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BACKGROUND: Poor sleep quality is associated with higher mortality and lower quality of life in patients with chronic kidney disease-associated pruritus (CKD-aP). Difelikefalin reduces itch in patients with CKD-aP undergoing haemodialysis (HD). This post hoc analysis of the Phase 3 difelikefalin studies (Study 3105 and the pooled dataset from KALM-1 and KALM-2) evaluated whether itch reduction in individuals with CKD-aP improved sleep quality. METHODS: Itch intensity was assessed in patients undergoing HD who had moderate-to-severe CKD-aP treated with intravenous difelikefalin (0.5 µg/kg, three times weekly) (N = 222, Study 3105; N = 426, KALM-1 and -2) or placebo (N = 425, KALM-1 and -2) for 12 weeks, using the Worst Itch Intensity Numerical Rating Scale (WI-NRS). Sleep quality was assessed using the sleep disability question of the 5-D Itch Scale (5-D SDQ) in all studies and, in Study 3105, with the Sleep Quality Numeric Rating Scale (SQ-NRS). RESULTS: Greater improvements in sleep quality were observed in patients with ≥3-point versus

The clinical manifestations of atopic dermatitis (AD) and chronic nodular prurigo (CNPG) include pruritus and eczema/lesions, posing significant challenges for patients. Th2 cells and ILC2, marked by cytokine production—particularly IL-4/13—are crucial therapeutic targets. Despite displaying a dose-dependent lack of pruritus induction post-injection, IL-13 acts through the IL-13Rα1 and IL-13Rα2 receptor system. Our study focused on investigating ex vivo skin biopsies in AD (n = 17), CNPG (n = 14) and healthy controls (HC; n = 10), examining the gene expression landscape of interleukins linked with pruritus (IL-13, IL-4, IL-31) and their corresponding receptors. Compared to HC, results revealed a significant upregulation of IL-4, IL-13, and IL-13RA1 in AD, whereas CNPG did not show increased IL13 expression. Notably, the decoy receptor IL-13RA2 displayed intriguing patterns, with AD showing a marked increase compared to both HC and CNPG. Positive correlations between receptor expression and itch intensity and hyperkinesis sensation underscore clinical relevance, potentially serving as biomarkers. The findings suggest a pivotal role of IL-4 and IL-13, along with IL-13RA1, in pruritus pathogenesis in both entities, while IL-13 upregulation in AD is countered by IL-13RA2. The comparable expression of IL-13RA2 to HC in CNPG suggests the absence of this regulatory mechanism, potentially worsening the disease and leading to prolonged scratching behavior. These insights illuminate the intricate interplay of interleukins and receptors in different pruritus phenotypes, laying the groundwork for understanding underlying mechanisms and offering avenues for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Patient-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. Methods: Using 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. Results: The 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. Conclusions: Using 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. [ABSTRACT FROM AUTHOR]

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Summary: Background: Chronic pruritus is a clinically heterogeneous symptom that manifests itself with varying duration, intensity, or quality. To date, there is no validated German‐language instrument that systematically assesses the relevant parameters. With the support of the Pruritus Research Working Group (Arbeitsgemeinschaft Pruritusforschung, AGP), a questionnaire for the assessment of chronic pruritus (AGP questionnaire) was developed in 2008. The subsequently revised instrument, now called the German Pruritus Questionnaire, records pruritus‐specific parameters such as localization, course, intensity and quality, anamnestic data on the general state of health, sociodemographic data, quality of life, and coping methods. It is to be validated in the study presented here. Patients and methods: The questionnaire was used in 366 patients with chronic pruritus of different etiologies from Germany (University Hospitals Heidelberg, Münster, Mainz, Erlangen, Giessen, private practice Bad Bentheim, TU Munich, Wiesbaden Kidney Center), Austria (Graz University Hospital) and Switzerland (Aarau Cantonal Hospital). Results: The reliability for repeated completion (retest reliability) with regard to localization, first occurrence, and concomitant diseases showed high values for Cohen's kappa (> 0.8). The data on the retest reliability of the pruritus characteristics showed lower values (< 0.7). With regard to the measurability of practically relevant changes (change sensitivity), medium to strong effect sizes were found (0.09–0.19). A statistically significant differentiation of the pruritus etiologies based on the recorded parameters was not possible. Conclusions: The German Pruritus Questionnaire allows a comprehensive and structured recording of patient‐ and clinician‐reported, relevant dimensions of chronic pruritus of different etiologies. Further adaptation and development are planned. [ABSTRACT FROM AUTHOR]

Background: Prurigo nodularis (PN) is a rare chronic inflammatory skin disease with a high disease burden, but data on clinical and economic burden are still scarce. Objective: To describe the real-world epidemiologic, clinical and therapeutic characteristics and related economic burden of patients with PN compared to a benchmark population in Germany. Methods: This retrospective study was based on an excerpt of German Statutory Health Insurance data of patients with an initial PN diagnosis between 2012 and 2016. PN cohort contained no record of PN in eight quarters before the index quarter and was followed up for eight quarters (unless deceased). Benchmark cohort without PN was calculated using direct standardization and 1:1 matching to PN cohort. Results: Out of 4,536,002 insured patients, 2309 incident patients with PN were identified and matched to the benchmark cohort out of 3,018,382 patients without PN. Patients were mostly between 45 and 80 years when diagnosed with PN. Higher comorbidity rates were reported for PN than benchmark, with a rising disease burden at follow-up. Most patients with PN (91.3%) were diagnosed outpatient and had >50% more outpatient visits than the benchmark cohort. Hospitalization rates were higher in PN (53.9%) versus benchmark (35.1%), yielding twice longer mean hospital stays for PN (12 days) compared to benchmark (6 days) (p < 0.001). The most common initial therapy for patients with PN was topical corticosteroids (47.6%); ≥10% of patients were treated with antidepressants, antihistamines or systemic corticosteroids. Therapy rates were higher for PN compared to benchmark (p < 0.001). Mean initial costs were twofold higher in PN versus benchmark for outpatient, inpatient and drugs. During follow-up, an increase of >70% in mean PN costs compared to benchmark was identified for outpatient, inpatient and concomitant treatments (p < 0.001). Conclusion: This study highlights the significantly higher clinical and economic burden incurred by PN compared to benchmark patients in Germany, reflecting the unmet medical need for PN. [ABSTRACT FROM AUTHOR]

Background: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden. Objectives: The aim of the study was to evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD. Methods: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]). Patients received oral, once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 or 16 weeks (JADE COMPARE). Skin pain was rated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) skin pain Numerical Rating Scale (NRS) item ("How painful was your skin over the past 24 h?") on a scale from 0 (not painful) to 10 (extremely painful). Itch (Peak Pruritus NRS) and QoL (Dermatology Life Quality Index or Children's Dermatology Life Quality Index) were assessed. Least squares mean (LSM) change from baseline was analyzed using mixed-effects repeated measures modeling. Results: A total of 1,822 patients (monotherapy pool, n = 942; JADE COMPARE, n = 595; and JADE TEEN, n = 285) were analyzed. LSM change from baseline in PSAAD skin pain score was significantly greater with abrocitinib versus placebo from week 2 through week 12 or 16 across all 3 study populations and occurred in a dose-dependent manner. A greater proportion of patients achieved a ≥4-point improvement from baseline in PSAAD skin pain score with abrocitinib (200 mg and 100 mg) versus placebo in the monotherapy pool (56% and 38% vs. 12%; week 12), JADE COMPARE (72% and 52% vs. 26%; week 16), and JADE TEEN (51% and 60% vs. 31%; week 12). Additionally, a greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score <2) with abrocitinib versus placebo. Adults and adolescents who achieved a ≥4-point improvement in skin pain reported greater QoL improvement than those who did not achieve a ≥4-point improvement. A positive correlation (≥0.3) was observed between skin pain and QoL and separately between skin pain and itch across the 3 study populations. Conclusion: Abrocitinib as monotherapy or in combination with topical therapy improved skin pain and was associated with improved QoL in both adults and adolescents with moderate-to-severe AD across all evaluated studies. [ABSTRACT FROM AUTHOR]

Introduction Patients with prurigo nodularis (PN) often report high disease burden with substantial impact on quality of life. Patient Global Impression of Change (PGIC) and Severity (PGIS) are patient self-assessment measures that quantify their experience of disease during treatment. Dupilumab has recently been approved as the first systemic treatment for PN in the US and Europe. Objectives: To evaluate patient-reported global impression of disease severity improvement in dupilumab-treated patients with PN during the LIBERTY-PN PRIME and PRIME 2 trials. Materials & Methods: PRIME and PRIME2 were randomized, double-blind, multicenter, parallel-group, 24-week, phase 3 trials in adults with PN with ≥20 nodules and severe itch, inadequately controlled with topical prescription therapies or for whom these are inadvisable. Patients received 300 mg dupilumab subcutaneously (600 mg loading dose; n = 153) or matched placebo (n = 158) every 2 weeks. In this analysis, data from the two studies were pooled. Patient satisfaction was assessed in the overall placebo group, overall dupilumab-treated group, and those treated with dupilumab who did not achieve the stringent multicomponent endpoint (n = 99) of ≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS, range: 0-10) and an Investigator's Global Assessment PN Stage (IGA PN-S, score range: 0-4) score 0 or 1 (clear or almost clear; ≤5 nodules) at Week (W) 24. Endpoints include proportion of patients achieving: PGIC (range: 0-6) scores of 0 or 1 (very much better or moderately better) at W12, and W24; and PGIS (range: 1-4) score of 1 or 2 (none or mild) at baseline, W12, and W24. Safety was also assessed. Results: Baseline demographic and clinical characteristics were generally similar between groups. In the overall dupilumab and placebo groups, baseline mean (SD) WI-NRS scores were 8.6 (0.9) and 8.4 (1.1), respectively; 32.7% and 34.2% had an IGA PN-S score of 4 (remaining patients had IGA PN-S 3); and mean (SD) PGIS scores were 3.7 (0.5) and 3.7 (0.5) respectively. In dupilumab multicomponent endpoint non-responders, mean (SD) WI-NRS score was 8.6 (0.9). 35.4% and 64.6% had an IGA PN-S score of 4 and 3 respectively; and mean (SD) PGIS score was 3.7 (0.5). At W12, 68.0% vs 38.0% (P < 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIC 0 or 1, while 55.6% of dupilumab multicomponent non-responders achieved this endpoint (P = 0.0099 vs placebo). At W24, this increased to 74.5% vs 32.9% (P < 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieving PGIC 0 or 1, and 61.6% of multicomponent non-achievers (P < 0.0001 vs placebo). At W12, 51.6% vs 22.2% (P < 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIS 1 or 2, while 40.4% of multicomponent non-responders achieved the endpoint (P = 0.0027 vs placebo). At W24, 61.4% vs 24.1% (P < 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIS 1 or 2, while 44.4% of multicomponent non-responders achieved the endpoint (P = 0.0025 vs placebo). Safety findings were consistent with the known dupilumab safety profile. Conclusions: While not all patients achieved the stringent multicomponent endpoint within the 24-week treatment period during PRIME and PRIME 2 trials, around half of the dupilumab-treated patients still reported significantly more improvement in disease severity and satisfaction with therapy. Overall safety was consistent with the known dupilumab safety profile. [ABSTRACT FROM AUTHOR]

The article discusses the results of two phase III clinical trials, ADvocate1 and ADvocate2, which examined the efficacy and safety of lebrikizumab monotherapy in patients with moderate-to-severe atopic dermatitis (AD). The trials found that lebrikizumab significantly improved patient-reported itch and reduced sleep loss due to itch. The improvements in itch and sleep loss were observed as early as the first few days of treatment and were consistent with previous studies on lebrikizumab. The study was funded by Dermira, a subsidiary of Eli Lilly and Company, and medical writing assistance was provided by ProScribe–Envision Pharma Group. [Extracted from the article]

Introduction/Background Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by itchy skin lesions presenting as nodules, papules, plaques, or ulcers. These different clinical morphologies may present simultaneously and an individual patient may exhibit different morphologic variants over time. Dupilumab is the first systemic treatment approved by the US Food and Drug Administration and European Medicines Agency for the treatment of adults with PN. LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were two phase 3 randomized placebo-controlled clinical trials that demonstrated the efficacy and safety of dupilumab in adults with PN inadequately controlled with topical medications or for whom those were inadvisable. Objectives To report baseline lesion morphologies and the effect of dupilumab on the number of skin lesions present, as measured by the Prurigo Activity and Severity (PAS) score, in patients with PN presenting with multiple lesion morphologies. Methods In LIBERTY-PN PRIME and PRIME2, patients received 300 mg dupilumab subcutaneously (600 mg loading dose; n = 153) or matched placebo (n = 158) every 2 weeks over 24 weeks. PAS, a simplified 5-item questionnaire, was used to assess the types of lesions present (PAS Item 1a) and the numbers of lesions in a representative body area (PAS Item 4). Safety endpoints included treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs). Data from both studies were pooled and comparisons analyzed using analysis of covariance. Results All patients in PRIME and PRIME2 had nodules and an Investigator's Global Assessment for PN-Stage (IGA PN-S) score of 3 or 4 at baseline. Additional PN lesion types included papules (dupilumab: 69.9%, placebo: 69.4% at baseline), hypo- or hyper-pigmented macules (dupilumab: 50.3%, placebo: 55.4%), plaques (dupilumab: 30.7%, placebo: 39.5%), and ulcers (dupilumab: 32.0%, placebo: 28.7%). At least 2 types of lesions at baseline were reported by 77.1% of the dupilumab group and 79.0% of the placebo group, while 10.5% of the dupilumab and 13.4% of the placebo group reported 5 concomitant lesion types at baseline (nodules, papules, hypo- or hyper-pigmented macules, ulcers, and plaques). After 24 weeks of treatment, 3.3% of patients given dupilumab and 7.6% of patients given placebo reported 5 types of concomitant lesions. Dupilumab reduced the overall number of lesions (SD) in a representative area of the body by 61.1% (45.7) at Week 24, compared with a 22.9% (63.3) reduction in the placebo group. Treatment-emergent adverse events (TEAEs) occurred in 91 (59.9%) and 80 (51.0%) patients from the dupilumab and placebo groups, respectively. TEAEs leading to discontinuation occurred in 0 patients given dupilumab and 3 (1.9%) given placebo. Conclusions Patients with PN experienced a high baseline lesion burden; >75% of patients reported ≥2 types of concomitant lesions, and >10% of patients reported 5 types of concomitant lesions. Dupilumab treatment reduced the number of lesions and the percentage of patients reporting 5 concomitant lesion morphologies. Safety data were generally consistent with the known safety profile of dupilumab. [ABSTRACT FROM AUTHOR]

Introduction/Background Pruritus is one of the essential features of atopic dermatitis (AD) and is consistently reported by patients as the most burdensome symptom of the disease. Itch not only impacts quality of life but also contributes to furthering AD pathogenesis through the itch-scratch cycle and additional breakdown of the epidermal barrier. A treat-to-target concept established goals to guide treatment with systemic therapies in AD, including those for itch.1-3 Objectives To assess onset and maintenance of optimal itch response according to the treat-to-target concept in adult patients with moderate-to-severe AD treated with dupilumab + concomitant topical corticosteroids (TCS). Methods LIBERTY AD CHRONOS (NCT02260986), a 52-week trial, enrolled patients aged ≥18 years with moderate-to-severe AD. Patients treated with dupilumab every 2 weeks + TCS or placebo + TCS were included in this post hoc analysis. Optimal itch response per the treat-to-target concept was defined as Peak Pruritus Numerical Rating Scale (PP-NRS) score of ≤4, achieved after 6 months of treatment1. We assessed time to optimal itch response, percentage of patients achieving optimal itch response, and maintenance of optimal itch response. For maintenance of optimal itch response, the total number and percentage of weeks with PP-NRS ≤4 were calculated for each patient, and maximum duration was assessed as the longest period of consecutive weeks with PP-NRS ≤4 for each patient. Results Median (interquartile range) PP-NRS score at baseline was 7.7 (6.6–8.5) for patients treated with dupilumab + TCS and 7.6 (6.3–8.6) for patients who received placebo + TCS. Median time (95% CI) to achieve optimal itch response was 29 (22–43) days for patients treated with dupilumab+ TCS and 64 (43–105) days for patients who received placebo + TCS (HR [95% CI] = 1.668 [1.292–2.153]; P < 0.0001). 61.3% of patients treated with dupilumab + TCS achieved optimal itch response at 6 months, compared with 26.7% of those who received placebo + TCS (P < 0.0001). Significantly more patients treated with dupilumab + TCS maintained optimal itch response than patients who received placebo + TCS through 52 weeks. In the dupilumab group, median (Q1–Q3) maintenance of optimal itch response was 40 (11–50) weeks, compared with 3 (0–23) weeks in the placebo group (P < 0.0001), which corresponds to 77.1% of the total study duration (52 weeks) in the dupilumab group, compared with 5.7% in the placebo group. Maximum consecutive duration with optimal itch response was also significantly longer in dupilumab-treated patients than in patients who received placebo (median [Q1–Q3]: 29.2 [4–50] weeks for dupilumab vs 2.0 [0–13] weeks for placebo; P < 0.0001). Conclusions Patients treated with dupilumab + TCS achieved optimal itch response rapidly and significantly faster than patients who received placebo + TCS; 29 days in dupilumab-treated patients compared with 64 days in those who received placebo. Significantly more patients treated with dupilumab + TCS achieved and maintained optimal itch response than patients who received placebo + TCS through 52 weeks. Dupilumab + TCS also led to a significantly longer maintenance of optimal itch response (40 weeks) compared with placebo + TCS (3 weeks). [ABSTRACT FROM AUTHOR]

Introduction Nemolizumab demonstrated clinically and statistically significant improvements in itch, sleep disturbance, and skin lesions in adults with moderate-to-severe prurigo nodularis (PN) in two phase 3 pivotal studies (OLYMPIA 1 [NCT04501666]1 and OLYMPIA 2 [NCT04501679]2). Objectives To report pooled efficacy and safety from two phase 3 studies of nemolizumab in the treatment of PN. Materials & Methods A pooled analysis of two phase 3 pivotal studies in adults with moderate-to-severe PN, randomized (2:1) to receive either nemolizumab (initial 60 mg subcutaneous dose followed by 30 mg or 60 mg [depending on a baseline weight below or ≥90 kg, respectively]) or matching placebo every 4 weeks (Q4W). Results Nemolizumab significantly improved all pre-specified efficacy endpoints vs placebo. At Week 16, a ≥4-point improvement from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) was achieved in 57.4% of nemolizumab- vs 18.7% placebo-treated patients (P <0.0001), an Investigator's Global Assessment score of 0/1 [clear/almost clear skin] with ≥2-point reduction from baseline was achieved in 31.9% of nemolizumab- vs 9.1% of placebo-treated patients (P <0.0001) at Week 16, itch-free/nearly itch-free state (defined as PP-NRS<2) was achieved in 34.6% of nemolizumab- vs 5.9% of placebo-treated patients (P <0.0001) and a ≥4-point improvement from baseline in weekly average Sleep Disturbance NRS was achieved in 50.9% of nemolizumab- vs 16.0% of placebo-treated patients (P <0.0001). Treatment-emergent adverse events (TEAEs) were reported in 66.5% of patients (nemolizumab) and 59.1% (placebo). Of these patients, the majority in each treatment group experienced that were considered mild or moderate in severity. Conclusion Nemolizumab monotherapy administered Q4W was well-tolerated and led to rapid and sustained clinically meaningful improvements in itch intensity and sleep disturbance along with improvement in skin lesions. Pooled results were consistent with those observed in individual pivotal phase 3 studies.2,3 [ABSTRACT FROM AUTHOR]

Introduction Prurigo nodularis (PN), a chronic inflammatory and pruritic skin condition with severely itchy skin nodules, substantially affects quality of life. Patients with PN are affected by highly pruritic lesions that can feature other sensations, such as stinging, burning, tingling, heat, and cold. These lesions can range in severity from a few nodules to several hundred, and in sizes from 10 millimeters to 2–3 cm. Objective To report the effect of dupilumab on pruritus and skin lesions in patients with PN according to the severity of their lesions at baseline, in a post hoc analysis of pooled data from two phase 3 trials. Materials & Methods In the two randomized, double-blind, placebo-controlled, 24-week studies LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679), adults with PN inadequately controlled by topical prescription therapies, or for whom those therapies are inadvisable, were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. Efficacy was assessed from baseline to Week 24 through the Worst Itch Numerical Rating Scale (WI-NRS; scored 0–10; high scores represent a poorer outcome), and the Investigator's Global Assessment for PN-Stage score (IGA PN-S; scored 0–4; high scores represent more severe nodular disease). The PRIME and PRIME2 studies enrolled only patients with an IGA PN-S of 3 (moderate; 20−100 nodules) or 4 (severe; >100 nodules) at baseline. Results 311 patients were randomized (dupilumab/placebo n = 153/158), including 205 patients with moderate PN (IGA PN-S = 3) at baseline (dupilumab/placebo N = 103/102) and 104 patients with severe PN (IGA PN-S = 4) at baseline (dupilumab/placebo N = 50/54). Baseline demographics and disease characteristics were well balanced in both subgroups. At Week 24, significantly more dupilumab-treated patients achieved an IGA PN-S of 0 (no nodules) or 1 (almost clear; 1−5 nodules), whether they had moderate (52.4% vs 24.5%; nominal P = 0.0008) or severe (40.0% vs 7.4%; nominal P = 0.0014) PN at baseline, with a similar treatment effect (TE) vs placebo in both the moderate (27.9%) and severe (32.6%) subgroups. The proportion of patients with ≥3-point and ≥4-point improvement in WI-NRS, was also significantly greater in the dupilumab group than in the placebo group, whether their PN was moderate (68.9%/62.1% vs 34.3%/22.6%; nominal P = 0.0002/ P < 0.0001, respectively) or severe (72.0%/66.0% vs 31.5%/25.9%; nominal P = 0.0064/ P = 0.0046, resp.) at baseline. Treatment-emergent adverse events (TEAEs) occurred with higher rates in dupilumab-treated patients with moderate PN at baseline (71.6%) compared with placebo (57.8%). Patients with severe PN at baseline had similar rates of TEAEs in the dupilumab (48.0%) and placebo (55.6%) groups. Nevertheless, dupilumab-treated patients with moderate PN at baseline, and those with severe PN at baseline, had overall similar or lower rates vs placebo of serious TEAEs (3.9%/6.0% vs 8.8%/5.6%, resp.), severe TEAEs (4.9%/0.0% vs 5.9%/5.6%, resp.), and frequent TEAEs such as headache (6.9%/2.0% vs 5.9%/5.6%, resp.) and neurodermatitis (2.9%/2.0% vs 2.9%/14.8%, resp.). The incidence of conjunctivitis in dupilumab-treated patients was consistent with the known safety profile vs placebo in both the moderate and severe groups (4.9%/2.0% vs 2.0%/0.0%, resp.). Conclusion Dupilumab treatment for 24 weeks improves itch and skin lesions in patients with PN regardless of lesion severity at baseline, with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Introduction It is unknown whether baseline demographics and disease characteristics have an influence on efficacy and safety of nemolizumab in adults with moderate-to-severe prurigo nodularis (PN). Objectives To report safety and efficacy of nemolizumab in the phase 3 studies (OLYMPIA-1 [NCT04501666]1 and OLYMPIA-2 [NCT04501679]2) for different subgroups. Materials & Methods Data were pooled from the pivotal studies in which adults with moderate-to-severe PN were randomized (2:1) to receive nemolizumab (initial 60mg subcutaneous dose, followed by 30mg/60mg [depending on a baseline weight: <90kg/≥90kg] every 4 weeks) or matching placebo. Results Comparisons in all subgroups (age, sex, race, weight, disease severity, atopy, prior treatment) identified efficacy of nemolizumab versus placebo consistent with the overall intention-to-treat population. At Week (W) 16, a ≥4-point improvement in weekly average Peak Pruritus Numerical Rating Scale of nemolizumab vs. placebo was found in 18- to 65-year-old/>65-year-old: 58.6%/54.0% vs 20.0%/14.3%; males/females: 54.7%/59.2% vs 21.1%/17.1%; White/Black/Asian/Other race: 60.3%/56.5%/36.4%/40.0% vs 20.8%/11.8%/12.5%/0%, <90kg/≥90kg baseline weight: 55.6%/60.8% vs 17.9%/20.8%, baseline Investigator's Global Assessment [IGA] score of 3 [moderate]/4 [severe]: 54.9%/60.8% vs 23.6%/11.7%, with/without history of atopy: 53.8%/59.0% vs 20.3%/17.9% and with/without prior systemic treatment for PN: 57.9%/56.8% vs 14.4%/22.7%. An IGA success (score of 0/1 [clear/almost clear skin] with ≥2-point reduction from baseline) was found in 18- to 65-year-old/>65-year-old: 34.8%/24.0% vs 11.0%/2.4%; males/females: 28.0%/34.5% vs 10.5%/8.1%; White/Black/Asian/Other race: 32.2%/26.1%/33.3%/30.0% vs 8.1%/11.8%/18.8%/0%, <90kg/≥90kg baseline weight: 34.3%/27.2% vs 9.0%/9.4%, baseline IGA score of 3 [moderate]/4 [severe]: 34.0%/29.1% vs 12.7%/3.9%, with/without history of atopy: 29.9%/32.8% vs 4.7%/11.4% and with/without prior systemic treatment for PN: 37.2%/26.8% vs 8.9%/9.3%. Similar results were noted for sleep disturbance. No major difference was reported in the safety profile of nemolizumab between the subgroups. Conclusion Safety and efficacy of nemolizumab monotherapy in itch, skin lesions and sleep disturbance were consistent between the subgroups. [ABSTRACT FROM AUTHOR]

Background Skin pain is a common and burdensome symptom of atopic dermatitis (AD), and its severity increases with disease progression. The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) is a validated 11-item patient-reported instrument developed in accordance with regulatory agency guidance for assessment of the daily symptoms of patients with AD, including skin pain. Objective To establish content validity and evaluate the psychometric properties of the skin pain numerical rating scale (NRS) item of the PSAAD. Methods: The skin pain NRS is a single-item measure from the PSAAD and is used to assess skin pain severity over the past 24 hours with the question "How painful was your skin over the past 24 hours?" on a 10-point scale from 0 (not painful) to 10 (extremely painful). A qualitative validation analysis consisting of concept elicitation (CE) interviews; electronic completion of the PSAAD measure, including the skin pain NRS; and cognitive debriefing (CD) interviews was conducted for adults and adolescents with mild-to-severe AD. Evaluation of psychometric properties of the skin pain NRS--including test-retest reliability, estimation of meaningful within-patient change (MWPC), known-group validity, ability to detect change, construct validity, quality of completion, and ceiling and floor effects--was conducted based on a post hoc qualitative and quantitative analysis of pooled data, with skin pain NRS as part of the PSAAD in the abrocitinib monotherapy phase 3 trials JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871). Data from patients (≥12 years of age) with moderate-to-severe AD were pooled across all treatment arms. Results: Among 30 CE interviews (adolescents [12-17 years], n=15; adults [≥18 years], n=15) conducted over 2 rounds of testing, 20 of 30 (67%) patients reported skin pain. During CD interviews (n=30), 100% of patients interpreted the skin pain NRS item as intended, and 73% reported it as relevant. The psychometric validation analysis included 736 patients (JADE MONO-1, N=347; JADE MONO-2, N=389). The test-retest reliability of the skin pain NRS was evidenced by large intraclass correlation coefficients (ICC; 0.76 and 0.72 in JADE MONO-1 and MONO-2, respectively) for a single daily skin pain score, which increased to 0.93 and 0.91 for a measurement averaging at least 4 scores per week. Convergent validity was demonstrated by correlations between skin pain and other clinician- and patient-reported AD measures (median correlation >0.4 starting at week 4). The skin pain NRS distinguished between "clear" and "severe" disease severity groups, assessed using the Patient Global Assessment (PtGA) and Investigator's Global Assessment (IGA) as continuous and categorical anchors (P<0.0001); differences were also significant among other disease severity groups using the PtGA and IGA as continuous anchors (P<0.0001). Based on the PtGA and IGA anchor analysis, the estimated MWPC was 1.9 and ranged from 2.7 to 3.9 points using the empirical cumulative distribution function analysis. Ability to detect change was demonstrated by linear relationships between disease severity measures and skin pain scores (correlation of ≥0.5 between the skin pain NRS and the PtGA). More than 90% of patients provided at least 4 daily skin pain scores each week. No floor or ceiling effects were observed. Conclusions: The qualitative and quantitative data from initial PSAAD development and psychometric evaluation of the skin pain NRS from the PSAAD support its content validity, reliability, construct validity, and ability to detect change. These findings corroborate the 4-point improvement in skin pain as the adequate and meaningful cut-off to define a skin pain responder in JADE MONO-1 and MONO-2. [ABSTRACT FROM AUTHOR]

Introduction Chronic pruritus is a characteristic of atopic dermatitis (AD), contributing to poor quality of life in patients. Alterations in neuroanatomy and neuroarchitecture associated with pruritus secondary to AD are not fully understood. Objectives: To explore the role of dupilumab treatment effect on epidermal neuroanatomy by quantifying intraepidermal nerve fiber density (IENFD). Method DIFFERENSTAD (NCT04823130) was an open-label, exploratory study that enrolled patients = 18 years old with moderate-to-severe AD, pruritus lasting > 6 weeks, and Worst Itch Numerical Rating Scale (WI-NRS) = 4, and matched healthy controls. Patients with AD received dupilumab 300 mg every 2 weeks for 16 weeks. Skin biopsies were obtained from patients' lesional skin at baseline and localization-matched skin at Week 17 (end of treatment, EoT) and from healthy controls. The primary endpoint, IENFD, was defined as number of nerve fibers crossing the basement membrane per millimeter. Results: 31 patients with moderate-to-severe AD and 10 matched controls were enrolled. IENFD in patients with AD significantly increased from baseline to EoT (mean [SE]: 7.7 [1.3] at baseline vs 12.1 [2.0] at EoT for patients with AD; P = 0.0017), to levels comparable with the control group (mean [SE]: 12.4 [2.3]; P for control group vs EoT in patients with AD = 0.9374). Mean (SE) Eczema Area and Severity Index (EASI) total score and WI-NRS in dupilumab-treated patients were 22.5 (1.5) and 8.5 (0.3) at baseline, and 5.1 (1.1) and 3.1 (0.5) at EoT (both change from baseline P < 0.0001), respectively. The safety profile was consistent with the known safety profile for dupilumab. Conclusions: Dupilumab treatment significantly increased IENFD to levels similar to those of healthy subjects, suggesting restored neuroanatomy in patients with moderate-to-severe AD. Dupilumab also significantly improved clinical signs and pruritus symptoms of AD. [ABSTRACT FROM AUTHOR]

Introduction Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy skin nodules, which substantially affects quality of life. Although topical treatments are frequently prescribed, these therapies are limited by insufficient demonstrated evidence for efficacy, and/or associated side effects. Objectives: This study reports the effect of dupilumab on pruritus, skin lesions, and quality of life in patients with PN, with or without stable use of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI), in an analysis of pooled data from two phase 3 trials. Materials & Methods: LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were two randomized, double-blind, placebo-controlled, 24-week studies. Adults with PN inadequately controlled by topical prescription therapies, or for whom those therapies are inadvisable, were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. "Stable use" was defined as maintaining the same medicine (low-to-medium potency TCS and/or TCI) during the study, with the same frequency of treatment (once or twice daily) as from 2 weeks prior to screening. Efficacy was assessed from baseline to Week 24 through the Worst Itch Numerical Rating Scale (WI-NRS; scored 0-10; high scores represent a poorer outcome), and the Investigator's Global Assessment for PN-Stage score (IGA PN-S; scored 0-4; high scores represent a poorer outcome). Impact on Health-Related Quality of Life (HRQoL) was assessed through the Dermatology Life Quality Index questionnaire (DLQI; 10 questions scored 0-3 with a maximum score of 30; high scores represent poorer HRQoL). Results: 311 patients were randomized (dupilumab/placebo n = 153/158), including 182 patients with stable use of TCI/TCS (dupilumab/placebo N = 91/91) and 129 patients without (dupilumab/placebo N = 62/67). Baseline demographics and disease characteristics were well balanced in both subgroups. At Week 24, significantly more patients treated with dupilumab with or without stable use of TCI/TCS achieved a = 4-point improvement in WI-NRS (59.3%/58.1%) vs placebo (13.2%/26.9% [nominal P < 0.0001/P < 0.0001]). The proportion of patients achieving an IGA PN-S score of 0 or 1 at Week 24 was also significantly higher in the dupilumab group for patients with or without stable use of TCI/TCS (48.4%/43.5%), vs placebo (11.0%/25.4% [nominal P < 0.0001/P = 0.0319]). The positive impact of dupilumab treatment on HRQoL was greater, for patients with and without a stable use of TCI/TCS vs placebo, as suggested by the mean change from baseline in DLQI at Week 24 (-12.9/-11.9 vs -5.5/-7.1 [nominal P < 0.0001/P < 0.0001], respectively). Although the placebo response was higher for patients without stable use of TCI/TCS, the effect of dupilumab treatment was comparable in the two subgroups. Treatment-emergent adverse events (TEAEs) occurred with similar rates in dupilumab-treated patients with or without stable use of TCI/TCS (59.3%/60.7%), compared with placebo (53.3%/47.8%). Patients with or without stable use of TCI/TCS had similar rates of severe TEAEs in the dupilumab groups (2.2%/4.9%) and placebo groups (3.3%/4.5%). Conclusion: Dupilumab treatment improves itch, skin lesions, and quality of life in patients with PN, with an acceptable safety profile, with little to no influence from concomitant treatment with topical therapies (TCI/TCS). [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Technological advances in the field of virtual reality (VR) offer new opportunities in many areas of life, including medical education. The University of Münster has been using VR scenarios in the education of medical students for several years, especially for situations that are difficult to reproduce in reality (e.g., brain death). Due to the consistently positive feedback from students, a dermatological VR scenario for skin cancer screening was developed.Presentation and first evaluation of the skin cancer screening VR scenario to determine to what extent the technical implementation of the scenario was evaluated overall by the students and how their subjective competence to perform a skin cancer screening changed over the course of the teaching unit (theory seminar, VR scenario, theoretical debriefing).Students (n = 140) participating in the curricular pilot project during the 2023 summer term were surveyed throughout the teaching unit using several established questionnaires (System Usability Scale, Simulation Task‐Load‐Index, Realism and Presence Questionnaire) as well as additional questions on cybersickness and subjective learning.(i) The use of VR is technically feasible, (ii) students evaluate the VR scenario as a useful curricular supplement, and (iii) from the students' subjective perspective, a good learning outcome is achieved. Although preparation and follow‐up appear to be important for overall learning, the greatest increase in subjective competence to perform a skin cancer screening is achieved by the VR scenario.Technically feasible and positively evaluated by students, VR can already be a useful addition to dermatology education, although costs are still high. As a visual discipline, dermatology offers special opportunities to create VR scenarios that are not always available or comfortable for patients in reality. Additionally, VR scenarios guarantee the same conditions for all students, which is essential for a high‐quality education. [ABSTRACT FROM AUTHOR]

Notalgia paresthetica (NP) is a sensory neuropathy characterized by chronic pruritus, skin pain, and other pathologic sensations affecting the mid-to-upper back. NP may be under-recognized and under-diagnosed, with limited data available on its symptom presentation and treatment patterns. NP-DERM was an internet-based survey of dermatologists (n = 650) from 8 different countries on their perspectives on NP symptoms and current treatment practices. Dermatologists typically treated a median of 12 patients with NP per month. Dermatologists reported that itch (pruritus) was the most common symptom for their patients with NP, followed by hyperpigmentation and sensitive skin. The most burdensome NP symptom was pruritus, followed by burning or hot sensation, and painful or raw skin. The most prescribed treatments included non-medicated skin care, topical corticosteroids, oral antihistamines, medicated topicals, and gabapentin or pregabalin. Physicians reported low satisfaction with available treatments. The most common reason for physicians to discontinue patients' therapy was lack of response.

Background: Janus kinase inhibitors (JAKinibs) have the potential to dramatically alter the landscape of atopic dermatitis (AD) management due to their promising efficacy results from phase 3 trials and rapid onset of action. However, JAKinibs are not without risk, and their use is not appropriate for all AD patients, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD., Objective: This consensus expert opinion statement from the International Eczema Council (IEC) provides a pragmatic approach to prescribing JAKinibs, including choosing appropriate patients, dosing, clinical and lab monitoring, as well as long-term use., Methods: An international cohort of authors from the IEC with expertise in JAKinibs selected topics of interest and were formed into authorship groups covering 10 subsections. The groups performed topic-specific literature reviews, consulted up-to-date adverse event (AE) data, referred to product labels and provided analysis and expert opinion. The manuscript guidance and recommendations were reviewed by all authors as well as the IEC Research Committee., Results: We recommend JAKinibs be considered for patients with moderate to severe AD seeking the benefits of rapid reduction in disease burden and itch, oral administration, and the potential for flexible dosing. Baseline risk factors should be assessed prior to prescribing JAKinibs, including increasing age, venous thromboembolisms, malignancy, cardiovascular health, kidney/liver function, pregnancy and lactation, and immunocompetence. Patients being considered for JAKinib therapy should be current on vaccinations and we provide a generalized framework for laboratory monitoring, though clinicians should consult individual product labels for recommendations as there are variations among the JAKinib class. Patients who achieve disease control should be maintained on the lowest possible dose, as many of the observed AEs occurred in a dose-dependent manner. Future studies are needed in AD patients to assess the durability and safety of continuous long-term use of JAKinibs, combination medication regimens, and the effects of flexible, episodic treatment over time., Conclusions: The decision to initiate a JAKinib should be shared among patient and provider, accounting for AD severity and personal risk/benefit assessment, including consideration of baseline health risk factors, monitoring requirements and treatment costs., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Prurigo nodularis (PN) is a chronic, inflammatory skin condition characterized by multiple, intensely pruritic, distinctive nodular lesions. Subsequent scratching can further intensify the pruritus, culminating in a self-reinforcing itch-scratch cycle, which drives lesion development. The latest data indicate dysregulation of the neuroimmune axis in PN pathogenesis, including the involvement of sensory neurons, key effector immune cells, proinflammatory cytokines, dermal fibroblasts, and pruritogens. In this review, we highlight evidence supporting the role of type 2 immune axis dysregulation in driving the clinical presentation of PN and discuss how related signaling pathways may offer effective therapeutic targets to control PN signs and symptoms., (Copyright © 2024 Sanofi and Regeneron Pharmaceuticals Inc. Published by Elsevier Inc. All rights reserved.)

Anhedonia, the reduced ability to experience pleasure, is a prevalent symptom in various psychiatric disorders, but has not been investigated in dermatological conditions, particularly those characterized by chronic itch. This study aimed to examine the prevalence and clinical correlates of anhedonia in patients with chronic itch. A cross-sectional study was conducted in 137 patients with chronic itch, classified according to the International Forum for the Study of Itch (IFSI) classification. Anhedonia was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS) and Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS). Itch severity, quality of life, and psychological distress were assessed using the Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), ItchyQoL, and Hospital Anxiety and Depression Scale (HADS), respectively. The mean SHAPS score was 1.0 ± 1.7 points, and the mean ACIPS total score was 76.9 ± 16.2 points. In the study sample, 13.1% of patients were identified as anhedonic, with a higher prevalence observed in those with severe and very severe itch. Anhedonia was significantly correlated with itch severity (R = 0.2, p=0.02 for 24 h VASmean and SHAPS; R = 0.2, p = 0.01 for 24 h VASmax and SHAPS), anxiety symptoms (R = 0.3, p < 0.001 for SHAPS and HADS-anxiety), depression symptoms (R = 0.4, p < 0.001 for SHAPS and HADS-depression), and impairment in quality of life (R = 0.2, p = 0.014 for SHAPS and ItchyQoL). Anhedonia is a significant and prevalent aspect of psychological distress in patients with chronic itch. Addressing this symptom may not only improve patients' overall mental health but also enhance the effectiveness of treatments for chronic itch. Future research is needed to elucidate further the mechanisms underlying the relationship between anhedonia and chronic itch and to develop targeted interventions for this population.

The 4th Davos Declaration was developed during the Global Allergy Forum in Davos which aimed to elevate the care of patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field. This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient-centric care. The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy. The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to collaborate to improve patient outcomes in AD, reflecting a commitment to adapt and respond to the dynamic challenges of AD in a changing world., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Chronic prurigo (CPG) is a neuroinflammatory dermatosis characterized by prolonged pruritus lasting more than 6 weeks, pruriginous skin lesions, and repeated scratching. Patients with CPG suffer significantly from psychological distress and a marked impairment in their quality of life. The most common subtype of CPG is chronic nodular prurigo (CNPG, also called prurigo nodularis). In addition to the clinical features of CPG and the burden of disease, this CME article provides an overview of the significant advances in understanding the pathophysiology, including the associated therapeutic options for CPG. Dupilumab is the first approved therapy for moderate and severe CNPG to date from the European Medicines Agency (EMA) and the US Food & Drug Administration (FDA). It also highlights other agents currently being studied in Phase II and Phase III clinical, randomized, placebo-controlled trials. These include biologics such as nemolizumab (anti-IL-31-RA-mAb), vixarelimab/KPL-716 (anti-Oncostatin-M receptor β-mAb), and barzolvolimab/CDX-0159 (anti-KIT-mAb), as well as Janus kinase inhibitors such as povorcitinib/INCB054707 and abrocitinib, and opioid modulators such as nalbuphine., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)