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Introduction: In pivotal phase 3 tralokinumab monotherapy (ECZTRA 1/2) and topical corticosteroid (TCS) combination (ECZTRA 3) trials in adults with moderate-to-severe atopic dermatitis (AD), tralokinumab significantly improved signs and symptoms of AD. Geographic region may impact treatment response due to potential differences in race and ethnicity, and based on findings in other therapy areas. Here, we evaluated the efficacy and safety of tralokinumab in the ECZTRA 1/2/3 North American population at week 16, as well as maintenance of responses over time, and compared these data side-by-side with those of the ECZTRA 1/2/3 non-North American population. Methods: Primary endpoints were Investigator's Global Assessment score of 0 or 1 (IGA 0/1; clear or almost clear) or at least 75% improvement in Eczema Area and Severity Index (EASI-75) at week 16. At week 16, tralokinumab-treated IGA 0/1 or EASI-75 responders were re-randomized 2:2:1 to tralokinumab 300 mg q2w, or q4w, or placebo (ECZTRA 1/2) and 1:1 to tralokinumab 300 mg q2w or q4w (ECZTRA 3). Results: Overall, 559/1596 (35%) and 160/380 (42.1%) patients randomized in ECZTRA 1/2 and ECZTRA 3 were from North America, respectively. At week 16, IGA 0/1 and EASI-75 response rates were greater with tralokinumab versus placebo in ECZTRA 1/2 (IGA 0/1: 25.3% vs 15.1%; 95% confidence interval [CI] 3.0, 17.3; p = 0.012; EASI-75, 40.1% vs 19.4%; 95% CI 12.6, 28.7; p < 0.001) and ECZTRA 3 (IGA 0/1, 40.0% vs 25.9%; 95% CI − 0.5, 28.3; p = 0.074; EASI-75: 58.1% vs 37.0%; 95% CI 4.9, 37.0; p = 0.012) and tralokinumab was well tolerated in the North American population. Patients with IGA 0/1 or EASI-75 response at week 16 demonstrated sustained responses at week 52 and week 32 in ECZTRA 1/2 and ECZTRA 3, respectively. Similar findings were observed in the non-North American trial populations. Conclusions: Tralokinumab, with or without TCS, displayed similar efficacy and safety in patients with moderate-to-severe AD across the North American population, and was comparable to the non-North American population. Clinical Trial Registration: NCT03131648 (registered 27-Apr-2017); NCT03160885 (registered 19-May-2017); NCT03363854 (registered 6-Dec-2017). [ABSTRACT FROM AUTHOR]

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.

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]

Background: Additional long-term treatments are needed for moderate-to-severe atopic dermatitis (AD). An ongoing, open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses tralokinumab plus optional topical corticosteroids in participants from previous tralokinumab parent trials (PTs) with moderate-to-severe AD.Objective: To evaluate the safety and efficacy of up to 2 years tralokinumab treatment in a post hoc interim analysis.Methods: Safety analyses included adults from completed PTs enrolled in ECZTEND, regardless of tralokinumab exposure duration. Efficacy analyses included adult participants treated with tralokinumab in ECZTEND for ≥1 year and subgroup analyses of those on tralokinumab for 2 years (1 year from PT, 1 year in ECZTEND). Primary end point was the number of adverse events with additional efficacy end points.Results: Participants on tralokinumab had an exposure-adjusted rate of 237.8 adverse events/100 patient-years' exposure (N = 1174) in the safety analysis set. Exposure-adjusted incidence rates of common adverse events were comparable to PTs, although at lower rates. With 2 years of tralokinumab, improvements in extent and severity of AD were sustained, with Eczema Area and Severity Index (EASI-75) in 82.5% of participants (N = 345).Limitations: Possible selection bias; no placebo arm; some participants experienced treatment gaps between PTs and ECZTEND.Conclusion: Over 2 years, tralokinumab was well tolerated and maintained long-term control of AD signs and symptoms. [ABSTRACT FROM AUTHOR]

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]

Background: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases worldwide. AD pathogenesis is multifactorial, involving environmental and genetic factors. IL-13 stands out as one of the main cytokines in the pathophysiology of AD. Currently, dupilumab, which targets both IL-4 and IL-13 signalling, is the only biologic agent approved for the treatment of moderate-to-severe AD. New targeted biologic therapies are being developed, such as lebrikizumab and tralokinumab, two selective IL-13 inhibitors. This article reviews the role of IL-13 in AD and the most recent data on lebrikizumab and tralokinumab. Methods: A narrative review of the literature was written after retrieving relevant articles in the PubMed database (up until December 2020) using the following keywords present in the title, abstract or body: atopic dermatitis; interleukin 13; IL-13; tralokinumab; lebrikizumab, biologic therapy. Discussion: A phase IIb trial showed that all three dosing regimens evaluated (lebrikizumab 125 mg every 4 weeks (Q4W), 250 mg Q4W or 250 mg every 2 weeks) achieved rapid and dose-dependent efficacy concerning the signs and symptoms of AD, with a statistically significant improvement, at week 16. Tralokinumab was studied in three phase III clinical trials and reached its primary endpoints at week 16 (ECZTRA 1 and 2 in monotherapy and ECZTRA 3 with concomitant topical corticosteroids), with response maintained over time. Both lebrikizumab and tralokinumab exhibited good safety profiles in AD trials, with adverse effects usually being comparable between the control and treatment groups. Conclusion: The evidence supports the hypothesis that selective antagonism of IL-13 is sufficient to control AD, providing an improvement in the patient’s quality of life. Therefore, the development of lebrikizumab and tralokinumab represents a new and exciting phase in the management of AD.

As atopic dermatitis (AD) is a chronic and potentially lifelong disease, it is important to determine the long-term safety of new treatments. Tralokinumab, which specifically targets interleukin-13, is approved in Europe, Canada and the United States for the treatment of adults with moderate-to-severe AD. During the initial 12–16 week placebo-controlled treatment period of Phase 2 and 3 trials, tralokinumab was well-tolerated with an overall frequency of adverse events (AEs) similar to the placebo. An ongoing open-label extension trial, ECZTEND (NCT03587805), is assessing the safety and efficacy of tralokinumab up to 5 years after parent trials (PT). To report an interim safety analysis of patients treated with tralokinumab for up to 42 months (≤ 1 year in PT and ≤ 2.5 years in the open-label extension ECZTEND), including AEs of special interest (AESI). In ECZTEND, moderate-to-severe AD patients who completed the previous tralokinumab PT received subcutaneous tralokinumab 300 mg every 2 weeks after a 600 mg loading dose; topical corticosteroid use was optional. All AEs were recorded, coded, and classified by severity, causality and outcome. AESIs were predefined in PT based on areas of safety interest for monoclonal antibodies in AD, including eye disorders (e.g. conjunctivitis), skin infections requiring systemic treatment, eczema herpeticum and malignancies diagnosed after dosing. Event rates are presented as the number of events (nE) per 100 patient-years of exposure (PYE). All AEs described were treatment-emergent AEs, defined as AEs reported after the first dosing of the study drug. As of 30 April 2021, the interim safety analysis included 1442 patients from the PT ECZTRA 1, 2, 3, 4, 5 and 7 who had received ≥1 dose of tralokinumab in ECZTEND, with 121.0 weeks mean exposure time on tralokinumab [median 131.5 weeks (IQR 83.4–161.8); min 0.0, max 186.4 weeks]. Total exposure time in ECZTEND was 2446.2 PYE. Overall, 1127 patients experienced an AE (198.7 nE/100 PYE), the majority of which were mild (132.6 nE/100 PYE). The most frequently reported AEs (≥5.0% of patients) were the same as in the PT, including viral upper respiratory tract infection (18.2 nE/100 PYE, mainly reported as the common cold), atopic dermatitis (17.9 nE/100 PYE), upper respiratory tract infection (5.8 nE/100 PYE), headache (4.4 nE/100 PYE) and conjunctivitis (3.8 nE/100 PYE). The rates of AEs were generally lower as compared to short-term rates in the PT. Most of the serious AEs (SAEs; 4.9 nE/100 PYE) were reported as single events without clustering on the type. No events of conjunctivitis AEs were SAEs, and only five patients discontinued due to conjunctivitis AEs. AESI eye disorders, skin infections requiring systemic treatment, eczema herpeticum and malignancies were observed at rates similar to or lower than reported in PT. Consistent safety was demonstrated during up to 42 months of tralokinumab treatment in patients with moderate-to-severe AD. Exposure-adjusted incidence rates of AESIs, including eczema herpeticum and skin infections requiring systemic treatment, were generally lower than rates reported during the short-term, placebo-controlled period up to week 16. Exposure-adjusted incidence rates of conjunctivitis were lower with long-term exposure, and only five patients discontinued due to conjunctivitis. This analysis supports the long-term benefit-risk profile of targeted IL-13 inhibition with tralokinumab for patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

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

Introduction/Background Tralokinumab is a high-affinity, fully human IgG4 monoclonal antibody that specifically targets interleukin-13, a key driver of atopic dermatitis (AD) disease progression. Clinical trials have shown that tralokinumab is efficacious in patients with moderate-to-severe AD and has a favorable safety profile, including a low frequency of adverse events such as conjunctivitis. Management of patients in routine clinical practice differs from those enrolled in clinical trials due to strict protocol criteria, and there is a lack of clinical data on tralokinumab use in the real-world setting. Objectives: TRACE is a real-world study in patients with AD, aiming to better understand the effectiveness, safety, and clinical use of tralokinumab in daily practice. Here, we describe baseline characteristics from the first patients enrolled into TRACE in Germany. Methods: TRACE is an observational, prospective, single-cohort study of adult patients with moderate-to-severe AD who are treated with tralokinumab, according to national approved labels. Eleven countries are participating in the study across Europe, North America and the Middle East. The primary objective is to assess changes in clinical signs and symptoms of AD in tralokinumab-treated patients. Secondary objectives are to investigate safety, quality of life, patient-reported outcomes and treatment adherence, among others. Results: Of the first 100 patients initiated on tralokinumab, the mean age (standard deviation [SD]) was 44.7 years (17.9) and 58% were male. Most patients had moderate-to-severe AD with a mean Investigator's Global Assessment (IGA) score of 3.5 (SD 0.7) and mean Eczema Area and Severity Index (EASI) of 22.5 (SD 12.9). Patients reported heavy symptomatic burden of disease; the mean eczema-related sleep numerical rating scale (NRS) was 5.6 (SD 2.9) and mean worst daily pruritus NRS was 6.2 (SD 2.7). Patients also reported a substantial impact on quality of life, demonstrated by a mean Dermatology Life Quality Index of 15.6 (SD 6.9). Overall, 79 patients were biologic-naïve and 19 were biologic-experienced (data missing; n=2). All biologic-experienced patients were previously treated with dupilumab, of whom most experienced one or more treatment failures. Reasons for switching from dupilumab included lack or loss of effectiveness, and adverse events, which most commonly included conjunctivitis. Conclusions: Initial findings showed that most adult patients with moderate-to-severe AD who were treated with tralokinumab were biologic-naïve, indicating tralokinumab is prescribed as firstline systemic treatment in real-world clinical practice, in line with European Dermatology Forum guidelines. The main reasons for switching from dupilumab were lack or loss of effectiveness, and adverse events, such as conjunctivitis, indicating the need for alternative biologic treatments such as tralokinumab. [ABSTRACT FROM AUTHOR]

Introduction/Background Tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, is indicated for the treatment of patients (pts) with moderate-to-severe AD. Clinical trials of up to 52 weeks' duration, showed that tralokinumab was efficacious and well tolerated as monotherapy and in combination with topical therapy. Objectives: To evaluate the long-term safety of tralokinumab in an integrated analysis of seven phase 3 parent trials of up to 52 weeks' duration (NCT03131648, NCT03160885, NCT03363854, NCT03562377, NCT03526861, NCT03761537, NCT04587453), and the ongoing, up to 5-year extension study (ECZTEND; NCT03587805). Methods: Two datasets were analyzed: a placebo-controlled (PC) dataset from the initial 16-wk period of the parent trials and an all-tralokinumab (AT) dataset combining the parent trials with the subsequent ECZTEND trial including pts from first dose of tralokinumab until end of tralokinumab exposure or data cut-off (April 30th, 2022). Exposure was defined over the active treatment periods. For the AT dataset, periods on placebo were disregarded. All treatment-emergent adverse events (AEs) were recorded. AEs of special interest (AESIs) were predefined. Proportions of pts with events and incidence rates (IR) per 100 patient-years of exposure (PYE) were calculated. PYE was defined as the time until the first event or exposure end, whichever came first, and incidence was defined as the first event. Results: In total, 2693 pts (≥12 years) received tralokinumab for up to 238.5 weeks (≈4.5 years) with a median exposure time of 76.5 weeks in the AT dataset. Total exposure time was 5320.2 patient years. Median age at baseline was 33.0 years (min-max; 12-92). 10.4% of pts were 12-17 years. Overall, 2307 pts experienced an AE (IR=202.0), most (97.3%) of which were mild-to-moderate. Serious AEs (SAEs) were reported in 226 pts (IR=4.5); SAEs were considered possibly or probably related by the investigator in 50 pts (IR=0.9). No SAEs at the preferred term level were reported with an IR≥0.1. Discontinuation of treatment due to AEs was low (IR=2.8). AEs leading to drug withdrawal with an IR>0.1 were dermatitis atopic (IR=0.5) and injection site reaction (ISR) (IR=0.2). The most frequently reported AEs in the AT dataset were consistent with the PC dataset, including nasopharyngitis (IR=18.4), upper respiratory tract infection (IR=6.9), conjunctivitis (IR=5.0), ISR (IR=3.6), conjunctivitis allergic (IR=2.7), and injection site pain (IR=1.5). AESIs, including eye disorders, skin infections requiring systemic treatment, eczema herpeticum, and malignancies, were observed in the AT dataset at rates similar to or lower than reported in the PC dataset. Conclusions: Long-term use of tralokinumab, for up to 4.5 years, was well tolerated, and the pattern of AEs was consistent with the initial placebo-controlled treatment period and with no new safety signals identified. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a chronic, inflammatory skin disease that has higher prevalence, persistence, and severity, as well as different response to treatment, in skin of color (SOC) patients. This underscores the importance of clinical trial diversity and real-world case reports to help reduce health inequity, improve clinical understanding, and enhance treatment access for all patient populations. Tralokinumab specifically targets interleukin-13, and the onset, efficacy, and safety outcomes from the initial clinical trials revealed striking therapeutic potential. Objectives: To provide examples of rapid tralokinumab onset of action in SOC patients, including improvement of the difficult-to-treat head and neck subtype and of hyperpigmentation on the hands. Methods: The authors describe the clinical outcomes of two SOC patients: an 18-year-old Asian male [patient 1] and a 37-yearold African-American male [patient 2]. Data related to tralokinumab treatment were collected during routine clinical practice. Results: Both patients were diagnosed with AD in infancy and continued to suffer from AD. At baseline, each had clearly perceptible erythema, induration, and lichenification and were assigned IGA scores of 3. Patient 1 had a BSA of 22%, managed with clobetasol 0.05% ointment for the body and ruxolitonib 1.5% cream for the face. He had never received systemic treatment. Patient 2 had previous medical history of mild asthma and BSA of 29%. His AD was managed with clobetasol 0.05% ointment. Over the prior two decades, he had been managed with myriad topical corticosteroids, prednisone tapers, as well as methotrexate. Due to insurance barriers, there were challenges obtaining tralokinumab immediately for both patients. The lapse in time was less than 6 weeks in each case. Not surprisingly, IGA 3 was assigned at both time of initial presentation and at time of tralokinumab initiation. Both patients were prescribed an initial dose of 600 mg (four 150 mg subcutaneous injections) followed by 300 mg (two 150 mg subcutaneous injections) administered every other week. After 10 weeks, patient 1 experienced a decrease in IGA from 3 to 1; his BSA decreased from 22% to 7%. After only 6 weeks, patient 2 also exhibited a decrease in IGA from 3 to 1; his BSA decreased from 29% to 6%. The improvement was sustained throughout a 6-month follow-up period in both patients. The authors observed significant improvement in the quality of life for both patients, subjectively and objectively. To date, no patient-reported or investigator-recognized adverse outcomes have occurred. Conclusions: Treatment with tralokinumab 300 mg, every other week, showed a rapid onset of action, with superior efficacy to the original clinical trials in two SOC patients with moderate-to-severe AD, one of which had involvement of the difficult-to-treat area of the head and neck. With no patient-or physician-adverse events reported to date, this observational study underscores the importance of future real-world reports to potentially corroborate our findings. [ABSTRACT FROM AUTHOR]

Introduction/Background Tralokinumab, an IL-13 targeted biologic approved in the United States (US) for adult patients with moderate-to-severe atopic dermatitis (AD), improved patient-reported outcomes (PROs) in clinical trials and after 4 weeks of use in the real-world setting. Objectives: This 6-month interim analysis evaluated the real-world impact of tralokinumab on PROs in adult patients. Methods: This is an interim analysis of an ongoing 52-week patient survey study enrolling US AD patients from the AdbryTM AdvocateTM Program. Patients completed the baseline survey close to tralokinumab initiation. Data on demographics and PROs including weekly itch numeric rating scale (NRS), eczema-related weekly sleep NRS, Dermatology Life Quality Index (DLQI), and Treatment Satisfaction Questionnaire for Medication (TSQM-9) were collected. Percent and absolute changes from baseline to 6 months of treatment were calculated. Outcomes are stratified by previous dupilumab use. The percentage of patients experiencing minimal clinically important difference (MCID) was also calculated for itch NRS (3-point reduction) and DLQI (4-point reduction). Results: As of May 2023, 102 patients completed baseline, 1-month, and 6-month surveys. Of these, 59.8% were female, mean age was 44.2 years (SD=15.7), 82.4% were white, and 85.3% had private insurance. 84.3% were previously treated with topical corticosteroids (TCS) and 52.9% were dupilumab-experienced patients. Over 6 months, there was an improvement in the mean sleep interference NRS (40%), average weekly itch NRS (39%), worst weekly itch NRS (33%), PO-SCORAD (37%), and DLQI (52%). There were improvements in mean TSQM-9 global satisfaction (11.06 points), TSQM-9 convenience (3.92 points), and TSQM-9 effectiveness (14.60 points) scores. Median MCIDs were met by 57.1% on the sleep interference NRS, 51.7% of patients on the average weekly itch NRS, 50.0% on the worst weekly itch NRS, and 68.7% on the DLQI. Relative to the dupilumab-experienced cohort, the dupilumab-naïve patients showed markedly improved outcomes [median MCIDs of 65.6% v 48.4% on sleep NRS; 59.5% v 44.4% on average weekly itch NRS; 61.4% v 39.6% on worst weekly itch NRS; 61.4% v 35.3% on PO-SCORAD; and 75.6% v 61.9% on DLQI]. Conclusions: This 6-month interim analysis shows that tralokinumab improved quality of life outcomes related to itch, sleep, and treatment satisfaction when used either in dupilumab-naïve or in dupilumab-experienced patients. These patients will continue to be followed for up to 52 weeks of treatment with tralokinumab. [ABSTRACT FROM AUTHOR]

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

Introduction/Background There is a need for additional long-term treatment options for patients with moderate-to-severe atopic dermatitis (AD) that provide sustained disease control with a favorable safety profile. Tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, is approved for the treatment of moderate-to-severe AD in multiple countries. Clinical trials of up to 52-wk duration showed that tralokinumab was effective and well tolerated as monotherapy and in combination with topical therapy. ECZTEND (NCT03587805) is an ongoing open-label, 5-yr extension trial investigating the long-term safety and efficacy of tralokinumab ± optional topical corticosteroids (TCS). Objectives: To assess the efficacy of long-term tralokinumab treatment, we conducted a post hoc interim subgroup analysis restricted to the largest, most homogenous patient population, with the longest treatment duration. Methods: Adult patients with moderate-to-severe AD who were continuously treated with tralokinumab ± optional TCS for 52 wks in the parent phase 3 trials ECZTRA 1 (NCT03131648) or ECZTRA 2 (NCT03160885) and for up to 152 wks in ECZTEND as of data cutoff April 30, 2022, were included. Endpoints included proportion of patients achieving Investigator's Global Assessment (IGA) score of 0/1 (clear/almost clear skin), at least 75% or 90% improvement in Eczema Area and Severity Index (EASI) relative to parent trial baseline (EASI-75 or EASI-90), EASI =7, worst weekly pruritus Numeric Rating Scale (NRS) =4, and Dermatology Life Quality Index (DLQI) =5. Results are presented using observed data. Sensitivity analyses on patients who completed Wk 152 in ECZTEND (or who withdrew, but were enrolled in the study at least 152 wks prior to the study cutoff) were performed using modified non-responder imputation (mNRI) with discontinuations due to AEs or lack of efficacy imputed as non-responders and a 2-step multiple imputation (MI) for other missing data [Step 1: Missing data up to 1 year in ECZTEND were imputed using a standard regression-based MI method; Step 2: Missing data post 1 year imputed by carrying forward the within-subject area under the curve of days in-response]. Results: 347 adult patients with a mean age (SD) of 42.2 (14.5) yrs and a mean EASI (SD) of 30.8 (13.7) at parent trial baseline were included in this analysis. After 4 yrs of total tralokinumab treatment (at Wk 152 in ECZTEND), IGA 0/1 [% (n/N)] was observed in 52.6% (92/175) of patients. EASI-75 {% (n/N) [95% CI]} was achieved in 84.5% (147/174) [78.4, 89.1] of patients as observed, and in 73.4% (254.8/347) [68.6, 78.3] using mNRI. EASI-90 was achieved in 64.4% (112/174) [57.0, 71.1] of patients as observed, and in 53.4% (185.2/347) [47.8, 59.0] using mNRI. Additionally, EASI =7 (mild disease) was observed in 84.5% (147/174) of patients, worst weekly pruritus NRS =4 (no to mild itch) in 68.0% (119/175), and DLQI =5 (no to small effect of AD on quality of life) in 79.0% (128/162) of patients. The safety profile was favorable and consistent with earlier analyses, with no new safety signals arising with continued tralokinumab use. Conclusions: Continuous use of tralokinumab ± optional TCS provided long-term disease control over 4 yrs in adult patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Introduction/Background Tralokinumab, a high-affinity, monoclonal antibody that targets IL-13, is approved in the EU and Canada for adolescents (aged ≥12 years) with inadequately controlled moderate-to-severe atopic dermatitis (AD), and it does not require laboratory monitoring. The phase 3 ECZTRA 6 (NCT03526861) clinical trial demonstrated efficacy and safety up to 52 weeks in that population. Objectives: To further characterize the safety profile of tralokinumab by evaluating laboratory parameters of adolescents in the ECZTRA 6 trial. Methods: ECZTRA 6 subjects received tralokinumab 150mg (n=98), 300mg (n=97) or placebo (n=94) every 2 weeks (Q2W) from week 0-16 after a loading dose at week 0 (twice the subsequent dose), and then randomized to maintenance [original tralokinumab dose either Q2W or every 4 weeks (Q4W) or placebo Q2W] or open-label (tralokinumab 300mg Q2W) until week 52. Laboratory parameters included hematology, serum biochemistry, and urinalysis throughout the trial (weeks 0, 8, 16, 28, and 52). Results: Overall (n= 289 subjects), laboratory baseline parameters were similar across treatment groups. Mean and median changes of most hematology parameters showed minor fluctuations within the normal ranges through week 52, except for eosinophils. At baseline, elevated mean eosinophil counts (>0.5 109/L) were observed for 40.8% (tralokinumab 150mg), 48.5% (tralokinumab 300mg), and 43.6% (placebo) of subjects in each respective treatment group. Some tralokinumab-treated patients had small transient increases in eosinophils (maximum mean change from baseline 0.2×109/L) before week 16. Continued treatment with tralokinumab or placebo did not correspond with further increase in eosinophil levels over time, and no adverse events of eosinophilia were reported. Mean levels of most biochemistry parameters, including electrolytes, renal and liver function parameters, and lipid panel, were within normal range at baseline, and mean and median changes showed minor fluctuations within normal ranges in all treatment arms. Mean lactate dehydrogenase levels were around or above the upper limit of normal at baseline and decreased to within the normal ranges during the trial across all groups. Overall, no clinically meaningful differences were observed in hematology, biochemistry, or urinalysis parameters between active treatment groups or placebo. Conclusions: Similar to findings in adult trials, no meaningful changes in laboratory parameters were observed in adolescents through week 52 with tralokinumab treatment. No routine laboratory monitoring is needed for adult or adolescent AD patients treated with tralokinumab. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is an inflammatory skin disease associated with atopic comorbidities, including asthma, food allergy, hay fever, and allergic conjunctivitis. Tralokinumab, a high-affinity monoclonal antibody that specifically targets IL-13, is indicated for the treatment of moderate-to-severe AD. Objectives: To assess the impact of atopic comorbidities on the efficacy and safety of tralokinumab vs. placebo for moderateto-severe AD in patients age ≥12 years. Methods: This post-hoc analysis presents data from the adult trials ECZTRA 1 and 2 (NCT03131648 and NCT03160885 pooled; 300 mg tralokinumab every 2 weeks [Q2W] vs. placebo) and ECZTRA 3 (NCT03363854; 300 mg tralokinumab Q2W vs. placebo, both plus TCS as needed), and the ECZTRA 6 adolescent trial (NCT03526861; pooled 150 mg and 300 mg tralokinumab Q2W vs. placebo). Tralokinumab-treated patients received a loading dose. Proportion of patients achieving IGA 0/1 and EASI-75 at Week 16 according to patient-reported current or past atopic comorbidity are presented as observed regardless of rescue medication use; missing data were imputed as non-responders. Results: In total 2,223 patients were included across four trials. Among patients in ECZTRA 1 and 2, 50.5% reported history of asthma, 38.5% food allergy, 53.8% hay fever, and 33.5% allergic conjunctivitis, while 19.8% reported no atopic comorbidities and 79.3% reported ≥1 atopic comorbidity. Proportions of patients in ECZTRA 3 and 6 reporting history of atopic comorbidities were largely similar, although more adolescent patients reported food allergy. In all subgroups at Week 16, higher proportions of patients receiving tralokinumab vs. placebo achieved EASI-75. In ECZTRA 1 and 2, response rates among patients in each subgroup were asthma: 35.3% vs. 12.8%, food allergy: 33.2% vs. 14.7%, hay fever: 36.8% vs. 16.5%, allergic conjunctivitis: 34.8% vs. 12.7%, none: 34.6% vs. 20.5%; and ≥1 atopic comorbidity: 35.5% vs. 15.2% (P<0.05 for all). A similar pattern of response was observed in ECZTRA 3 and 6, and for IGA 0/1 across trials. EASI-75 response rates for tralokinumab-treated patients were consistent across patients with different numbers of atopic comorbidities. Safety across subgroups was consistent with the safety profile of tralokinumab observed overall in adults and adolescents. Conclusions: 16 weeks of tralokinumab treatment improved AD signs and symptoms in adult and adolescent patients with and without atopic comorbidities, regardless of type or number of atopic comorbidities. The safety profile of tralokinumab was consistent between patients with and without atopic comorbidities. [ABSTRACT FROM AUTHOR]

Introduction/Background Biologic treatments such as tralokinumab and dupilumab are therapeutic options for adult patients with moderate-to-severe atopic dermatitis (AD) who do not achieve adequate control with topical treatments or phototherapy. To date, no trials have been conducted to directly evaluate the relative efficacy of these biologic treatments. Objectives: Applying indirect comparison of efficacy, we examined the cost-per-responder of tralokinumab compared to dupilumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-serve AD in the United States (US) and Canada. Methods: A cost-per-responder analysis was undertaken considering the Eczema Area and Severity Index 75 (EASI-75) and Investigator's Global Assessment (IGA-0/1) response criteria over a 32-week period. For each treatment, the cost-per-responder was computed by multiplying the treatment cost by the number needed to treat (NNT). Efficacy data were derived from an unanchored matching-adjusted indirect comparison (MAIC) utilizing patient-level data from ECZTRA-3 (tralokinumab) and aggregate data from LIBERTY AD CHRONOS (dupilumab). Treatment cost was defined as the drug cost of the biologic treatment with a duration corresponding to 32 weeks. TCS cost was not considered. Treatments were assumed to be administered every 2 weeks (Q2W). The costs were estimated based on Wholesale Acquisition Costs (WAC) from the US and ex-factory prices via the McKesson price list for Canada. All prices were converted to US dollars ($). Sensitivity analyses (SA) were conducted with every 4 week (Q4W) dosing beginning at week 16 for 10% and 20% of patients treated with tralokinumab. Results: For the US, the average cost-per-responder was $62,714 (Q4W SA: 10%: $61,239; 20%: $59,763) for tralokinumab versus $63,993 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $82,419 (Q4W SA: 10%: $80,480; 20%: $78,450) for tralokinumab versus $118,835 for dupilumab considering the IGA 0/1 response criteria. For Canada, the average cost-per-responder was $22,846 (Q4W SA: 10%: $22,308; 20%: $21,771) for tralokinumab versus $26,475 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $30,024 (Q4W SA: 10%: $29,317; 20%: $28,611) for tralokinumab versus $49,165 for dupilumab considering the IGA 0/1 response criteria. Conclusions: Assessing EASI-75 and IGA-0/1 response criteria at 32 weeks, this analysis indicates that tralokinumab in combination with TCS is associated with lower costs-per-responder compared with dupilumab in combination with TCS in the treatment of moderate-to-severe AD in the US and Canada. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Interleukin (IL) 13 is a type 2 cytokine that is key to the inflammation underlying AD. Tralokinumab is a first-in-class, fully human, monoclonal antibody that specifically binds with high affinity to IL-13, neutralizing it in AD. Immunomodulatory treatments may impair vaccine-induced immune responses.Objective: Assess the immune responses to standard vaccines in adults with moderate-to-severe AD who are undergoing treatment with tralokinumab.Methods: ECZema TRAlokinumab Trial No. 5 (ECZTRA 5; NCT03562377) was a phase 2, double-blind, randomized, placebo-controlled trial taking place over 30 weeks. Eligible adults were randomized 1:1, with 107 patients receiving tralokinumab 300 mg and 108 patients receiving a placebo every 2 weeks for 16 weeks. All patients received Tdap (tetanus/diphtheria/pertussis) and meningococcal vaccines at week 12. The primary end points were positive antitetanus and antimeningococcal responses between weeks 12 and 16 (noninferiority margin, -25%; responder, >3-fold increase in IgG).Results: The noninferiority of tralokinumab versus placebo for immune response to Tdap (91.9% vs 96.1%) and meningococcal (86.0% vs 84.2%) vaccines was demonstrated at week 16. During treatment, the rates of adverse events were lower for tralokinumab than for the placebo, with most events being mild or moderate.Limitations: Responses to other vaccines (including influenza) were not examined.Conclusions: Treatment with tralokinumab 300 mg every 2 weeks did not affect immune responses to Tdap and meningococcal vaccines. Treatment was well tolerated when administered concomitantly with the vaccines and demonstrated a safety profile comparable to phase 3 trials. [ABSTRACT FROM AUTHOR]

Dupilumab, a monoclonal antibody against the common receptor of interleukin (IL)-4 and IL-13, was the first biologic therapy approved in Canada for treatment of moderate-to-severe atopic dermatitis (AD). While it is considered safe and effective, dupilumab is not universally effective and 8%-38% of patients develop conjunctivitis, while some patients develop head and neck dermatitis. Thus, new therapeutic options are warranted. While both IL-4 and IL-13 play important roles in the pathogenesis of AD, it has been recently demonstrated that IL-13 is the primary upregulated cytokine in AD skin biopsy samples. A placebo-controlled phase 2b clinical trial evaluating the efficacy and safety of lebrikizumab, an IL-13 inhibitor, in AD demonstrated that, at 16 weeks, Eczema Area and Severity Index (EASI) 75 and Investigator's Global Assessment (IGA) 0/1 were achieved by 60.6% and 44.6% of patients taking lebrikizumab at its highest dose (vs 24.3% and 15.3% of patients taking placebo, respectively). Moreover, treatment with lebrikizumab was associated with rapid improvement of pruritus and low rates of conjunctivitis (1.4%-3.8%). Another IL-13 monoclonal antibody, tralokinumab, was evaluated for safety and efficacy in moderate-to-severe AD. By week 12, among adults receiving 300 mg tralokinumab, 42.5% achieved EASI-75 and 26.7% achieved IGA 0/1 score (vs 15.5% and 11.8% in the placebo group, respectively). Both lebrikizumab and tralokinumab demonstrated acceptable safety profiles in AD (and non-AD) trials with adverse events often being comparable between treatment and control groups. Thus, IL-13 inhibitors may provide a safe and effective treatment alternative for patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

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.

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.

Tralokinumab is a high-affinity, fully human IgG4 monoclonal antibody that specifically inhibits interleukin-13 (IL-13), a key driver of atopic dermatitis (AD) disease progression. Clinical trials have shown that tralokinumab is efficacious in patients with moderate-to-severe AD and has a favorable safety profile, including a low frequency of adverse events (AEs) such as conjunctivitis. However, management of patients in routine clinical practice differ from those enrolled in clinical trials due to strict inclusion/exclusion criteria, and there is currently a lack of clinical data on tralokinumab use in the real-world setting. TRACE is an observational cohort study of patients with AD, which aims to better understand the effectiveness, safety and clinical use of tralokinumab in the real-world setting. This study aims to describe baseline characteristics and initial insights from the first 100 patients enrolled into TRACE in Germany. TRACE is a longitudinal, prospective, new user, noncomparative, observational, single-cohort study, with primary data collection of adult patients with AD who are treated with tralokinumab, according to national approved labels. The study is taking place across countries in Europe, North America and the Middle East. The primary objective is to assess changes in clinical signs and symptoms of AD in tralokinumab-treated patients. Secondary objectives are to investigate safety, quality of life, patient-reported outcomes and adherence, among others. This analysis includes the first 100 patients enrolled from 39 sites across Germany. Of the first 100 patients in TRACE initiated on tralokinumab in Germany, the majority were males. Most patients had moderate-to-severe disease as indicated by their mean Investigator's Global Assessment score and mean Eczema Area and Severity Index. Patients reported heavy symptomatic burden of disease, as demonstrated by their mean eczema-related sleep numerical rating scale (NRS) and mean worst daily pruritus NRS. Patients also reported a substantial impact on quality of life, as demonstrated by mean Dermatology Life Quality Index. Overall, approximately 4/5 of the patients were biologic-naïve. All biologic-experienced patients were previously treated with dupilumab, of whom most experienced one or more treatment failures. Reasons for switching from dupilumab included lack or loss of efficacy, and AEs, which included mainly conjunctivitis. Initial findings from the first 100 patients from TRACE in Germany showed that the majority of adult patients with moderate-to-severe AD treated with tralokinumab were biologic-naïve, indicating that tralokinumab is prescribed as first-line systemic treatment in the real world, in line with European Dermatology Forum guidelines. Of patients who switched from dupilumab, the main reasons for switching were lack or loss of efficacy, and conjunctivitis, indicating the need for an alternative biologic treatment such as tralokinumab. [ABSTRACT FROM AUTHOR]

Approximately 5–10% of asthmatic patients worldwide suffer from severe asthma. Experimental and clinical studies have demonstrated that IL-13 is an important cytokine in chronic airways inflammation. IL-13 is involved in Th2 inflammation and has been identified as a possible therapeutic target in the treatment of asthma. Two different human monoclonal antibodies (mAbs) anti-IL-13 (tralokinumab and lebrikizumab) block binding and signaling of IL-13 to its receptors, IL-13Rα1 and IL-13Rα2. Several randomized, double-blind, placebo-controlled multicenter studies have evaluated the safety and efficacy of tralokinumab and lebrikizumab in the treatment of adult patients with severe asthma, but all have failed to meet their primary endpoints. No serious adverse events related to the treatment with these anti-IL-13 mAbs have been reported in these studies. These negative clinical results contrast with positive findings from blocking IL-13 signaling in experimental models of asthma, raising doubts about the transferrable value of some models. Interestingly, dupilumab, a mAb which blocks both IL-4 and IL-13 signaling reduces exacerbation rates and improves lung function in severe asthmatics. These results suggest that IL-4 and IL-13 share some, but not all functional activities in airway inflammation. Tralokinumab might show efficacy in a highly selected cohort of asthmatics characterized by overexpression of IL-13. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, systemic, inflammatory disease that affects the skin and is characterized by persistent itch and marked redness. AD is associated with an increased risk of skin infections and a reduced quality of life. Most AD treatment options to date were not designed to selectively target disease‐causing pathways that have been established for this indication. Topical therapies have limited efficacy in moderate‐to‐severe disease, and systemic agents such as corticosteroids and immunosuppressants present with tolerability issues. Advances in the understanding of AD pathobiology have made possible a new generation of more disease‐specific AD therapies. AD is characterized by the inappropriate activation of type 2 T helper (Th2) cells and type 2 innate lymphoid (ILC2) cells, with a predominant increase in type 2 cytokines in the skin, including interleukin (IL)‐13 and IL‐4. Both cytokines are implicated in tissue inflammation and epidermal barrier dysfunction, and monoclonal antibodies targeting each of these interleukins or their receptors are in clinical development in AD. In March 2017, dupilumab, a human anti–IL‐4Rα antibody, became the first biologic to receive approval in the United States for the treatment of moderate‐to‐severe AD. The anti–IL‐13 monoclonal antibodies lebrikizumab and tralokinumab, which bind different IL‐13 epitopes with potentially different effects, are currently in advanced‐stage trials. Here, we briefly review the underlying pathobiology of AD, the scientific basis for current AD targets, and summarize current clinical studies of these agents, including new research to develop both predictive and response biomarkers to further advance AD therapy in the era of precision medicine. [ABSTRACT FROM AUTHOR]

Severe atopic dermatitis, which affects both adults and children, is a debilitating disorder with a significant decline of patients' quality of life. Although aetiopathogenic factors are currently a topic of study and interpretation, the main features of atopic eczema are skin barrier disturbance and immune dysregulation. Severe refractory disease that fails to improve with conventional therapy may benefit from biologic therapy. Progress in understanding immunopathology of atopic dermatitis have allowed identification of therapeutic molecular targets in the field of biological therapy. We reviewed the different biological treatments with a focus on novel targeted agents: Systemic immunotherapy (Omalizumab, Dupilumab, Lebrikizumab, Tralokinumab, Nemolizumab, Ustekinumab, Fezakinumab, Tezepelumab, Apremilast, allergen specific immunotherapy), and topical agents (Tofacitinib, Crisaborole). [ABSTRACT FROM AUTHOR]

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Limited treatment options are available for adolescents with moderate-to-severe atopic dermatitis (AD). Tralokinumab is a high-affinity, fully human monoclonal antibody that specifically neutralizes interleukin-13, a key driver of inflammation in AD. In the phase III ECZTRA 6 trial (NCT03526861), tralokinumab 150 or 300 mg monotherapy every 2 weeks (Q2W) was effective and well tolerated in paediatric patients aged 12–17 years, and tralokinumab 300 mg was recently approved in Europe for the treatment of adolescents with moderate-to-severe AD. To report the efficacy and safety of tralokinumab 300 mg in adolescents with AD over the entire 52-week ECZTRA 6 study period. Patients were randomized to tralokinumab 300 mg Q2W (n=97) or placebo (n=94) for 16 weeks. At week 16, patients were initiated on tralokinumab and achieved the primary endpoints (Investigator’s Global Assessment [IGA] 0/1 and/or Eczema Area and Severity Index [EASI]-75), without the use of rescue treatment (topical/systemic AD therapy), were re-randomized to tralokinumab 300 mg Q2W/Q4W monotherapy for 36 additional weeks. During this blinded maintenance period, patients exhibiting a pre-defined relapse relative to their week 16 response were transferred to the open-label arm and treatment with tralokinumab 300 mg Q2W plus optional topical calcineurin inhibitors (TCIs) or topical corticosteroids (TCSs). Patients not achieving the primary endpoints were transferred to the open-label arm at week 16. A pre-specified treatment policy approach for the analyses was adopted using observed data, regardless of rescue medication and treatment discontinuation, to better reflect real-world treatment scenarios. Missing data were imputed using multiple imputations. Treatment differences for the binary endpoints were analysed using the Cochran-Mantel-Haenszel method stratified by region, and baseline IGA. Continuous endpoints were analysed using analysis of covariance accounting for the treatment, region, baseline IGA and baseline outcome value. Post-hoc analyses were conducted by pooling week 16–52 data for all patients initially randomized to tralokinumab 300 mg Q2W, irrespective of the response achieved at week 16, the dosing regimen received beyond week 16, or whether discontinuing treatment before week 16. At week 16, greater proportions of tralokinumab-treated patients (300 mg Q2W vs. placebo) achieved EASI-75 (38.4% vs. 23.5%; difference 15.4% [standard error, SE 6.53%]; P=0.0186) and EASI-90 (23.9% vs. 10.4%, difference 13.6% [SE 5.55%]; P=0.0142). Pooling all patients initially randomized to tralokinumab 300 mg Q2W and subsequently continuing on Q2W/Q4W monotherapy or Q2W plus optional TCI/TCS, response rates increased to 68.8% (EASI-75) and 42.8% (EASI-90) at week 52. Similarly, mean [SE] EASI and SCORing AD (SCORAD) improved with tralokinumab vs. placebo (EASI: 59.62% [4.36%] vs. 37.90% [5.16%]; P=0.0006 and SCORAD: 43.72% [3.13%] vs. 24.91% [3.31%]; P<0.0001) at week 16, with further improvement to 77.95% [2.96%] and 60.77% [2.81%] at week 52, respectively. Cumulative proportions of patients using concomitant TCI/TCS as rescue therapy during the first 16 weeks were lower with tralokinumab (29.9%) vs. placebo (54.3%). Over 52 weeks, the cumulative proportion of tralokinumab-treated patients using TCI/TCS increased to 47.4%, as TCI/TCS was permitted as optional concomitant medication in the open-label arm. Through week 16, proportions of patients with ≥1 adverse event (AE) were (tralokinumab 300 mg vs. placebo) 64.9 vs. 61.7%; ≥1 serious AE, 1.0 vs. 5.3%; AEs leading to discontinuation, 0% vs. 0%. The number of patients with conjunctivitis (incl. bacterial and allergic) was low (3.1% vs. 2.1%). The safety profile of tralokinumab 300 mg through week 52 was consistent with that at week 16. At week 16, tralokinumab 300 mg improved the extent and severity of AD compared with a placebo in adolescent patients with moderate-to-severe AD. Response rates progressively improved with continued tralokinumab plus optional TCS/TCI. Tralokinumab was well tolerated with a reassuring long-term safety profile over 52 weeks. [ABSTRACT FROM AUTHOR]

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.)

Background IL-13 has an important role in atopic dermatitis (AD) pathogenesis. Tralokinumab is a fully human mAb that potently and specifically neutralizes IL-13. Objective We sought to evaluate the efficacy and safety of tralokinumab in adults with moderate-to-severe AD. Methods In this phase 2b study (NCT02347176), 204 adults were randomized 1:1:1:1 to receive 45, 150, or 300 mg of subcutaneous tralokinumab, or placebo, every 2 weeks for 12 weeks with concomitant topical glucocorticoids. Coprimary end points were change from baseline in Eczema Area Severity Index score and percentage of participants with an Investigator's Global Assessment response (0/1 score and reduction of ≥2 grades from baseline) at week 12. Results At week 12, 300 mg of tralokinumab significantly improved change from baseline in Eczema Area Severity Index score versus placebo (adjusted mean difference, −4.94; 95% CI, −8.76 to −1.13; P =.01), and a greater percentage of participants achieved an Investigator's Global Assessment response (26.7% vs 11.8%). Greater responses were found in participants with greater concentrations of biomarkers of increased IL-13 activity. Participants treated with 300 mg of tralokinumab demonstrated improvements in SCORAD, Dermatology Life Quality Index, and pruritus numeric rating scale (7-day mean) scores versus placebo. Upper respiratory tract infection was the most frequent treatment-emergent adverse event reported as related to study drug in the placebo (3.9%) and pooled tralokinumab (3.9%) groups. Conclusions Tralokinumab treatment was associated with early and sustained improvements in AD symptoms and an acceptable safety and tolerability profile, thereby providing evidence for targeting IL-13 in patients with AD. [ABSTRACT FROM AUTHOR]