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Zusammenfassung Die chronische spontane Urtikaria (CSU) stellt in der vertragsärztlichen dermatologischen Versorgung eine häufige und herausfordernde Erkrankung dar. Ist beispielsweise ein Antihistaminikum der 2. Generation nicht erfolgreich, empfiehlt die aktuelle Leitlinie weitere therapeutische Optionen, jedoch sind die meisten außerhalb der Zulassung. Diese erhebliche Diskrepanz zwischen leitliniengerechter Behandlung und der Verordnungsfähigkeit von Arzneimitteln verunsichert den behandelnden Arzt. Zudem fragen sich Behandler, wie der Behandlungserfolg zu messen und dokumentieren ist. Messinstrumente sind in der täglichen Praxis bisher nicht etabliert. Eine Arbeitsgruppe aus niedergelassenen Dermatologen und spezialisierten Urtikaria-Zentren hat im Konsensverfahren die Therapieempfehlungen der aktuellen Urtikaria-Leitlinie für die Praxis umsetzbar definiert. Ein diagnostischer und therapeutischer CSU-Behandlungspfad werden vorgestellt. Die Verordnung inklusive Aufdosierung von Antihistaminika in der täglichen Praxis entsprechend Wirtschaftlichkeitsgebot und Zulassungsstatus wird anhand der Studienlage und aktuellen Rechtsprechung erläutert. In der höchsten Therapiestufe werden der Einsatz von Ciclosporin A, Montelukast und die neu verfügbare Option Omalizumab besprochen. Als Dokumentationshilfe wird der Urtikariakontrolltest (UCT) vorgestellt. Der entwickelte Behandlungspfad soll niedergelassenen Ärzten als leitlinienadaptierte Entscheidungshilfe dienen. Er berücksichtigt die Anforderungen kassenärztlicher Tätigkeit. Es werden hiermit die individualisierte Anamneseerhebung oder Therapie der CSU nicht ersetzt, sondern vielmehr Orientierungspunkte und Hilfestellungen für Diagnostik und Behandlung gegeben. [ABSTRACT FROM AUTHOR]

Chronic urticaria (CU) is a debilitating mast cell–driven disease, often refractory to standard therapy (ie, antihistamines). Lirentelimab, an anti–sialic acid–binding immunoglobulin-like lectin 8 mAb, selectively inhibits mast cells and depletes eosinophils. We sought to determine safety and efficacy of lirentelimab in patients with CU. This phase 2a study enrolled patients with CU refractory to up to 4-fold H1-antihistamine doses. Patients received 6 monthly intravenous doses of lirentelimab (0.3, 1, and up to 3 mg/kg). Primary efficacy end point was change in Urticaria Control Test score at week 22. Urticaria Activity Score weekly average (UAS7) was assessed in patients with chronic spontaneous urticaria (CSU), and Cholinergic UAS7 was used for patients with cholinergic urticaria (CholU). A total of 45 patients were enrolled in 4 cohorts (n = 13 omalizumab-naive CSU, n = 11 omalizumab-refractory CSU, n = 11 CholU, n = 10 symptomatic dermographism). Urticaria Control Test scores increased with lirentelimab across cohorts, with mean changes at week 22 of 11.1 ± 4.1, 4.8 ± 7.0, 6.5 ± 6.2, and 3.4 ± 4.1 and complete response rates (Urticaria Control Test score ≥ 12) of 92%, 36%, 82%, and 40%, respectively. In omalizumab-naive and omalizumab-refractory patients with CSU, disease activity decreased at week 22 (mean UAS7 change, −73% and −47%, respectively), with UAS7 response rates (≥50% reduction) of 77% and 45%, respectively. In patients with symptomatic dermographism, 50% (5 of 10) and 40% (4 of 10) had complete itch and hive resolution by FricTest, respectively, and 100% (7 of 7) evaluable patients with CholU had negative responses to Pulse-Controlled Ergometry exercise test. Most common adverse events included infusion-related reactions (43%; all mild/moderate and transient), nasopharyngitis (21%), and headache (19%). No treatment-related serious adverse events occurred. Lirentelimab demonstrated activity across 3 forms of antihistamine-refractory CU. [ABSTRACT FROM AUTHOR]

Quality of life, which is impaired in patients with chronic spontaneous urticaria (CSU), is influenced by comorbid mental disorders. The aim of this study was to assess the prevalence and spectrum of mental disorders and to de-termine levels of emotional distress in patients with CSU. One hundred patients with CSU were investigated for mental disorders (by specialized diagnostic interviews and psychometric instruments), levels of emotional dist-ress (by the Global Severity Index of the Symptom Check List; SCL-90R GSI) and underlying causes of their urti-caria (by dermatological assessment). Forty-eight percent of patients with CSU were diagnosed with one or more psychosomatic disorders; most common were anxiety disorders (especially phobias), followed by depressive and somatoform disorders. The use of psychometric in-struments confirmed these findings. Levels of emotional distress were significantly higher and more commonly increased in patients with CSU with mental disorders. In conclusion, patients with CSU frequently experience anxiety, depression, and somatoform disorders, and the-se disorders are linked to increased emotional distress. These findings call for screening of patients with CSU for mental disorders in routine clinical practice as well as for controlled clinical trials. [ABSTRACT FROM AUTHOR]

Background: The guidelines recommend that first line treatment of chronic spontaneous urticaria should be second generation non-sedating H1-antihistamines with a positive recommendation against the use of old sedating first generation antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. The objective of this study was to obtain the chronic spontaneous urticaria-patient perspective on the effectiveness and unwanted effects of H1-antihistamines in standard and higher doses. Methodology/Principal Findings: This was a questionnaire based survey, initially completed by 368 individuals. 319 (248 female, 71 male, median age 42 years) had a physician-confirmed diagnosis of chronic spontaneous urticaria and were included in the results. Participants believed standard doses (manufacturers recommended dose) of second generation antihistamines to be significantly (P<0.005) more effective than first generation drugs. Furthermore, they believed that second generation drugs caused significantly (P<0.001) fewer unwanted effects and caused significantly (P<0.001) less sedation than first generation antihistamines. Three-quarters of the patients stated that they had up-dosed with antihistamines with 40%, 42% and 54% reporting significant added benefit from taking 2, 3 or 4 tablets daily respectively. The number of reports of unwanted effects and sedation following up-dosing were not significantly different from those reported for standard doses. Conclusions: This survey supports the urticaria guidelines recommendations that the first line treatment for chronic spontaneous urticaria should be second generation rather than first generation H1-antihistamines and that, if standard dosing is not effective, the dosage should be increased up to four-fold. [ABSTRACT FROM AUTHOR]

Background and Study Aim: Data from the AWARE study (A Worldwide Antihistamine‐Refractory chronic urticaria patient Evaluation) illustrate a substantial disease burden in German patients with H1‐antihistamine (‐H1‐AH)‐refractory chronic spontaneous urticaria (CSU). Detrimental effects on patients' quality of life, poor disease control and impairment in the ability to work and perform other daily activities are reported. Based on these findings, this study aims to quantify the epidemiological and socio‐economic burden of H1‐AH‐refractory CSU in Germany. Methods: To determine the epidemiological burden of H1‐AH‐refractory CSU, the age‐ and gender‐specific prevalence of CSU and the proportion of H1‐AH‐refractory patients in Germany anonymized data from the InGef research database have been used. In a second step, the socio‐economic burden in terms of lost numbers of hours in paid and unpaid work was calculated by extrapolating the age‐ and gender‐specific work productivity and activity impairment (WPAI) observed in AWARE to the H1‐AH‐refractory CSU population in Germany. Finally, productivity losses in paid and unpaid work were monetized using the human capital and the friction cost approach respectively. Moreover, socio‐economic burden was calculated depending on symptom control of the patients (measured by urticaria control test [UCT]). Results: In Germany, over 203,000 patients (20 years or older) had H1‐AH‐refractory CSU in 2018. The avoided lost paid and unpaid work hours attributable to H1‐AH‐refractory CSU summed up to over 100 million. Overall, the socio‐economic burden of H1‐AH‐refractory CSU in monetary terms was evaluated at € 2.2 billion and the majority of this was due to unpaid work loss. Patients with poor disease control, as indicated by UCT score < 12, were more likely to suffer from high impairment than patients with controlled disease, resulting in a higher socio‐economic burden. Conclusions: The results of our analyses picture the substantial socio‐economic burden of H1‐AH‐refractory CSU and therefore the tremendous impact it has on daily lives of individuals and society overall. [ABSTRACT FROM AUTHOR]

Background: Chronic spontaneous urticaria (CSU) is both physically and emotionally stressful, and guideline recommendations are often not optimally implemented in clinical practice. The objective of this study was to provide an overview on the patient journey in CSU and to develop a mathematical model based on solid data. Methods: The journey of CSU patients in Germany was traced through literature review and expert meetings that included medical experts, pharmacists and representatives of patient organizations. The current situation's main challenges in the patient journey (education, collaboration and disease management) were discussed in depth. Then, a probabilistic model was developed in a co‐creation approach to simulate the impact of three potential improvement strategies: (1) patient education campaign, (2) medical professional education programme and (3) implementation of a disease management programme (DMP). Results: Chronic spontaneous urticaria patients are severely burdened by delays in diagnosis and optimal medical care. Our simulation indicates that in Germany, it takes on average of 3.8 years for patients to achieve disease control in Germany. Modelling all three optimization strategies resulted in a reduction to 2.5 years until CSU symptom control. On a population level, the proportion of CSU patients with disease control increased from 44.2% to 58.1%. Conclusions: In principle, effective CSU medications and a disease‐specific guideline are available. However, implementation of recommendations is lagging in practice. The approach of quantitative modelling of the patient journey validates obstacles and shows a clear effect of multiple interventions on the patient journey. The data generated by our simulation can be used to identify strategies for improving patient care. Our approach might helping in understanding and improving the management of patients beyond CSU. [ABSTRACT FROM AUTHOR]

Background: Allergen immunotherapy (AIT) is an approved treatment for seasonal respiratory allergic diseases. A depigmented polymerized birch pollen extract for subcutaneous allergen immunotherapy (SCIT) has been demonstrated to be efficacious and safe in patients allergic to birch pollen and its homologous group. Objective: To determine whether SCIT with a birch pollen formulation (5000 depigmented polymerized (DPP) units/mL) shows sustained and long‐term efficacy in adults and adolescents with birch‐pollen induced allergic rhinitis with or without intermittent asthma. Methods: A multicentre (n = 66), double‐blind, placebo‐controlled Phase III clinical trial was performed in the Czech Republic, Finland, Germany, Latvia, Lithuania, Poland and Russia. Participants were randomized 2:1 to active treatment (birch 5000 DPP/ml) or placebo for three years of SCIT and followed up for two treatment‐free years. The primary efficacy endpoint was the EAACI's combined symptom and medication score for rhinoconjunctivitis (CSMSEAACI). Results: A total of 973 participants were screened and 649 were randomized (active treatment: n = 434; placebo: n = 215). The intention‐to‐treat analysis of the CSMSEAACI in the overall study population did not demonstrate statistically significant differences in years 1, 2 and 3. In a post‐hoc analysis, among the subgroup of patients monosensitized to birch pollen allergen only (n = 200), we observed a statistically significant difference (active treatment vs. placebo) in the CSMSEAACI in year 2, 3 and 5. The AIT's safety profile was good. Conclusions: SCIT with a depigmented polymerized birch pollen extract was safe. Sustained and long‐term efficacy in years 2, 3 and 5 in monosensitized patients, but not in polysensitized patients was demonstrated. (EudraCT 2012‐000414‐11) [ABSTRACT FROM AUTHOR]

Introduction: Sexual health, a critical aspect of overall well-being, is often compromised in individuals with chronic disorders. Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that mainly affects intertriginous areas, potentially impacting sexual health as a result of its specific symptoms and psychosocial burden. Methods: This cross-sectional study utilized data from the EpiCAi project, focusing on 199 patients with HS. Participants completed digital questionnaires assessing sexual health via sex-specific instruments: the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men, alongside different psychosocial scales. The disease severity was assessed using the Hurley stage and the Lesion Identification Scheme for Acne Inversa (LISAI). Results: The majority of the participants reported impaired sexual health, with significant clinical sexual dysfunctions noted in 71.8% of women (FSFI score < 26) and erectile dysfunction in 63.8% of men. Sexual dysfunction was associated with several factors, including age, and marital status. Psychosocial factors, notably depression and quality of life, showed strong correlations with sexual health outcomes. Notably, women over 40 and those treated with biologics reported more severe dysfunction, while among men, employment status significantly influenced sexual health. Conclusions: HS profoundly affects the sexual health of both male and female patients, with significant impacts on their quality of life and psychological well-being. The findings underscore the necessity for healthcare providers to address sexual health proactively in the management of HS, considering both physical symptoms and psychosocial impacts. This holistic approach is essential for improving patient outcomes and overall quality of life. Trial Registration: German Register for Clinical Trials, identifier DRKS00025315. [ABSTRACT FROM AUTHOR]

Professor Marcus Maurer, a renowned clinical allergy researcher, tragically passed away at the age of 58 while hiking in Italy. His contributions to mast cell and urticaria research were exceptional, and he played a pivotal role in advancing treatments for patients with urticaria and angioedema. Beyond his academic achievements, he was known for his ability to connect with people, educate patients, and inspire colleagues in the field of allergology. His untimely death is mourned by the European and global allergology community, and his memory will be honored for years to come. [Extracted from the article]

Afamelanotide is a synthetic alpha melanocyte stimulating hormone presenting a higher activity than natural hormones. Its main properties are related to the enhanced production of eumelanin by agonistically binding to the melanocortin-1 receptor. Since 2016 afamelanotide has been especially applied to treat cases of erythropoietic porphyria (EPP), where painful photosensitivity has been observed since early childhood. The positive effect of afamelanotide in EPP administered subcutaneously improved tolerance to artificial white light and increased pain-free time spent in direct sunlight. In this review we summarize the possible use of afamelanotide in dermatology, with special emphasis on EPP and encourage including afamelanotide as a treatment option in patient care. [ABSTRACT FROM AUTHOR]

Background: Non‐sedating H1‐antihistamines (nsAH) are the most commonly used treatment for chronic spontaneous urticaria (CSU). Many patients use them as on‐demand (OD) therapy rather than a maintenance treatment. Here, we compared OD versus daily maintenance treatment with the nsAH rupatadine, assessed the efficacy of rupatadine updosing, and investigated potential long‐term disease‐modifying effects. Methods: This multicenter, randomized study consisted of 2 weeks of screening, 8 weeks of double‐blind treatment, and 6 weeks of treatment‐free follow‐up (OD allowed). Adult patients were randomized to 10 mg rupatadine OD or 10 mg rupatadine daily. At Week 4, if patients did not have a complete response, they switched from 10 to 20 mg rupatadine daily or underwent sham updosing (patients on 10 mg rupatadine OD). The primary aim was to compare CSU disease activity at the end of follow‐up between daily versus OD. Additionally, we assessed the efficacy of rupatadine updosing. Major outcomes were disease activity, CSU‐related quality of life (QoL), and disease control. Results: At Week 4, disease activity and QoL significantly improved in daily versus OD‐treated patients. Updosing of rupatadine did not improve the mean disease activity, but the number of complete responders increased during updosing from 5% to 22%. At the end of follow‐up, the disease activity of patients treated OD versus daily was not significantly different. Conclusions: Daily rupatadine treatment significantly improved CSU disease activity and QoL during treatment versus OD treatment but not after discontinuation of rupatadine, indicating the benefits of a daily maintenance nsAH schedule. [ABSTRACT FROM AUTHOR]

Background: Urticarial vasculitis (UV) should be differentiated from chronic spontaneous urticaria (CSU) in patients initially presenting with recurrent wheals, although criteria for differential diagnosis remain ill‐defined. Objectives: To set the goals, define criteria and unmet needs in UV diagnosis and differential diagnosis with CSU, and explore the possibility of coexistence of both diseases. Methods: Thirteen experts experienced in UV research participated in a Delphi survey of European Academy of Allergy and Clinical Immunology taskforce. This Delphi survey involved three rounds of anonymous responses to n = 32 questions with the aim to aggregate the experts' opinions and to achieve consensus. Urticaria specialists (n = 130, most from Urticaria Centers of Reference and Excellence) evaluated the consensus statements and recommendations in the fourth and final round. Results: The panel agreed that essential criteria to guide a skin biopsy in patients with recurrent wheals should include at least one of the following features: wheal duration >24 h, bruising/postinflammatory hyperpigmentation, and systemic symptoms. Leukocytoclasia and fibrin deposits were identified as a minimum set of UV histological criteria. As agreed by the panel members, CSU and normocomplementemic UV (NUV) may coexist in some patients. Conclusions: The use of established criteria for the diagnosis and differential diagnosis of UV in patients with recurrent wheals can help guide the diagnostic approach and prompt earlier treatment. Further studies should investigate whether CSU and NUV are different entities or part of a disease spectrum. [ABSTRACT FROM AUTHOR]

Background: Chronic urticaria is a frequent and debilitating skin disease. Its symptoms commonly fluctuate considerably from day to day. As of yet, the only reliable tool to assess disease activity is the Urticaria Activity Score, which prospectively documents the signs and symptoms of urticaria for several days. Objective: We sought to develop and validate a novel patient-reported outcome instrument to retrospectively assess urticaria control, the Urticaria Control Test (UCT). Methods: Potential UCT items were developed by using established methods (literature research and expert and patient involvement). Subsequently, item reduction was performed by using a combined approach, applying impact and regression analysis. The resulting UCT instrument was then tested for its validity, reliability, and screening accuracy. Results: A 4-item UCT with a recall period of 4 weeks was developed based on 25 potential UCT items tested in 508 patients with chronic urticaria. A subsequent validation study with the 4-item UCT in 120 patients with chronic urticaria demonstrated that this new tool exhibits good convergent and known-groups validity, as well as excellent test-retest reliability. In addition, the screening accuracy to identify patients with urticaria with insufficiently controlled disease was found to be high. Conclusions: The UCT is the first valid and reliable tool to assess disease control in patients with chronic urticaria (spontaneous and inducible). Its retrospective approach and simple scoring system make it an ideal instrument for the management of patients with chronic urticaria in clinical practice. [Copyright &y& Elsevier]

Elevated total IgE has been proposed as a biomarker, but study results are inconsistent[[3]] and total IgE levels in autoallergic CSU may be elevated due to comorbid sensitization rather than the presence of pathogenetically relevant IgE autoantibodies. SFc RI levels need to be assessed and compared in CSU patients with and without IgE autoantibodies, and human skin MCs should be investigated for their release of sFc RI following activation by IgE versus IgG autoantibodies. Based on our findings, we hypothesize that sFc RI may be a suitable marker for autoallergic CSU since it is solely released upon IgE-mediated crosslinking, that is, in patients with relevant IgE sensitization. [Extracted from the article]

This study investigated the association between urticaria activity and health-related quality of life (HRQoL). Patient evaluations from the ligelizumab Phase 2b clinical trial (N = 382) were pooled (NCT02477332). Daily patient diaries assessed urticaria activity, sleep and activity interference, the dermatology life quality index (DLQI), and work productivity and activity impairment-chronic urticaria (WPAI-CU). The number of DLQI scores, weekly sleep interference scores (SIS7), weekly activity interference scores (AIS7), and overall work impairment (OWI) evaluations with a complete response per weekly urticaria activity score (UAS7) using bands (0, 1–6, 7–15, 16–27, and 28–42) were reported. Over 50% of the patients had a mean DLQI of > 10 at baseline, indicating a significant effect of chronic spontaneous urticaria (CSU) on their HRQoL. Complete response (UAS7 = 0) evaluations corresponded with no impacts on other patient-reported outcomes. In total, 91.1% of UAS7 = 0 evaluations corresponded to DLQI scores of 0–1, 99.7% to SIS7 scores of 0, 99.7% to AIS7 scores of 0, and 85.3% to OWI scores of 0. This was significantly different compared with the UAS7 = 1–6 evaluations (61.9%, 68.5%, 67.7%, and 65.4%, respectively; p < 0.0001). Complete responses to treatment were associated with no impairments on the dermatology-QoL, no interferences with sleep and activity, and significantly improved capacities to work compared to patients who continued to have signs and symptoms, even for those with minimal disease activity. [ABSTRACT FROM AUTHOR]

Hereditary angioedema is a rare and potentially life-threatening genetic disease that is associated with kallikrein–kinin system dysregulation. Garadacimab (CSL312), a novel, fully-human monoclonal antibody that inhibits activated factor XII (FXIIa), is being studied for the prevention of hereditary angioedema attacks. The aim of this study was to evaluate the efficacy and safety of once-monthly subcutaneous administrations of garadacimab as prophylaxis for hereditary angioedema. VANGUARD was a pivotal, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial that recruited patients (aged ≥12 years) with type I or type II hereditary angioedema across seven countries (Canada, Germany, Hungary, Israel, Japan, the Netherlands, and the USA). Eligible patients were randomly assigned (3:2) to receive garadacimab or placebo for 6 months (182 days) by an interactive response technology (IRT) system. Randomisation was stratified by age (≤17 years vs >17 years) and baseline attack rate (1 to <3 attacks per month vs ≥3 attacks per month) for the adult group. The randomisation list and code were kept by the IRT provider during the study, with no access by site staff and funding representatives. All patients and investigational site staff, and representatives from the funder (or their delegates) with direct interaction with the study sites or patients, were masked to treatment assignment in a double-blind fashion. Randomly assigned patients received a 400-mg loading dose of subcutaneous garadacimab as two 200-mg injections or volume-matched placebo on day 1 of the treatment period, followed by five additional self-administered (or caregiver-administered) monthly doses of 200-mg subcutaneous garadacimab or volume-matched placebo. The primary endpoint was the investigator-assessed time-normalised number of hereditary angioedema attacks (number of hereditary angioedema attacks per month) during the 6-month treatment period (day 1 to day 182). Safety was evaluated in patients who received at least one dose of garadacimab or placebo. The study is registered with the EU Clinical Trials Register, 2020-000570-25 and ClinicalTrials.gov , NCT04656418. Between Jan 27, 2021, and June 7, 2022, we screened 80 patients, 76 of whom were eligible to enter the run-in period of the study. Of 65 eligible patients with type I or type II hereditary angioedema, 39 were randomly assigned to garadacimab and 26 to placebo. One patient was randomly assigned in error and did not enter the treatment period (no dose of study drug received), resulting in 39 patients assigned to garadacimab and 25 patients assigned to placebo being included. 38 (59%) of 64 participants were female and 26 (41%) were male. 55 (86%) of 64 participants were White, six (9%) were Asian (Japanese), one (2%) was Black or African American, one (2%) was Native Hawaiian or Other Pacific Islander, and one (2%) was listed as other. During the 6-month treatment period (day 1 to day 182), the mean number of investigator-confirmed hereditary angioedema attacks per month was significantly lower in the garadacimab group (0·27, 95% CI 0·05 to 0·49) than in the placebo group (2·01, 1·44 to 2·57; p<0·0001), corresponding to a percentage difference in means of –87% (95% CI –96 to –58; p<0·0001). The median number of hereditary angioedema attacks per month was 0 (IQR 0·00–0·31) for garadacimab and 1·35 (1·00–3·20) for placebo. The most common treatment-emergent adverse events were upper-respiratory tract infections, nasopharyngitis, and headaches. FXIIa inhibition was not associated with an increased risk of bleeding or thromboembolic events. Monthly garadacimab administration significantly reduced hereditary angioedema attacks in patients aged 12 years and older compared with placebo and had a favourable safety profile. Our results support the use of garadacimab as a potential prophylactic therapy for the treatment of hereditary angioedema in adolescents and adults. CSL Behring. [ABSTRACT FROM AUTHOR]

Background: Cold urticaria (ColdU) is characterized by pruritic wheals following exposure of the skin to cold. Many patients show insufficient response to antihistamines, the first line treatment. Based on the high efficacy of interleukin‐1(IL‐1)‐inhibition in cold‐induced urticarial autoinflammatory diseases, we assessed the effects of rilonacept, an IL‐1 inhibitor, in ColdU patients unresponsive to standard treatment. Methods: In this randomized, double‐blind, placebo‐controlled two‐center study, we included 20 patients with ColdU. In the first part, patients received 320 mg rilonacept or placebo (1:1) followed by weekly doses of 160 mg rilonacept or placebo for 6 weeks. In the second part, all patients received weekly 160 mg or 320 mg rilonacept for 6 weeks, open‐label. The primary endpoint was change in critical temperature threshold (CTT). Secondary endpoints included changes in quality of life impairment (Dermatology Life Quality Index, DLQI), differences of inflammatory mediators upon cold provocation and safety assessment over the study period. Results: Baseline mean CTTs were 20.2°C (placebo) and 17.3°C (rilonacept). Mean CTTs did not change significantly during the 6‐week double‐blind treatment (placebo – 0.45°C; rilonacept +0.89°C). IL‐6, IL‐18 and HSP‐70 blood levels showed interindividual variability without significant changes during hand cold water bath provocation in placebo‐ or rilonacept‐treated patients. In contrast, DLQI significantly improved in the rilonacept (mean DLQI reduction of 3.8; p = 0.002) but not in the placebo group (mean DLQI reduction of 0). Comparing baseline with the rilonacept open‐label treatment, there were no changes in CTTs or DLQI scores. Conclusion: IL‐1 inhibition with rilonacept did not improve ColdU, but demonstrated a good safety profile. Clinical Trial Registration: EudraCT number: 2012‐005726‐30. ClinicalTrials.gov identifier: NCT02171416. [ABSTRACT FROM AUTHOR]

The present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatment of actinic keratosis (AK) against the comparator Aldara (EudraCT: 2015-002203-28). The design of the QbD elements of a quality target product profile (QTPP) enables the identification of the critical quality attributes (CQAs) of the drug product as the content of IMQ, the particle-size distribution, the pH, the rheological properties, the permeation rate and the chemical, physical and microbiological stability. Critical material attributes (CMAs) and critical process parameters (CPPs) are identified by using a risk-based approach in an Ishikawa diagram and in a risk-estimation matrix. In this study, the identified CPPs of the wet media ball-milling process's milling time and milling speed are evaluated in a central composite design of experiments (DoEs) approach, revealing criticality for both factors for the resulting mean particle size, while only the milling time is significantly affecting the polydispersity. To achieve a mean particle size in the range of 300–400 nm with a minimal PdI, the optimal process conditions are found to be 650 rpm for 135 min. Validating the model reveals a good correlation between the predicted and observed values. Adequate control strategies were implemented for intermediate products as in-process controls (IPCs) and quality control (QC) tests of the identified CQAs. The IPC and QC data from 13 "IMI-Gel" batches manufactured in adherence to good manufacturing practice (GMP) reveal consistent quality with minimal batch-to-batch variability. [ABSTRACT FROM AUTHOR]

Simple Summary: Sleep is a restorative state that is crucial for all human beings. Sleep is important for many biological processes in the body and has a huge impact on quality of life. According to previous studies, we know that patients with hives report sleep impairments. However, there are no data objectifying the sleep pattern. Guideline-based therapy for hives includes second-generation antihistamines of up to fourfold dosage. It is known that first-generation antihistamines lead to changes in sleep pattern and increased daytime sleepiness. However, the effect of second-generation antihistamines on sleep is not known. This pilot study was conducted to better understand the pathobiology of sleep in patients suffering from hives, who are medicated with high-dosed second-generation antihistamines. As healthy sleep in many dermatologic patients is still an unmet need, it is of utmost importance to raise awareness and eventually include sleep improvement in the therapy of urticaria patients. Background: Standard treatment options for urticaria are second-generation antihistamines; however, their effect on sleep is uncertain. This study measures the influence of different antihistamines on the biologic sleep pattern of urticaria patients and the relevance of sleep in urticaria patients. Methods: Ten patients with chronic spontaneous urticaria (CSU) and uncontrolled symptoms under a single dose of second-generation antihistamines were included. Two nights were monitored: the first night after 5 days on single dosage and the second night after 5 days on fourfold dosage. Patient-rated questionnaires were used and sleep was monitored using polygraphy. Results: The patients' rated daytime sleepiness decreased (p = 0.0319), as did their insomnia severity (p = 0.0349). The urticaria control (UCT) improved (p = 0.0007), as did the quality of life (p < 0.0001). There was no significant change of nightly pruritus (p = 0.1173), but there was an improvement of daytime pruritus (p = 0.0120). A significant increase in rapid eye movement (REM) sleep was seen (p = 0.0002) (from a mean of 3.9% to 14.3%). The deep sleep state (N3) also improved (8.7% to 12.3%) (p = 0.1172). Conclusion: This study has demonstrated an improvement of the sleep pattern in CSU patients under up-dosed second-generation antihistamines, without increased daytime sleepiness, alongside an improvement of urticaria symptoms and quality of life. [ABSTRACT FROM AUTHOR]

Background: Chronic spontaneous urticaria (CSU) negatively impacts patients' sleep, thereby reducing health‐related quality of life (HRQoL). Half of patients with inadequately controlled CSU report sleep interference often or every night, which can lead to depression, anxiety, social, and work‐related problems. Methods: This randomized, double‐blind, placebo‐controlled Phase 2b core study (NCT02477332) included adult patients ≥18 years with moderate to severe CSU inadequately controlled with H1‐antihistamines. The current analysis includes patients randomized to receive ligelizumab 72 or 240 mg, omalizumab 300 mg or placebo every 4 weeks (q4w) for five injections over 20 weeks with treatment‐free follow‐up for 24 weeks. Patients could enter the open‐label extension study (NCT02649218) from Week 32 onwards if their weekly urticaria activity score was ≥12, which included an open‐label treatment (52 weeks of ligelizumab 240 mg q4w) and a 48‐week post‐treatment follow‐up. Weekly Sleep Interference Scores (SIS7, range 0 [no interference]–21 [substantial interference]), Weekly Activity Interference Score (AIS7), Dermatology Life Quality Index (DLQI) scores, and Overall Work Impairment were assessed. Results: Mean baseline SIS7 scores were balanced between the treatment arms for ligelizumab 72 mg (n = 84) and 240 mg (n = 85), omalizumab 300 mg (n = 85), and placebo (n = 43). By Week 12, patients experienced large improvements in sleep interference, with least square mean (standard error) changes from baseline (CFB) in SIS7 of −7.84 (0.58), −7.55 (0.61), −6.98 (0.60), and −5.85 (0.81), respectively. By Week 12, CFB in AIS7 were −8.25 (0.57), −8.25 (0.59), −7.30 (0.60), and −5.62 (0.79), DLQI scores were −9.79 (0.77), −9.93 (0.81), −8.35 (0.79), and −6.99 (1.11), and Overall Work Impairment scores were −28.96 (3.73), −30.76 (3.71), −25.74 (3.91), and −20.13 (5.10) for ligelizumab 72 and 240 mg, omalizumab 300 mg and placebo, respectively. Improvements in each patient‐reported outcome were sustained with ligelizumab 240 mg treatment during the extension study. Conclusions: Ligelizumab showed effective and sustained responses in managing sleep interference in patients with CSU, and numerically higher responses than with omalizumab and placebo. Treating the symptoms of CSU with ligelizumab improved disease burden, HRQoL, and markedly improved sleep quality. [ABSTRACT FROM AUTHOR]

Background: Actinic keratoses (AK) are increasing in incidence and represent the most common (pre-)cancerous lesion in the fair-skinned population, with a high unmet medical need. In order to increase treatment adherence, it is very important to assess patients' therapy-related evaluations of different treatment options., Patients and Methods: 100 patients with AK who were treated with at least two different treatment options were included. They rated their therapies using the Treatment Satisfaction Questionnaire for Medication (TSQM, maximum 100 points per category) and a Likert scale (LS, 1  =  very satisfied; 6  =  not satisfied). Patients were also asked about their needs in terms of treatment goal, cost, type, duration, and location of treatment., Results: 81% of the study participants were male and on average 74 years old. 95% had field cancerization. Eight frequently used therapy procedures were evaluated by the patients (surgery, cryotherapy, various topical agents, photodynamic therapy). The TSQM satisfaction scores ranged from 78.47 ± 16.07 (surgical procedures) to 53.03 ± 22.13 (diclofenac-HA). Statistically significant differences between the procedures were only found in the area of efficacy. Side effects were classified as low. Low recurrence rate and safe removal were the most important treatment goals (LS: 1.18 ± 0.44 and 1.27 ± 0.53, respectively)., Conclusions: Understanding patient preferences is essential for adherence and is therefore of great importance for the success of AK therapy. Personalized approaches should be considered in the choice of therapy., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Vitiligo is a common disorder characterized by the visible loss of skin pigmentation. Non-segmental vitiligo (NSV) is the major subtype. The disease is caused by autoimmune-mediated destruction of melanocytes. Vitiligo leads to stigmatization and a significant reduction in quality of life. Disregarding the psychosocial burden, vitiligo is sometimes viewed solely as a cosmetic problem and, according to a global survey, is diagnosed on average only after 2.4 years. This delay contributes to a considerable burden of disease, including suicidal ideation. Stigmatization promotes the development of psychological comorbidities such as anxiety and depressive disorders, with prevalence rates varying by country and study (0.1%-67.9%). Data for Germany are heterogeneous and largely based on estimates. Due to psychosocial factors, the inflammatory component, and a higher incidence of somatic comorbidities, NSV may be regarded as an inflammatory systemic disease. We recommend optimizing care by incorporating the assessment of quality of life as a standard in routine care, in addition to monitoring disease activity. Moreover, early screening for psychological comorbidities is crucial to initiate appropriate treatment before the condition becomes chronic and cumulative (irreversible) impairments occur. The goal is a personalized and patient-centered integrated care approach that sustainably improves the health status of those affected., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities., Methods: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines., Results: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria., Conclusions: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.

Pruritus is defined as a symptom that leads to scratching. Clinically, a heterogeneous group of clinical pictures of different etiology must be considered. Pruritus is characterized by varying intensity and duration. Many patients and/or their social environment, which is influenced by this, cite the impact on sleep quality as an accompanying main symptom. The patient's quality of life is affected depending on the severity of the pruritus and often leads to comorbidity such as depressive disorders or sleep disorders as well as to an impact on psychosocial well-being if it becomes chronic. To date, in addition to the medical history, the established examination methods have been the determination of the disease burden by assessing disease activity, e.g., with validated disease-specific scores, plus the assessment of quality of life using a dermatological quality of life index (DLQI). The latest studies show that this is by no means sufficient to determine the severity of disease and, as a result, to identify adequate treatment options., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment., Objective: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE)., Methods: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022)., Results: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms., Conclusion: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care., (Copyright © 2024. Published by Elsevier Inc.)

Background: Chronic spontaneous urticaria (CSU) can present with non-skin related symptoms (NSRS), including recurrent unexplained fever, joint, bone, or muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (eg, urticarial vasculitis or autoinflammatory disorders) or without wheals (eg, infection)., Objective: We sought to determine the rate of patients with CSU affected by fever, JBMP, and malaise, their trigger factors, links with clinical and laboratory characteristics, and their impact on everyday life and treatment responses., Methods: We analyzed baseline data from the Chronic Urticaria Registry of 2,521 patients with CSU who were aged 16 years or older., Results: One third of CSU patients (31.2%; 786 of 2,521) had one or more NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having one or more of these NSRS correlated with food and infection as trigger factors of urticaria (adjusted odds ratio [aOR] = 1.7 and 1.5), wheals of 24 hours or greater duration (aOR = 2.5), sleep disturbance (aOR = 2.4), anxiety (aOR = 2.8), comorbid atopic dermatitis (aOR = 2.1), gastrointestinal disease (aOR = 1.8), elevated leukocytes (aOR = 1.7) and erythrocyte sedimentation rate (aOR = 1.5). In a bivariate analysis, these NSRS were additionally associated with higher disease activity (weekly Urticaria Activity Score, median: 21 vs 14; P = .009), longer disease duration (years, median: 2 vs 1; P = .001), the presence of angioedema (74.6% vs 58.7%; P < .001), worse quality of life (Chronic Urticaria Quality of Life Questionnaire, median: 42 vs 29; P < .001) and more frequent poor control of CSU (78% vs 69%; P < .001)., Conclusions: The presence of NSRS in a subpopulation of patients with CSU points to the need for better control of the disease, exclusion of comorbid conditions, and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Hidradenitis suppurativa (HS)/Acne inversa (Ai) is a chronic debilitating disease with limited therapy options. The device-based LAight therapy was approved in Europe in 2017. The aim of this study was to evaluate the effect of real-world care with at least one treatment with LAight therapy on disease activity and burden in 3,437 patients., Patients and Methods: Patients were included in the analysis if they had a diagnosis of HS and received at least one treatment. The endpoints Hidradenitis Suppurativa Severity Score System (IHS4), pain on the numeric rating scale (pain-NRS) and Dermatology Life Quality Index (DLQI) were analyzed using a linear mixed model for repeated measures (MMRM) over 26 weeks of care with LAight therapy. Furthermore, responder rates were calculated for all endpoints, and the therapy's safety profile and patient satisfaction were thoroughly examined., Results: A significant decrease in IHS4, pain-NRS, and DLQI was achieved during 26 weeks of care with LAight. The BMI at baseline had a significant negative effect on therapy response for pain-NRS and DLQI., Conclusions: This study confirms that LAight therapy leads to satisfactory disease control in all stages of severity and is a valuable addition to the therapeutic repertoire of HS., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Data on the course of urticaria in children exist, but there is a lack of sound data on patient management to ensure high-quality care., Methods: Retrospective secondary data analysis in the field of health care and epidemiology in children with urticaria based on routine data from a German health insurance company (DAK-Gesundheit). Data from insured persons under 18 years of age who were treated as outpatients or inpatients with a diagnosis of urticaria (according to ICD-10 classification) in 2010-2015 were included. The control group consisted of children without a corresponding diagnosis, in order to clarify health economic and care-related differences after adjusting for age and gender., Results: In 2015, 1904 (1.3%) of 151,248 insured minors had a diagnosis of urticaria. Of the children with urticaria, 70.9% visited at least one physician on an outpatient basis. Of these visits, 70.9% were made to a pediatrician, 52.5% to a general practitioner and 33.0% to a dermatologist; 11% were treated as inpatients. With a total of 151,248 insured persons, 1904 of whom were diagnosed with urticaria, 72.9% of children and adolescents with versus 28.9% without urticaria were treated topically or systemically in 2015, including 10.5% of children with urticaria vs. 2.6% without urticaria received topical therapy and 70.0% with urticaria received systemic therapy vs. 27.5% without urticaria with systemic therapy. The most commonly used oral medications for urticaria were cetirizine (44.2%), prednisolone (9.8%), and dimetindene (2.0%) . Topical methylprednisolone aceponate (49.8%) was prescribed most frequently. The therapy costs for systemic drugs was € 24.00 per patient, while topical drugs cost € 1.58 per patient., Conclusion: The lack of guidelines for the standardization of treatment in children still leads to ambiguities and different treatment concepts among the specialist groups, which must be eliminated in order to enable more efficient therapies. The treatment of chronic urticaria in children and adolescents is mainly carried out by pediatricians, general practitioners and dermatologists. Systemic and topical medications as well as inpatient services are the most important cost factors., (© 2024. The Author(s).)

The scalp is the most common site affected in patients with psoriasis with up to 80% of these patients having some degree of scalp involvement. In this narrative review, we evaluate available data on the use of an innovative aerosol foam formulation of calcipotriol plus betamethasone dipropionate (Cal/BD) to treat patients with psoriasis and scalp involvement. The full PubMed database was searched using the terms "calcipotriol", "betamethasone dipropionate" and "aerosol foam", and all articles relating to "psoriasis with scalp involvement" were retrieved and used in the preparation of this review. The evidence supporting the clinical effectiveness, tolerability and impact on health outcomes of Cal/BD aerosol foam in patients with scalp psoriasis was obtained from a phase II clinical trial and real-world evidence data from a non-interventional study as well as from two case series. The findings from these studies show that Cal/BD aerosol foam is rapidly effective, improves skin condition, alleviates symptoms such as itch, and has a positive impact on patient quality of life. These attributes address several unmet needs for patients with psoriasis with scalp involvement and have the potential to improve individual adherence to treatment., Competing Interests: Disclosure and potential conflicts of interest: P Staubach has received honoraria and payment for expert testimony and for attending meetings from Leo Pharma. A Körber has participated in advisory board and received consulting fees, honoraria and support for attending meetings from Abbvie, Novartis, BMS, Janssen Cilag, Leo Pharma, Almirall, UCB, Lilly Pharma and Sanofi Aventis; he is also a speaker for the Scientific Board of the German Psoriasis Bund and Head of PsoNet Ruhr. C Mann has received grants from Novartis and Almirall, consulting fees from Almirall, Abbvie and Apogee, honoraria from Almirall, L’Oreal, Pfizer, Janssen, PER, UNEV and Novartis, support for attending meetings from AbbVie, Almirall-Hermal, Eli-Lilly, Janssen, L’Oreal, Novartis, Pfizer and Takeda, and participated in advisory boards for Almirall, AbbVie and Apogee. R von Kiedrowski has received consulting fees, honoraria, expert testimony fees and support for attending meetings from Leo Pharma. RM Trüeb has nothing to declare. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2024/04/dic.2024-1-6-COI.pdf, (Copyright © 2024 Staubach P, Körber A, Trüeb RM, Mann C, von Kiedrowski R.)

Background: Limited data are available characterizing the impact of the SARS-CoV-2 pandemic on psoriasis care for patients in Germany., Objective: To analyze patient perception and impact of the pandemic on well-being and psoriasis management of German patients with moderate-to-severe psoriasis or psoriasis arthritis under systemic therapies., Methods: The CoronaBest registry captures events of SARS-CoV-2 infections and analyzes the impact of the pandemic on patients with psoriasis or psoriasis arthritis. In June 2020, and independently in February 2022, patients with psoriasis or psoriasis arthritis received a standardized questionnaire for current treatment, protective measures, well-being, and individual risks for COVID-19, among others., Results: Included were 4,194 patients in 2020 (mean age of 47.7 years and 41.8% women) and 4,818 patients in 2022 (mean age of 56.4 and 42.9% women). Treatment discontinuations were observed in 2.7% and 1.7% of patients in 2020 and 2022, respectively. In the vast majority of the cases (>92%), no additional measures were taken concerning the management of psoriasis treatments in either 2020 or 2022. Those patients with changes reported most frequently: telephone calls instead of face-to-face visits (80.2%, in 2020 vs 40.5% in 2022) or more frequent controls (27.1%, 2020 vs 22.0%, 2022). A majority (66.7%, 2020, and 70.6%, 2022) did not perceive the virus as a considerable threat. The proportion of patients feeling well informed about COVID-19 by physicians increased from 42.6% in 2020 to 51.8% in 2022. About 81.1% of patients in 2020 and 67.5% in 2022 stated that their overall personal condition was not affected due to the pandemic. Physicians attributed no special risk of contracting SARS-CoV-2 in most of the patients., Conclusion: A high rate of systemic treatment persistence and awareness of risks and protective measures indicate that health care for psoriasis largely followed current national and international recommendations during the COVID-19 pandemic., Competing Interests: B. Stephan received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for AbbVie, UCB. D. Thaçi received grants or contracts from Novartis, Leo-Pharma; Consulting fees from AbbVie, Almirall, Lilly, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Novartis, UCB; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Amgen, Almirall, Lilly, Janssen, MSD, Medac, Novartis, Pfizer, UCB; participated on a Data Safety Monitoring Board or Advisory Board at AbbVie, Almirall, Celltrion, Lilly, Janssen, Novartis, Pfizer, UCB. U. Mrowietz has been an advisor and/or received speakers’ honoraria and/or received grants and/or participated in clinical trials of the following companies: AbbVie, Aditxt, Almirall, Amgen, Aristea, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Dr. Reddy’s, Eli Lilly, Foamix, Formycon, GlaxoSmithKline, Immunic, Janssen, LEO Pharma, Medac, MetrioPharm, Novartis, Phi-Stone, Pierre Fabre, Sanofi-Aventis, UCB Pharma, UNION Therapeutics. K. Reich received consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Forward Pharma, Gilead, Galderma, Janssen-Cilag, Kyowa Kirin, LEO, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, UCB; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Forward Pharma, Galderma, Janssen-Cilag, Kyowa Kirin, LEO, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, UCB; support for attending meetings and/or travel from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Forward Pharma, Galderma, Janssen-Cilag, Kyowa Kirin, LEO, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, UCB; participated on a Data Safety Monitoring Board or Advisory Board at AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Forward Pharma, Galderma, Janssen-Cilag, Kyowa Kirin, LEO, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, UCB and is co-founder of Moonlake Immunotherapeutics. P. Staubach received grants or contracts from Novartis; consulting fees from AbbVie, Almirall, Lilly, Janssen, Novartis, UCB, Leo, Amgen, BMS; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Amgen, Almirall, BMS; leo, Lilly, Janssen, Novartis, Pfizer, UCB. R. von Kiedrowski provides with his service company CMS3 GmbH consulting services, registry research, activities as an investigator in interventional and non-interventional studies, other services, and scientific lectures for the following companies: AbbVie, ALK Scherax, Almirall Hermal, Amgen, Beiersdorf Dermo Medical, Biofrontera, Biogen, BMS, Boehringer Ingelheim, Celgene, DermaPharm, Foamix, Gilead, Hexal, Janssen-Cilag, LEO Pharma, Lilly Pharma, Medac, Menlo, MSD, Mylan/Viatris, Novartis, Dr. R. Pfleger, Pfizer, Regeneron, Sanofi, Stallergens, Stiefel GSK, Tigercut and UCB. M. Augustin served as a consultant for or has been a paid speaker for clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Almirall, Amgen, Beiersdorf, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Eli Lilly, Galderma, Hexal, Janssen, LEO, Medac, MSD, Mylan B.V., Novartis, Pfizer, Sandoz, UCB and Viatris. The authors report no other conflicts of interest in this work., (© 2024 Valencia López et al.)

Introduction: Patients with chronic inflammatory skin diseases often suffer from sleep disturbances. However, objective data on sleep architecture, especially to evaluate potential overall influences under therapy, are lacking., Patients and Methods: Pilot study on sleep quality changes including psoriasis and atopic dermatitis patients before and 2 weeks after intensive topical treatment. In addition to disease activity rating, patient-rated outcomes for itch severity and sleep quality and polygraphy was performed before and after topical therapy., Results: 14 psoriasis, eleven atopic dermatitis patients (10 female, 15 male) with a mean age of 49 years were included. Disease activity scores (EASI and PASI) were significantly reduced with topical therapy after 2 weeks (p < 0.001). Pruritus intensity (NRS) showed a significant influence on deep sleep, which resolved after therapy. Insomnia severity significantly decreased (r > 0.50, p < 0.05) and daytime sleepiness showed a significant reduction in 40% of patients. N3 (deep sleep) and REM sleep significantly improved, showing a strong effect (r > 0.50). The apnea-hypopnea index decreased in one of four patients independent of the individual BMI., Conclusions: Through polygraphy, we demonstrated impaired sleep patterns in psoriasis and atopic dermatitis patients with itch as a relevant factor and beyond that, rapid sleep improvement under 2 weeks of topical treatment., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment., Objective: To assess the efficacy and safety of apremilast 30 mg twice daily in patients with genital psoriasis., Methods: DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area <10% or ≥10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented., Results: Patients were randomized to apremilast (n = 143) or placebo (n = 146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment of Genitalia response (primary endpoint; score of 0/1, ≥2-point reduction); treatment difference was significant (20.1%, P = .0003). Improvements in genital signs and symptoms, skin involvement, and quality of life were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis., Limitations: Lack of active-comparator., Conclusions: Apremilast demonstrated statistically and clinically meaningful genital Physician Global Assessment responses and improvement of signs, symptoms, severity, and quality of life in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis., Competing Interests: Conflicts of interest JFM: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB – consultant and/or investigator. LCP: AbbVie, Alfasigma, Amgen, Amytrx, Bristol Myers Squibb, Eli Lilly, Fibrocell, Galderma, GlaxoSmithKline, Kiniksa, Olix, Oneness, Pfizer, Trevi, and UCB – investigator. LG: AbbVie, Amgen, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck Frosst, Novartis, Pfizer, Sun Pharmaceuticals, and UCB – consultant, investigator, and/or speaker. CL: AbbVie, Actelion, Amgen, Astella, Bausch Health, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, and Valeant – principal investigator and/or consultant. JPL: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Galderma, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, and Sanofi – grant/research support. PS: AbbVie, Allergika, Almirall-Hermal, Amgen, Beiersdorf, Biocryst, Biogen Idec, BMS, Boehringer-Ingelheim, Celgene, CSL-Behring, Eli-Lilly, Galderma, Hexal, Janssen, Klinge, LEO Pharma, LETI-Pharma, L'Oreal, Medice, Novartis, Octapharma, Pfizer, Pflüger, Pharming, Pierre-Fabre, Regeneron, Sanofi-Genzyme, Shire, Takeda, and UCB Pharma – personal fee/non-financial support/study fee. SC, MP, SJ, & MC: Amgen Inc – employees and stockholders. HP: Amgen Inc – former employee and stockholder. Mitsubishi Tanabe Pharma America – current employee. KAP: AbbVie, Actelion, Amgen, Astellas Pharma US, Bausch Health, Boehringer Ingelheim, Celgene Corporation, Dermira, Dow Pharmaceuticals, Eli Lilly, Frontier, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co, Inc, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals, UCB, and Valeant – honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant; PSOLAR, PURE – steering committee member., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Hidradenitis suppurativa (HS) is an inflammatory disease of the inverse skin regions with an age peak at around 40 years and an estimated prevalence of 1%. Nodules and abscesses can develop into fistules and scarring, which cause severe pain. HS is a progressive, life-defining disease that leads to physical limitations, inability to work, and social isolation. There is still little data on the drivers of disease severity and burden., Method: The cross-sectional study is based on the baseline data of 553 participants of the health care research project "EsmAiL," which was carried out as a multicenter randomized controlled trial. It included adult HS-patients presenting with at least three inflammatory lesions and at least a moderate impact on quality of life., Results: Disease activity increases with age. Men are more severely affected than women but feel less burdened. Obesity negatively influences disease activity and disease burden. Affected individuals have a higher level of education than the age adjusted population, but the unemployment rate is significantly higher. Disease activity significantly reduces quality of life and promotes depression and anxiety., Conclusions: HS is a severe and debilitating dermatosis. As a result of the well-established factors involved, HS requires a multi-causal approach to management, in addition to medical and surgical treatment. This must take into account all available therapeutic options, as well as patient education to reduce risk factors and pain, and psychological support. HS requires interdisciplinary and multi-professional care. To prevent disease progression, a structured treatment plan is needed., (© 2023 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies., Methods: PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete., Findings: Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, -8·0 (95% CI -10·6 to -5·4; PEARL-1), -10·0 (-12·6 to -7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (-1·2 to 2·5; PEARL-1), 0·4 (-1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo -8·0 (-10·5 to -5·4; PEARL-1), -11·1 (-13·7 to -8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (-1·1 to 2·5; PEARL-1), -0·7 (-2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab., Interpretation: In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies., Funding: Novartis Pharma., Competing Interests: Declaration of interests MM is or recently was a speaker, an adviser for, or has received research funding from Amgen, Allakos, Aralez, AstraZeneca, Celldex, FAES, Genentech, GI Innovation, Kyowa Kirin, Leo Pharma, Menarini, Novartis, Moxie, MSD, Roche, Sanofi, Third Harmonic, UCB, and Uriach. LFE is or recently was a speaker or adviser for Novartis, Sanofi, and AbbVie, and has received research support from Novartis and Sanofi. AMG-A reports roles as a medical adviser for Uriach Pharma, Sanofi, Genentech, Novartis, FAES, GSK, AMGEN, Thermo Fisher, and has received research grants supported by Uriach Pharma, Novartis, and Instituto Carlos III- FEDER; she also participates in educational activities for Uriach Pharma, Novartis, Genentech, Menarini, LEO-PHARMA, GSK, MSD, Almirall, AVENE, and Sanofi. GS has received research support from Aimmune, Amgen, AstraZeneca, DBV technologies, Genentech, Kedrion, Leo Pharma, Novartis, Nuvo Pharmaceuticals, Sanofi, Stallergenes, Merck, and Schering-Plough; and is a medical adviser or has received payment for lectures from Merck, Novartis, CSL Behring, Pfizer, Anaphylaxis Canada, the Allergy Asthma and Immunology Society of Ontario, and the Canadian Hereditary Angioedema Network. MH has received lecture or consultation fees from TAIHO Pharmaceutical, Novartis, MSD, Teikoku Seiyaku, Mitsubishi Tanabe Pharma, Kaken Pharmaceutical, Kyorin Pharmaceutical, Uriach, Sanofi, and Kyowa-Kirin and GI Innovation. SS received grant, research, or clinical trial support from the National Institutes of Health, ITN, Novartis, Regeneron, and is a consultant or advisery board member for Genentech, Novartis, Medimmune, AstraZeneca, Pfizer, Allakos, Eli Lily, and Gossamer Bio. CG has recently been an adviser for Celltrion and has participated in an advisery board for Sanofi. DF is, or recently was, a speaker or adviser for Novartis, Sanofi, AbbVie, Takeda, AstraZeneca, CSL Behring, and Roche. DR received fees as lecturer and advisery board member for Novartis, Leo, Lilly, MSD, UCB, Janssen, Sanofi, Menarini, Genesis pharma, and AbbVie. FB has received payment or honoraria as speaker fees from Novartis. GWC reports having received research grants, as well as being a lecturer or having received advisery board fees, from Menarini, Alk-Abello', Allergy Therapeutics, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Genentech, Guidotti-Malesci, GSK, Hal Allergy, Mylan, Merck, Merck Sharp & Dome, Mundipharma, Novartis, Regeneron, Roche, Sanofi-Aventis, Sanofi-Genzyme, Stallergenes-Greer, UCB Pharma, Uriach Pharma, Valeas, and Vibor-Pharma. HR reports receiving speaker's fees, advisery board fees or funds for research to the institution from Novartis Pharma, Pharming, Sanofi-Genzyme, Third Harmonic, and Leo Pharma. CI reports having received research or clinical trial support, or fees for lectures from Novartis, Sanofi, AstraZeneca, Takeda, and Stallergenes Greer. JCS reports receiving fees for being consultant or advisery board member for Leo Pharma, Novartis, Pfizer, Sanofi-Genzyme, Trevi, UCB, and Vifor; for being speaker for AbbVie, Almirall, Alvotech, Janssen-Cilag, Eli-Lilly, Leo Pharma, Novartis, Pfizer, and Sanofi-Genzyme; for being the investigator in clinical trials for AbbVie, Almirall, Amgen, AnaptysBio, BMS, Boehringer Ingelheim, Celtrion, Galderma, Galapagos, Helm, Kliniksa, Incyte, InfraRX, Janssen-Cilag, Leo Pharma, Medimmune, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, UCB, Teva, and Trevi. JAB reports grants and personal fees from Novartis, AstraZeneca, Allakos, Amgen, Celldex, Genentech, and Sanofi Regeneron outside the submitted work. JGP has received travel support, speakers' honoraria, and educational grants from Novartis, Sanofi Regeneron, Takeda, Pharming, and CSL Behring. KK is or recently was a speaker or adviser for Novartis, Sanofi, Takeda, and A Menarini, and has received research grants from Novartis. LA is or recently was a speaker, adviser, or has received research funding from AstraZeneca, GSK, Novartis, OM-Pharma, Regeneron, Shire, Takeda, and Sanofi-Genzyme. PS is or recently was a speaker, adviser, or has received research funding from AbbVie, Allergika, Almirall, Amgen, Beiersdorf, Biocryst, Biogen, BMS, Boehringer-Ingelheim, Celgene, CSL-Behring, Eli-Lilly, Galderma, Hexal, Janssen, Klinge, Klosterfrau, LEO-Pharma, LETI-Pharma, L'Oreal, Medice, Novartis, Octapharma, Pfizer, Pflüger, Pharming, Pierre Fabre, Regeneron, Shire, Takeda, Regeneron, Sanofi-Genzyme, und UCB Pharma. RS is Director and Founder of Samson Medical Pty, and serves on the pharmaceutical advisery board of Eli Lilly, Pfizer, Leo Pharmaceutical, and reports being on the speaker bureau of Pfizer, AbbVie, and Novartis. He has also been principal investigator in clinical trials for AbbVie, Aerotech, Akesobio, Amgen, Arcutis, Arena, Ascend AstraZeneca, Bayer, Biotherapeutics Boehringer Ingelheim, Bristol Myer Squibb, Celgene, Coherus BioSciences, Connect, Demira, Eli Lilly, Galderma, GSK, F. Hoffman–La Roche, Janssen, MedImmune, Merck, Merck Sharpe & Dohme, Novartis, Oncobiologics, Pfizer, Principia, Regeneron, Roche, Reistone Biopharma, Samson Clinical, Sanofi-Genzyme, Sun Pharma UCB, Valeant, and Zai Labs. He is President of the Australasian Hair and Wool Research Society, Vice President of the International Society of Dermatology, and The International Academy of Dermatology. SG has consulted or advised for Novartis and IgGenix. SFT is or recently was a speaker, adviser for, or has received research funding from AbbVie, Almirall, Boehringer Ingelheim, CSL, Eli Lilly, Janssen, Leo Pharma, Novartis, Sanofi, Pfizer, UCB, and Union Therapeutics. TT received clinical trial support from Novartis, AstraZeneca, Celldex Therapeutics, Genentech, and GSK. YMY has received research or clinical trial support from Novartis, Amgen, Yuhan, Takeda, and Daewoong ABa, DM, and ES are employees of Novartis Pharmaceuticals, East Hanover, New Jersey, NJ, USA. EH is an employee of Novartis Institutes for Biomedical Research, China. VV is an employee of Novartis Healthcare Private, Hyderabad, India. ABu, KL, MP, and TS are employees of Novartis Pharma, Basel, Switzerland. KG, JL, and OU report no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of the pilosebaceous unit, often affecting and deforming intimate regions. HS is associated with severe pain, pruritus, and constant, purulent, malodorous discharge expected to impair sexual health of patients., Methods: We performed a cross-sectional, multicentric study involving 199 German patients from the health services research project "Epidemiology and Care in Acne inversa (EpiCAi)." The sexual health, HS severity, and quality of life of the studied group were evaluated using a specially designed questionnaire., Results: Regardless of gender, HS has an enormous impact on patients' sexual health. The patients scored, on average, 28.8 ± 5.3 points on the Relation and Sexuality Scale (RSS). Multiple linear regression revealed that females and patients with Hurley III stage had higher sexual dysfunction (p = 0.012). Sexual dysfunction is associated with pain (β = 0.25), the number of active lesions, the affected areas (β = 0.14), and psychosocial aspects, including low quality of life (β = 0.404), stigmatization (β = 0.411), depression (β = 0.413), and anxiety (β = 0.300). Patients already see a substantial decrease in sexual frequency in the early stages of HS, while functional impairment and fear increase with the severity of the disease., Conclusion: Sexual health and management of its dysfunctions should be part of a holistic approach to HS patients., (© 2024 S. Karger AG, Basel.)