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Background: Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient-reported outcome (PRO) instruments, Worst Itch-Numeric Rating Scale (WI-NRS), Skin Pain-NRS, Sleep-NRS and Dermatology Life Quality Index (DLQI) have been psychometrically validated and the clinically meaningful within-patient improvement thresholds (responder definition) have been established through data pooled from the two Phase-3 trials (PRIME, NCT04183335 and PRIME2, NCT04202679) of dupilumab in adults with PN uncontrolled on topical therapies., Objectives: To estimate the proportion of dupilumab-treated patients (vs. placebo) achieving clinically meaningful improvement in itch, skin pain, sleep and QoL, either alone or in combination, from the data pooled from PRIME and PRIME2 trials., Methods: The patient-level data pooled from the two Phase-3 trials (N = 311) were used for this post hoc analysis. Thresholds of clinically meaningful within-patient improvement in PRO instrument scores from baseline at Week 24 used for defining responders were 4 (WI-NRS and Skin Pain-NRS), 2 (Sleep-NRS) and 9 points (DLQI). The proportion of dupilumab-treated patients, versus placebo, achieving the thresholds, and the time taken to achieve the thresholds were evaluated for the individual and combination of PROs., Results: Responder rates were significantly higher with dupilumab, versus placebo at Week 24 for WI-NRS (58.8% vs. 19.0%, p < 0.0001), Skin Pain-NRS (49.7% vs. 20.9%, p < 0.0001), Sleep-NRS (42.5% vs. 23.4%, p < 0.0001) and DLQI (64.7% vs. 22.8%, p < 0.0001). Proportion of patients achieving simultaneous improvement in symptoms and QoL (24.8% vs. 6.3%, p < 0.0001) were significantly higher in dupilumab-treated patients versus placebo. The time needed for achieving clinically meaningful improvement in symptoms were significantly lower in dupilumab-treated patients, versus placebo., Conclusions: Significantly greater proportion of dupilumab-treated patients with PN, versus placebo, demonstrated clinically meaningful improvements in PRO measures of symptoms and QoL., (© 2024 Sanofi. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

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.

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.)

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., (© 2023 European Academy of Dermatology and Venereology.)

Importance: Chronic prurigo (CPG), including prurigo nodularis, is a difficult disease to treat and considerably affects patients' quality of life. Helping patients obtain control of CPG is a major treatment goal., Objective: To develop and validate the Prurigo Control Test (PCT), a tool for assessing disease control in CPG, and to identify a cutoff value for controlled disease to aid treatment decisions., Design, Setting, and Participants: This qualitative study followed the current recommendations for patient-reported outcome measure development in the generation and validation of the PCT. The final PCT was obtained after item generation, followed by reduction and selection, and was then tested for internal consistency and test-retest reliability, convergent validity, known-group validity, screening accuracy, and banding. The item-generation phase resulted in an unselected list of 69 potential PCT items. Impact analysis, interitem correlation, and review for content (face) validity resulted in final set of 5 PCT items. The validation study was performed among patients across 2 expert centers in Germany. Data were analyzed from February 2017 to November 2019., Main Outcomes and Measures: A 5-item PCT with a recall period of 2 weeks was developed. A cutoff value of 10 points or higher was determined as suitable for identifying patients with well-controlled vs poorly controlled CPG., Results: Of the 95 patients included in the validation study, the median (range) age was 63 (19-87) years, 50 patients (53%) were women, and the median (range) disease duration was 72 (9-774) months. The validation study yielded good internal consistency reliability (Cronbach α, 0.86) and a high degree of convergent validity. The PCT demonstrated good known-group validity and could discriminate between patients who differed in prurigo control. Test-retest reliability was high, and the intraclass correlation coefficient was 0.94, indicating excellent reproducibility., Conclusions and Relevance: This qualitative study showed that the PCT is able to assess disease control in patients with CPG. Its retrospective approach, brevity, and simple scoring likely make the PCT suitable for clinical practice and trials.

Chronic prurigo (CPG) is a neuroinflammatory, fibrotic dermatosis that is defined by the presence of chronic pruritus (itch lasting longer than 6 weeks), scratch-associated pruriginous skin lesions and history of repeated scratching. Patients with CPG experience a significant psychological burden and a notable impairment in their quality of life. Chronic prurigo of nodular type (CNPG; synonym: prurigo nodularis) represents the most common subtype of CPG. As CNPG is representative for all CPG subtypes, we refer in this review to both CNPG and CPG. We provide an overview of the clinical characteristics and assessment of CPG, the burden of disease and the underlying pathophysiology including associated therapeutic targets. The information provided results from a PubMed search for the latest publications and a database search for current clinical trials (ClinicalTrials.gov, EU Clinical Trials Register [European Medicines Agency]; using the following terms or combinations of terms: 'chronic prurigo', 'prurigo', 'prurigo nodularis', 'pathophysiology', 'therapy', 'biologics', 'treatment'). Dupilumab is the first authorized systemic therapy by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for CNPG to date. Topical and systemic agents that are currently under investigation in clinical randomized, placebo-controlled phase II and III trials such as biologics (e.g., nemolizumab, vixarelimab/KPL-716, barzolvolimab/CDX-0159), small molecules (ruxolitinib cream, povorcitinib/INCB054707, abrocitinib) and the opioid modulator nalbuphine are highlighted. In the last past 15 years, several milestones have been reached regarding the disease understanding of CPG such as first transcriptomic analysis, first terminology, first guideline, and first therapy approval in 2022, which contributed to improved medical care of affected patients. The broad range of identified targets, current case observations and initiated trials offers the possibility of more drug approvals in the near future., (© 2023. The Author(s).)

Background: Prurigo nodularis is a chronic, debilitating, and severely pruritic neuroimmunologic skin disease. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis., Methods: In this phase 3, double-blind, multicenter, randomized trial, we assigned adults with moderate-to-severe prurigo nodularis to receive an initial 60-mg dose of nemolizumab followed by subcutaneous injections of 30 mg or 60 mg (depending on baseline weight) every 4 weeks for 16 weeks or matching placebo. The primary end points were an itch response (a reduction of ≥4 points on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10, with higher scores indicating more severe itch]) and an Investigator's Global Assessment (IGA) response (a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4] and a reduction from baseline to week 16 of ≥2 points). There were five key secondary end points., Results: A total of 274 patients underwent randomization; 183 were assigned to the nemolizumab group, and 91 to the placebo group. Treatment efficacy was shown with respect to both primary end points at week 16; a greater percentage of patients in the nemolizumab group than in the placebo group had an itch response (56.3% vs. 20.9%; strata-adjusted difference, 37.4 percentage points; 95% confidence interval [CI], 26.3 to 48.5), and a greater percentage in the nemolizumab group had an IGA response (37.7% vs. 11.0%; strata-adjusted difference, 28.5 percentage points; 95% CI, 18.8 to 38.2) (P<0.001 for both comparisons). Benefits were observed for the five key secondary end points: itch response at week 4 (41.0% vs. 7.7%), PP-NRS score of less than 2 at week 4 (19.7% vs. 2.2%) and week 16 (35.0% vs. 7.7%), and an improvement of 4 or more points on the sleep disturbance numerical rating scale (range, 0 [no sleep loss] to 10 [unable to sleep at all]) at week 4 (37.2% vs. 9.9%) and week 16 (51.9% vs. 20.9%) (P<0.001 for all comparisons). The most common individual adverse events were headache (6.6% vs. 4.4%) and atopic dermatitis (5.5% vs. 0%)., Conclusions: Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.)., (Copyright © 2023 Massachusetts Medical Society.)

Importance: Prurigo nodularis (PN) is a debilitating skin disease characterized by intense pruritus and hyperkeratotic skin nodules. Nemolizumab, a monoclonal antibody targeting interleukin 31 receptor α, is a promising novel therapy for the treatment of moderate to severe PN. The biological mechanisms by which nemolizumab promotes improvement of itch and skin lesions in PN are unknown., Objective: To characterize changes in plasma protein biomarkers associated with clinical response to nemolizumab in patients with PN., Design, Setting, and Participants: This multicenter cohort study included patients recruited from Austria, France, Germany, Poland, and the US from a phase 2 clinical trial. Adults diagnosed with moderate to severe PN with severe pruritus for at least 6 months were included in the original trial. Patients in the nemolizumab group were included in the present study if they achieved at least a 4-point decrease in the Peak Pruritus Numerical Rating Scale (PP-NRS) from baseline to week 12 during nemolizumab treatment. Placebo controls did not experience a 4-point decrease in PP-NRS. Mass spectrometry with tandem mass tags to enrich skin-specific protein detection was used to characterize changes in plasma protein expression in nemolizumab and placebo groups. Data were collected from November 2, 2017, to September 26, 2018, and analyzed from December 6, 2019, to April 8, 2022., Intervention: As part of the clinical trial, patients were treated with 3 doses of nemolizumab or placebo at 0, 4, and 8 weeks., Main Outcomes and Measures: Changes in plasma and epidermal protein expression in nemolizumab-treated patients compared with the placebo group at 0, 4, and 12 weeks., Results: Among the 38 patients included in the analysis (22 women and 16 men; mean [SD] age, 55.8 [15.8] years), enrichment analysis of canonical pathways, biological functions, and upstream regulators showed downregulation of terms involving inflammation (IL-6, acute-phase response, signal transducer and activator of transcription 3, and interferon γ), neural processes (synaptogenesis signaling and neuritogenesis), tissue remodeling and fibrosis (transforming growth factor β1 and endothelin-1), and epidermal differentiation (epithelial mesenchymal transition) in the plasma of nemolizumab group., Conclusions and Relevance: In this cohort study, differences between nemolizumab and placebo groups included modulation of inflammatory signaling, neural development, and epithelial differentiation, suggesting a promising potential approach for clinical management of PN.

Chronic pruritus (CP) (ie, itch that persists for more than 6 weeks) poses significant challenges to patients' health and quality of life. It is a common reason for visits to dermatologists and general practitioners and can be caused by a range of conditions, including systemic diseases such as chronic kidney disease or liver diseases, malignancies, neuropathic conditions, and dermatoses such as atopic dermatitis. CP often does not develop in parallel with the course of the disease and can become an entity of its own, which must be treated with antipruritic drugs, even if the underlying cause is already under therapy. Depending on the etiology of CP, different pathways in the pathogenesis have been analyzed recently, following which new treatments have been developed and tested in randomized controlled trials. This article discusses the recent results of these studies and highlights how best to manage health care for patients with CP., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Prurigo nodularis (PN) is a chronic inflammatory skin disease with intensely pruritic nodules. The LIBERTY-PN PRIME and PRIME2 phase 3 trials enrolled adults with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13. Patients were randomized 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, measured by proportion of patients with a ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included nodule number reduction to ≤5 at week 24. PRIME and PRIME2 enrolled 151 and 160 patients, respectively. Both trials met all the pre-specified primary and key secondary endpoints. A ≥4-point WI-NRS reduction at week 24 in the dupilumab and placebo arms was achieved by 60.0% and 18.4% of patients, respectively, in PRIME (95% confidence interval (CI), 27.8-57.7 for the difference, P < 0.001) and at week 12 by 37.2% and 22.0% of patients, respectively, in PRIME2 (95% CI, 2.3-31.2; P = 0.022). Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions versus placebo in PN. Safety was consistent with the known dupilumab safety profile.ClinicalTrials.gov identifiers: NCT04183335 and NCT04202679 ., (© 2023. The Author(s).)

Scratching and scratch-induced injuries, including neuroanatomical alterations, are key characteristics of chronic pruritus entities of different origins. The aim of this study was to link gene expression (array hybridization, qPCR) with DNA methylation (array hybridization) and neuroanatomy (PGP9.5 staining) in chronic nodular prurigo (CNPG), atopic dermatitis (AD), brachioradial pruritus (BRP), and matched healthy controls. Specific signatures of gene expression and DNA methylation clearly discriminated pruritic lesional skin from nonpruritic skin in CNPG and from healthy skin of volunteers, respectively. Although intraepidermal nerve fiber density was indiscriminately reduced, the level of epidermal branching, assessed by a semiquantitative pattern analysis, differentiated the entities (CNPG > BRP > AD). Correspondingly, repellent SEMA3A showed the highest expression in AD, whereas axonal growth-promoting nerve GF was most prominent in CNPG and BRP. Overexpression of genes for nerve fiber regeneration (NELL2/NFKB/ARTN) was found in AD and CNPG but not in BRP. Our findings suggest that differential branching patterns rather than mere innervation density separate chronic itch conditions and reflect disease-specific local expression profiles. In pruritic dermatoses (AD and CNPG), nerve injury and subsequent sprouting may primarily result from chronic scratching, whereas genuine neuropathy is expected to underlie BRP., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Pruritus is a cross-disciplinary leading symptom of numerous diseases and represents an interdisciplinary diagnostic and therapeutic challenge. In contrast to acute pruritus, chronic pruritus (CP) is a symptom of various diseases that is usually difficult to treat. Scratching and the development of scratch-associated skin lesions can alter the original skin status. In the presence of an itch-scratch-cycle, even secondary diseases such as chronic prurigo can develop. Chronic pruritus leads to considerable subjective suffering of those affected, which can result in restrictions on the health-related quality of life such as sleep disturbances, anxiety, depressiveness, experience of stigmatization and/or social withdrawal up to clinically relevant psychic comorbidities. Medical care of patients should therefore include (a) interdisciplinary diagnosis and therapy of the triggering underlying disease, (b) therapy of the secondary symptoms of pruritus (dermatological therapy, sleep promotion, in the case of an accompanying or underlying psychological or psychosomatic disease an appropriate psychological-psychotherapeutic treatment) and (c) symptomatic antipruritic therapy. The aim of this interdisciplinary guideline is to define and standardize the therapeutic procedure as well as the interdisciplinary diagnosis of CP. This is the short version of the updated S2k-guideline for chronic pruritus. The long version can be found at www.awmf.org., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Prurigo nodularis is a debilitating skin condition that is classified as rare by the Genetic and Rare Diseases Information Center (GARD) and the National Organization for Rare Diseases (NORD). There are currently no estimates of the prevalence of prurigo nodularis in England., Objectives: We aimed to address this data gap by describing the epidemiology of prurigo nodularis in a representative dataset derived from the English National Health Service., Methods: The study utilized data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics inpatient data. Patients with a diagnosis of prurigo nodularis were selected by clinical code in the primary care or inpatient datasets. Case definition was based on a minimum of two distinct diagnoses to maximize specificity. Point prevalence was calculated for the midpoint of 2018 and incidence rates from 2008 to 2018 were presented. For those classified as incident cases, demographic and clinical characteristics were reported. In sensitivity analyses the case definition was modified to relax the multiple diagnosis criteria and to restrict cases to those diagnosed within a maximum of 4 or 10 years of the midpoint prevalence date., Results: Overall, 11 656 patients within the dataset had at least one prurigo nodularis diagnosis. Following application of the relevant inclusion criteria, 2743 patients formed the point prevalent cohort; the estimated prevalence was 3·27 patients per 10 000 population [95% confidence interval (CI) 3·15-3·40]. In sensitivity analyses the estimated prevalence ranged from 2·24 (95% CI 2·14-2·34) to 6·98 (95% CI 6·80-7·16). Incidence over the study period was 2·88 per 100 000 patient-years. Comorbidity was relatively high in this population, notably for atopic dermatitis (52·2%), depression (41·1%) and anxiety (35·4%)., Conclusions: This study supports the NORD/GARD classification of prurigo nodularis as a rare disease with a prevalence of 3·27 patients per 10 000 population, which equates to 18 471 patients living with the disease in England in 2018. The relatively high prevalence of comorbidity observed for these patients may increase the complexity of management., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Chronic prurigo is an inflammatory dermatosis defined by the presence of chronic pruritus and single to multiple symmetrically distributed pruriginous lesions such as nodules, papules, and plaques. Various dermatological, systemic, neurological, and/or psychiatric diseases are associated with chronic prurigo. The care of these patients is very complex due to the multifactorial character and also because of the sometimes very pronounced consequences such as an impairment of quality of life with sleep disorders. Furthermore, there are no approved therapies. The current guideline-based treatment recommendations include topical application of steroids, capsaicin, calcineurin inhibitors, phototherapy, and systemic use of gabapentinoids, μ‑opioid receptor antagonists, immunosuppressants, or dupilumab. Results from randomized controlled trials and case series on new therapies including biologics (e.g., nemolizumab) and Janus kinase inhibitors are promising. This article provides an overview of currently available treatment options and discusses the latest data on the efficacy of future therapies., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Prurigo nodularis (PN) is a debilitating, difficult-to-treat, intensely pruritic, chronic inflammatory skin disease characterized by hyperkeratotic skin nodules. The pathogenesis of PN is not well understood but is believed to involve cross talk between sensory nerve fibers, immune cells, and the epidermis. It is centered around the neuroimmune cytokine IL-31, driving an intractable itch-scratch cycle., Objective: We sought to provide a comprehensive view of the transcriptomic changes in PN skin and characterize the mechanism of action of the anti-IL-31 receptor inhibitor nemolizumab., Method: RNA sequencing of biopsy samples obtained from a cohort of patients treated with the anti-IL-31 receptor inhibitor nemolizumab and taken at baseline and week 12. Generation and integration of patient data with RNA-Seq data generated from reconstructed human epidermis stimulated with IL-31 and other proinflammatory cytokines., Results: Our results demonstrate that nemolizumab effectively decreases IL-31 responses in PN skin, leading to effective suppression of downstream inflammatory responses including T H 2/IL-13 and T H 17/IL-17 responses. This is accompanied by decreased keratinocyte proliferation and normalization of epidermal differentiation and function. Furthermore, our results demonstrate how transcriptomic changes associated with nemolizumab treatment correlate with improvement in lesions, pruritus, stabilization of extracellular matrix remodeling, and processes associated with cutaneous nerve function., Conclusion: These data demonstrate a broad response to IL-31 receptor inhibition with nemolizumab and confirm the critical upstream role of IL-31 in PN pathogenesis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To date, there have been no large studies describing real-world treatment of chronic prurigo (CPG) and pruritus (CPR) in Germany., Objective: To determine the healthcare utilization, treatment patterns, and costs associated with CPG and CPR in Germany., Methods: Retrospective analysis using anonymized claims data (German DAK-Gesundheit), based on a 40% sample of all insured adults of the DAK-Gesundheit on December 31, 2010 (N = 2,006,003)., Results: Patients with CPR (prevalence 2.2%) most commonly visited general medicine/general practitioners (GPs, 80.1%), followed by gynecologists (66.1%) and dermatologists (51.1%). Patients with CPG (prevalence 0.2%) most commonly visited dermatologists (85.7%), GPs (78.1%), and ophthalmologists (47.2%). Of adult patients, 44% received at least one drug prescription. Two thirds of patients with a drug prescription received ≥1 topical drug (66.2%), and 54.3% ≥1 systemic drug (total costs of approximately EUR 550,000 and 2,500,000, respectively). Of patients with CPG, 33.8% received ≥1 systemic and 45.1% ≥1 topical drug prescription (costs of approximately EUR 360,000 vs. 105,000). Of patients with CPR, 23.5% received ≥1 systemic and 28.6% ≥1 topical drug prescription (costs of approximately EUR 2,000,000 vs. 500,000). Of patients with CPG, 5.8% received ≥1 phototherapy application vs. 1.2% of patients with CPR., Conclusions: These findings reflect the reality of care and can form a basis for the identification of overuse, underuse, and misuse in order to design CPG and CPR healthcare more effectively and efficiently., (© 2022 S. Karger AG, Basel.)

Introduction: Prurigo nodularis (PN) or chronic prurigo of nodular type (CNPG) is a subtype of chronic prurigo with severe pruritus and neuroimmune underlying pathophysiology occurring in a plethora of dermatological, systemic, neurologic, and psychiatric conditions., Areas Covered: We review the increasing repertoire of biologics in the treatment of CNPG focusing on those targeting interleukins 4, 13, 31, oncostatin M and IgE. Presented information is based on a database research on current clinical trials (clinicaltrials.gov, European Clinical Trials Database (EudraCT), US clinical trial registry ICH-GCP) and a PubMed search for latest publications conducted with the combinations of the terms 'chronic prurigo,' 'prurigo nodularis,' 'pathophysiology,' 'treatment,' 'therapy', and 'biologics.', Expert Opinion: CNPG gets more and more attention as new therapeutic targets have been revealed in recent years, thus allowing the use of targeted approaches. The off-label advent of dupilumab offered advanced insight into the pathogenesis of CNPG and showed an impressive relief of pruritus in the vast majority of patients. New therapies including biologics (e.g. nemolizumab, tralokinumab, lebrikizumab), small molecules (e.g. neurokinin-1 receptor antagonists, janus kinase inhibitors) as well as mu-opioid receptor antagonists and nalbuphine, a μ-antagonist/κ-agonist, are in the pipeline and offer new hope for an improved future patient care.

Chronic prurigo is a pruritic disease characterized by the development of pruriginous lesions due to scratching. The number of lesions is representative of the stage of the disease, while the presence of excoriations reflects the scratching activity. Aim of this study was to validate a new developed tool for the objective assessment of chronic prurigo. Investigator's Global Assessment scales for stage and activity were completed for 187 patients with chronic prurigo, who also reported patient-reported outcomes for itch intensity and quality of life. To assess the reliability and objectivity of the Investigator's Global Assessment, 5 independent raters completed the Investigator's Global Assessment scales for 8 patients twice. The scores increased with increased intensity of pruritus. The Investigator's Global Assessment stage scales correlated strongly with each other (Kendall's-tau-b 0.62) and moderately with the Investigator's Global Assessment activity scale (Kendall's-tau-b 0.47). Intra-rater test-retest reliability was excellent for all items, while the congruence among raters was very good for Investigator's Global Assessment - chronic prurigo activity (Kendall's W 0.84) and good for Investigator's Global Assessment stage scales (Kendall's W 0.747). Investigator's Global Assessment - chronic prurigo stage and activity are thus the best Investigator's Global Assessment instruments for use in assessing chronic prurigo.

Chronic nodular prurigo is characterized by recalcitrant itch. Patient perspectives on therapeutic goals, satisfaction with therapy and efficacy of therapeutic regimens for this condition are unknown. This questionnaire study examined these issues in 406 patients with chronic nodular prurigo from 15 European dermatological centres. Improvements in itch, skin lesions and sleep were the most important goals. Emollients, topical corticosteroids and antihistamines were the most frequently used treatments, while a minority of patients were prescribed potent medications, such as systemic immunosuppressants and gabapentinoids. Most patients were not satisfied with their previous therapy (56.8%), while 9.8% did not receive any therapy despite having active disease. A substantial number of respondents (28.7%) considered none of the therapeutic options effective. Although chronic nodular prurigo is a severe disease, most patients were not treated with potent systemic drugs, which may contribute to the high levels of dissatisfaction and disbelief in available therapies. Specific guidelines for chronic nodular prurigo and the development of novel therapies are necessary to improve care.

Importance: There is an unmet need for psychometrically sound instruments to measure pruritus associated with prurigo nodularis (PN)., Objective: To evaluate the psychometric properties of the itch numeric rating scale (itch NRS), both the Worst Itch Numeric Rating Scale (WI-NRS) and the Average Itch Numeric Rating Scale (AI-NRS)., Design, Setting, and Participants: This secondary analysis is based on a secondary end point of a phase 2 randomized clinical trial of serlopitant for treatment of pruritus associated with PN. This randomized, double-blind, placebo-controlled study was conducted at 15 sites in Germany. Eligible patients were aged 18 to 80 years and had generalized PN for more than 6 weeks that was refractory to previous antipruritic therapies. Patients were required to have a visual analog scale itch score of 7 or higher at screening. Data were collected from July 2014 to June 2016 and analyzed from June 2016 to January 2017., Main Outcomes and Measures: The itch NRS (AI-NRS and WI-NRS) was correlated together with the following measures: the electronic verbal rating scale (eVRS) for itch self-categorization, average itch visual analog scale (AI-VAS), worst itch visual analog scale (WI-VAS), the pruritus-specific quality-of-life rating instrument ItchyQoL, Dermatology Life Quality Index (DLQI), and Prurigo Activity and Severity Score (items 7b and 7a: percentage healed prurigo lesions and percentage of prurigo lesions with excoriations)., Results: There were 123 participants in this study; the mean (SD) age of participants was 57.3 (11.58) years, and 58 (47.2%) were male. Strong associations (r ≥ 0.5) were observed between itch NRS items (WI-NRS and AI-NRS) and AI-VAS (24 hours) at weeks 2, 4, and 8 (r = 0.72-0.90; P < .001). Similar strong associations were also observed between itch NRS items and WI-VAS (24 hours) and eVRS for itch severity across weeks 2, 4, and 8 (r = 0.65-0.92; all P < .001). Strong correlations were seen between change scores for WI-NRS and WI-VAS and AI-VAS (r = 0.76 and 0.70, respectively; both P < .001). Similar findings were seen for AI-NRS, where correlations between change scores for WI-VAS and AI-VAS were 0.71 and 0.72, respectively (both P < .001). Analyses for the itch NRS items also showed that test-retest reliability was acceptable and provided evidence of acceptable convergent validity based on the eVRS and visit verbal rating score for itch self-categorization, ItchyQoL, and DLQI., Conclusions and Relevance: Results from this secondary analysis show that the itch NRS items WI-NRS and AI-NRS have good psychometric properties for pruritus associated with PN and should be considered acceptable tools for assessing pruritus in future clinical trials of PN., Trial Registration: ClinicalTrials.gov Identifier: NCT02196324.

Prurigo nodularis is an itchy skin disease with unknown epidemiology. This study aimed to describe the epidemiology of prurigo nodularis compared with that of psoriasis. The German sickness fund claims database, with 2,783,175 continuously insured patients, included 1,720 patients diagnosed with prurigo nodularis and 51,390 with psoriasis. Patients with prurigo nodularis were averagely 8 years older than psoriasis patients and more often were women (p < 0.001). Annual incidence was a constant 0.02% in prurigo nodularis, and decreased steadily from 0.53 to 0.42% in psoriasis; cumulative incidence was 0.1% for prurigo nodularis and 1.9% for psoriasis. Prevalence was 0.1% for prurigo nodularis and 4.7% for psoriasis, with a 1-year mortality of 5.4% for prurigo nodularis and 1.2% for psoriasis (p < 0.001). The most frequent pre-existing comorbidities in patients with prurigo nodularis were inflammatory dermatoses and depression. This epidemiological study found a low prevalence of prurigo nodularis, manifesting different demographics and comorbidities compared with psoriasis.

Chronic nodular prurigo presents with multiple pruriginous nodules and severe pruritus. This study aims to explore the treatment course and regimens in patients with chronic nodular prurigo and to analyse predictive factors contributing to therapeutic success. A total of 325 patients with chronic nodular prurigo (male 37.5%) were analysed concerning demographic data, pruritus intensity, medical history, psychological impairment, quality of life, treatment duration, regimens and outcome. These parameters were compared with 325 sex- and age-matched patients with chronic pruritus on non-lesional skin. Treatment success was dependent on duration and regime of treatment and independent of age, sex and initial itch intensity. Non-responders displayed a higher percentage of inflamed nodules, a higher portion of excoriated nodules and a higher impairment of quality of life and mood factors before initiation of treatment. Gabapentinoids and immunosuppressants proved to be the most successful therapeutic agents. Compared with patients with chronic pruritus, those with chronic nodular prurigo needed longer duration of therapy.

Background: Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis., Methods: We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18., Results: A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms., Conclusions: Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.)., (Copyright © 2020 Massachusetts Medical Society.)

Chronic nodular prurigo (CNPG) is a subtype of chronic prurigo, also called prurigo nodularis, and a chronic skin condition characterized by intensely pruritic nodular lesions. Although the exact cause of CNPG is unknown, it appears to result from a repetitive itch-scratch cycle induced by neuronal sensitization to chronic pruritus. CNPG is associated with an underlying dermatologic condition in about half of patients, and it can also be attributed to systemic, neurologic, psychogenic, or unknown causes. For most patients, multiple underlying causes are identified. Patients with CNPG often experience impaired quality of life, sleep disturbance, anxiety, and depression. To encourage consistent and accurate diagnosis and treatment of CNPG across regions, we are proposing a diagnostic and treatment algorithm that includes initial assessment of core symptoms, detailed dermatologic history and clinical examination, patient-reported outcomes, diagnostic workup, and recommended therapies. This information is supplemented with photographs to illustrate clinical appearance and disease severity. Because CNPG is often multifactorial and it can take months to years for lesions to heal, interdisciplinary cooperation and long-term management are important., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Neurophysiological mechanisms leading to chronicity of pruritus are not yet fully understood and it is not known whether these mechanisms diverge between different underlying diseases of chronic pruritus (CP). This study aimed to detect such mechanisms in CP of various origins. A total of 120 patients with CP of inflammatory origin (atopic dermatitis), neuropathic origin (brachioradial pruritus), and chronic prurigo of nodular type, the latter as a model for chronic scratching, as well as 40 matched healthy controls participated in this study. Stimulation with cowhage induced a more intensive itch sensation compared with stimulation with other substances in all patient groups but not in healthy controls, arguing for sensitization of cutaneous mechano- and heat-sensitive C-fibers in CP. All patient groups showed a decreased intraepidermal nerve fiber density compared with controls. A decreased condition pain modulation effect was observed in all patient groups compared with controls, suggesting a reduced descending inhibitory system in CP. In sum, CP of different etiologies showed a mixed peripheral and central pattern of neuronal alterations, which might contribute to the chronicity of pruritus with no differences between pruritus entities. Our findings may contribute to the development of future treatment strategies targeting these pathomechanisms., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic prurigo impairs quality of life and is immensely challenging to treat. Until recently, no clear definition or classification system was available for this disease. A European task force specialized in pruritus defined chronic prurigo as a distinct disease characterized by chronic pruritus, a lengthy scratching behaviour and the presence of pruriginous lesions. Papular, nodular, plaque, umbilicated and linear prurigo were identified as clinical subtypes according to the most prominent lesion type observed in the physical examination. Various clinical and pathophysiological aspects, which are common across the range of clinical manifestations of chronic prurigo, argue for chronic prurigo as a disease in its own right. Chronic prurigo should be clearly demarcated from other conditions such as so-called acute or subacute prurigo forms as well as from psychogenic self-inflicted skin lesions, since different diagnostic criteria apply for these diseases. This viewpoint essay provides a detailed definition and classification of chronic prurigo including its obligatory and associated diagnostic criteria and discusses chronic prurigo as a distinct disease as well as the demarcation to other relevant conditions., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossed-over to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. (DRKS00005594; EudraCT Number: 2013-001601-85).

Prurigo nodularis occurs with chronic pruritus and the presence of single to multiple symmetrically distributed, hyperkeratotic, and intensively itching nodules. Diverse dermatologic, systemic, neurologic, or psychiatric conditions can lead to prurigo nodularis. Structural analysis demonstrated a reduced intraepidermal nerve fiber density and increased dermal levels of nerve growth factor and neuropeptides such as substance P and calcitonin gene-related peptide. Novel therapy concepts such as inhibitors at neurokinin-1, opioid receptors, and interleukin-31 receptors have been developed. The mainstays of prurigo nodularis therapy comprise topical steroids, capsaicin, calcineurin inhibitors, phototherapy, and the systemic application of anticonvulsants, μ-opioid receptor antagonists, or immunosuppressants., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Prurigo nodularis (PN) is a subtype of chronic prurigo presenting single to multiple symmetrically distributed, hyperkeratotic and intensively itching papules and nodules. PN evolves along with chronic pruritus in the context of diverse dermatological, systemic, neurological or psychiatric conditions. Permanent scratching is possibly a major trigger of PN, although its exact pathophysiology remains unclear. Current state-of-the-art therapy for PN consists of topical steroids, capsaicin, calcineurin inhibitors, ultraviolet (UV) therapy, systemic administration of gabapentinoids, μ-opioid receptor antagonists, antidepressants or immunosuppressants. Novel treatment concepts, such as inhibitors of neurokinin-1, opioid and interleukin-31 receptors, have been developed and are currently being clinically tested.

Patients with chronic pruritus may develop scratch-induced lesions with elevated borders and central necrosis. This so-called umbilicated type of prurigo (UP) is rare and is assumed to develop preferentially in the context of metabolic diseases. The aim of this study was to characterize UP in its clinical and histological dimension. Demographic and clinical data were collected from 23 patients with UP. Intensive light microscopical analysis of biopsied lesions was performed. Statistical comparison with previous results for prurigo nodularis (PN) showed that UP is clearly a subtype of PN. In addition, clinical and microscopic features of epidermal perforation identical to those in acquired reactive perforating dermatosis (ARDP) were observed. Hence, we suggest that ARDP is identical to UP and is therefore a subtype of PN. We assume that reduced wound healing capacities due to underlying systemic disorders, particularly diabetes mellitus and uraemia, underlie the pathomechanism of development of umbilicated skin lesions with a perforating aspect.

Characterized by the clinical presentation of individual to multiple symmetrically distributed, hyperkeratotic, and intensely itchy papules and nodules, prurigo nodularis (PN) is a rare disease that emerges in patients with chronic pruritus due to continuous scratching over a long period of time. The itching and scratching of the lesions contribute to the vicious cycle that makes this disease difficult to treat, thus reducing the quality of life of affected patients. The pathogenesis of PN is ambiguous, although immunoneuronal crosstalk is implicated. Its etiology was found to be heterogenous. It can emerge as the symptom of various dermatological, neurological, psychiatric, and systemic diseases. There is currently no approved therapy for PN. However, contemporary therapies consist of calcineurin inhibitors, capsaicin, topical steroids, UV therapy, and a systemic application of antihistamines, anticonvulsants, μ-opioid receptor antagonists, and immunosuppressants. Multimodal therapy should be utilized in order to achieve optimal results, including topical and systemic symptomatic therapies., (© 2016 S. Karger AG, Basel.)

Background: In the treatment of atopic dermatitis, pimecrolimus has high antipruritic effects., Objective: To investigate the efficacy of 1% pimecrolimus cream in comparison to 1% hydrocortisone cream in non-atopic prurigo nodularis (PN)., Methods: A randomized, controlled, double-blind study with intraindividual randomization was done in 30 patients (17 females, 13 males; mean age 58.5 years) with PN., Results: Pruritus intensity decreased significantly (p < 0.001) on both treated sides as early as after 10 days of treatment; scratch lesions improved (p < 0.001). Quality of life as assessed by the Dermatology Life Quality Index improved significantly. However, a significant advantage of pimecrolimus over hydrocortisone was not found., Conclusion: The results suggest that the non-steroid pimecrolimus is an effective alternative for PN treatment.

Background: In prurigo nodularis (PN), an increase in the density of dermal substance P-positive (SP+) sensory nerve fibers has been demonstrated. In addition, the density of sympathetic nerve fibers is unchanged., Objective: We aimed to investigate the density and balance of sensory and sympathetic dermal nerves in pruritus on normally appearing skin in comparison to PN., Methods: In a parallel investigation in lesional and non-lesional skin routine histological and immunofluorescence staining against SP and tyrosine hydroxylase (TH) were performed., Results: We found an increased density of dermal SP+ nerve fibers in PN and also in pruritus relative to sympathetic nerve fibers in affected areas compared to the unaffected site. The density of SP+ and TH+ nerves did not correlate with clinical parameters such as itch quality, duration or intensity. Sparse lymphocytic infiltration as found in affected pruritus skin may be a source of nerve growth factor and explain the hyperinnervation., Conclusion: Similar to the situation in PN, chronic pruritus lesions also demonstrate a preponderance of SP+ sensory nerve fibers relative to sympathetic nerve fibers, which probably acts as a causal pro-inflammatory signal in development of pruritus. These findings suggest new therapeutic approaches in patients with chronic pruritus., (Copyright 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: To date, there has been no systematic investigation of the detailed histological features of prurigo nodularis (PN) in a large cohort of patients., Methods: This retrospective study includes skin biopsies of 136 patients (63 males, 73 females; mean age: 58.38 years) with PN., Results: Highly characteristic for PN is the presence of thick compact orthohyperkeratosis; the hairy palm sign (folliculosebaceous units in nonvolar skin in conjunction with a thick and compact cornified layer, like that of volar skin); irregular epidermal hyperplasia or pseudoepitheliomatous hyperplasia; focal parakeratosis; hypergranulosis; fibrosis of the papillary dermis with vertically arranged collagen fibers; increased number of fibroblasts and capillaries; a superficial, perivascular and/or interstitial inflammatory infiltrate of lymphocytes, macrophages and, to a lesser extent, eosinophils and neutrophils. For comparison, histological findings in 45 patients (18 males, 27 females; mean, 55.64 years) with lichen simplex (LS) were studied. PN and LS, both of them scratch-induced, had 50 of 58 (86.2%) histological features in common., Conclusions: PN revealed a characteristic histological pattern. Absence of pseudoepitheliomatous hyperplasia or nerve fiber thickening, however, does not rule out the histological diagnosis of PN. A correlation of clinical and histological findings is necessary to reliably distinguish between PN and LS.

Background: Prurigo nodularis shows intense itching nodules, which are often persistent and therapy refractory. Histological alterations include fibrosis of collagen fibers and presence of inflammatory infiltrate, which partly explains the clinical persistence of lesions. Inflammatory cells may directly contribute to induction and maintenance of pruritus at nerve fibers. Cyclosporine microemulsion (ME) suppresses the migration and proliferation of inflammatory cells and may thereby interfere with pathogenesis of prurigo nodularis. The aim of this investigation was to assess the antipruritic efficiency of cyclosporine ME in therapy of prurigo nodularis., Patients and Methods: 14 patients with prurigo nodularis of diverse origin and failure to previous therapy were treated with oral cyclosporine ME (3 to 5 mg per kg daily). Blood pressure, liver enzymes, renal function and differential blood count were monitored., Results: In 13 of 14 prurigo patients (92.9 %) there was a significant response to monotherapy with cyclosporine ME. The maximal antipruritic effect occurred after 2 weeks to 12 months. Prurigo nodules also healed during therapy. Seven patients (50.0 %) described side effects. In one case the therapy was stopped., Conclusions: Oral cyclosporine ME is an effective therapy for prurigo nodularis of diverse origin. It appears to function by inhibiting dermal inflammatory cells.

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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]

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 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]

Introduction: Sleep is often disturbed in patients with prurigo nodularis (PN). To address the lack of validated patient-reported outcome (PRO) measures for quantifying sleep disturbance in PN, we evaluated the Sleep Disturbance Numerical Rating Scale (SD NRS) as a single-item PRO measure for quantifying sleep disturbance in PN. Methods: Adults with PN participated in qualitative interviews, which included concept elicitation and cognitive debriefing of the SD NRS. The SD NRS was evaluated psychometrically using data from a phase 2 randomized trial in adults with PN (NCT03181503). Other PRO assessments included the Average Pruritus (AP) NRS, AP Verbal Rating Scale (VRS), peak pruritus (PP) NRS, PP VRS, and Dermatology Life Quality Index (DLQI). Reliability, validity, and responsiveness of the SD NRS were evaluated, and meaningful within-patient change was estimated from qualitative interview responses and quantitative trial data. Results: All interview participants (N = 21) experienced sleep disturbance and most (95%) understood the SD NRS as intended. The SD NRS demonstrated test–retest reliability based on intra-class correlation coefficients for itch-stable participants of 0.87 for the AP VRS and 0.76 for the PP VRS. At baseline, Spearman's rank-order correlation coefficients were moderate to strong (0.3–0.8) between the SD NRS and the AP NRS, AP VRS, PP NRS, PP VRS, and DLQI. Known-groups validity was demonstrated by higher (worse) SD NRS scores in participants with worse scores on the AP NRS, AP VRS, PP VRS, and DLQI. Improvements in SD NRS scores were greater in participants classified as "improved" versus "worsened/unchanged" on the anchor PROs. A 2- to 4-point decrease on the 11-point SD NRS scale was identified as a meaningful within-patient change. Conclusion: The SD NRS is a well-defined, reliable, and valid PRO measure that can be used in daily practice and clinical trials to capture sleep disturbance in adults with PN. Plain Language Summary: Patients with the skin disease prurigo nodularis often sleep badly because their skin is very itchy in the evening and at night. In assessing the effectiveness of new treatments for prurigo nodularis, it is useful to know whether patients sleep better when taking them. Here, we tested whether the "Sleep Disturbance Numerical Rating Scale" (SD NRS), a tool for measuring sleep, can be used by patients with prurigo nodularis. The SD NRS asks patients to score their sleep loss during the previous night on a scale of 0 ("no sleep loss") to 10 ("I did not sleep at all"). When we interviewed 21 patients with prurigo nodularis, 19 of them had problems falling asleep and 18 of them woke up every night. Most of the patients found the SD NRS easy to use. To further explore whether the SD NRS is suitable for patients with prurigo nodularis, we also analyzed data from a European clinical study in which patients with prurigo nodularis received nemolizumab, a new treatment being developed for the disease. Patients completed the SD NRS each morning during the clinical study. We found that the SD NRS has the necessary properties to be useful for assessing sleep on a daily basis. We also determined that a 2- to 4-point decrease on the SD NRS scale would represent a meaningful improvement in sleep for patients with prurigo nodularis. We conclude that the SD NRS is a useful tool for assessing sleep in prurigo nodularis patients participating in clinical studies. [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]

Prurigo nodularis (PN) is a chronic inflammatory and pruritic skin disease. Clinically it is characterized by intense pruritus accompanied by hyperkeratotic nodules often associated with a very low quality of life including sleep disruption. The FDA has recently approved dupilumab as the only treatment for PN, but it is unknown to what extent within-patient categorical improvements in itch and skin lesions occurred concurrently or independently. Two phase 3 clinical trials, LIBERTY-PN PRIME and PRIME2, demonstrated dupilumab efficacy and safety in patients with PN. To report the efficacy of dupilumab on signs and symptoms in adult patients with PN who did and did not achieve the multicomponent endpoint. LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were randomized, double-blind, placebo-controlled, multicentre, parallel-group, phase 3 trials in adult patients with PN with ≥20 PN lesions and severe itch, inadequately controlled with topical prescription therapies or for whom these are inadvisable. Here, data were pooled from the two studies. Patients received 300 mg dupilumab subcutaneously (600 mg loading dose; n=153) or matched placebo (n=158) every 2 weeks for 24 weeks. This abstract assesses efficacy in patients who did and those who did not achieve the stringent multicomponent endpoint of ≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS, range: 0–10) and Investigator’s Global Assessment PN Stage (IGA PN-S, score range: 0–4) score 0 or 1 (clear or almost clear; defined as 5 or fewer nodules) at week 24. Endpoints include a proportion of patients with concomitant ≥4-point reduction in WI-NRS from baseline and IGA PN-S score 0 or 1 at week 24; the proportion of patients with ≥4-point reduction in WI-NRS from baseline or IGA PN-S score 0 or 1 at week 24; and proportion of patients not achieving ≥4-point reduction in WI-NRS from baseline and IGA PN-S score 0 or 1 at week 24. Safety was also assessed. Baseline demographic and clinical characteristics were generally balanced between subgroups. The proportion of patients treated with dupilumab and placebo who achieved the multicomponent endpoints was 35.3% and 8.9%, respectively; and who achieved WI-NRS reduction of ≥4 points from baseline or IGA PN-S score 0 or 1 at week 24 was 69.9% and 27.2%, respectively. Among multicomponent nonresponders in the dupilumab group (n=99), 36.4% achieved WI-NRS reduction of ≥4 points and 17.2% achieved IGA PN-S score 0 or 1; in the placebo group (n=144), corresponding values were 11.1% and 9.0%, respectively. In the dupilumab group, 23.5% achieved only WI-NRS ≥4-point reduction from baseline at week 24, and 11.1% achieved only IGA PN-S score 0 or 1 at week 24. In the placebo group, corresponding data were 10.1%, and 8.2%, respectively. Safety findings were consistent with the known dupilumab safety profile. More than one-third of dupilumab-treated patients achieved the multicomponent endpoint at week 24, constituting concurrent responses on both itch and skin lesions. However, more than two-thirds had clinically meaningful improvement by week 24, defined as either ≥4-point reduction in WI-NRS from baseline, IGA PN-S score 0/1, or both. Almost one-quarter of dupilumab-treated patients met only WI-NRS ≥4-point improvement at week 24, suggesting that skin lesion improvement may lag behind the improvement of itch. Conversely, one-ninth met only IGA PN-S score of 0 or 1 at week 24 suggesting that, in addition to the overlapping mechanisms by which dupilumab ameliorates pruritus and skin lesions, there are independent treatment effects on itch and skin remodelling. Safety was consistent with the known safety profile of dupilumab across approved indications. [ABSTRACT FROM AUTHOR]