Galderma (Switzerland)

In chronic skin diseases such as atopic dermatitis (AD) or prurigo nodularis (PN), interactions between keratinocytes, immune cells, and nerve endings exacerbate both epidermal damage and the sensation of pruritus. ET-1, encoded by EDN1 is a non-histaminergic itch mediator that induces dose-dependent scratching in BALB/c mice and a burning itch in humans upon intradermal injection (Katugampola et al., 2000, McQueen et al., 2007). Elevated ET-1 levels are associated with increased disease severity in AD and psoriasis (Bonifati et al., 1998, Tsybikov et al., 2015).

This study aimed to describe treatment patterns, frequency of comorbidities, and healthcare cost burden among patients with atopic dermatitis (AD) initiating systemic therapy (or re-initiating it after more than 12 months) versus matched controls without AD. Patients with AD initiating oral corticosteroids (OCS), immunosuppressants (SIS), or biologics between 1/1/2017 and 6/30/2022 (index=first treatment) were identified for analysis in the MarketScan claims databases. Patients were continuously enrolled 12 months before (baseline) and after index (follow-up). Direct and propensity score matching were used to adjust for baseline differences between cases and controls. Comorbidities and all-cause healthcare costs within service categories were compared between AD cases and matched controls during follow-up and treatment patterns were described for all patients with AD. A total of 20,503 patients with AD were identified. On index,12% initiated biologics, 86% OCS, and 2% SIS, and discontinuation rates were high during follow-up (SIS: 80%; biologics: 35%) The incidence of several comorbidities, including cardiovascular disease, atopic conditions, and mental health disorders, was higher in the AD cohort compared with matched controls (p<0.001). Patients with AD (vs. matched controls) also had significantly higher mean total all-cause healthcare costs (US$15,134 vs. $6832; p<0.001). Patients with AD who are initiating systemic treatment experience an increased risk of being newly diagnosed with several comorbidities and higher healthcare costs compared with matched controls, which places increased burden on patients and healthcare systems.

IntroductionPatients with prurigo nodularis (PN) often experience sleep disturbance. A psychometric evaluation was conducted to assess the suitability of a PN-adapted multi-item subject sleep diary (SSD) for measuring PN-related sleep disturbance.MethodsContent validity of the SSD was evaluated through qualitative interviews with adults with PN (N = 21). Psychometric properties of SSD parameters (sleep onset latency [SOL], wakefulness after sleep onset [WASO], total awake time [TWT], total sleep time [TST], sleep efficiency [SE], PN-related WASO [WASO-PN], number of WASO-PN, and sleep quality/refresh [SQR]) were evaluated using data from adults with moderate-to-severe PN in the phase 3 OLYMPIA trials (NCT04501666 [N = 286], NCT04501679 [N = 274]). The relationship between SSD parameters and the single-item Sleep Disturbance Numerical Rating Scale (SD-NRS) was examined using equipercentile linking.ResultsMost interview participants who responded to cognitive debriefing questions understood the SSD as intended (≥ 80% for each item), confirming content validity. All SSD parameters showed good test–retest reliability. At week 16, all SSD parameters but TST showed moderate-to-strong correlations, in the expected direction, with the SD-NRS, Peak Pruritus NRS (PP-NRS), Average Pruritus (AP) NRS, Dermatology Life Quality Index (DLQI), PN-related pain frequency and intensity, Prurigo Activity and Severity Score (PAS), and/or Investigator’s Global Assessment (IGA). Known-groups validity was adequate for all SSD parameters based on the Patient Global Impression of Severity–Sleep Disturbance (PGIS-SD), Patient Global Assessment of Disease (PGAD), PP-NRS, DLQI, and/or IGA. All parameters but TST were responsive to improvements on the PGIS-SD, Patient Global Impression of Change–Sleep Disturbance, PGAD, PP-NRS, AP NRS, PN-related pain intensity, DLQI, and/or IGA. Cross-sectional values or value changes of the SD-NRS were moderately to strongly correlated with SSD parameters, and equipercentile linking analyses revealed non-linear relationships between the measures.ConclusionsThe findings suggest that the SSD is a fit-for-purpose measure that can be used to assess sleep disturbance in moderate-to-severe PN.Clinical Trial RegistrationNCT04501666, NCT04501679.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-025-01406-1.

Artificial daylight photodynamic therapy with methyl aminolevulinate is an effective and almost painless treatment approach for actinic keratoses. The objective of the prospective, non-interventional, multicentre study ArtLight (NCT05725213) was to gain comprehensive insights into the cosmetic effect of methyl aminolevulinate-artificial daylight photodynamic therapy in patients with actinic keratoses using different artificial daylight systems under real-world conditions. The study enrolled patients with Olsen grade 1 or 2 actinic keratoses on the face and scalp in Germany. Patients were treated with methyl aminolevulinate-artificial daylight photodynamic therapy. The cosmetic effect was assessed via photodamage parameters (global score for photoaging, mottled pigmentation, tactile roughness, telangiectasias, fine lines). Each photodamage variable was recorded on a 5-point scale (0–4). In total, 224 patients (median age: 75.0 years [range 50–91], 85.3% male, 62.5% Olsen grade 2, 55.4% treatment-naive) were treated with methyl aminolevulinate-artificial daylight photodynamic therapy. At month 3, all 5 parameters of photoaging were significantly reduced from baseline (p < 0.001). The majority of patients (81.3%) and investigators (83.6%) rated the cosmetic result as good or very good. Beyond effective eradication of actinic keratoses, field-directed methyl aminolevulinate-artificial daylight photodynamic therapy can improve photoaging symptoms, including tactile roughness, mottled pigmentation, telangiectasis, and fine lines. Thus methyl aminolevulinate-artificial daylight photodynamic therapy provides additional benefits, particularly for patients concerned with cosmetic outcomes during or after treatment.

Prurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by intense itch with multiple nodular lesions. Nemolizumab demonstrated significant improvements in itch and skin nodules in adults with moderate to severe PN in a previous 16-week phase 3 study (OLYMPIA 2). To assess the efficacy and occurrence of adverse events in adults with moderate to severe PN treated with nemolizumab vs those receiving placebo. OLYMPIA 1 was a multicenter, placebo-controlled, phase 3 randomized clinical trial, conducted from August 2020 to March 2023 at 77 centers across 10 countries in adults with moderate to severe PN (at least 20 nodules and an Investigator's Global Assessment [IGA] score ≥3) and Peak Pruritus Numerical Rating Scale (PP-NRS) score of at least 7.0; consisted of screening (up to 4 weeks), 24-week treatment, and 8-week follow-up periods. Patients were randomized (2:1) to nemolizumab monotherapy, 30 mg or 60 mg (depending on baseline weight of less than 90 kg vs 90 kg or greater, respectively), or matching placebo administered every 4 weeks for 24 weeks. The primary end points were the proportion of patients with itch response (≥4-point improvement from baseline in weekly average PP-NRS) and IGA success (score of 0/1 [clear/almost clear] and 2-grade or more improvement from baseline) at week 16. Of 286 patients (mean [SD] age, 57.5 [13.0] years; mean [SD] body weight, 85.0 [20.7] kg; 166 [58.0%] female), 190 were randomized to receive nemolizumab, and 96 were randomized to placebo. A significantly greater proportion of patients assigned to nemolizumab vs placebo achieved itch response (111/190 [58.4%] vs 16/96 [16.7%]; Δ, 40.1% [95% CI, 29.4%-50.8%]; P < .001) and IGA success (50/190 [26.3%] vs 7/96 [7.3%]; Δ, 14.6% [95% CI, 6.7%-22.6%]; P = .003) at week 16. At week 24, the proportion of patients with itch response was 58.3% vs 20.4% (Δ, 38.7% [95% CI, 27.5%-49.9%]) in the ad hoc analysis, and IGA success was 58/190 (30.5%) vs 9/96 (9.4%) (Δ, 19.2% [95% CI, 10.3%-28.1%]) in the nemolizumab-treated vs placebo group. During the treatment period, 134 patients (71.7%) receiving nemolizumab vs 62 patients (65.3%) receiving placebo had at least 1 adverse event; most events were of mild to moderate severity. In this randomized clinical trial, nemolizumab monotherapy led to clinically meaningful and statistically significant improvements in core signs and symptoms of PN. ClinicalTrials.gov Identifier: NCT04501666.

Background: As the available treatments for moderate-to-severe atopic dermatitis (AD) expand, understanding patient and physician preferences becomes crucial for informed decision-making. Objective: To quantify patient and physician preferences for biologics and oral systemic AD treatment attributes. Materials and methods: We conducted a cross-sectional, online discrete choice experiment (DCE) involving 306 AD patients and 206 physicians throughout the United Kingdom and Germany. Qualitative interviews identified the key attributes for inclusion in the DCE. Each choice task comprised two hypothetical patient profiles. Data were analyzed using a random-parameters logit model. Results: Results indicated a significant emphasis on efficacy, with reducing sleep disturbance and itch ranking first and second among patients, and the reverse for physicians. Time to itch relief was the third most important efficacy attribute for both groups, but relatively more important for patients than for physicians. For both groups, the risk of eye problems was the most important safety concern of those included. Mode of administration was not of great importance compared to efficacy and safety attributes. Conclusions: Our findings suggest patients prioritize sleep disturbance, an attribute not captured in prior preference studies in AD, time to itch relief and itch. These findings emphasize the importance of addressing sleep-related issues, whilst also targeting fast itch control, to enhance patients’ well-being.