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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.)

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.)

Background: Clinical trials and real-life data have reported an increased incidence of conjunctivitis in patients treated with dupilumab for their atopic dermatitis (AD). Although mostly mild in severity, in some cases conjunctivitis will appear or increase after dupilumab initiation, which can lead to dupilumab discontinuation., Objectives: (1) To describe the characteristics of patients developing conjunctivitis requiring discontinuation of dupilumab; and (2) to analyse the factors associated with a complete conjunctivitis improvement after dupilumab discontinuation and a switch to tralokinumab or Janus kinase inhibitors., Methods: This was a multicentre retrospective cohort study that included all patients with AD treated with dupilumab who developed conjunctivitis leading to dupilumab discontinuation and switching to tralokinumab or Janus kinase inhibitors in daily practice. Data on patients, their AD and conjunctivitis were analysed at the inclusion visit (corresponding to discontinuation of dupilumab and the institution of new AD treatment), at visit 2 (3-6 months after inclusion) and at visit 3 (corresponding to the last medical visit)., Results: After multivariate analysis, the only factors associated with a complete resolution of dupilumab-associated conjunctivitis at visit 2 and/or visit 3 were conjunctivitis duration (OR 8.98, 95% CI 1.47-55) (p = 0.018), personal history of asthma (OR 10.66, 95% CI 1.82-62.63) (p = 0.009) and switching from dupilumab to Janus kinase inhibitors (OR 17.11, 95% CI 2.94-99.66) (p = 0.002)., Conclusions: Although uncommon, severe dupilumab-associated conjunctivitis is more frequent in daily life compared to its incidence in the dupilumab pivotal trials. In these cases, our study suggests that a rapid switch to another molecule, particularly a Janus kinase inhibitor, should be considered., (© 2024 European Academy of Dermatology and Venereology.)

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.)

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]

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.)

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]

Patient 3 still required dexamethasone eye drops during treatment with tralokinumab, although less frequently than during treatment with dupilumab. Additionally, at week 28 of tralokinumab treatment, less OSD symptoms were reported compared with dupilumab treatment in patients 2 and 4 (Table 1). Keywords: atopic dermatitis; autoimmunity; basic mechanisms; dermatology; ocular allergy EN atopic dermatitis autoimmunity basic mechanisms dermatology ocular allergy 586 589 4 05/10/23 20230501 NES 230501 Key messages This prospective case series describes the dermatological and ophthalmological characteristics of four atopic dermatitis patients. [Extracted from the article]

This article explores the use of tralokinumab as an alternative treatment for patients with atopic dermatitis (AD) who do not respond to dupilumab. It presents evidence from case reports and case series suggesting that tralokinumab may be effective in reducing symptoms in patients with different phenotypes of AD. However, the response to tralokinumab was slightly lower in patients who had previously been exposed to dupilumab. While tralokinumab shows promise, further controlled studies are needed to confirm its efficacy. [Extracted from the article]

Therapeutic IgG4 antibodies engage in Fab‐arm exchange with endogenous human immunoglobulin G4 (IgG4) to form monovalent hybrid molecules. A mechanistic population model was developed to quantitatively characterize the dynamic Fab‐arm exchange of tralokinumab, a human IgG4 monoclonal antibody currently being developed for the treatment of atopic dermatitis, with endogenous IgG4 in healthy volunteers. The estimated pharmacokinetic parameters for IgG4 were similar to those of immunoglobulin G1 or immunoglobulin G2 in humans. However, the mechanistically modeled clearance of half molecules is 21‐fold higher, likely due to the loss of avidity for the neonatal Fc receptor. Half molecules of tralokinumab randomly associate with those of endogenous IgG4 to form monovalent hybrid molecules, which became the dominant form of tralokinumab within 1 day postdose in healthy volunteers. As the potency of monovalent tralokinumab is comparable with that of bivalent tralokinumab, the IgG4 Fab‐arm exchange with endogenous IgG4 is not expected to affect the potency of neutralization of interleukin‐13 in vivo. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a patient with atopic dermatitis who experienced a relapse of psoriasis after being treated with tralokinumab, a monoclonal antibody targeting interleukin-13. The patient initially had a history of childhood psoriasis and was diagnosed with late-onset atopic dermatitis. Tralokinumab significantly improved the patient's atopic dermatitis symptoms but led to a severe exacerbation of psoriasis. The article highlights the complex interactions within the cytokine network and the need for further research to understand and manage these paradoxical reactions to biological therapies. [Extracted from the article]

Tralokinumab is the first biologic therapy for moderate‐to‐severe atopic dermatitis (AD) that specifically neutralizes interleukin‐13 activity, a key driver of AD signs and symptoms. Tralokinumab is a human immunoglobulin G4 monoclonal antibody administered subcutaneously every 2 weeks (with possibility of maintenance dosing every 4 weeks). This population pharmacokinetic (PK) analysis aimed to identify sources of PK variability and relevant predictors of tralokinumab exposure in adults with moderate to severe AD. Nonlinear mixed‐effect modeling, including covariate analysis, was used on a data set including 2561 subjects (AD, asthma, healthy) from 10 clinical trials. A 2‐compartment model with first‐order absorption and elimination adequately described the tralokinumab PK. Body weight was identified as a relevant predictor of tralokinumab exposure; other covariates including age, sex, race, ethnicity, disease type, AD severity, and renal and hepatic impairment were not. For body weight, the difference in exposure between the upper‐ and lower‐weight quartiles in patients with AD was <2‐fold, supporting the appropriateness of flat dosing (300 mg). Given the reduced exposure associated with higher body weight, coupled with the reduced exposure provided by dosing every 4 weeks, it is uncertain whether higher‐weight patients will achieve sufficient exposure to maintain efficacy if dosed every 4 weeks instead of the standard every 2 weeks. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Atopic dermatitis (AD) is a common chronic inflammatory disease characterized by recurrent eczematous lesions and intense pruritus, and it can have marked negative impact on those affected. Pathophysiologically, AD is complex with genetic predisposition and environmental provocation being important contributors. Mechanistically these can promote epidermal barrier dysfunction, skin microbiome abnormalities and a skewed immune response which is predominantly type‐2 immunity‐based. Our increased understanding of the immunological processes involved highlight a key role for interleukin‐13 (IL‐13). This mini‐review evaluates tralokinumab, a high‐affinity monoclonal antibody that specifically binds to and inhibits IL‐13. Based on dose‐finding study results, tralokinumab 300 mg every two weeks (Q2W) subcutaneously (SC) was investigated in three pivotal phase III clinical trials in adults with moderate‐to‐severe AD not adequately controlled on topical corticosteroids alone. Tralokinumab was significantly superior to placebo regarding the proportion of patients achieving IGA 0/1 and EASI‐75 at week 16 (primary endpoints), as well as improving scores for worst daily pruritus, Dermatology Life Quality Index (DLQI), and Scoring Atopic Dermatitis (SCORAD) (secondary endpoints). The week 16 response was sustained during follow‐up, and treatment with tralokinumab was found to be well‐tolerated with an overall frequency and severity of adverse events comparable to placebo. [ABSTRACT FROM AUTHOR]

Tralokinumab (Adtralza) is a new anti‐IL‐13 monoclonal antibody for the treatment of moderate to severe atopic dermatitis. This article summarises its administration, clinical trial efficacy and adverse effects. [ABSTRACT FROM AUTHOR]

This article discusses the potential use of tralokinumab, a human monoclonal antibody that targets interleukin-13 (IL-13), as a therapeutic option for patients with concurrent atopic dermatitis (AD) and alopecia areata (AA). The study presents the case of a 33-year-old female patient with lifelong AD and a diagnosis of AA since the age of 10. The patient's AD and AA showed minimal response to previous treatments, but remarkable improvement was observed after tralokinumab treatment, with a reduction in AD severity and almost complete hair regrowth. These findings suggest that IL-13 inhibitors could be a viable treatment option for AA in individuals with AD, warranting further investigation. [Extracted from the article]

Aims: Tralokinumab, an investigational human immunoglobulin G4 monoclonal antibody, potently and specifically neutralizes interleukin-13, a central mediator of asthma. Tralokinumab has shown improvements in clinical endpoints in adults with uncontrolled asthma. The present study explored the pharmacokinetics (PK) and safety of a single tralokinumab dose, and utilized a population PK modelling and simulation approach to evaluate the optimal dosing strategy for adolescents., Methods: Adolescent subjects with asthma, using daily controller medication, received a single subcutaneous dose of tralokinumab 300 mg. Safety, immunogenicity and PK data were collected during a 57-day follow-up. A population PK model was developed using data from the present study and prior studies in adults. Simulations were performed to evaluate dose adjustment requirements for adolescents., Results: Twenty adolescents (12-17 years) were enrolled; all completed the study. No clinically relevant safety findings or antidrug antibodies were detected. PK parameters were similar to those observed in adults. PK modelling showed that body weight was a minor predictor of tralokinumab PK; after incorporating body weight into the PK model, a 15% (nonparametric 95% confidence interval 5%, 26%) lower clearance was found in adolescents compared with adults [173 (151, 209) vs. 204 (191, 229) ml day(-1)]. Simulations showed no therapeutically relevant differences in exposures between adolescent and adult populations, and similar PK profiles for weight-based (4 mg kg(-1)) and fixed (300 mg) fortnightly subcutaneous doses of tralokinumab., Conclusion: Single-dose administration of tralokinumab 300 mg in adolescents was well tolerated, with a PK profile similar to that in adults. Exposure predictions suggest that dose adjustment is not required for adolescents., (© 2015 The British Pharmacological Society.)

Interleukin (IL)‐13 is involved in the pathogenesis of some types of asthma. Tralokinumab is a human immunoglobulin G4 monoclonal antibody that specifically binds to IL‐13. Two placebo‐controlled phase II studies (phase IIa, NCT00873860 and phase IIb, NCT01402986) have been conducted in which tralokinumab was administered subcutaneously. This investigation aimed to characterize tralokinumab's dose‐exposure‐response (forced expiratory volume in 1 s (FEV1)) relationship in patients with asthma and to predict the most appropriate dose for phase III. An integrated population pharmacokinetic‐pharmacodynamic (PK/PD) modeling analysis was required for phase III dose selection, due to differing phase II patient populations, designs, and regimens. Analysis of combined datasets enabled the identification of tralokinumab's dose‐exposure‐FEV1 response relationship in patients with asthma. Near‐maximal FEV1 increase was predicted at a dose of 300 mg SC once every 2 weeks (Q2W). This dose was chosen for tralokinumab in the phase III clinical development program for treatment of severe, uncontrolled asthma. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: The present S3 guideline was created based on the European English‐language S3 guideline, with special consideration given to the medical conditions in the German‐speaking region, and with additions from the previous German‐language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off‐label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non‐drug therapy approaches, and addresses aspects related to special patient groups. [ABSTRACT FROM AUTHOR]

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]

Children and adolescents suffering from moderate‐to‐severe atopic dermatitis (AD) face a significant disease burden that greatly impacts their quality of life. Treatment options for AD are currently limited. To assess the safety and efficacy of biologic drugs, dupilumab, lebrikizumab, or tralokinumab, in improving outcomes in patients with moderate to severe inadequately controlled AD. We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) comparing dupilumab, lebrikizumab or tralokinumab to placebo in patients with AD. We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs), random effects model was used and a p‐value <0.05 was considered as statistically significant. We analysed data into Review Manager 5.4. A total of five RCTs and 973 patients were included, of whom 592 were prescribed a biologic drug. Compared with placebo, patients receiving a biologic drug had a greater improvement, achieved an Investigator Global Assessment (IGA) score of 0 or 1 (OR 5.05; 95% CI 3.08–8.29), Eczema Area and Severity Index (EASI) 75 (OR 6.87; 95% CI 4.71–10.02), EASI 50 (OR 8.89; 95% CI 6.18–12.78) and EASI 90 (8.30; 95% CI 4.81–14.31). The proportion of patients with 3 points or more (OR 6.56; 95% CI 4.34–9.90) or 4 points or more (OR 8.09; 95% CI 5.19–12.59) improvement from baseline in peak pruritus NRS was significantly higher with biologic drugs than placebo. There were no significant differences between groups regarding adverse events (OR 0.79; 95% CI 0.58–1.07), and conjunctivitis (OR 2.08; 95% CI 1.00–4.33). In this meta‐analysis, dupilumab, lebrikizumab, and tralokinumab have shown significant improvements in signs, symptoms and quality of life in children or adolescents with moderate to severe AD. Larger studies may be needed to continue evaluating the safety and efficacy of these biologic drugs in this patient population. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) represents the most common skin disease characterized by heterogeneous endophenotypes and a high disease burden. In Europe, six new systemic therapies for AD have been approved: the biologics dupilumab (anti‐interleukin‐4 receptor (IL‐4R) α in 2017), tralokinumab (anti‐IL‐13 in 2021), lebrikizumab (anti‐IL‐13 in 2023), and the oral janus kinase (JAK) inhibitors (JAKi) targeting JAK1/2 (baricitinib in 2020 in the EU) or JAK1 (upadacitinib in 2021 and abrocitinib in 2022). Herein, we give an update on new approvals, long‐term safety, and efficacy. Upadacitinib and abrocitinib have the highest short‐term efficacy among the approved systemic therapies. In responders, dupilumab and tralokinumab catch up regarding long‐term efficacy and incremental clinical benefit within continuous use. Recently, the European Medicines Agency has released recommendations for the use of JAKi in patients at risk (cardiovascular and thromboembolic diseases, malignancies, (former) smoking, and age ≥65 years). Furthermore, we give an overview on emerging therapies currently in Phase III trials. Among the topical therapies, tapinarof (aryl hydrocarbon receptor), ruxolitinib (JAK1/2i), delgocitinib (pan‐JAKi), asivatrep (anti‐transient receptor potential vanilloid), and phosphodiesterase‐4‐inhibitors (roflumilast, difamilast) are discussed. Among systemic therapies, current data on cord‐blood‐derived mesenchymal stem cells, CM310 (anti IL‐4Rα), nemolizumab (anti‐IL‐31RA), anti‐OX40/OX40L‐antibodies, neurokinin‐receptor‐1‐antagonists, and difelikefalin (κ‐opioid‐R) are reported. [ABSTRACT FROM AUTHOR]

Allergic conditions, such as asthma, chronic urticaria, atopic dermatitis (AD), and eosinophilic esophagitis, have long been treated with oral and topical steroids which resulted in negative off‐target effects. However, newer biologic medications are increasingly being developed and approved for treatment of these conditions. These medications have a variety of mechanisms of action to target pathophysiology specific to these diseases. As biologics become more targeted, fewer off‐target effects are seen improving tolerability for patients as well as expanded options for treatment of these conditions. This review discusses monoclonal antibody therapies (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab, and tralokinumab) including their safety and use in asthma, chronic urticaria, AD, and eosinophilic esophagitis. [ABSTRACT FROM AUTHOR]

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]

Emerging T-helper type 2 (Th2) cytokine-based asthma therapies, such as tralokinumab, lebrikizumab (anti-interleukin (IL)-13), and mepolizumab (anti-IL-5), have shown differences in their blood eosinophil (EOS) response. To better understand these effects, we developed a mathematical model of EOS dynamics. For the anti-IL-13 therapies, lebrikizumab and tralokinumab, the model predicted an increase of 30% and 10% in total and activated EOS in the blood, respectively, and a decrease in the total and activated EOS in the airways. The model predicted a rapid decrease in total and activated EOS levels in blood and airways for the anti-IL-5 therapy mepolizumab. All model-based predictions were consistent with published clinical observations. The modeling approach provided insights into EOS response after treatment with Th2-targeted therapies, and supports the hypothesis that an increase in blood EOS after anti-IL-13 therapy is part of the pharmacological action of these therapies. [ABSTRACT FROM AUTHOR]

T cell-and non T cell-mediated delayed hypersensitivity to dupilumab We hypothesize that Patient 1 was sensitized to T-cell epitopes in the tralokinumab primary sequence with cross-reactivity with dupilumab[6]; (ii) an Arthus-like reaction, that is, an immune complex-mediated reaction produced under conditions of excess antigens, for the second patient. We report the cases of a 52-year-old (Patient 1) and a 56-year-old (Patient 2) female patients, followed for severe AD with multiple previous treatment failures. [Extracted from the article]

The evidence‐ and consensus‐based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty‐nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients. [ABSTRACT FROM AUTHOR]

Background: Monoclonal antibody therapies have a growing role in treating refractory airway disease. Objective: The review aimed to summarize the response of respiratory mucosa to monoclonal antibody treatments in inflammatory airway conditions. Design: We conducted a systematic review including risk of bias assessment. Data sources: MEDLINE, EMBASE and PubMed from 1 January 2000 to 16 November 2019 were searched. Eligibility criteria: Eligible studies assessed the immunological and histological response of airway mucosa to monoclonal antibody therapy compared with baseline or a comparison group in patients with respiratory diseases (asthma, chronic rhinosinusitis and allergic rhinitis). Any prospective interventional studies, including randomized controlled trials (RCTs) and single‐arm trials, were eligible. Results: There were 4195 articles screened, and full‐text analysis produced n = 11 studies with extractable data. Nine were RCTs, and two were single‐arm trials. These studies focused on asthma (n = 9 articles), chronic rhinosinusitis (n = 1) and allergic rhinitis (n = 1). Five monoclonal antibody drugs were assessed (omalizumab, mepolizumab, dupilumab, benralizumab and tralokinumab). Risk of bias was low (n = 6) or unclear (n = 3) in the RCTs and moderate in the single‐arm trials. Omalizumab reduced the mucosal concentration of its target, IgE. Dupilumab reduced the concentration of one of its targets, IL‐13, but not IL‐4. Omalizumab, mepolizumab and benralizumab reduced tissue eosinophil cell density. Dupilumab decreased mucosal eosinophil granule proteins. Tralokinumab did not affect airway mucosa. Conclusions: Knowledge of the expected biological response of monoclonal antibody therapy on biomarkers in disease tissue provides an important supplement to data about clinical outcomes. An understanding of the biological effect is essential to identify likely responders, reasons for treatment failure and necessary adjustments to monoclonal antibody treatment. Further investigation into the effect of monoclonal antibody therapy on disease mucosa and more precise endotyping are required to move closer to achieving personalized medicine. [ABSTRACT FROM AUTHOR]

The results of polymerase chain reaction tests for SARS-CoV-2 were positive for 4 (%9,3) patients, and the results of SARS-CoV-2 immunoglobulin G tests were positive for 39 (%90,7) patients. 21 (%48,8) of the patients had urticarial, 12 (%27,9) of them maculopapular, 5 (%11,6) patients livedoid and 1 (%2,3) patient had a skin rash compatible with pseudopernio. For patients not achieving the primary endpoints at Week 16, 33.3% and 57.8% of 135 patients initially treated with tralokinumab and transferred to open-label treatment at Week 16 achieved IGA 0/1 or EASI-75 at Week 52. With regard to skin-related QoL measured with Children's Dermatology Life Quality Index (CDLQI), 5 patients suffered from moderate QoL impairment whereas 42 individuals revealed only mild and 39 patients no QoL reduction. [Extracted from the article]

Background: Several biologics for atopic dermatitis (AD) have demonstrated good efficacy in clinical trials, but with a substantial proportion of patients being identified as poor responders. This study aims to understand the pathophysiological backgrounds of patient variability in drug response, especially for dupilumab, and to identify promising drug targets in dupilumab poor responders. Methods: We conducted model‐based meta‐analysis of recent clinical trials of AD biologics and developed a mathematical model that reproduces reported clinical efficacies for nine biological drugs (dupilumab, lebrikizumab, tralokinumab, secukinumab, fezakinumab, nemolizumab, tezepelumab, GBR 830, and recombinant interferon‐gamma) by describing system‐level AD pathogenesis. Using this model, we simulated the clinical efficacy of hypothetical therapies on virtual patients. Results: Our model reproduced reported time courses of %improved EASI and EASI‐75 of the nine drugs. The global sensitivity analysis and model simulation indicated the baseline level of IL‐13 could stratify dupilumab good responders. Model simulation on the efficacies of hypothetical therapies revealed that simultaneous inhibition of IL‐13 and IL‐22 was effective, whereas application of the nine biologic drugs was ineffective, for dupilumab poor responders (EASI‐75 at 24 weeks: 21.6% vs. max. 1.9%). Conclusion: Our model identified IL‐13 as a potential predictive biomarker to stratify dupilumab good responders, and simultaneous inhibition of IL‐13 and IL‐22 as a promising drug therapy for dupilumab poor responders. This model will serve as a computational platform for model‐informed drug development for precision medicine, as it allows evaluation of the effects of new potential drug targets and the mechanisms behind patient variability in drug response. [ABSTRACT FROM AUTHOR]

With the increasing number of options for the treatment of moderate‐to‐severe atopic dermatitis, clinicians need guidance on a practical approach to selecting a systemic agent for specific patient populations. We convened an expert panel consisting of 12 members to conduct a literature review and summarize relevant data related to six scenarios of clinical interest: comorbid asthma, ocular surface disease, history of cancer, past and ongoing infections of interest (including herpes simplex virus, herpes zoster, hepatitis B, and tuberculosis), pregnancy and lactation, and the elderly. We performed a literature search and examined each clinical scenario with respect to three major categories of available systemic agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, and mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib), and biologics (dupilumab, lebrikizumab, and tralokinumab). The expert panel and steering committee met virtually to review the data and discuss the drafted consensus statements. A modified Delphi process was used to arrive at a set of final consensus statements related to the systemic treatment of AD in these specific patient populations. To provide practical guidance on the choice of systemic therapy for atopic dermatitis in these six topics of clinical interest, 25 expert consensus statements and a summary of the supporting data are presented herein. [ABSTRACT FROM AUTHOR]

Given the lack of head‐to‐head studies of systemic therapies in moderate‐to‐severe atopic dermatitis (AD), network meta‐analyses (NMAs) can provide comparative efficacy and safety data to inform clinical decision‐making. In this NMA, eligible randomized controlled trials (RCTs) published before 24 October 2019 were identified by a systematic literature review. Short‐term (12–16 weeks) efficacy (Investigator's Global Assessment [IGA] and Eczema Area and Severity Index [EASI] responses), patient‐reported outcomes (PROs) and safety data from each trial were abstracted and analysed separately for monotherapy and combination therapy (systemic plus topical anti‐inflammatory therapy). RCTs were analysed in fixed‐effects and random‐effects Bayesian NMA models. Overall, 19 phase 2 and phase 3 RCTs of abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab and upadacitinib were included. In monotherapy RCTs, upadacitinib 30 mg once daily (QD) had the numerically highest efficacy (83.6% achieved ≥50% improvement in EASI [EASI‐50 response]), followed by abrocitinib 200 mg QD (74.6%), upadacitinib 15 mg QD (70.5%), dupilumab 300 mg every 2 weeks (Q2W) (63.4%) and abrocitinib 100 mg QD (56.7%). Similar trends in EASI‐75 and EASI‐90 response were observed. In combination therapy RCTs, abrocitinib 200 mg QD had the highest EASI‐50 (86.6%), followed by dupilumab 300 mg Q2W (82.4%) and abrocitinib 100 mg QD (79.7%). Similar findings were observed for IGA response and PROs. In monotherapy and combination therapy RCTs, the probability of treatment‐emergent adverse events (TEAEs) was higher among all active treatments than with placebo (except for dupilumab 300 mg Q2W [odds ratio (OR), 0.96; 95% credible interval (CrI), 0.45–2.18] and abrocitinib 100 mg QD [OR, 0.95; 95% CrI, 0.35–2.66] in combination therapy RCTs), although active treatments did not significantly differ from one another. Abrocitinib, dupilumab and upadacitinib were consistently the most effective systemic therapies in adult and adolescent patients with AD, with no significant TEAE differences in short‐term RCTs. [ABSTRACT FROM AUTHOR]

Biologics approved and in development for atopic dermatitis offer life-changing clinical efficacy with a relatively banal long-term safety profile requiring no laboratory monitoring. Biologic therapies also have their drawbacks, including high payor cost and the need to be administered as every other week subcutaneous injections. Addressing these concerns, studies of longer dosing intervals have been performed in the formal clinical trial setting and during real-world clinical care. Here, we review the current progress and evidence of dose elongation strategies in biologics for atopic dermatitis. We find that across a diverse investigational landscape, a large patient population exists that is able to maintain adequate disease control on a prolonged dosing interval. Evidence of clinical predictors of maintenance of disease control using this approach is emerging, although the impact of increased dosing intervals as a strategy to mitigate side effects is lacking. Patients experiencing good disease control are ideal candidates to engage in a shared decision-making process between patients and providers that will facilitate an individualized dosing approach in practice., (© 2025 European Academy of Dermatology and Venereology.)