Worst Itch Research Articles

Efficacy of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis of KALM-1 and KALM-2 Phase 3 Studies

Rationale & ObjectiveChronic kidney disease–associated pruritus (CKD-aP) in patients treated by hemodialysis (HD) impairs quality of life (QoL). Difelikefalin, a selective κ-opioid receptor agonist, decreased the intensity of CKD-aP in patients undergoing HD. This pooled analysis evaluated difelikefalin’s efficacy and the itch-related QoL overall and in subgroups defined by demographics or disease characteristics.Study DesignIn KALM-1 and KALM-2, participants were randomized (1:1) to receive intravenous difelikefalin or placebo 3 times/wk for 12 weeks, followed by a 52-week open-label extension.Setting & ParticipantsAdults with moderate to severe CKD-aP treated by HD in North America, Europe, and the Asia-Pacific region.InterventionIntravenous difelikefalin at 0.5 mcg/kg or placebo.OutcomesItch intensity (Worst Itching Intensity Numerical Rating Scale [WI-NRS]) and itch-related QoL (Skindex-10 and 5-D Itch questionnaires).Results851 participants were randomized (difelikefalin, n = 426; placebo, n = 425). This pooled analysis demonstrated early (week 1), sustained difelikefalin efficacy, with significantly greater achievement of ≥3-point WI-NRS reduction with difelikefalin (51.1%) versus placebo (35.2%; P < 0.001). Achievement of a ≥4-point WI-NRS reduction was significantly greater with difelikefalin (38.7%) versus placebo (23.4%; P < 0.001). Difelikefalin reduced itch intensity in subgroups based on age, sex, anti-itch medication use, the presence of specific medical conditions, and gabapentin or pregabalin use. More participants receiving difelikefalin versus placebo achieved clinically meaningful decreases of ≥15 points on the Skindex-10 scale (55.5% vs 40.5%, respectively; P < 0.001) and ≥5 points on the 5-D Itch scale (52.1% vs 42.3%, respectively; P = 0.01), with sustained 5-D Itch effects up to 64 weeks.LimitationsSubgroup samples were small. The WI-NRS, Skindex-10, and 5-D Itch are not used in routine clinical care of dialysis patients; therefore, findings may not reflect the real-world effectiveness of difelikefalin.ConclusionsDifelikefalin demonstrated rapid, sustained efficacy, with consistent results in diverse populations of patients treated by HD.FundingCara Therapeutics, Inc.Trial RegistrationThe KALM-1 trial is registered as NCT03422653 and the KALM-2 trial is registered as NCT03636269.

Efficacy and Safety of Difelikefalin in Japanese Patients With Moderate to Severe Pruritus Receiving Hemodialysis

Patients with pruritus receiving hemodialysis frequently experience oppressive physical and psychiatric symptoms that directly affect their quality of life and increase mortality. However, treatment options are limited. To determine the clinically recommended dose of difelikefalin, a κ-opioid receptor agonist, based on the efficacy, dose response, safety, and pharmacokinetics. This randomized, double-blind, placebo-controlled, 4-arm phase 2 trial was conducted from February 1, 2019, to October 22, 2019, at 94 sites in Japan. Patients with moderate to severe pruritus receiving hemodialysis were enrolled. Difelikefalin (0.25, 0.5, and 1.0 μg/kg) and placebo were intravenously administered 3 times a week at the end of each hemodialysis session for 8 weeks. The primary end point was the change from baseline in the weekly mean Worst Itching Intensity Numerical Rating Scale (NRS) score at week 8. Secondary outcomes measured changes in itch-related quality-of-life score using the Skindex-16 and 5-D itch scale. Safety was assessed according to adverse events, laboratory tests, vital signs, body weight, and 12-lead electrocardiogram. A total of 247 Japanese patients (186 male [75%]; mean [SD] age, 64.5 [11.7] years) were randomized to placebo (n = 63), 0.25 μg/kg of difelikefalin (n = 61), 0.5 μg/kg of difelikefalin (n = 61), or 1.0 μg/kg of difelikefalin (n = 62). The changes from baseline in the adjusted mean (SE) of the 24-hour Worst Itching Intensity NRS score at week 8 were -2.86 (0.29) in the placebo group, -2.97 (0.29) in the 0.25 μg/kg of difelikefalin group, -3.65 (0.30) in the 0.5 μg/kg of difelikefalin group, and -3.64 (0.30) in the 1.0 μg/kg of difelikefalin group. Significant differences were found in the 0.5 μg/kg of difelikefalin group (adjusted mean difference, -0.80; 95% CI, -1.55 to -0.04; P = .04) and the 1.0 μg/kg of difelikefalin group (adjusted mean difference, -0.78; 95% CI, -1.54 to -0.03; P = .04) compared with placebo. The Skindex-16 overall score and 5-D itch scale total score indicated an improvement with treatment with 0.5 and 1.0 μg/kg of difelikefalin (adjusted weekly mean [SE] Skindex-16 overall score at week 8, -27.79 [2.05]; 95% CI, -31.83 to -23.74 for 0.5 μg/kg of difelikefalin and -22.69 [2.04]; 95% CI, -26.71 to -18.68 for 1.0 μg/kg of difelikefalin; adjusted weekly mean [SE] 5-D itch scale total score at week 8, -6.5 [0.4]; 95% CI, -7.2 to -5.8 for 0.5 μg/kg of difelikefalin and -6.8 [0.3]; 95% CI, -7.5 to -6.2 for 1.0 μg/kg of difelikefalin). The incidence of adverse events was 67% (42 of 63 patients) in the placebo group, 72% (44 of 61 patients) in the 0.25 μg/kg of difelikefalin group, 77% (47 of 61 patients) in the 0.5 μg/kg of difelikefalin group, and 85% (53 of 62 patients) in the 1.0 μg/kg of difelikefalin group. No dependency was reported. The findings of this phase 2 randomized clinical trial of difelikefalin suggest that 0.5 μg/kg of difelikefalin should be the clinically recommended dose as a new option for treating moderate to severe pruritus in patients undergoing hemodialysis because of its efficacy, acceptable tolerability, and manageable safety profile. ClinicalTrials.gov Identifier: NCT03802617.

POS-601 IMPROVEMENT IN SLEEP QUALITY FROM REDUCTION OF ITCH INTENSITY IN PATIENTS WITH MODERATE-TO-SEVERE PRURITUS UNDERGOING HEMODIALYSIS

Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in patients with CKD undergoing hemodialysis (HD). Night-time pruritus may be a particularly burdensome symptom: In CKD-aP patients this results in poor sleep quality, an important marker of worse health-related quality of life (QoL). In phase 3 trials in patients with moderate-to-severe CKD-aP, difelikefalin (a peripherally restricted kappa-opioid receptor agonist), demonstrated significant improvements in itch intensity versus placebo at week 12, and improvements in sleep quality and itch-related QoL. The aim of the study was to evaluate the impact of reduced itch intensity on sleep quality among HD patients treated with difelikefalin or placebo in the KALM-1 and KALM-2 Phase 3 clinical trials. This post-hoc analysis used pooled data for all patients. Improvement from baseline to week 12 in itch intensity was evaluated by weekly mean of the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS) score (range 0 [no itch] to 10 [worst itch imaginable]). Change in sleep quality was assessed by the 5-D Itch scale sleep disability question (1 [never affects sleep] to 5 [delays falling asleep and frequently wakes me up at night]). Spearman’s correlation analysis was performed. Patients with a clinically meaningful (≥3-point) reduction in WI-NRS score had significantly greater improvements in mean 5-D Itch sleep disability question score (−1.5 vs −0.6 for <3-point WI-NRS score reduction; p<0.0001) from baseline to week 12 (n=709) (Figure ). A moderate correlation was observed between WI-NRS and 5-D Itch sleep disability question scores at week 12 (r =0.499, 95% confidence interval 0.442, 0.552). A significant improvement was also observed at the first assessment of sleep quality (4 weeks) for patients with a ≥3-point (vs <3-point) reduction in WI-NRS score (−1.2 vs −0.4, p<0.0001, n=761). Reduction of itch intensity correlates with improvement in sleep quality in HD patients.

Onset of Symptom Relief Reported in Daily Diaries of Patients With Atopic Dermatitis Treated With Baricitinib in a United States Clinical Trial (BREEZE-AD5)

Itch and sleep disturbance due to itch are burdensome symptoms associated with atopic dermatitis (AD). Rapid onset of action is important for AD treatments to improve quality of life and relieve suffering. This subanalysis evaluated how quickly baricitinib 1-mg and 2-mg reduced itch and associated sleep disturbance during the first 7 days after treatment initiation in a phase 3, double-blind, placebo-controlled trial. Adult patients with AD were randomized 1:1:1 to placebo (N = 147), baricitinib 1 mg (N = 147) or baricitinib 2 mg (N = 146). Patients kept daily diaries, completing the Itch Numeric Rating Scale (NRS) (itch severity from 0 = no itch to 10 = worst itch imaginable) and the Atopic Dermatitis Sleep Scale (ADSS) to measure sleep disturbance (number of nighttime awakenings because of itch). Mixed model repeated measures analysis was used to analyze change from day 1 to day 7 values. Patients receiving either dose of baricitinib had a 9.9% decrease in itch NRS scores from baseline to Day 2 vs 1.5% decrease for placebo (significant between-group least squares mean [LSM] difference: 8.3; 95% CI -12.66 to -3.89; P = .0002). Baricitinib 2 mg reduced nighttime awakenings due to itch (ADSS item 2) at day 2 by 25.2% vs 3.9% in the placebo group (between-group LSM difference: -21.4, P = .0025). Baricitinib 2 mg continued to demonstrate a statistically significant difference from placebo in sleep symptoms at day 7 (LSM difference -23.9; P = .001). Baricitinib 2-mg provided relief from itching and sleep disturbance in patients with AD, beginning the day after taking first dose.Clinical trials at www.clinicaltrials.gov: BREEZE-AD5 (NCT03435081).

Disease characteristics, comorbidities, treatment patterns and quality of life impact in children

Disease characteristics, comorbidities, treatment patterns and quality of life impact in children <12 years old with atopic dermatitis: Interim results from the PEDISTAD Real-World Registry

Validation of the 5-D Itch Scale in Three Ethnic Groups and Exploring Optimal Cutoff Values Using the Itch Numerical Rating Scale.

Background Chronic pruritus is a common and distressing condition that has serious emotional and psychosocial consequences. Due to its subjective nature, self-report questionnaires are widely implemented as cost-effective measures to gauge the severity of chronic pruritus. The current study is aimed at validating the 5-D itch scale in three ethnic groups—Black, Asian, and Hispanic—with the well-validated Itch Numerical Rating Scale (NRS) and Worst Itch NRS (WI-NRS) and developing its cutoff value using receiver operating characteristics (ROC) and inspection of the area under the curve (AUC) across ethnic groups. At the same time, it is aimed at comparing the concurrent prevalence of itch and depression in these populations, who often form ethnic minorities in many countries. The current study addresses the knowledge gap of cultural adaptation of the 5-D pruritus scale for greater usage. Methods Community samples of three ethnic groups were recruited from an online platform of Qualtrics and administered the self-report questionnaires of Itch-NRS, 5-D itch scale, and Patient Health Questionnaire-9 (PHQ-9) to measure their pruritus domains, itch intensity, depression screening, and its severity. Informed consent was obtained from all participants. Subgroup analysis was conducted, including concurrent validity and cutoff values compared between each ethnic group. Concurrent prevalence of itch and depression was evaluated using the cutoff value of Itch-NRS and PHQ-9. Result A total of 2323 participants were included in the study. A significant positive correlation (p < 0.001) was found between the Itch-NRS, WI-NRS, and 5-D itch scale. The cutoff value of the 5-D itch scale was established for the three ethnic groups using ROC, with a cutoff value of Itch-NRS as a reference. Conclusions The 5-D itch scale has demonstrated sound psychometric properties in three ethnic groups and is closely related to Itch-NRS. The analysis of the cutoff value of the 5-D itch scale suggests that different cutoff values should be considered to reduce the inflation of pruritus severity.

Psychometric validation and meaningful change thresholds of the Worst Itching Intensity Numerical Rating Scale for assessing itch in patients with chronic kidney disease-associated pruritus

BackgroundChronic kidney disease-associated pruritus (CKD-aP) is characterized by persistent itch that often leads to substantially impaired quality of life. The Worst Itching Intensity Numerical Rating Scale (WI-NRS) is a single-item patient-reported outcome measure in which patients indicate the intensity of the worst itching they experienced over the past 24 h. Here, we evaluated the content validity and psychometric properties of the WI-NRS and confirmed the threshold of meaningful change in hemodialysis patients with moderate-to-severe CKD-aP.MethodsContent validity interviews were conducted in 23 patients. Psychometric properties of the WI-NRS were assessed using data from one phase 2 (N = 174) and two phase 3 (N = 848) clinical trials investigating an anti-pruritic treatment. Anchor-based methods were used to confirm meaningful within-patient change score thresholds in the phase 3 trial patients and mixed-method exit interviews (N = 70) contributed further insight.ResultsContent validity interviews indicated patients considered the WI-NRS to be straightforward, comprehensive, and relevant. Test–retest reliability was strong in both trial cohorts (intraclass correlation coefficients > 0.75). Construct validity analyses indicated high correlation between the WI-NRS and other measures of itch. Anchor-based analyses showed a reduction of ≥ 3 points from baseline score represented an appropriate clinically meaningful within-patient change on the WI-NRS. In the exit interviews, all patients with a reduction ≥ 3 points considered the change meaningful.ConclusionsThe WI-NRS is a reliable, valid, and responsive measure of itch intensity for patients with moderate-to-severe CKD-aP. These results support its use to assess treatment efficacy and in clinical evaluation and management of pruritus in hemodialysis patients.

Longitudinal course and phenotypes of health-related quality of life in adults with atopic dermatitis.

The real-world course of health-related quality of life (HRQoL) in atopic dermatitis (AD) is not well established. To examine predictors, longitudinal course and phenotypes of HRQoL in adult patients with AD. This was a prospective dermatology-practice based study of 955 patients with AD (age 18-97 years). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. HRQoL was assessed using the 10-item short-form Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health (PGH). AD severity and impact was assessed by patient-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI), Objective SCORing Atopic Dermatitis (O-SCORAD), Investigator's Global Assessment (IGA), Numerical Rating Scale (NRS) average and worst itch, PROMIS sleep-related impairment (SRI), and nine-item Patient Health Questionnaire (PHQ)-9. Repeated-measures regression models were constructed to examine itch over time. In multivariable linear regression models controlling for age, race/ethnicity, history of asthma, hay fever and food allergy, baseline PGH-physical (PGH-P4) T scores were inversely associated with patient-reported global AD severity, POEM, EASI, objective SCORAD, IGA, NRS average and worst itch, PROMIS SRI and PHQ-9, with stepwise decreases of physical health with worsening severity. PGH-mental health (PGH-M4) T scores were associated with all aforementioned severity measures aside from POEM. In multivariable repeated measures linear regression models, decreased PGH-P4 and PGH-M4 T scores and mapped five-dimension EuroQoL over time were associated with self-reported global AD severity, NRS worst and mean itch, POEM, PROMIS sleep disturbance and SRI, EASI, objective SCORAD, IGA and PHQ-9. Latent class analysis identified six classes of HRQoL, which were associated with measures of AD severity, nonwhite race, Hispanic ethnicity and having only public health insurance, but not age or sex. Patients with AD have a heterogeneous longitudinal course and distinct patterns of HRQoL. Many patients had fluctuating HRQoL over time. Most patients with moderate to severe disease at baseline had persistent HRQoL impairment over time.

Dupilumab Provides Rapid and Sustained Clinically Meaningful Responses in Adults with Moderate-to-severe Atopic Dermatitis.

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a realworld setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo-controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis.

Cluster Analysis of Circulating Plasma Biomarkers in Prurigo Nodularis Reveals a Distinct Systemic Inflammatory Signature in African Americans

Patients with prurigo nodularis (PN) suffer from intractable itch and dramatic reduction in QOL. Although there is significant clinical heterogeneity in the presentation of PN, disease endotypes remain unknown. We assayed circulating plasma cytokine concentrations in patients with PN (n= 20) along with matched healthy controls and utilized an unsupervised machine learning algorithm to identify disease endotypes. We found two distinct clusters of patients with PN with noninflammatory (cluster 1) and inflammatory (cluster 2) plasma profiles. Cluster 2 had more African Americans (82%, n= 9 vs. 33%, n= 3; P= 0.028), higher Worst Itch Numeric Rating Scale scores (9.5 ± 0.9 vs. 8.3 ± 1.2; P= 0.036), and lower QOL as reflected by higher Dermatology Life Quality Index scores (21.9 ± 6.4 vs. 13.0 ± 4.1; P= 0.015). In addition, cluster 1 had a higher rate of myelopathy (67%, n= 6 vs. 18%, n= 2; P= 0.028). Compared with cluster 1, cluster 2 had higher levels of IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, IL-25, and IFN-α. With population-level analysis, African American patients with PN had higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils and lower transferrin than Caucasian patients with PN. These findings indicate discrete clusters of patients with PN with plasma biomarker profiles corresponding to distinct demographic and clinical characteristics, potentially allowing for precision medicine approaches to treat PN.

27595 Neurokinin-1 receptor antagonist tradipitant improves itch associated with mild atopic dermatitis: Results from EPIONE, a randomized clinical trial

Atopic dermatitis (AD) is a relapsing disease affecting 4.9% of the US population and is characterized by intense pruritus that can lead to eczematous lesions in varying severity. EPIONE was a randomized, double-blind, placebo-controlled study in adults with chronic pruritus associated with AD. Participants were men and women (18-70 years), who were refractory to treatment, had a ≥ 7 average daily pruritus intensity by the Worst Itch Numerical Rating Scale (WI-NRS), and ≥ 1% body surface area of AD. All enrolled patients (N = 375) were randomly assigned to twice-daily placebo (n = 187) or tradipitant (n = 188) for 8 weeks. EPIONE did not meet its primary endpoint of mean improvement in WI-NRS (baseline to Week 8) (P = .567). However, robust antipruritic effect was observed in mild AD patients (rated 1 or 2 at baseline by the validated Investigator Global Assessment for Atopic Dermatitis, P = .015). This result was confirmed by daily diary (P = .001) and observed after one full day of treatment (P = .0457). During 8 weeks of treatment, tradipitant was well-tolerated by all participants and although worst itch was not improved over placebo in the overall study population, there was a large and rapid antipruritic effect in the subset of patients with mild AD. These data support the role of neurokinin-1 antagonism in chronic pruritus related to mild AD. Tradipitant may represent a new oral systemic option for mild AD patients based on the well-tolerated safety profile and immediate robust improvement in itch.

27874 Correlation of itch response to roflumilast cream with disease severity and patient-reported outcomes in patients with chronic plaque psoriasis

Roflumilast cream is a nonsteroidal, selective phosphodiesterase-4 inhibitor in development for plaque psoriasis (PsO). A Phase 2b, double-blinded trial randomized adults with PsO (2-20% body surface area) to once daily roflumilast 0.3%, roflumilast 0.15%, or vehicle for 12 weeks (NCT03638258). Throughout the trial, itch and its impact were evaluated via patient reported outcomes (PROs): Worst Itch Numeric Rating Scale (WI–NRS), Itch related Sleep Loss (IRSL), and Dermatology Life Quality Index (DLQI).

Scabies itch: an update on neuroimmune interactions and novel targets.

Frequently described as 'the worst itch' one can ever experience scabies itch is the hallmark of Sarcoptes scabiei mite infestation. Notably, the itchiness often persists for weeks despite scabicides therapy. The mechanism of scabies itch is not yet fully understood, and effective treatment modalities are still missing which can severely affect the quality of life. The aim of this review is to provide an overview of the scope of itch in scabies and highlight candidate mechanisms underlying this itch. We herein discuss scabies itch, with a focus on the nature, candidate underlying mechanisms and treatment options. We also synthesize this information with current understanding of the mechanisms contributing to non-histaminergic itch in other conditions. Itch is a major problem in scabies and can lead to grave consequences. We provide the latest insights on host-mite interaction, secondary microbial infection and neural sensitization with special emphasis on keratinocytes and mast cells to better understand the mechanism of itch in scabies. Also, the most relevant current modalities remaining under investigation that possess promising perspectives for scabies itch (i.e. protease-activated receptor-2 (PAR-2) inhibitor, Mas-related G protein-coupled receptor X2 (MRGPRX2) antagonist) are discussed. Greater understanding of these diverse mechanisms may provide a rational basis for the development of improved and targeted approaches to control itch in individuals with scabies.

FC 022AN OPEN-LABEL, MULTICENTER STUDY TO EVALUATE THE SAFETY AND EFFECTIVENESS OF INTRAVENOUS DIFELIKEFALIN IN PATIENTS WITH MODERATE-TO-SEVERE CKD–ASSOCIATED PRURITUS UNDERGOING HEMODIALYSIS

Abstract Background and Aims Chronic kidney disease–associated pruritus (CKD-aP) is a common and highly distressing condition in patients undergoing hemodialysis (HD). CKD-aP is associated with sleep disturbances, significant quality-of-life (QoL) impairment, and increased morbidity and mortality. Difelikefalin (DFK) is a selective kappa opioid receptor agonist in development for CKD-aP that has minimal central nervous system penetration. In placebo-controlled phase 3 trials of patients with moderate to severe CKD-aP undergoing HD, intravenous (IV) DFK had an acceptable safety profile and demonstrated significant reductions vs placebo in itch intensity. We report safety and effectiveness outcomes, including itch-related QoL and sleep measures, from a phase 3 open-label study of DFK in patients with moderate to severe CKD-aP. Method This multicenter, open-label study conducted in the United States and Europe enrolled patients with moderate to severe CKD-aP (mean baseline 24-hour Worst Itching Intensity Numerical Rating Scale [WI-NRS] score ≥5) undergoing HD for ≥3 months. Patients received IV DFK 0.5 mcg/kg 3 times/week at the end of each HD session for up to 12 weeks. Predefined effectiveness endpoints at week 12 included ≥3-point and ≥4-point improvement in the weekly mean of the 24-hour WI-NRS score (range from 0 [no itching] to 10 [worst itching imaginable]). Change from baseline in QoL at week 12 was assessed using the 5-D itch and Skindex-10, multidimensional itch-related questionnaires validated in CKD-aP (higher scores indicate worse QoL). The proportion of patients with no problems (score of 1) on the skin irritation and self-confidence domains of the EQ-PSO questionnaire was evaluated. Post hoc endpoints included complete resolution in WI-NRS (≥75% of week 12 scores 0 or 1) and Sleep Quality Questionnaire total score assessments (range of possible scores, 0 [did not interfere] to 10 [completely interfered]), including ≥3-point and ≥4-point improvement in weekly mean score and complete resolution (all scores of 0) at week 12. Safety assessments and adverse events (AEs) were evaluated. Data were summarized descriptively. Results Among 222 patients who received DFK, 197 (88.7%) completed the study. At baseline, mean ±SD age was 58.1 ±12.8 years and 54.5% of patients were male. Baseline mean ±SD WI-NRS score was 7.6 ±1.3, Sleep Quality score was 6.6 ±2.2, 5-D itch score was 17.1 ±3.5, and Skindex-10 score was 32.9 ±14.3. At week 12, the majority of patients achieved ≥3-point and ≥4-point improvement in WI-NRS (73.7% and 59.3%) and Sleep Quality score (66.0% and 56.7%). Complete resolution of WI-NRS and Sleep Quality score was observed in 29.4% and 19.1% of patients, respectively (Figure). DFK was associated with improvements in mean 5-D itch (−7.1 ±4.3) and Skindex-10 (−21.0 ±15.6) scores at week 12. The proportion of patients reporting no problems in the skin irritation EQ-PSO domain increased from 1.4% at baseline to 28.9% at week 12, and self-confidence EQ-PSO domain scores increased from 63.5% at baseline to 73.2% at week 12. Overall, 64.4% (143/222) of patients reported ≥1 treatment-emergent AE (TEAE). The most commonly reported TEAEs (≥4% of patients) were diarrhea (5.0% [11/222]), nausea (4.5% [10/222]), and hyperkalemia (4.1% [9/222]). Serious TEAEs were reported by 20.3% (45/222) of patients; no serious TEAEs were related to study drug. Conclusion In this phase 3 open-label study in patients with moderate to severe CKD-aP undergoing HD, DFK was generally well tolerated with an acceptable safety profile. DFK demonstrated effectiveness based on reduction of itch intensity, and improvements in sleep quality and itch-related QoL at week 12. The majority of patients reported ≥3-point or ≥4-point improvement in WI-NRS and Sleep Quality scores, with some reporting complete resolution. Findings from this open-label study provide insight into the potential real-world effectiveness of DFK in moderate to severe CKD-aP.

Clinical phenotyping of atopic dermatitis using combined itch and lesional severity: A prospective observational study

BackgroundPatients with atopic dermatitis (AD) have heterogeneous clinical phenotypes, including different combinations of itch and lesional severity. Little is known about the characteristics and course of these subtypes. ObjectiveTo determine the characteristics, associations, burden, and course of patients with AD using combined itch and lesional severity. MethodsA prospective practice-based study was performed using questionnaires and physical examination (n=592). AD subsets were defined using verbal rating scale for average itch combined with either eczema area and severity index, objective—scoring atopic dermatitis (SCORAD), or validated investigator's global assessment as follows: mild-moderate itch and lesions (MI-ML), mild-moderate itch and severe lesions (MI-SL), severe itch and mild-moderate lesions (SI-ML), and severe itch and lesions (SI-SL). ResultsAt baseline, there were only weak-moderate correlations of numerical rating scales for worst itch or average itch or SCORAD itch with eczema area and severity index, objective-SCORAD, body surface area, and validated investigator's global assessment (Spearman's rho = 0.32-0.62). Most patients had MI-ML (59.4%-62.3%), followed by SI-ML (21.3%-29.1%), SI-SL (6.0%-12.9%), and MI-SL (3.8%-6.4%). Patients with SI-SL, followed by SI-ML and MI-SL, described their AD as being more severe overall and had worse impairment in sleep, mental health, and quality of life. However, those with MI-SL or SI-SL were far more likely to be classified as severe by a physician (multivariable logistic and linear regression, P < .005 for all). Baseline MI-SL, SI-ML, and SI-SL were associated with similar longitudinal courses over time and more AD flares and itch triggers than MI-ML. ConclusionCombined itch and lesional severity seem to describe unique AD phenotypes. Further studies are needed to confirm these findings and understand the optimal treatments for these groups.

70 Measuring Itch Intensity in Young Children with Burns: What We Learnt from Parents. A Mixed-Methods Study

Abstract Introduction Despite the persistence and debilitating symptoms among inflicted children and their families, little is known about children’s itching behavior as perceived and described by parents. This study examined the parental description of young children’s itching behavior corresponding to the itch intensity rating, which can inform the future development of itch measurements for young children. Methods This analysis was part of a larger descriptive study that examined parental behavioral and psychological responses to children’s itch following the child’s unintentional burn injury. Parents of young children with deep second or third-degree burns were recruited. Parents were asked to rate the child’s itching intensity under four situations during the 7-day time frame using a 0–10 numerical rating scale (0 indicates no itch, and 10 indicates the worst itch possible). Parents were subsequently interviewed to describe the child’s observed behavior that reflected the itch intensity rating. The four itch situations were the current itch, the worst intense itch, the least intense itch, and the itch by a mosquito bite. Qualitative data were analyzed using inductive content analysis methods. Results Twenty parents of children 34 (±11.5) months old participated in the study. The average length of time since the child’s burn accident was 6.4 (±3.1) months. The mean ratings of the current itch, the worst intense itch, the least intense itch, and the itch by a mosquito bite were 3.45 (±2.4), 8.35 (±2.3), 1.5 (±1.7), and 4 (±1.2), respectively. Two themes that described a child’s itching behavior were identified: the level of a child’s needs for parental comfort and the frequency and disturbance (to activity and sleep) of scratching behavior. Conclusions Results suggest that the parent’s description of a child’s needs for parental comfort and scratching behaviors may serve as objective indicators of itching intensity. Interpreting inching intensive based on a child’s needs for parental comfort offered a creative way to evaluate itch considering the developmental perspective in young children. Future development of itch measures for children under 5 years of age shall consider these two important aspects.

Two identically designed studies to test the effectiveness of tralokinumab for treatment of atopic dermatitis in adults

British Journal of DermatologyVolume 184, Issue 3 p. e101-e102 Plain Language SummaryFree Access Two identically designed studies to test the effectiveness of tralokinumab for treatment of atopic dermatitis in adults First published: 05 March 2021 https://doi.org/10.1111/bjd.19778AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Atopic dermatitis, or eczema, is a chronic, itchy skin disease that is common in children and adults. Atopic dermatitis occurs when the barrier function of the skin is disrupted, allowing chemicals and allergens (that cause an allergic reaction) to enter the skin and cause inflammation. Tralokinumab is a drug injected under the skin that targets interleukin (IL)-13, a molecule that is important in causing the skin inflammation associated with atopic dermatitis. Tralokinumab, which belongs to a class of drugs called biologics, is not yet licensed for medical use, but is being investigated in clinical trials as a potential treatment for atopic dermatitis. Two identically designed clinical trials, ECZTRA 1 and ECZTRA 2, investigated if tralokinumab alone (used without any other atopic dermatitis treatment) was more effective than a nonactive drug (placebo) for improving the severity and symptoms of atopic dermatitis. The trials, funded by LEO Pharma, involved over 1500 patients from Europe, North America, Asia and Australia. Adult patients who had moderate-to-severe atopic dermatitis for more than 1 year that had not improved sufficiently with topical treatments (treatments applied directly to the skin) were included. Patients received tralokinumab 300 mg or placebo every 2 weeks for an initial 16 weeks. Patients who showed a good response to tralokinumab either continued with the same treatment, received less-frequent dosing of tralokinumab (once every 4 weeks), or received placebo for a further 36 weeks to assess long-term safety. Neither the patients nor the medical team knew which treatment the patients were receiving. The medical team monitored patients throughout the trials to assess changes in the amount and severity of atopic dermatitis. Patients also self-recorded changes in itch, sleep disruption and quality of life. The medical team also documented the occurrence of any side-effects of the drug. In both trials at week 16, more patients receiving tralokinumab had an improvement in their atopic dermatitis compared with patients receiving placebo. Patients felt meaningful improvements in itch (Figure 1), sleep and quality of life as early as 1–2 weeks after starting tralokinumab. Figure 1Open in figure viewerPowerPoint Top panel: Graphs show the percentage of patients who had a meaningful improvement in their perceived itch at 16 weeks. In the ECZTRA 1 trial (left), more tralokinumab-treated patients (20.0%, green bar) had a meaningful improvement in their perceived itch compared with those who received placebo (10.3%, blue bar). In the ECZTRA 2 trial (right), more tralokinumab-treated patients (25.0%) had a meaningful improvement in their perceived itch compared with placebo (9.5%). Bottom panel: Patients recorded how bad their itch was each day on a scale of 0 (no itch) to 10 (worst itch imaginable); a meaningful improvement was defined as a reduction of 4 points or more from the start of the trial on the itch scale. The majority of patients who had high levels of improvement at week 16 with tralokinumab maintained that level of improvement after another 36 weeks of treatment with dosing every 2 weeks. In addition, some patients maintained their improved skin with less-frequent dosing every 4 weeks. The most common side-effects with tralokinumab were upper respiratory tract infections (mainly common cold) and conjunctivitis (inflammation of the eye or eyelid). Based on the results from these trials, tralokinumab may be a long-term treatment option for adult patients with moderate-to-severe atopic dermatitis. Acknowledgements: the authors thank Korey Capozza, MPH, Director, Global Parents for Eczema Research, for critical review of this summary. Linked Article: Wollenberg et al. Br J Dermatol 2021; 184:437–449. Volume184, Issue3March 2021Pages e101-e102 FiguresRelatedInformation

Validity and reliability of Patient-Reported Outcomes Measurement Information System Global Health scale in adults with atopic dermatitis

Patient-Reported Outcomes Measurement Information System Global Health (PGH) was validated to assess health-related quality of life in several diseases. Little is known about its measurement properties in adult atopic dermatitis. Examine the measurement properties of PGH in adult atopic dermatitis. A prospective dermatology practice-based study of 994 atopic dermatitis patients (18-97years). PGH physical and mental health 4-item and abridged 2-item T scores, as well as mapped EuroQol-5D score, showed strong to very strong correlation with one another and moderate to strong Spearman correlations with Patient-Oriented Scoring Atopic Dermatitis, Patient-Health Questionnaire-9, Patient-Reported Outcomes Measurement Information System sleep disturbance and related impairment, Eczema Area and Severity Index, objective Scoring Atopic Dermatitis; and weak to moderate correlations with Patient Oriented Eczema Measure, numeric rating scale worst itch and average itch, and Scoring Atopic Dermatitis. The Dermatology Life Quality Index (DLQI) had stronger correlations with Patient Oriented Eczema Measure, Patient-Oriented Scoring Atopic Dermatitis, numeric rating scale worst itch and average itch, Eczema Area and Severity Index, and Scoring Atopic Dermatitis, but weaker correlations with Patient-Health Questionnaire-9 and Patient-Reported Outcomes Measurement Information System sleep disturbance and related impairment (convergent/divergent validity). PGH and DLQI scores had similarly poor ability to differentiate between levels of self-reported global atopic dermatitis severity (known-groups validity). No floor or ceiling effects were observed. No PGH or DLQI items had differential item functioning by demographics. PGH and DLQI scores showed fair to good responsiveness. Finally, PGH and DLQI showed similarly good test-retest reliability. Single-center study. PGH scores had sufficient validity and reliability to assess health-related quality of life in atopic dermatitis.

Chronic Pruritus of Unknown Origin: Clinical Profile and Disease-Related Burden.

Chronic pruritus of unknown origin is established when no underlying origin for pruritus can be determined. This retrospective cohort study aimed to determine the clinical profile and disease-related burden of chronic pruritus of unknown origin. A total of 263 patients (female/male: 154/109, median age 55 years) were included. Moderate to severe itch intensities were recorded (median average itch: 5.5/10, n = 200; median worst itch: 7.5/10, n = 199). In most cases pruritus lasted longer than 1 year (77.6%), occurred daily (68.2%), occurred in attacks (72.8%), and was often accompanied by dysaesthesias, such as burning, tingling and stinging. Quality of life was moderately impaired, while 22.2% and 12.4% of patients showed pathological anxiety and depression scores. Scratch lesions were associated with higher intensities of itch and greater impairment of quality of life, while women were more burdened by the disease than men. Chronic pruritus of unknown origin may occur at any age and the majority of patients endure severe itch with substantial disease-related burden.

PMU90 Exploring Symptoms, Impacts, and Patient-Reported Outcome (PRO) Measures in Prurigo Nodularis: A Review of the Literature

Prurigo nodularis (PN) is a skin disease characterized by the presence of multiple nodules and papules that cause intense itch. This review aimed to identify the most bothersome symptoms in individuals living with PN, impacts of PN on health-related quality of life (HRQL), and patient-reported outcomes (PROs) used to collect patient experience data. Searches for published articles and conference abstracts were conducted in MEDLINE and EMBASE from January 2011 to March 2020. Selected studies included adults diagnosed with PN, and reported patients’ experiences of PN symptoms, impacts, and treatment. Of the 134 identified articles, 27 studies of varied designs were included. These were observational (n=14), randomized controlled trials (n=5), quasi-experimental (n=5), and reviews (n=2). No qualitative studies were identified. Overall, studies showed itch was an important concept to measure among patients with PN. PN impacted HRQL, including sleep, emotional functioning, relationships, and daily activities. A total of 41 PROs assessing symptoms or impacts were identified. The most frequently used PRO for itch intensity is the Visual Analogue Scale (n=10). Other measures included the Worst Itch Numerical Rating Scale (n=5) and the Itch Verbal Rating Scale (n=5). Eight PROs assessing sleep were identified, using either multi-item (n=5) or single-item scales (n=3). Eight studies reported using the Dermatological Life Quality Index (DLQI), and three studies reported using ItchyQOL to assess HRQL. Psychological distress was measured using the Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS). Chronic itch is the most bothersome symptom in PN, interfering significantly with sleep and HRQL and causing high levels of anxiety and depression. Several different PROs have been used to assess symptoms and impacts; however, validation evidence through qualitative and psychometric evaluations is needed to support PRO use as key endpoints in future PN clinical trials.