Atopic Dermatitis Clinical Trials Research Articles

Indigenous Underrepresentation in American and Canadian Atopic Dermatitis Clinical Trials: A 10-year Cross-Sectional Analysis.

Indigenous Underrepresentation in American and Canadian Atopic Dermatitis Clinical Trials: A 10-year Cross-Sectional Analysis.

Stability of Long-Term Therapeutic Responses to Tralokinumab in Adults with Moderate-to-Severe Atopic Dermatitis

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

Capturing patient-reported sleep disturbance in atopic dermatitis clinical trials

BackgroundPatient-focused approaches to capturing day-to-day variability in sleep disturbance are needed to properly evaluate the sleep benefits of new treatments. Such approaches rely on patient-reported outcome (PRO) measures validated in the target patient population.MethodsUsing atopic dermatitis (AD) as an example of a disease in which sleep is commonly disturbed, we developed a strategy for measuring sleep disturbance in AD trials. In developing this strategy, we conducted a targeted literature review and held concept elicitation interviews with adolescents and adults with AD. We subsequently identified potentially suitable PRO measures and cognitively debriefed them. Finally, we evaluated their psychometric properties using data from phase 2b (NCT03100344) and phase 3 (NCT03985943 and NCT03989349) clinical trials.ResultsThe literature review confirmed that sleep disturbance is a key impact of AD but failed to identify validated PRO measures for assessing fluctuations in sleep disturbance. Subsequent concept elicitation interviews confirmed the multidimensional nature of sleep disturbance in AD and supported use of a single-item measure to assess overall sleep disturbance severity, complemented by a diary to capture individual components of sleep disturbance. The single-item sleep disturbance numerical rating scale (SD NRS) and multi-item Subject Sleep Diary (SSD)—an AD-adapted version of the Consensus Sleep Diary—were identified as potentially suitable PRO measures. Cognitive debriefing of the SD NRS and SSD demonstrated their content validity and their understandability to patients. Psychometric analyses based on AD trial data showed that the SD NRS is a well-defined, reliable, and fit-for-purpose measure of sleep disturbance in adults with AD. Furthermore, the SD NRS correlated with many SSD sleep parameters, suggesting that most concepts from the SSD can be covered using the SD NRS.ConclusionsUsing these findings, we developed an approach for measuring sleep disturbance in AD trials. Subject to further research, the same approach could also be applied to future trials of other skin diseases where itch causes sleep disturbance.

506 Examining Participant Representation in Atopic Dermatitis Clinical Trials from 2011-2022

OBJECTIVES/GOALS: This study seeks to comprehensively evaluate the extent to which participants in clinical trials (CT) for Atopic Dermatitis (AD) accurately mirror the demographics and characteristics of the broader AD-affected populations. We will achieve this objective by analyzing data from AD CTs spanning the years 2011 to 2022. METHODS/STUDY POPULATION: We examined completed trials for 10 FDA approved treatments for AD, utilizing data sourced fromclinicaltrials.gov [http://clinicaltrials.gov]. In light of the increased number of AD clinical trials over the past decade, we tailored our search parameters to encampass all trials related to approved treatments from 2011-2022. To assess the characteristics of the participant population in these trials, information including inclusion and exclusion criteria, age, location, sex, and disease severity were collected for each trial. Furthermore, race and ethnicity data were also extracted and analyzed. Additionally, comparisons were drawn between trials completed before and after April 2017, when the FDA began requiring that researchers publish race and ethnicity data toclinicaltrials.gov [http://clinicaltrials.gov]. RESULTS/ANTICIPATED RESULTS: Across 67 CTs examined, 45% of trials were restricted to adult patients, 28% were restricted to pediatric patients, and 27% included both. 77% of CTs occurred in urban settings and 23% occurred in rural settings according to the The Economic Research Service definition. 36% of CTs included mild-to-moderate AD patients, and 64% of CTs included moderate-to-severe AD patients. Race distribution of CTs revealed 67% White, 14% Black/African American, 16% Asian, and 3% others. 13% of participants identified as Hispanic or Latino. With further analysis, we will determine whether there is a difference in ethnic distribution between trials completed before and after April 2017, when the FDA started requiring race/ethnicity data to be submitted. DISCUSSION/SIGNIFICANCE: The findings highlight a significant concern in AD CTs: the insufficient representation of Black and Asian populations. The findings emphasize the need for a more inclusive selection process that accurately reflects the diversity of patients. Failing to do so could undermine the assessment of treatment effectiveness in such populations.

A quantitative systems pharmacology workflow toward optimal design and biomarker stratification of atopic dermatitis clinical trials

BackgroundThe development of atopic dermatitis (AD) drugs is confronted by many disease phenotypes and trial design options, which are hard to explore experimentally. ObjectiveOptimize AD trial design using simulations. MethodsWe constructed a quantitative systems pharmacology (QSP) model of AD and standard of care (SoC) treatments and generated a phenotypically diverse virtual population whose parameter distribution is a) derived from known relationships between AD biomarkers and disease severity and b) calibrated using disease severity evolution under SoC regimens. ResultsWe applied this workflow to the immunomodulator OM-85, currently being investigated for its potential use in AD, and calibrated investigational treatment model with the efficacy profile of an existing trial (thereby enriching it with plausible marker levels and dynamics). We assessed the sensitivity of trial outcomes to trial protocol and found that for this particular example, a) the choice of endpoint is more important than the choice of dosing-regimen and b) patient selection by model-based responder enrichment could increase the expected effect size. A global sensitivity analysis revealed that only a limited subset of baseline biomarkers is needed to predict the drug response of the full virtual population. ConclusionThis AD QSP workflow built around knowledge of marker-severity relationships as well as SoC efficacy can be tailored to specific development cases so as to optimize several trial protocol parameters and biomarker-stratification and therefore holds promise to become a powerful model-informed AD drug development and personalized medicine tool.

A Mini Review of the Impact of Baseline Disease Severity on Clinical Outcomes: Should We Compare Atopic Dermatitis Clinical Trials?

Based on clinical trials of systemic treatments in adults with moderate-to-severe atopic dermatitis (AD) reported between 2014 and 2023, we used linear regression to investigate relationships between baseline Eczema Area and Severity Index (EASI) scores and (1) study start date, (2) EASI response, and (3) rescue medication rates. Analysis 1 was conducted with all patients from monotherapy and combination therapy trials; analyses 2 and 3 used monotherapy trial placebo arms. Across 32 trials with a baseline inclusion criterion of EASI ≥ 16, baseline mean EASI scores decreased with study start date. The lowest and highest baseline mean EASI scores were 25.1 and 33.6 (median 21.1 and 30.5), reported for the WW001 Phase 2 trial of rademikibart (formerly CBP-201; start date, July 2020) and the SOLO1 Phase 3 trial of dupilumab (start date, December 2014), respectively. In placebo arms, lower baseline EASI scores tended to be associated with greater percent reductions in EASI scores at Week 16 and less rescue medication usage. The WW001 trial placebo arm had the lowest baseline EASI score (mean 25.2; median 22.1), lowest rescue medication rate (14.3%), and a large reduction in least squares mean EASI scores (- 39.7%) at Week 16. In summary, baseline mean EASI scores have decreased across clinical trials conducted during the last decade. Less severe AD at baseline tended to be associated with greater placebo response and less use of rescue medications in placebo arms. Intertrial differences in variables, such as baseline AD severity, limit the validity of indirectly comparing clinical trials.

373 Safety of lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis: data from eight trials

Abstract Lebrikizumab (LEB) is a monoclonal antibody that binds with high affinity to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. To report integrated safety information in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with LEB, from an integrated safety analysis of eight clinical Phase 2 and 3 trials. These data include adult and adolescent patients who received at least one dose of study drug from a total of eight atopic dermatitis clinical trials: ADvocate1, ADvocate2, ADhere, ADore, ADjoin (ongoing), ARBAN, TREBLE and a Phase 2b study. Treatment duration ranged from a single dose to 100 weeks. This analysis includes all placebo-controlled Week 0- to 16-safety data in patients treated with LEB 250 mg every 2 weeks (LEBQ2W, n = 783) compared with placebo (n = 404) known as ALL PC Weeks 0–16, and all patients who received at least one dose of LEB (n = 1720) known as ALL LEB. Conjunctivitis cluster is defined by MedDRA-preferred terms of conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis and giant papillary conjunctivitis. Exposure adjusted incidence rates (IR) are provided as per 100 patient-years. In ALL PC Weeks 0–16 analysis, the frequency of treatment-emergent adverse events (TEAE) was 49.2% in LEBQ2W (n = 384) compared with 53.1% in placebo (n = 215). The majority of TEAEs reported were mild or moderate in severity with 2.3% (n = 18) reported as severe in LEBQ2W and 4.4% (n = 18) in placebo. Serious adverse events (SAEs) were reported by 1.3% (n = 10) in LEBQ2W and 1.9% (n = 8) in placebo. No deaths reported in LEBQ2W and one death in placebo. The most frequently reported TEAE in LEBQ2W was conjunctivitis and in placebo was atopic dermatitis. Conjunctivitis cluster was reported by 8.5% (n = 67) in LEBQ2W and 2.5% (n = 10) in placebo. All conjunctivitis cluster events were mild or moderate. Injection site reactions (ISRs) were reported by 2.6% (n = 20) in LEBQ2W and 1.5% (n = 6) in placebo. Adverse events leading to discontinuation were reported by 2.3% (n = 18) in LEBQ2W and 1.4% (n = 6) in placebo. In ALL LEB, the frequency of TEAEs was 64.3% (n = 1106, IR: 137.9), with the majority being mild or moderate in severity. Severe TEAEs were reported by 5.3% (n = 91). The incidence rates of TEAE did not increase with duration of treatment exposure. The SAEs were reported by 3.3% (n = 56, IR: 3.5). Three (0.2%) deaths occurred in ALL LEB. Conjunctivitis cluster was reported by 10.6% (n = 183, IR:12.2) with the majority being mild or moderate in severity and 0.3% (n = 6) being reported as severe. The ISRs were reported by 3.1% (n = 53, IR: 3.3). Adverse events leading to discontinuation were reported by 4.2% (n = 73, IR: 4.5). The overall safety profile for lebrikizumab consisted of AEs that were mostly nonserious, mild or moderate in severity, and did not lead to treatment discontinuation. Safety profile was similar in both adults and adolescents.

Ethnicity, Race and Skin Color: Challenges and Opportunities for Atopic Dermatitis Clinical Trials.

The number of clinical trials conducted in patients with atopic dermatitis is increasing steadily. These trials are conducted in several countries across all continents and include patients of different ethnicity, race and skin color. This diversity is desired, but it also brings challenges, including the diagnosis and evaluation of disease severity in patients with different skin colors; the influence of ethnicity on the perception of quality of life and patient reported outcomes; the inclusion of ethnicities that are only present in one country or that live far from clinical research sites; and the reporting of drug safety information. There is a need to better train physicians on the evaluation of atopic dermatitis in patients with different skin colors and a need to improve the systematic reporting of ethnicity, race and skin color in clinical trial publications.

Estimands for atopic dermatitis clinical trials: Expert opinion on the importance of intercurrent events.

Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.

314 Injection site reactions from an integrated analysis of phase 2 and phase 3 clinical trials of lebrikizumab treatment in moderate-to-severe atopic dermatitis

Abstract 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 (<3%) with a numerically higher frequency of LEB-treated patients who reported ISRs compared to placebo (1.5%). Most events were mild or moderate in severity, did not lead to treatment discontinuation, occurred within the first 16 weeks of treatment, and ISRs incidence did not increase with a longer duration of exposure.

Subjective Evaluation Using Patient-Oriented Eczema Measure of the Clinical Effects of 1-Kestose on Atopic Dermatitis in Children: A Pilot Study

Several objective evaluation methods are used to evaluate treatment outcomes in atopic dermatitis clinical trials. We previously demonstrated the clinical efficacy of 1-kestose, the smallest fructooligosaccharide, in the treatment of atopic dermatitis in infants using an objective evaluation method. The utility of the Patient-Oriented Eczema Measure, in which patients themselves or their guardians evaluate the pathophysiology of atopic dermatitis, has recently been reported. In the present study, we used the Patient-Oriented Eczema Measure to confirm the efficiency of the clinical effect of 1-kestose on pediatric atopic dermatitis. An open pilot study was conducted on 22 children with atopic dermatitis. Subjects were orally administered 2 g of 1-kestose daily for 12 weeks and the symptoms of atopic dermatitis were evaluated using the Patient-Oriented Eczema Measure. The median total score of the Patient-Oriented Eczema Measure was significantly decreased by the 1-kestose treatment from 14.2 to 7.7 (P < 0.001). There was no correlation between decreases in the total score of the Patient-Oriented Eczema Measure and the age of subjects. Although the present study was a small pilot study, results suggest that 1-kestose may have attenuated atopic dermatitis to a degree that the patients themselves could recognize.

A cross-sectional study of ethnic and racial disparities in pediatric atopic dermatitis clinical trials

To the Editor: Atopic dermatitis is a chronic, relapsing inflammatory skin condition affecting approximately 0.2% to 24.6% of children globally.1 Racial and ethnic differences exist in the epidemiology of atopic dermatitis with the prevalence of eczema 15.9% and 15.0% among Black and multirace children, respectively, versus 9.7% in White children.2 However, clinical trials continue to have an underrepresentation of non-White races and ethnicities.3

25942 Dupilumab-associated facial dermatitis: A case series

Recent publications have described the development of an eczematous facial rash after initiation of dupilumab, though this adverse reaction had not described in the original dupilumab atopic dermatitis clinical trials. The pathogenesis is unknown, but has been postulated to be a hypersensitivity reaction to dupilumab, an uncovered allergic contact dermatitis, rosacea, a seborrheic-like dermatitis reaction, or a treatment site–specific failure. The management of facial dermatitis after dupilumab is challenging and reports of an array of topical and systemic medications as well as clinical testing have been pursued.

Baricitinib: therapeutic potential for moderate to severe atopic dermatitis

ABSTRACT Introduction Atopic dermatitis (AD) is a chronic inflammatory skin disease mediated by multiple signals including janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Current therapeutic armamentarium consists of a limited number of drugs which may result in the insufficient management of AD. Preclinical evidence regarding inhibition of JAK/STAT led to the development of a promising class of therapeutics, namely, JAK inhibitors. Baricitinib, a novel JAK1/JAK2 inhibitor is currently under investigation in AD clinical trials. Areas covered This review offers an overview of Baricitinib and examines clinical efficacy and safety data in patients with moderate-to-severe AD. Expert opinion Baricitinib showed promising preliminary data in terms of efficacy in phase II and III trials, with a very rapid onset of response and great improvements of itch and sleep disturbances. These aforementioned aspects combined with the advantage of an oral formulation have reduced drug production costs compared to biologic agents and could lead to consideration of baricitinib as a first line systemic treatment. Also, in some countries, it could be a therapeutic option in the case of contraindication or failure of conventional systemic drugs prior to biologic therapies. Data related to long-term safety and efficacy will be important to refine the place-in-therapy of this drug.

The Patient-Oriented Eczema Measure: estimating the minimal important change in an outpatient clinic cohort.

Patient-Oriented Eczema Measure (POEM) measures patient-reported symptoms in atopic dermatitis (AD). It is the recommended core outcome instrument to capture the symptoms domain in AD clinical trials. Understanding the minimal important change (MIC) in the POEM score is therefore important in both trial and clinical care settings. Previous studies have mainly evaluated MIC estimates among children in trial settings. The MIC estimate for POEM in a clinical setting is often lacking. We aim to estimate the MIC of the POEM using both distribution-based and anchor-based methods in a clinical cohort of adult eczema patients. Both distribution-based and anchor-based methods were used to calculate the MIC of the POEM in a clinical cohort of Asian adult patients attending the eczema clinic at a tertiary dermatology centre in Singapore. Scoring AD (SCORAD) was used as the disease severity anchor for the anchor-based methods. The smallest detectable change (SDC) for POEM was also calculated as the threshold for any measurement error. There were a total of 85 adult AD patients in the cohort that contributed a total of 114 paired measurements of both POEM and SCORAD. The SDC in our study was 1.68. The MIC estimates were 3.64 and 1.46 based on 0.5 standard deviation (SD) and 0.2 SD distribution-based methods. Anchor-based methods such as the receiver operating curve and predictive modelling methods yielded MIC values of 0.50 and 1.05, respectively. Minimal important change for POEM varied according to the methods and approaches used. Only a change of two points or more in POEM could be considered beyond any measurement errors and clinically important. This finding is consistent even in a clinical setting of Asian adults with eczema.

Long-Term Safety Follow-Up Study of SCM-AGH in Subjects Who Participated and Administered SCM-AGH in to Severe Atopic Dermatitis Clinical Trials

Long-Term Safety Follow-Up Study of SCM-AGH in Subjects Who Participated and Administered SCM-AGH in to Severe Atopic Dermatitis Clinical Trials

Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy - international eczema council survey and opinion.

BackgroundConjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab.ObjectiveTo survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC).MethodsElectronic survey and in‐person discussion of management strategies.ResultsForty‐six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new‐onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist.LimitationsThe study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey.ConclusionThe IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

Validation of a novel smartphone application-enabled, patient-operated skin barrier device.

Transepidermal water loss (TEWL) and surface capacitance measure skin barrier permeability and stratum corneum (SC) hydration, respectively, and are frequently utilized in atopic dermatitis clinical trials. Many barrier devices are costly and often used only in the academic setting. GPSkin is a low-cost, patient-operated device that measures both TEWL and SC hydration. This study aimed to test the reliability of GPSkin and assess its correlation with current industry standards. GPSkin was compared to the Biox AquaFlux (TEWL) and Courage-Khazaka Corneometer (SC hydration). Participants with healthy skin (n=50) collected measurements with GPSkin in Trial 1 without any device education and in Trial 2 with additional instruction. In Trial 2, the investigator also performed measurements with GPSkin. Spearman's coefficients (rs ) were performed to assess device correlation. Intraclass correlation coefficients (ICC) were calculated to determine reliability. Overall, GPSkin was moderately correlated with current industry device measurements for TEWL (Trial 1 rs :0.48; Trial 2 rs :0.40 participant, 0.34 investigator) and SC hydration (Trial 1 rs :0.63; Trial 2 rs :0.45). GPSkin demonstrated "good" test-retest reliability for both TEWL (ICC: 0.89) and SC hydration (ICC: 0.85) measurements when participants were provided with some device education. There was no difference in reliability between participants provided with device education and investigators. Based on these findings, we concluded that GPSkin provides reasonably precise and reliable measurements of SC hydration and TEWL as compared to current devices.

Optimization of placebo use in clinical trials with systemic treatments for atopic dermatitis: an International Eczema Council survey-based position statement.

BackgroundAs novel systemic therapeutics for patients with atopic dermatitis (AD) are developed, ethical and methodological concerns regarding placebo‐controlled‐trials (PCT) have surfaced.ObjectiveTo guide the design and implementation of PCT in AD, focusing on trials with systemic medications.MethodsA subgroup of the International Eczema Council (IEC) developed a consensus e‐survey, which was disseminated to IEC members.ResultsThe response rate was 43/82 (52%). Consensus was reached on 24/27 statements and on 3/11 options from multiple‐selection statements, including: performing monotherapy studies in proof‐of‐concept phases; avoiding concomitant topical corticosteroids or calcineurin inhibitors until a predefined timepoint as rescue (borderline consensus); selection of sites and assessors with recognized expertise in AD clinical trials; clear definition and identification of baseline disease severity; minimizing time and proportion of patients on placebo; using daily emollients with several options provided; instigating open‐label extension studies for enrolment after a predefined timepoint; and including outcomes which set a higher bar for disease clearance.ConclusionConducting PCT in AD requires balancing several, sometimes opposing principles, including ethics, methodology, regulatory requirements and real‐world needs. This paper can provide a framework for conducting PCT with systemic medications for patients with AD.

Severity assessments used for inclusion criteria and baseline severity evaluation in atopic dermatitis clinical trials: a systematic review.

Numerous inclusion criteria and baseline severity assessments are used in clinical trials of atopic dermatitis (AD), which may limit comparison of results. We sought to characterize the inclusion criteria and baseline severity assessments used in randomized controlled trials (RCT) of AD internationally. We performed a systematic review of RCT with a pharmacological intervention from 2007 to 2016. Cochrane Library, EMBASE, GREAT, LILACS, MEDLINE and Scopus were searched. Two authors independently performed study selection and data extraction. Overall, 212 RCT met inclusion/exclusion criteria. Target population and inclusion criteria based on AD severity were not documented in 78 (36.8%) and 25 (18.7%) studies, respectively. Thirty and 58 severity assessments were used for inclusion criteria and baseline severity, respectively, with only 60.3% concordance between their uses. Global assessments were most frequently used for both inclusion criteria and baseline severity assessment in North America (39.5% and 32.1%), while SCORing AD (SCORAD) or objective-SCORAD index was most frequently used in Europe (23.5% and 23.0%) and Asia (34.2% and 43.5%). Minimum and maximum thresholds of severity assessments were inconsistently used between studies for inclusion criteria, even within similar target populations. SCORAD, global assessments and body surface area were most frequently used for both inclusion criteria and baseline severity assessment. IGA was particularly used in trials of topical agents. There were considerable variability and poor documentation of inclusion criteria and baseline severity assessments in RCT for AD. These differences may limit interpretation of a study and comparison of results between studies.