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ImportanceSafe and effective long-term treatments for adolescents with moderate to severe atopic dermatitis (AD) are limited.ObjectiveTo evaluate the efficacy and safety of interleukin-13–targeted treatment with tralokinumab monotherapy in adolescents with AD.Design, Setting, and ParticipantsThe 52-week, randomized, double-blinded, placebo-controlled, phase 3 ECZTRA 6 trial was conducted from July 17, 2018, through March 16, 2021, at 72 centers across 10 countries in North America, Europe, Asia, and Australia. Enrolled patients were 12 to 17 years old with moderate to severe AD (Investigator’s Global Assessment [IGA] score ≥3; Eczema Area and Severity Index [EASI] ≥16).InterventionsPatients were randomized (1:1:1) to tralokinumab (150 or 300 mg) or placebo every 2 weeks for 16 weeks. Patients with an IGA score of 0 (clear) or 1 (almost clear) and/or 75% or higher improvement in EASI (EASI 75) at week 16 without rescue medication received maintenance treatment; other patients switched to open-label tralokinumab, 300 mg, every 2 weeks.Main Outcomes and MeasuresPrimary end points at week 16 were an IGA score of 0 or 1 and/or achieving EASI 75. Key secondary end points were a reduction of Adolescent Worst Pruritus Numeric Rating Scale of 4 or more, change in SCORing AD, and change in Children’s Dermatology Life Quality Index from baseline to week 16. Safety end points were the number of adverse events and serious adverse events.ResultsOf 301 patients randomized, 289 comprised the full analysis set (median [IQR] age, 15.0 [13.0-16.0] years; 149 [51.6%] male). More patients receiving tralokinumab, 150 mg, (n = 98), and tralokinumab, 300 mg (n = 97), achieved an IGA score of 0 or 1 without rescue medication at week 16 (21 [21.4%] and 17 [17.5%], respectively) vs placebo (n = 94; 4 [4.3%]) (adjusted difference, 17.5% [95% CI, 8.4%-24.6%]; P P = .002, respectively). More patients receiving tralokinumab, 150 mg (28 [28.6%]), and tralokinumab, 300 mg, (27 [27.8%]) vs placebo (6 [6.4%]) achieved EASI 75 without rescue at week 16 (adjusted difference, 22.5% [95% CI, 12.4%-32.6%]; P P Conclusions and RelevanceIn this randomized clinical trial, tralokinumab was efficacious and well tolerated, supporting its value for treating adolescents with moderate to severe AD.Trial RegistrationClinicalTrials.gov Identifier: NCT03526861

Background Baricitinib, an oral, selective Janus kinase 1/2 inhibitor, demonstrated long-term efficacy in moderate-to-severe atopic dermatitis in an ongoing double-blind, phase III, long-term extension study, BREEZE-AD3 (NCT03334435). Objectives To evaluate the efficacy and safety of downtitration and treatment withdrawal in a substudy of BREEZE-AD3. Methods The substudy included patients (N = 526) treated with baricitinib 4 mg or 2 mg at entry into BREEZE-AD3 who achieved a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD®) scale score of 0 (clear), 1 (almost clear) or 2 (mild) at week 52. Patients treated with baricitinib 4 mg were rerandomized to baricitinib 4 mg (continuous dosing), baricitinib 2 mg (downtitration) or placebo (treatment withdrawal, 4-mg cohort), and patients treated with baricitinib 2 mg were rerandomized to baricitinib 2 mg (continuous dosing), baricitinib 1 mg (downtitration), or placebo (treatment withdrawal, 2-mg cohort). After 16 weeks, we assessed the proportion of patients with vIGA-AD® 0/1, vIGA-AD® 0/1/2, vIGA-AD® ≥ 3 (loss of response; criterion to readminister the original baricitinib dose) and for patients who were readministered the original baricitinib dose, we assessed the proportion of patients who recaptured vIGA-AD® 0/1/2 within 16 weeks of treatment readministration (patients in the continuous dosing maintained the same dose). Results For the continuous dosing, downtitration, and treatment withdrawal groups 51%, 45% and 30% of patients in the 4-mg cohort achieved vIGA-AD® 0/1 and 87%, 61% and 50% of patients achieved vIGA-AD® 0/1/2, respectively. For the 2-mg cohort, the respective proportions of patients were 48%, 42% and 25% for vIGA-AD® 0/1 and 92%, 71% and 45% for vIGA-AD® 0/1/2. The respective proportions of patients with vIGA-AD® ≥ 3 were 39%, 49% and 56% in the 4-mg cohort and 41%, 41% and 64% in the 2-mg cohort. Of those who were readministered the original baricitinib dose, the proportions of patients who recaptured vIGA-AD® 0/1/2 among the continuous dosing, downtitration, and treatment withdrawal groups were 80%, 85% and 88% in the 4-mg cohort and 90%, 56% and 86% in the 2-mg cohort, respectively. Conclusions Baricitinib allows flexibility for patients to downtitrate or stop treatment. For patients who downtitrated treatment, the majority maintained efficacy through 16 weeks. Most patients who lost efficacy with downtitration or treatment withdrawal achieved clinically relevant efficacy upon readministration of their original dose.

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.To evaluate the safety and efficacy of up to 2 years tralokinumab treatment in a post hoc interim analysis.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.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).Possible selection bias; no placebo arm; some participants experienced treatment gaps between PTs and ECZTEND.Over 2 years, tralokinumab was well tolerated and maintained long-term control of AD signs and symptoms.

Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis.This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to15 kg: 200 mg; bodyweight ≥15 kg to30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434.Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation.Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults.Sanofi and Regeneron Pharmaceuticals.

This was a post-hoc analysis of patient-reported outcomes from the LIBERTY AD PEDS randomized, double-blind, placebo-controlled, phase 3 trial of dupilumab + topical corticosteroids (TCS) in 367 children aged 6–11 years with severe atopic dermatitis (AD). At week 16, significantly more dupilumab-treated patients vs placebo achieved a Patient-Oriented Eczema Measure (POEM) score of 0/1 (“clear skin”/“almost clear skin”), and significantly more reported Children’s Dermatology Life Quality Index (CDLQI) scores of 0/1 (“no effect on life”). Significantly more patients achieved a minimal clinically important difference (≥6 point reduction) in POEM and in CDLQI. Dupilumab (vs placebo) + TCS resulted clinically meaningful improvements in patients’ assessment of AD symptoms and quality of life.

Background: Atopic dermatitis (AD) patients display an altered skin microbiome which may not only be an indicator but also a driver of inflammation. We aimed to investi- gate associations among AD patients' skin microbiome, clinical data, and response to systemic therapy in patients of the TREATgermany registry. Methods: Skin swabs of 157 patients were profiled with 16S rRNA gene amplicon sequencing before and after 3 months of treatment with dupilumab or cyclosporine. For comparison, 16s microbiome data from 258 population-­based healthy controls were used. Disease severity was assessed using established instruments such as the Eczema Area and Severity Index (EASI). Results: We confirmed the previously shown correlation of Staphylococcus aureus abundance and bacterial alpha diversity with AD severity as measured by EASI. Therapy with Dupilumab shifted the bacterial community toward the pattern seen in healthy controls. The relative abundance of Staphylococci and in particular S. aureus significantly decreased on both lesional and non-­lesional skin, whereas the abundance of Staphylococcus hominis increased. These changes were largely independent from the degree of clinical improvement and were not observed for cyclosporine. Conclusions: Systemic treatment with dupilumab but not cyclosporine tends to re- store a healthy skin microbiome largely independent of the clinical response indicat- ing potential effects of IL-­4RA blockade on the microbiome.

(1) Inverse psoriasis (IP), also known as intertriginous, typically affects the groin, armpits, navel, intergluteal fissure, and external genitalia. Skin lesions are erythematous plaques of inflammatory nature, smooth, well-delimited, non-scaly, and non-infiltrated. Lesions may be accompanied by itching, pain, or burning sensation. The aim of this study is both to investigate the modulation of the skin microbiota induced by IP and, on the other hand, to test the effectiveness of the new biotechnological product LimpiAL 2.5%. (2) Patients affected by IP were recruited in a private practice and treated for 4 weeks with LimpiAL 2.5% exclusively. The clinical effects on the lesion skin were evaluated, and the skin microbiotas before and after treatment were compared. (3) The clinical outcomes reveled a significant beneficial effect of the tested product. At the same time, LimpiAL increased the biological diversity of the skin microbiota and exerted a significant decrease of some Corynebacterium species, and the increase of some Staphylococcus species. (4) Together, the clinical outcomes and the microbiota analysis suggest that LimpiAL treatment improves the skin condition of affected patients, basically restoring the eubiosis conditions of the affected sites and modulating the bacterial composition of the resident microbiota.

Patients with moderate-to-severe atopic dermatitis (AD) have increased risk of cutaneous and extracutaneous infections. Dupilumab has previously been associated with reduced risk of serious/severe infections and non-herpetic skin infections in adults with moderate-to-severe AD. This analysis assessed infection rates with dupilumab versus placebo in pediatric patients with moderate-to-severe and severe AD participating in clinical trials.This is a pooled analysis from two 16-week, randomized, placebo-controlled, phase 3 clinical trials of dupilumab: monotherapy in adolescents aged 12-17 years with moderate-to-severe AD (LIBERTY AD ADOL, NCT03054428) and with concomitant topical corticosteroids in children aged 6-11 years with severe AD (LIBERTY AD PEDS, NCT03345914). Data were pooled according to treatment received: placebo/approved dupilumab doses/other studied dupilumab doses/all dupilumab doses. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) were used to compare treatment groups.Overall, 612 patients were included: 205 received placebo and 407 received dupilumab (261 received approved dupilumab doses and 146 received other studied dupilumab doses). Overall infection rates were numerically lower with dupilumab versus placebo (nP/100 PY: placebo, 227; approved dupilumab, 173; other dupilumab, 206; all dupilumab, 184). Total skin infections were numerically less frequent in all dupilumab-treated groups versus placebo (nP/100 PY: placebo, 67; approved dupilumab, 30; other dupilumab, 46; all dupilumab, 36).These data suggest that dupilumab treatment in children and adolescents with AD does not increase infection risk overall and is associated with lower rates of skin infections compared with placebo.

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.

Inconsistent criteria are used to identify patients with atopic dermatitis (AD) who are candidates for systemic therapy and assess their response to systemic therapy. This may lead to undertreatment and treatment dissatisfaction. A treat-to-target (T2T) framework was previously proposed to guide systemic treatment decisions in patients with moderate-to-severe AD.1 While patient representatives were included in the T2T consensus voting process, no patient or caregiver stakeholders were included in the development of the T2T recommendations. Additionally, a recent analysis of the cross-sectional, 28-country MEASURE-AD study suggests that the treatment targets in the T2T criteria may be insufficient to ensure optimal treatment outcomes.2 To develop optimized and practical criteria for identifying patients who should receive systemic therapy, including definitions of treatment goals, treatment failure and disease severity. An executive steering committee (ESC) of seven international experts was formed in January 2021 to provide insights and perspectives on how to optimize the identification of patients who would most benefit from systemic therapy for AD. After discussing the gaps and needs in current AD management, the ESC agreed that there was a lack of evidence on patients’ treatment goals, needs, and expectations. The ESC, therefore, initiated a global, ethically and culturally diverse patient research study (N = 88) to collect these insights. Subsequently, nine regional sub-committees (SCs) were created to gain clinical perspectives from different regions worldwide (covering the USA and Puerto Rico, Latin America, Western Europe and Canada, Eastern Europe and Russia, the Middle East, Asia, and Australia and New Zealand). Overall, 87 experts from 44 countries contributed to the initiative, and 46 virtual ESC and SC meetings took place to discuss how to improve the lives of patients with AD. A virtual secure platform allowed discussions and contributions to continue outside these meetings. In April 2022, all experts rated their agreement with a series of recommendations regarding the identification and monitoring of patients eligible for systemic therapy, using a 10-point Likert scale in a modified eDelphi voting process. The consensus was pre-defined as ≥70% of all respondents rating agreement as 7 (‘mildly agree’), 8 (‘moderately agree’), 9 (‘agree’) or 10 (‘strongly agree’) with a recommendation. A strong consensus was defined as ≥90% agreement. Expert perspectives and patient insights led to the development of 34 patient-focused clinical recommendations on disease severity assessments, treatment goals and targets for clinician- and patient-reported outcomes, long-term disease control and a novel minimal disease activity (MDA) concept. A consensus of ≥80% was reached for all recommendations in one round of voting, with 88% of the recommendations reaching a ‘strong’ consensus. The MDA concept combines T2T principles with shared patient/clinician treatment decision-making principles. Patients are asked to select 1–3 feature(s) of AD which are most important to them (from the itch, skin appearance/condition, sleep disturbance, mental health, skin pain and impact on daily life). The clinician is asked to choose an objective measure of disease (from the Eczema Area and Severity Index [EASI], SCORing AD and/or the Investigator’s Global Assessment and body surface area). Treatment targets are then chosen from a list of ‘moderate’ and ‘optimal’ targets based on discussions between the clinician and patient. Optimal treatment targets include ≥90% improvement in EASI and a numeric rating scale of ≤ 1 for peak pruritus, sleep, and pain. Achievement of ‘optimal’ targets is defined as MDA. This international group of AD experts developed a novel MDA concept and criteria, which builds upon existing T2T work by providing a patient-centric approach to the optimal treatment of AD. The criteria and patient-focused clinical recommendations will help to identify and monitor patients with AD who could benefit from systemic therapy.

Patients with atopic dermatitis (AD) have an increased risk of infection, including skin infections. Previous studies in children aged 6–11 years and adolescents showed that dupilumab is not associated with an increased risk of overall infections and is associated with a lower incidence of skin infections compared with a placebo. This post-hoc analysis reports the impact of dupilumab treatment on infections, including skin infections, in children aged 6 months to 5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled trial (NCT03346434, part B), children aged 6 months to 5 years with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) were randomized 1 : 1 to subcutaneous dupilumab every 4 weeks (200 mg if baseline weight was ≥5 to

Many systemic therapies used for moderate-to-severe atopic dermatitis (AD) have immunosuppressive properties and necessitate laboratory screening and monitoring, adding to the treatment burden. Previous dupilumab studies in adults, adolescents and children aged 6–11 years with moderate-to-severe AD showed no clinically meaningful adverse changes in laboratory parameters. Here we evaluate hematology and chemistry laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (NCT03346434 part B), a randomized, double-blind placebo-controlled phase 3 study. 162 patients were randomized to either dupilumab 200/300 mg every 4 weeks (q4w; N = 83; baseline weight ≥5

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease often associated with a significant long-term disease burden. AD can profoundly impact a patient’s physical and mental health. Current AD management recommendations do not capture patient perspectives on their treatment needs, expectations and drivers of decision-making. Qualitative patient research is needed to support the creation of patient-centric recommendations for AD assessment and management. To study a large, international, ethnically diverse population of patients with AD that will enable the creation of patient-centric recommendations for AD management. Adult patients (≥18 years old) receiving treatment for AD were recruited from patient market research databases, clinician referrals, and local advertising. All patients were screened via a questionnaire to ensure a balanced and diverse range of ages, gender, educational levels, geographic locations, and AD severities, and to confirm that they were currently receiving treatment for AD. Patients participated in a 45-minute, 1 : 1 telephone interview conducted in their native language by the research team. These interviews explored the impact of AD on patients’ lives, patients’ most troublesome symptoms, how patients make treatment decisions and patients’ treatment expectations. Patients were also questioned on their current knowledge of AD scoring systems and what they thought was most important to include in AD scoring systems. A large ethnically diverse global patient population (N = 88; 15 countries) was included in the study. AD was reported to have a substantial, broad impact on patients’ lives, with patients being affected by AD at all times of the day and night. Itch, skin redness, dry/flaky skin and sleep disturbance were the most frequently reported signs and symptoms, with over 75% of patients experiencing them every 1–3 days. The itch was cited by 37% of patients as being the primary reason for changing AD treatments. In addition, the research revealed that mental health issues such as anxiety and depression are common in patients suffering from AD, and these features have the greatest negative impact on patients’ daily lives. Patients reported that AD impairs their quality of life, with many perceiving that clinicians underestimate this burden; this was reported more often for non-specialists compared with dermatologists. Patients also felt they were often not given enough time to express themselves in medical appointments and reported an inability to optimally communicate with their clinicians. Patients had little awareness of AD severity scoring systems, with almost no survey respondents reporting their use during previous healthcare encounters. When questioned about their preferences for different AD scoring systems, patients favoured using a combination of patient-reported outcomes to reflect disease burden and clinician-reported outcomes to ensure consistency across different physicians and patient populations. These preferences indicate that an optimal scoring system would consider a diverse range of symptoms, and the variable nature of AD, and be accessible regardless of education level. No single AD scoring system was preferred by all patients. Patients indicated that they would like AD scoring systems to be incorporated into clinical practice, to help them communicate their AD burden to clinicians, and to provide a clear framework for monitoring treatment response. This global patient study generated insights into the burden of AD on patients’ lives, their expectations of treatment, and their views on AD scoring methods. Results provided an evidence base for the development of patient-centric recommendations for AD management.

Lebrikizumab is an injectable, IgG4 monoclonal antibody that selectively binds to interleukin-13 with high affinity. Injection-site reactions (ISRs) are localized adverse events in the immediate site of administration of a drug and are common with injectable therapies. This analysis reports ISRs in patients from eight lebrikizumab (LEB) clinical trials in atopic dermatitis. To report ISRs in patients with moderate-to-severe atopic dermatitis treated with LEB, from an integrated safety analysis of phase 2 and 3 LEB clinical trials. These data sets include adolescents and adult patients who received at least one dose of LEB from a total of eight atopic dermatitis clinical trials, including four 16-week placebo-controlled clinical trials. Eight trials consist of: ADvocate1, ADvocate2, ADhere, ADore, ADjoin (ongoing), ARBAN, TREBLE and Phase 2b study. Treatment duration ranged from a single dose to 100 weeks. ISRs were defined using the preferred terms from the Medical Dictionary for Regulatory Activities high-level term, injection site reactions, excluding terms related to joints. This analysis includes ISRs frequencies in patients treated with LEB compared to placebo (ALL PC week 0–16), and all patients who received any dose of LEB (ALL LEB), and reports ISRs type, exposure adjusted incidence rates (EAIR) per 100 patient-years, the timing of ISRs occurrence, and ISRs leading to discontinuation. In the ALL PC week 0–16 analysis, 2.6% (n = 20/783, EAIR 9.0) of patients in the LEB group reported ISRs vs. 1.5% (n = 6/404 EAIR 5.4) in the placebo group. Injection site pain (n = 7, 0.9%) and injection site erythema (n = 7, 0.9%) were the most frequent reactions reported in the LEB group. Most ISRs were mild or moderate, with only 1 (0.1%) severe event. In the ALL LEB analysis, 3.1% of patients reported ISRs (n = 53/1720, EAIR 3.3). Injection site pain (n = 16, 0.9%) and injection site erythema (n = 12, 0.7%) were the most frequent reactions. Almost all reports were mild or moderate, with 3 (0.2%) severe. The incidence of ISRs did not increase with a longer duration of LEB exposure. The majority of ISRs were reported between weeks 0 and 16 (n = 38, 2.2%). The frequency of ISRs from week 16 to 32 was 1.0% (n = 15), from week 32 to 48 was 0.4% (n = 4) and from week 48 to 64 was 0.2% (n = 2). Treatment discontinuation due to ISRs occurred in a few patients (n = 5, 0.3%). Overall, a low proportion of patients reported ISRs (

Background and ObjectivePrevious studies of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents, and severe atopic dermatitis in children aged 6 to < 12 years demonstrate no clinically important changes in laboratory parameters. The objective of this study was to assess laboratory outcomes in children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis treated with dupilumab.MethodsIn this randomized, placebo-controlled, phase III trial of dupilumab, 161 children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis were enrolled from 31 sites in Europe and North America and randomized 1:1 to receive subcutaneous placebo or dupilumab (5 kg to < 15 kg: 200 mg; 15 kg to < 30 kg: 300 mg) every 4 weeks plus topical corticosteroids for 16 weeks. Hematology, serum chemistry, and urinalysis assessments were analyzed on blood and urine samples collected at screening and weeks 4 and 16; descriptive statistics are provided.ResultsNo clinically meaningful changes in laboratory parameters were observed. While two cases of eosinophilia and one case each of neutropenia and leukocytosis were reported as treatment-emergent adverse events in the dupilumab plus topical corticosteroids group, these events were not associated with clinical symptoms and did not lead to treatment discontinuation or study withdrawal.ConclusionsThese results suggest that routine laboratory monitoring of children aged 6 months to < 6 years treated with dupilumab plus topical corticosteroids is not required. Limitations of this study include short study duration, and exclusion of patients with abnormalities in laboratory test results at screening.

Previous studies of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents, and severe atopic dermatitis in children aged 6 to12 years demonstrate no clinically important changes in laboratory parameters. The objective of this study was to assess laboratory outcomes in children aged 6 months to 6 years with moderate-to-severe atopic dermatitis treated with dupilumab.In this randomized, placebo-controlled, phase III trial of dupilumab, 161 children aged 6 months to6 years with moderate-to-severe atopic dermatitis were enrolled from 31 sites in Europe and North America and randomized 1:1 to receive subcutaneous placebo or dupilumab (5 kg to 15 kg: 200 mg; 15 kg to 30 kg: 300 mg) every 4 weeks plus topical corticosteroids for 16 weeks. Hematology, serum chemistry, and urinalysis assessments were analyzed on blood and urine samples collected at screening and weeks 4 and 16; descriptive statistics are provided.No clinically meaningful changes in laboratory parameters were observed. While two cases of eosinophilia and one case each of neutropenia and leukocytosis were reported as treatment-emergent adverse events in the dupilumab plus topical corticosteroids group, these events were not associated with clinical symptoms and did not lead to treatment discontinuation or study withdrawal.These results suggest that routine laboratory monitoring of children aged 6 months to 6 years treated with dupilumab plus topical corticosteroids is not required. Limitations of this study include short study duration, and exclusion of patients with abnormalities in laboratory test results at screening.ClinicalTrials.gov: NCT03346434, part B.Atopic dermatitis (AD) is a chronic, inflammatory skin disease that often causes itchy rashes. To reduce persistent AD signs and symptoms, patients may need to take medications that require laboratory monitoring. This can add to treatment burden, especially among infants and children. Dupilumab is a drug that specifically targets key molecules that underlie AD and has been tested in several clinical trials, now in patients 6 months and older. Studies in adults, adolescents, and children as young as 6 years of age with moderate-to-severe AD have shown that dupilumab can be used without the need for regular laboratory tests. In this study, the authors analyzed blood and urine samples collected during a clinical trial of dupilumab in 161 infants and children aged 6 months to 5 years with moderate-to-severe AD. Routine laboratory tests revealed no clinically meaningful changes in patients’ blood and urine following treatment with dupilumab. In general, the laboratory results in these patients were similar to those in adults, adolescents, and children aged 6–11 years treated with dupilumab. Taken together, these findings suggest that dupilumab can be used for the continuous treatment of moderate-to-severe AD without the need for routine laboratory monitoring.

Atopische Dermatitis (AD) ist eine haufige chronisch-entzundliche Krankheit mit rezidivierenden ekzematosen Lasionen und starkem Pruritus. Sie kann erhebliche negative Auswirkungen auf die Betroffenen haben. Zur komplexen Pathophysiologie der AD tragen genetische Pradisposition und umweltbedingte Provokationen wesentlich bei. Mechanistisch konnen diese Einflusse die Storung der epidermalen Barriere, Anomalien des Mikrobioms der Haut und eine in Richtung Typ-2-Immunitat verschobene Immunantwort fordern. Unser zunehmendes Verstandnis der beteiligten immunologischen Prozesse unterstreicht eine Schlusselrolle von Interleukin-13 (IL-13). Diese Ubersicht bewertet Tralokinumab, einen hochaffinen monoklonalen Antikorper, der spezifisch an IL-13 bindet und dieses inhibiert. Basierend auf Ergebnissen einer Dosisfindungsstudie wurde Tralokinumab 300 mg alle zwei Wochen (Q2W) subkutan (SC) in drei relevanten klinischen Phase-III-Studien bei erwachsenen Patienten mit mittelschwerer bis schwerer AD untersucht, die unter alleiniger Behandlung mit topischen Kortikosteroiden unzureichend kontrolliert wurde. Tralokinumab war einem Placebo hinsichtlich des Anteils an Patienten, die IGA 0/1 und EASI-75 in Woche 16 (primare Endpunkte) erreichten, signifikant uberlegen und verbesserte zudem die Werte fur schlimmsten taglichen Pruritus, Dermatology Life Quality Index (DLQI) und Scoring Atopic Dermatitis (SCORAD) (sekundare Endpunkte). Das Ansprechen nach 16 Wochen dauerte wahrend der Nachsorge an. Zudem wurde die Behandlung mit Tralokinumab bei einer dem Placebo vergleichbaren Gesamthaufigkeit und Schwere unerwunschter Ereignisse gut vertragen.

Ratten können Streptobacillus moniliformis übertragen, das Rattenbissfieber (RBF), eine seltene und potenziell letale Zoonose, verursachen kann. Anspruchsvolle Kulturbedingungen und unspezifische Symptome, einschließlich Fieber, Arthralgie und polymorphe Hautläsionen, erschweren die Diagnose. Rattenbissfieber wird durch Exposition gegenüber kontaminierten Körperflüssigkeiten infizierter Nagetiere verursacht; Berichte über Infektionen durch Streptobacillus moniliformis sind bisher jedoch selten. Wir berichten über einen Fall von RBF durch Streptobacillus moniliformis bei einer Patientin, die Umgang mit Ratten hatte. Eine Patientin stellte sich mit schmerzhaften hämorrhagischen Pusteln und lividen Läsionen an Händen und Füßen vor. Sie entwickelte Fieber und eine migratorische Polyarthralgie. In Blutkulturen wuchs Streptobacillus moniliformis. Da die Patientin Ratten besaß und Kontakt mit kontaminiertem Rattenkot und -urin hatte, war dies die wahrscheinlichste Ursache der Infektion. Schwierigkeiten bei der klinischen und mikrobiologischen Diagnose unterstreichen die Notwendigkeit einer gründlichen und vollständigen Erfassung der Anamnese und eines besseren Verständnisses für diese seltene Infektionskrankheit.

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.

In adults with atopic dermatitis (AD), head and/or neck involvement is frequent, bothersome, and impacts quality of life, however, long-term topical corticosteroids (TCS) are contraindicated for this difficult-to-treat region. Baricitinib, an oral, selective, reversible inhibitor of Janus kinase 1/2 has demonstrated efficacy in adult patients with moderate-to-severe AD.For this post hoc analysis, data from five Phase III trials were used to investigate the efficacy of baricitinib in patients with head and neck involvement.Data were obtained from BREEZE-AD1, -AD2, -AD4, -AD5, and -AD7; Phase III, multicenter, randomized, double-blind, placebo-controlled studies conducted in patients ≥18 years with moderate-to-severe AD. BREEZE-AD1, -AD2, and -AD5 evaluated baricitinib as monotherapy, and BREEZE-AD4 and -AD7 evaluated baricitinib in combination with TCS, topical calcineurin inhibitors, or topical PDE-4 inhibitors, where available. The proportion of patients with improvement of Eczema Area and Severity Index (EASI) total score from baseline of ≥50% (EASI50) and ≥75% (EASI75), as well as head/neck EASI50 and EASI75 and erythema head/neck EASI50 and EASI75 response rates were assessed up to Week 16.Across the studies, 93-98% of patients had head/neck involvement at baseline (EASI head/neck score ≥1). Baricitinib was similarly effective based on EASI total score for the entire body in all studies. In the monotherapy studies, the proportion of patients achieving head/neck EASI50 and EASI75 scores was significantly higher for baricitinib 2-mg and 4-mg versus placebo at Weeks 1 and 16.Baricitinib 2-mg and 4-mg treatment showed rapid and substantial reduction in AD head and neck severity, including erythema.

Background Tralokinumab is a fully human monoclonal antibody that neutralizes the activity of interleukin-13, a key pathogenic driver of atopic dermatitis (AD). Clinical trials including adults with moderate-to-severe AD, of up to 52 weeks’ duration, showed tralokinumab was efficacious and well tolerated. Objectives To characterize the safety profile of tralokinumab for the treatment of moderate-to-severe AD. Methods Safety and laboratory measures were assessed in pooled analyses of phase II and III placebo-controlled clinical trials of tralokinumab in moderate-to-severe AD (NCT02347176, NCT03562377, NCT03131648, NCT03160885, NCT03363854). Results In total, 2285 patients were randomized in the initial treatment periods up to 16 weeks (1605 tralokinumab, 680 placebo). The frequencies of any adverse event (AE) were 65·7% for tralokinumab and 67·2% for placebo. The respective rates were 640 and 678 events per 100 patient-years of exposure (ep100PYE); rate ratio 1·0, 95% confidence interval (CI) 0·9–1·1. Serious AEs occurred in 2·1% of patients with tralokinumab and 2·8% with placebo (7·4 and 11·9 ep100PYE; rate ratio 0·7, 95% CI 0·4–1·2). The most common AEs occurring at a higher frequency and rate with tralokinumab vs. placebo were: viral upper respiratory tract infection (15·7% vs. 12·2%; 65·1 vs. 53·5 ep100PYE); upper respiratory tract infection (5·6% vs. 4·8%; 20·8 vs. 18·5 ep100PYE); conjunctivitis (5·4% vs. 1·9%; 21·0 vs. 6·9 ep100PYE); and injection-site reaction (3·5% vs. 0·3%; 22·9 vs. 4·0 ep100PYE). Some events in safety areas of interest occurred at a lower frequency and rate with tralokinumab vs. placebo: skin infections requiring systemic treatment (2·6% vs. 5·5%; 9·7 vs. 22·8 ep100PYE), eczema herpeticum (0·3% vs. 1·5%; 1·2 vs. 5·2 ep100PYE), opportunistic infections (3·4% vs. 4·9%; 13·0 vs. 21·3 ep100PYE) and serious infections (0·4% vs. 1·1%; 1·3 vs. 3·7 ep100PYE). AEs did not increase with continued maintenance and open-label treatment, including rates of common or serious AEs and AEs leading to study drug discontinuation. No clinically meaningful changes in mean laboratory measures were observed with treatment up to 1 year. Conclusions Across the AD population pool from five clinical trials, tralokinumab was well tolerated, with consistent safety findings during treatment of patients with moderate-to-severe AD. The safety profile during prolonged tralokinumab treatment was consistent with that during the initial treatment period; the frequency of events did not increase over time. What is already known about this topic? Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13, a key cytokine driving skin inflammation and epidermal barrier dysfunction in atopic dermatitis (AD).In clinical trials in moderate-to-severe AD, tralokinumab provided significant and early improvements in the extent and severity of AD and was well tolerated, with an overall safety profile comparable with placebo over 52 weeks. What does this study add? We report the frequency and rate of adverse events (AEs) from pooled observations of over 2000 patients from five phase II and phase III placebo-controlled clinical trials of tralokinumab in moderate-to-severe AD.During initial treatment up to 16 weeks, the frequencies of any AE and of serious AEs were similar for tralokinumab and placebo. AE rates did not increase with continued treatment up to 52 weeks.Common AEs occurring more frequently with tralokinumab vs. placebo were viral and upper respiratory tract infection, conjunctivitis and injection-site reaction. Some events occurred at a lower frequency and rate with tralokinumab vs. placebo, such as skin infections requiring systemic treatment, eczema herpeticum and opportunistic and serious infections.No clinically meaningful changes in mean laboratory measures were observed.

Rats can transmit Streptobacillus moniliformis, which may cause rat-bite fever (RBF), a rare and potentially lethal zoonosis. Fastidious in vitro growth and unspecific symptoms, including fever, arthralgia, and polymorphous skin lesions, complicate the diagnosis. Rat-bite fever follows exposure to contaminated bodily fluids of infected rodents; however, reports on Streptobacillus moniliformis-related infections are few so far. A female patient presented with painful hemorrhagic pustules and purpuric lesions on hands and feet. She developed fever and migratory polyarthralgia. Blood culture yielded growth with Streptobacillus moniliformis. The patient owned rats and handled contaminated rat feces and urine, making this the most likely etiology of infection. We report a case of RBF due to Streptobacillus moniliformis in a rat handling-patient. Difficulties in clinical and microbiological diagnosis highlight the need for a thorough and complete history-taking and a greater understanding of this rare infectious disease.