokinumab and lebrikizumab are selective IL-13 inhibitors that have demonstrated safety and efficacy as treatment options for AD in phase III trials. Tralokinumab is approved for use in Europe and the USA, while lebrikizumab is approved only in Europe. Cendakimab, which is another IL-13 selective inhibitor, has shown promising results in phase II trials, providing safe and effective outcomes. Eblasakimab, which disrupts IL-13 and IL-4 signaling pathways, is currently in phase II trials following well-tolerated administration in phase I studies. This narrative review aims to outline the current state of knowledge regarding the effectiveness and safety of these four biologic agents targeting IL-13 signaling., Competing Interests: Declaration of conflicting interestOrhan Yilmaz, Carlos Teixeira, and Diana Bernardo declare that there is no conflict of interest. Tiago Torres has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials sponsored by AbbVie, Amgen, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Janssen, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz, and UCB.

Tralokinumab is a human monoclonal anti-interleukin-13 antibody approved as systemic treatment for atopic dermatitis (AD). We aimed to evaluate effectiveness and safety of tralokinumab for AD in real-world clinical practice. We analysed Japanese patients with AD from October 2023 to March 2024. All patients were subcutaneously injected with tralokinumab, 300 mg every two weeks, after an initial injection of 600 mg and twice-daily topical corticosteroids of moderate to strongest class until week 12. In this study, 103 patients were analysed. At week 4 and 12, 54.7 % and 83.0 % achieved eczema area and severity index (EASI) 50, 22.7 % and 38.3 % achieved EASI 75, 90 8.0 % and 23.4 % achieved EASI, 32.0 % and 55.3 % achieved EASI ≤7, and 1.3 % and 14.0 % achieved Investigator's Global Assessment 0/1, respectively. At week 4 and 12, 52.9 % and 51.2 % achieved Peak Pruritus-Numerical Rating Scale (PP-NRS) 4, 16.5 % and 15.6 % achieved PP-NRS ≤1, and 57.9 % and 75.0 % achieved Atopic Dermatitis Control Tool 7, respectively. Serum levels of immunoglobulin E, thymus and activation-regulated chemokine, and lactate dehydrogenase significantly decreased at week 12 compared to baseline. Treatment-emergent adverse events occurred in 14.8 % of patients, which were mild and manageable. Notably, conjunctivitis occurred in 2.9 % of patients but was mild and resolved spontaneously. Tralokinumab for patients with AD was well-tolerated and provided favourable therapeutic effects in real-world clinical practice.

Competing Interests: Conflicts of interest Samantha Keow declares no conflicts of interest. Mohannad Abu-Hilal received consulting fees and/or honorarium from AbbVie, Bausch, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galderma, Hikma pharmaceuticals, Janssen, Leo, Medexus pharma, Novartis, Pfizer, Sanofi, Sun Pharma.

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., (© 2024 Australasian College of Dermatologists.)

Introduction: 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., Competing Interests: Cataldo Patruno reports personal fees from LeoPharma, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Potestio et al.)

Background: Tralokinumab, a humanized monoclonal antibody targeting interleukin-13, has been primarily used for the treatment of moderate-to-severe 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Zhao, Xiao and Tu.)

Competing Interests: Dr Tjahjono has served as a consultant for Bristol Myers Squibb. Dr Silverberg is an advisor, speaker, or consultant for AbbVie, Asana Biosciences, Dermavant, Galderma, GlaxoSmithKline, Glenmark, Kiniksa, LEO Pharma, Lilly, Menlo Therapeutics, Novartis, Pfizer, Realm Pharma, and Regeneron-Sanofi; and also a researcher for GlaxoSmithKline. Author Garg has no conflicts of interest to declare.

Introduction: Over the last decade, increasing understanding of the immunopathogenesis of atopic dermatitis (AD) enabled the recognition of multiple therapeutic targets and subsequently the development of novel, highly effective systemic treatments, including interleukin (IL)-antagonists. To date, the IL-4Ra-inhibitor dupilumab and the IL-13 inhibitor tralokinumab have gained regulatory approval in Europe for the treatment of moderate-to-severe AD, while more than 70 new therapeutics are currently in development., Areas Covered: In this review, we address the role of ILs in the pathogenesis of AD and provide an overview of the novel and investigational IL-antagonists, as regards their efficacy and safety on moderate-to-severe AD., Expert Opinion: Current data have established IL-4 and IL-13 inhibitors as effective and safe for the treatment of moderate-to-severe AD, as regards the rapid control of flares as well as the long-term remission of the disease. Data regarding the efficacy and safety of other IL-inhibitors, including those targeting IL-31, IL-22, IL-33, IL-36 and IL-18, are accumulating. There is still an unmet need for real-world-evidence studies and head-to-head studies for both currently available and future agents in AD treatment. Establishing predictive biomarkers of treatment response in a disorder of such considerable heterogenicity might help physicians pursue a patient-tailored therapeutic response.

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., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., (© 2024 Australasian College of Dermatologists.)

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., (© 2024. The Author(s).)

Introduction: 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)., Areas Covered: 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., Expert Opinion: 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.

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.

Competing Interests: Dr Herman has been an investigator for Lilly USA, CorEvitas Atopic Dermatitis Registry, and CorEvitas Psoriasis Registry and has been a consultant (received honoraria) for Bristol Myers Squibb and Leo Pharma. Dr Burgy has been an investigator for Lilly USA, CorEvitas Atopic Dermatitis Registry, and CorEvitas Psoriasis Registry. Dr Shahriari has been a consultant (received honoraria) for AbbVie, Arcutis, Amgen, Bristol Myers Squibb, Dermavant, Janssen, Leo Pharma, Lilly USA, Novartis, Ortho Dermatologics, Sanofi-Genzyme, Regeneron, and UCB, has served as a speaker for AbbVie, Arcutis, Bristol Myers Squibb, Lilly USA, Janssen, Dermavant, Leo Pharma, Sanofi-Genzyme, and Regeneron; and has been and investigator for AbbVie, CorEvitas Psoriasis Registry, Dermira, Cara, Dermavant, Novartis, Union, Mindera.

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.

Dupilumab and tralokinumab are currently the only FDA-approved biologic therapies for the treatment of moderate-to-severe atopic dermatitis. Tralokinumab is approved for patients greater than 18 years old, and dupilumab is approved for patients as young as 6 months old. Both medications are effective in clinical trials at improving atopic dermatitis. With a good safety profile and low-risk adverse events, dupilumab and tralokinumab are generally excellent treatment options for patients with severe or refractory atopic dermatitis., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

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.

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., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., (© 2023 Japanese Dermatological Association.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Huang and Chu.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Caffarelli, Giannetti, Giannì and Ricci.)

Competing Interests: Conflicts of interest Dr Pezzolo has been a consultant and speaker for Sanofi Genzyme, Leo Pharma, Novartis, and is a speaker for Sanofi Genzyme and Leo Pharma. Dr Naldi has been a consultant and speaker for AbbVie, Almirall, Bristol Myers Squibb, Janssen, Leo Pharma, Novartis, and Sanofi. Drs Gambardella, Guanti, Bianchelli, Bertoldi, Giacchetti, Donini, and Argenziano have no conflicts of interest to declare.

Competing Interests: None disclosed.

Background: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce., Research Design and Methods: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts., Results: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16., Conclusions: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.

A patient presented to clinic with atopic dermatitis that had been previously unresponsive to multiple topical and systemic therapies. They were successfully treated with a combination of tralokinumab and upadacitinib, showing significant improvement after 3 weeks and near-resolution after 6 months., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Introduction: IL-13 is a pleiotropic type 2 cytokine important in the pathogenesis of asthma and other eosinophilic disorders., Areas Covered: Different attempts to directly neutralize IL-13 or block its receptors and the possible impact that these approaches may have in the treatment of asthma., Expert Opinion: Collectively, specific anti-IL-13 agents are ineffective in treating severe asthma. Lebrikizumab and tralokinumab, the two most widely studied anti-IL-13 monoclonal antibodies, did not show any statistically significant improvement in quality of life or reduction in asthma exacerbation and/or symptoms in phase III studies. Consequently, their clinical development for the treatment of patients with asthma has been halted indefinitely. Other attempts to block or, at least limit, the impact of IL-13 in asthma, such as the use of protein-protein interaction modulators, kinase inhibitors, bispecific antibodies, or IL-13 peptide vaccines, are largely still in the preclinical stage of development, and it is difficult to predict whether they will reach clinical development. Nevertheless, since IL-13 directly affects airway contractility and is critical for mucus production and remodeling, and airflow limitation and mucus hypersecretion are commonly treatable features in asthma, we suggest including an anti-IL-13 drug before GINA step 5.

The U.S. Food and Drug Administration approval of dupilumab for moderate-to-severe atopic dermatitis shifted the paradigm from use of broad, systemic immunosuppressants to a safer, targeted treatment and led to the emergence of newer interleukin (IL)-4/IL-13 directed biologics and small molecule therapies, namely Janus kinase (JAK) inhibitors (JAKi). Tralokinumab and emerging (not yet approved) lebrikizumab, which both target IL-13, are alternative biologics to dupilumab. The emerging anti-IL-31 receptor nemolizumab is likely to be used second-line to other biologics, primarily for pruritus. Three JAKi are currently in use for treating atopic dermatitis, 2 of which, abrocitinib and upadacitinib, are U.S. Food and Drug Administration-approved. This review provides an in-depth, practical discussion on use of these biologics and JAKi that are approved or have completed phase 3 clinical trials in pediatric patients and adults, comparing the groups of medications based on available efficacy and safety data., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: 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., Objective: 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)., Methods: 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)., Results: Tralokinumab treatment led to increased microbial diversity, reduced S aureus abundance, and increased abundance of the commensal coagulase-negative Staphylococci., Limitations: Limitations include a lack of S aureus abundance data at week 8, sampling site variation between participants, and possible influence from concomitant systemic antiinfectives., Conclusion: Our findings indicate specific targeting of the interleukin 13 cytokine with tralokinumab can directly and/or indirectly improve microbial dysbiosis seen in AD skin., Competing Interests: Conflict of interest Dr Beck has been a consultant for Allakos, Arena Pharmaceuticals, DermTech, Evelo Biosciences, Galderma, Incyte, Janssen, LEO Pharma, Merck, Numab Therapeutics, Pfizer, Rapt Therapeutics, Regeneron, Ribon Therapeutics, Sanofi/Genzyme, Sanofi-Aventis, Stealth BioTherapeutics, Trevi Therapeutics, Union Therapeutics and Xencor; DMC member for Novartis; and investigator for AbbVie, Astra-Zeneca, DermTech, Kiniksa, Pfizer, Regeneron, and Ribon Therapeutics. Dr Bieber has been a speaker, and/or consultant, and/or investigator for AbbVie, Allmiral, AnaptysBio, Arena, Asana Biosciences, ASLAN pharma, Bayer Health, BioVerSys, Böhringer-Ingelheim, Bristol-Myers Squibb, Connect Pharma, Dermavant, Domain Therapeutics, Galderma, Glenmark, GSK, Incyte, Innovaderm, IQVIA, Janssen, Kirin, Kymab, LEO, LG Chem, Eli Lilly, L´Oréal, MSD, Novartis, Numab, OM-Pharma, Pfizer, Pierre Fabre, Q32bio, RAPT, Sanofi/Regeneron, and UCB. He is founder and chairman of the board of the non-profit biotech “Davos Biosciences.” Dr Weidinger received institutional research grants from La Roche Posay, LEO Pharma, and Sanofi Deutschland GmbH, and lecture and/or consultancy fees from AbbVie, Almirall, Eli Lilly, Kymab, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme. He is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of psoriasis and atopic dermatitis. Dr Tauber is an investigator for AbbVie, Boehringer Ingelheim, Eli Lilly, Galderma, LEO Pharma, Pierre Fabre, and Sanofi-Regeneron; a consultant or advisory board member for AbbVie, Eli Lilly, MEDAC, and Sanofi-Regeneron. Dr Saeki has received lecture fees from Kyorin, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Sanofi, Taiho, and Tokiwa; and scholarship donations from Esai, Maruho, Mitsubishi Tanabe, and Torii. Dr Irvine reports personal fees (Speaker fees and Consulting fees) from AbbVie, Arena, Dermavant, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi. Dr Eichenfield has been a scientific adviser and/or clinical study investigator for AbbVie, Almirall, Asana, Aslan, Dermavant, Eli Lilly, Forte, Galderma, Glenmark, Incyte, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer Inc., Regeneron, and Sanofi-Genzyme. Dr Werfel received lecture and/or consultancy fees from AbbVie, Almirall, Galderma, Eli Lilly, Janssen/JNJ, LEO Pharma, Novartis, Pfizer, and Regeneron/Sanofi. Drs Arlert, Jiang, and Røpke are employees of LEO Pharma. Dr Paller has been an investigator for AbbVie, Incyte, Eli Lilly, and Regeneron; Data Safety Monitoring Board for AbbVie, Bausch and Galderma; and consultant for AbbVie, Almirall, Anaptysbio, Arena, BiomX, Boehringer Ingelheim, Eli Lilly, Forte, LEO Pharma, Novartis, Pfizer, Regeneron, and Sanofi-Genzyme., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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.