Investigator's Global Assessment Research Articles

Comparative Efficacy Between Intense Pulsed Light Narrow Spectrum and Broad Spectrum in the Treatment of Post-Acne Erythema (PAE).

Post-acne erythema (PAE) is one of the most common physical sequelae of acne regression, PAE can resolve spontaneously, but in some patients it may last for years. This study aimed to evaluate the efficacy and safety of narrow and broad spectrum filters of intense pulsed light (IPL) for the treatment of PAE. This prospective study evaluated 60 patients with PAE for at least 6 months, assigned equally to three groups: 1st group received narrow-spectrum with vascular filter (530-650 nm and 900-1200 nm), 2nd group received broad-spectrum with (560/590-1200 nm) filters, the appropriate adjustments were made according to patient's skin colour. Every patient received four sessions one month apart. 3rd group is blank control group did not receive any treatment. CAT (CEA (Clinical Erythema Assessment), Area, and Telangiectasia) used to grade clearance of PAE before and after treatment, Investigators Global Assessment (IGA) used to assess the improvement score after the treatment, and Cardiff Acne Disability Index (CADI) used to evaluate the impact of PAE on patients' Quality of Life (QoL). Self-satisfaction scale completed at the follow-up. Adverse events and acne relapse were recorded. A significant decrease of CAT score in vascular group (P<0.05). IGA scale showed significant improvement after vascular treatment. A significant decrease in CADI (P<0.05) after vascular treatment. Patient satisfaction was higher in vascular group than control and blank control groups. Acne relapse observed in control and blank control groups (40% and 15%, respectively).10% of patients showed pigmentation, 15% had blisters after 590 nm treatment. IPL vascular filter (530-650 nm and 900-1200 nm) have efficacy in the treatment of PAE. CADI score, patient satisfaction, and acne relapse were significantly better after vascular narrow spectrum treatment than broad-spectrum treatment.

A Prospective Randomized Controlled Pilot Study to Assess the Response and Tolerability of Cold Atmospheric Plasma for Rosacea

Introduction: Rosacea is a common, facial, chronic inflammatory skin disease. Due to its complex pathogenesis, adequate therapy of rosacea can be challenging. An innovative recent therapeutic tool is cold atmospheric plasma (CAP), which is already established in the treatment of chronic wounds and promising in different other skin diseases. Methods: In a split-face pilot study we investigated dielectric-barrier-discharged CAP in erythemato-telangiectatic (ETR) and/or papulopustular rosacea (PPR). CAP treatment was applied on lesional skin of a randomized side once daily (90 s/area) for 6 weeks. The other untreated side served as control. Co-primary endpoints were ≥1 improvement of the Investigator Global Assessment (IGA) score on the treated side compared to control and a decline of the Dermatology Life Quality Index (DLQI) after 6 weeks. Secondary endpoints included inflammatory lesion count (papules and pustules), skin redness intensity and erythema size. Adverse events (AEs) were recorded constantly. Additionally, participants were weekly assessed for symptoms, skin condition, trigger factors, skin care, treatment success, and local tolerance parameters. All p values were calculated using the Wilcoxon signed-rank test. Results: Twelve subjects (ETR, n = 3; ETR and PPR, n = 9) completed the study. DLQI was significantly improved after 6 weeks (p = 0.007). On the CAP-treated side, lesions (p = 0.007) and erythema size (p = 0.041) were significantly reduced compared to the control. IGA (p = 0.2) and skin redness intensity (p = 0.5) did not differ significantly between control and CAP-treated side. No serious AEs occurred and treatment was well tolerated. Conclusion: CAP is a promising new treatment of rosacea, especially for PPR.

Effects of acne severity and acne-related quality of life on depressive symptoms among adolescents and young adults: a cross-sectional study in Bangladesh.

Depression is a common mental health disorder and one of the major causes of disability. This study aimed at investigating the relationship of acne severity and acne-related quality of life with depressive symptoms, and the mediating effect of acne-related quality of life in a relationship between acne severity and depressive symptoms. This is a cross-sectional study. Data were collected from acne patients attending a tertiary-level hospital, using a questionnaire that comprised three validated instruments - Investigator's Global Assessment (a single item) scale, Cardiff Acne Disability Index, and Beck Depression Inventory for measuring acne severity, acne-related quality of life, and depressive symptoms, respectively. Logistic regression and linear regression were used to examine the association between acne severity and depressive symptoms and a correlation between the acne-related quality of life and depressive symptoms, respectively. A mediation analysis was also performed to see the mediation effects of acne-related quality of life in a relationship between acne severity and depressive symptoms. A total of 185 acne patients (155 females, 83.8%) with a mean age was 22.55 ± 8.67 years were included in the study. Adolescents and young adults with severe and moderate acne had 6.14-and 2.28 times higher odds of depression compared to their peers with mild acne, respectively. Patients with low levels of acne-related quality of life had a higher level of depressive symptoms (β = 0.42, p < 0.001). The total effect (direct + indirect) was also significant (β = 0.27, 95% CI: 1.29-4.09), implying the effect of acne severity on depression. The present study suggests that acne severity and acne-related quality of life were associated with depressive symptoms among patients with acne vulgaris. The study also indicates that the relationship between acne severity and depressive symptoms might occur through a chain-mediating effect of acne disability in this population.

A single-centre prospective study comparing efficacy and safety of apremilast with cyclosporine in moderate to severe atopic dermatitis.

Apremilast regulates several pro-inflammatory signals involved in atopic dermatitis (AD). A randomized, open-labelled study was conducted at a tertiary care centre in India. Fifty patients with AD of >1 year duration were randomly assigned in a 1:1 ratio to receive either apremilast (30 mg twice daily after initial titration) or cyclosporine (5 mg/kg/day) for 24 weeks, followed by a 12-week follow-up period. Primary outcome was mean percentage change in Eczema Area and Severity Index (EASI) from baseline to week 24. Secondary outcome measures were proportion of patients achieving EASI 75, EASI 90, ≥2-point improvement in Investigator's Global Assessment (IGA), SCORing Atopic Dermatitis (SCORAD) 75 at week 24 and percentage of patients experiencing ≥1 adverse effect (AEs). Mean percentage change in EASI (standard deviation) was -67.79% [22.44] in the apremilast treatment group and -83.06% [21.20] in the cyclosporine treatment group (p < 0.05). At week 24, 52.38% of patients in the apremilast group and 78.26% in the cyclosporine group achieved EASI 75 (p < 0.05); 14.29% in the apremilast group and 52.17% in the cyclosporine group achieved EASI 90 (p < 0.05) and 80.95% in the apremilast group and 82.60% patients achieved ≥2 point reduction in IGA (p > 0.05). 57.14% of patients achieved SCORAD 75 in the apremilast group and 69.56% in the cyclosporine group (p > 0.05). Mean time taken to achieve EASI 75 in the apremilast group was 4.50 ± 4.62 weeks, while it was 3.96 ± 3.43 weeks in the cyclosporine group (p > 0.05). Incidence of AEs was 28.57% in the apremilast group and 21.74%) in the cyclosporine group. Apremilast demonstrated lesser efficacy in comparison to cyclosporine; it has the advantage of a favourable safety profile and requires no laboratory monitoring.

Tralokinumab therapy for moderate-to-severe atopic dermatitis: Clinical outcomes with targeted IL-13 inhibition.

Atopic dermatitis (AD) is a chronic, inflammatory, intensely pruritic skin disorder associated with significant patient burden. Interleukin (IL)-13 is a cytokine that acts as a driver of immune dysregulation, skin-barrier dysfunction, and microbiome dysbiosis that characterizes AD, and is consistently overexpressed in AD skin. Tralokinumab is a fully human immunoglobulin (Ig) G4 monoclonal antibody that binds specifically to IL-13 with high affinity, thereby inhibiting subsequent downstream IL-13 signaling. Three pivotal phase 3 clinical trials demonstrated that tralokinumab 300 mg every other week, as monotherapy or in combination with topical corticosteroids as needed, provides significant improvements in signs and symptoms of moderate-to-severe AD, as measured by Investigator's Global Assessment 0/1 (clear/almost clear) and Eczema Area and Severity Index-75 at Week 16. Improvements were observed soon after tralokinumab initiation and were maintained over 52 weeks of therapy. Tralokinumab significantly improved patient-reported outcomes such as itch and sleep, and demonstrated a safety profile comparable with placebo; conjunctivitis during tralokinumab therapy was generally mild. Similar results were observed in a phase 3 adolescent trial. The role of IL-13 in the pathophysiology of AD justifies a targeted approach and a wealth of clinical data supports tralokinumab as a new therapeutic option for people with moderate-to-severe AD.

Abrocitinib efficacy and safety in patients with moderate-to-severe atopic dermatitis: Results from phase 3 studies, including the long-term extension JADE EXTEND study.

Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at 12 or 16 weeks in phase 3 studies with a manageable safety profile. Further understanding of the abrocitinib long-term efficacy and safety profile is important for its appropriate use in treating chronic AD. To evaluate the abrocitinib efficacy up to 48 weeks and long-term safety in patients with moderate-to-severe AD. JADE EXTEND (NCT03422822) is an ongoing, phase 3, long-term extension study that enrolled patients from previous abrocitinib AD trials. This analysis focusses on patients from the phase 3 JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871) and JADE COMPARE (NCT03720470) studies who completed the full treatment period of placebo or abrocitinib (200 mg or 100 mg once daily) and subsequently entered JADE EXTEND. Efficacy endpoints included the proportion of patients achieving skin clearance (Investigator's Global Assessment [IGA] 0/1 [clear/almost clear]; ≥75% improvement in Eczema Area and Severity Index [EASI-75]) and itch response (Peak Pruritus Numerical Rating Scale [PP-NRS] severity ≥4-point improvement). Safety endpoints included treatment-emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation. Data cut-off: April 22, 2020. As of the data cut-off, ~70% and ~45% of patients received abrocitinib for ≥36 and ≥48 weeks, respectively. Nasopharyngitis, atopic dermatitis, nausea and upper respiratory tract infections were the most frequent TEAEs. Serious TEAEs occurred in 7% and 5% and TEAEs leading to study discontinuation occurred in 9% and 7% of patients receiving abrocitinib 200 mg and 100 mg, respectively. Week 48 efficacy responses with abrocitinib 200 mg and 100 mg were as follows: IGA 0/1 52% and 39%; EASI-75 82% and 67%, and PP-NRS severity ≥4-point improvement 68% and 51%. In patients with moderate-to-severe AD, long-term abrocitinib treatment resulted in clinically meaningful skin and pruritus improvement. The long-term safety profile was manageable and consistent with previous reports.

Integrated Omics Reveal the Molecular Characterization and Pathogenic Mechanism of Rosacea

Recent efforts have described the transcriptomic landscape of rosacea. However, little is known about its proteomic characteristics. In this study, the proteome and phosphoproteome of lesional skin, paired nonlesional skin, and healthy skin were analyzed by liquid chromatography coupled with tandem mass spectrometry. The molecular characteristics and potential pathogenic mechanism of rosacea were demonstrated by integrating the proteome, phosphoproteome, and previous transcriptome. The proteomic data revealed a significant upregulation of inflammation- and axon extension-related proteins in lesional skin and nonlesional skin versus in healthy skin, implying an inflammatory and nerve-hypersensitive microenvironment in rosacea skin. Of these, axon-related proteins (DPYSL2 and DBNL) were correlated with the Clinician's Erythema Assessment score, and neutrophil-related proteins (ELANE and S100A family) were correlated with the Investigator's Global Assessment score. Moreover, comorbidity-related proteins were differentially expressed in rosacea; of these, SNCA was positively correlated with Clinician's Erythema Assessment score, implying a potential correlation between rosacea and comorbidities. Subsequently, the integrated proteome and transcriptome demonstrated consistent immune disturbances at both the transcriptional and protein levels. The integrative analysis of the proteome and phosphoproteome revealed the key transcription factor network and kinase network that drive the dysregulation of immunity and vasculature in rosacea. In conclusion, our multiomics analysis enables more comprehensive insight into rosacea and offers an opportunity for, to our knowledge, previously unreported treatment strategies.

Prevalence and Predictors of Anxiety and Depressive Symptoms among Adult Patients with Atopic Dermatitis in Malaysia Tertiary Referral Hospital

Introduction: Atopic dermatitis (AD) is not only a cosmetic nuisance but is also associated with a significant impact on mental health and quality of life. Psychological symptoms are highly related to poor treatment adherence and recovery, more comorbidities, and a significant overall socioeconomic burden. Identifying the factors associated with anxiety and depression among patients with AD is important to modify and reduce the risk of developing these psychiatric complications. Methods: This was correlational research conducted in the dermatology clinic of four hospitals in Klang Valley, namely Hospital Kuala Lumpur, Hospital Tengku Ampuan Rahimah Klang, Hospital Selayang, and Hospital Ampang. By using a purposive sampling method, 128 samples (n=128) of adult patients with AD aged 18-65 were included. A questionnaire was administered regarding sociodemographic background, illness characteristics of AD, the Investigator’s Global Assessment (IGA), Malay version of the Automatic Thought Questionnaire-17, GAD-7, and PHQ-9. Results: The prevalence of anxiety and depressive symptoms among adult patients with AD is 31.3% and 46.9% respectively. Multivariable logistic regression analysis revealed that age and personal maladjustment (PM) predict anxiety symptoms, while only negative self-concept/expectation (NSNE) predicts depressive symptoms. The hierarchical logistic regression model explained 51% (Nagelkerke’s R2) of the variance in anxiety symptoms and 56% (Nagelkerke’s R2) of depressive symptoms. Conclusion: There is a high proportion of anxiety and depressive symptoms among adult patients with AD which is associated with negative automatic thoughts. In the management of adult patients with AD, clinicians should consider mental health symptom screening and monitoring.

The role of lebrikizumab in the treatment of atopic dermatitis in the adult population.

Although there are many atopic dermatitis (AD) treatments, finding a long-term medication with minimal side effects can be difficult. This review characterizes lebrikizumab as AD treatment in adults. A literature search was conducted to examine lebrikizumab's role in treating moderate to severe AD. In a phase III trial, 74% of adults with AD treated with lebrikizumab 250mg every 4weeks achieved an Investigator Global Assessment of 0/1, 79% achieved Eczema Area and Severity Index 75 and 79% experienced improvements in pruritus numeric rating scale scores relative to placebo. Common adverse effects in the ADvocate1 and ADvocate2 trials were conjunctivitis (7 and 8%, respectively), nasopharyngitis (4 and 5%, respectively) and headache (3 and 5%, respectively). Results from clinical trials suggest that lebrikizumab may be a viable alternative for AD management.

Safety and efficacy of pimecrolimus versus vehicle for the treatment of atopic dermatitis in adults and paediatric population: a systematic review and meta-analysis.

The authors conducted a comprehensive search of several databases, including PubMed, COCHRANE, MEDLINE, and Cochrane Central, from inception to May 2022, using a wide search strategy with Boolean operators. The authors also employed backward snowballing to identify any studies missed in the initial search. The authors included randomized controlled trials in our meta-analysis and extracted data from the identified studies. The authors used Review Manager (RevMan) Version 5.4 to analyze the data, selecting a random-effects model due to observed differences in study populations and settings. The authors considered a P-value of 0.05 or lower to be statistically significant. The authors initially identified 211 studies, of which 13 randomized controlled trials involving 4180 participants were selected for analysis. Our pooled analysis revealed that pimecrolimus 1% was more effective at reducing the severity of atopic dermatitis than its vehicles. However, no significant difference was observed in adverse effects between pimecrolimus and vehicle, except for pyrexia, nasopharyngitis, and headache, which were increased with pimecrolimus. Our meta-analysis showed that pimecrolimus 1% is more effective than vehicle, although the safety profile remains inconclusive. Pimecrolimus reduced the Investigator's Global Assessment score, Eczema Area and Severity Index score, and severity of pruritus when compared to its vehicle, indicating a higher efficacy profile. This is one of the first meta-analyses to assess the efficacy and safety profile of pimecrolimus 1% against a vehicle and may assist physicians in making informed decisions.

P84 Efficacy and safety of lebrikizumab at 16 weeks: pooled analyses from ADvocate1 and ADvocate2 phase III trials in patients with moderate-to-severe atopic dermatitis

Abstract Lebrikizumab (LEB) is a high-affinity monoclonal antibody targeting interleukin (IL)-13, preventing IL-13 signalling via the IL-4Rα/IL-13Rα1 receptor complex. Here, we report 16-week efficacy and safety outcomes of LEB monotherapy in patients with moderate-to-severe atopic dermatitis from two 52-week, randomized, double-blinded, placebo-controlled phase III trials, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Eligible adults and adolescents (aged 12–17 years, weighing ≥ 40 kg) from ADvocate1 and ADvocate2 were randomized (2 : 1) to subcutaneous LEB 250 mg (500 mg loading dose at baseline and week 2) or placebo every 2 weeks (Q2W). Efficacy analyses included proportions of patients achieving Investigator’s Global Assessment (IGA) 0/1 and Eczema Area and Severity Index (EASI)-75 (coprimary endpoints), EASI-90, and pruritus numeric rating scale (NRS) ≥ 4-point improvement from baseline to week 16. This was a pooled analysis of ADvocate1 and ADvocate2, where IGA 0/1 and EASI-75 and EASI-90 were analysed in 564 and 287 patients (LEB 250 mg and placebo), respectively, and pruritus NRS in 516 and 264 patients, respectively. Cochran–Mantel–Haenszel with Markov chain Monte Carlo multiple imputation was performed. Patients treated with LEB 250 mg and placebo for 16 weeks achieved, respectively, IGA 0/1 response rates of 38.1% (n = 215) and 11.7% (n = 34; P &amp;lt; 0.001); EASI-75 responses of 55.4% (n = 313) and 17.2% (n = 49; P &amp;lt; 0.001); EASI-90 responses of 34.5% (n = 195) and 9.2% (n = 26) (P &amp;lt; 0.001); and pruritus NRS ≥ 4-point improvement responses of 42.9% (n = 221) and 12.2% (n = 32; P &amp;lt; 0.001). The percentage of patients reporting one or more treatment emergent adverse event(s) was lower in the LEB group (49.6%) than in the placebo group (59.0%; P = 0.009). These data suggest that LEB 250 mg Q2W for 16 weeks is an efficacious and safe treatment option for adult and adolescent patients with moderate-to-severe atopic dermatitis. Funding sourcesThis study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including atopic dermatitis, in Europe. Lilly has exclusive rights for development and commercialization of lebrikizumab in the United States and the rest of world outside Europe.

PD05 Investigating the course of atopic eczema up to 1 year following completion of narrowband ultraviolet B phototherapy

Abstract Narrowband UVB (NBUVB) is a recommended second-line treatment for moderate-to-severe atopic eczema unresponsive to adequate topical therapy, and is known to induce good short-term improvement of eczema severity (Reynolds NJ, Franklin V, Gray JC et al. NBUVB and broad-band ultraviolet A phototherapy in adult atopic eczema: a randomised controlled trial. Lancet 2001; 357:2012–16). However, it is unclear how adult patients fare with their eczema severity long after completion of a course of NBUVB. We aimed to investigate the severity of atopic eczema in adults, 1 year following the completion of NBUVB, using validated clinical activity measures. We hypothesized that, after 1 year, eczema severity would remain better than at baseline (prior to having NBUVB). We undertook a multicentre prospective observational study of adults with atopic eczema (as per Hanifin and Rajka criteria) prescribed NBUVB as part of their standard clinical care. Participants had moderate-to-severe disease, with a minimum objective SCORAD of 15 and minimum Investigator’s Global Assessment (IGA) of 3, and were resistant to at least one conventional treatment (e.g. potent topical steroid). Eczema severity was assessed by selected investigators using SCORAD and IGA. Assessments were made at baseline, at the end of NBUVB and at 4, 8 and 12 months after completion of NBUVB. We aimed to recruit 80 patients at the outset to provide us with about 25–30 patients for analysis at the 1 year post-NBUVB follow-up. Eighty patients (47 men, 33 women) with a mean age of 37 years (range 18–83) were recruited, with a baseline mean (SD) SCORAD of 39.2 (12.5). Forty-nine patients could not attend to complete NBUVB or the follow-up visits thereafter. Three patients had to stop NBUVB as their eczema flared. Mean baseline SCORAD of the 28 patients who completed the study was 41.3 (14.7), with the mean IGA being 3 (range 3–4; reflecting moderate to severe disease, respectively). Compared with baseline, mean SCORAD was significantly lower at the end of NBUVB [19.1 (13); P &amp;lt; 0.001] and at 4 months post-NBUVB [21.9 (11.9); P &amp;lt; 0.001]. Furthermore, compared with baseline, there was a sustained ongoing reduction of mean SCORAD at 8 months [22.6 (13.1); P &amp;lt; 0.001] and 12 months post-NBUVB [21.1 (14.8); P &amp;lt; 0.001]. Mean SCORAD at 1 year was not statistically significantly different to that on completion of NBUVB (P &amp;gt; 0.5). Change in IGA matched similar sustained improvement trends with SCORAD. These findings indicate that NBUVB may provide a long-lasting effect for patients who complete a course, helping to diminish their eczema severity to a more manageable level. These data can further inform consultations with patients, when outlining the approach of NBUVB for their care.

Efficacy and safety of abrocitinib in patients with moderate‐to‐severe atopic dermatitis with prior exposure to oral systemic immunosuppressants or biologic therapies: A post hoc analysis of the JADE clinical trials

AbstractBackgroundPatients with moderate‐to‐severe atopic dermatitis (AD) refractory to topical therapy might require treatment with systemic therapies, including biologics.ObjectivesTo assess the efficacy and safety of abrocitinib monotherapy in patients who previously received systemic therapies.MethodsThis post hoc analysis included patients receiving abrocitinib (200 mg/100 mg) or placebo in the phase 2b and phase 3 JADE MONO‐1 and MONO‐2, REGIMEN (abrocitinib 200 mg; open‐label period) and EXTEND (patients enrolled from MONO‐1 and MONO‐2) trials. Patients who were systemic therapy‐naive or had received prior oral systemic or biologic therapies were assessed for Investigator's Global Assessment (IGA) response of 0 (clear) or 1 (almost clear) and ≥2‐point improvement from baseline, ≥75% or ≥90% improvement in Eczema Area and Severity Index (EASI‐75 or EASI‐90), ≥4‐point improvement in Peak Pruritus Numerical Rating Scale (PP‐NRS4), PP‐NRS score of 0 or 1 and change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) and Patient‐Oriented Eczema Measure (POEM) scores. Safety was assessed.ResultsThis analysis included 1579 patients (systemic therapy‐naive, n = 997; prior exposure to oral systemic, n = 429; biologic therapies, n = 153). At Week 12, IGA 0/1 response rates (95% confidence intervals) among patients who were systemic therapy‐naive, had received prior oral systemic therapy or had received biologic therapy were 44.4% (37.5–51.4), 34.5% (22.3–46.7) and 43.5% (23.2–63.7) with abrocitinib 200 mg, 30.9% (24.2–37.5), 16.4% (7.1–25.7) and 24.1% (8.6–39.7) with abrocitinib 100 mg and 9.6% (4.2–14.9), 5.9% (0.0–13.8) and 0.0% (0.0–23.2) with placebo in the pooled monotherapy trials; and 67.0% (62.8–71.2), 62.2% (56.4–68.0) and 53.5% (42.9–64.0) in REGIMEN. Across subgroups, abrocitinib showed greater improvement in EASI‐75, PP‐NRS4, EASI‐90, PP‐NRS 0/1, PSAAD and POEM scores versus placebo. Similar results were seen at Week 48. No new safety signals were observed.ConclusionsPrior use of oral systemic or biologic therapies did not seem to impact the efficacy and safety of abrocitinib in patients with moderate‐to‐severe AD.

RF04 Oral spironolactone for adult female acne (SAFA): a multicentre, double-blind, randomized trial

Abstract Acne is common and results in significant burden and patients with acne frequently receive prolonged oral antibiotics leading to antimicrobial resistance. Oral spironolactone is prescribed for acne, although there is a paucity of evidence on its effectiveness. The aim of this pragmatic parallel, double-blind, superiority trial was to assess the effectiveness of systemic spironolactone for acne in adult women. Participants were identified through primary and secondary health care and through community and social media advertising. Women aged ≥ 18 years with facial acne for at least 6 months, judged to warrant oral antibiotics, were invited to participate. Consented recruits were randomized 1 : 1 to either 50 mg daily spironolactone or matched placebo until week 6, increasing to 100 mg daily spironolactone or placebo until week 24. Topical treatment could be continued. The primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12. Secondary outcomes included Acne-QoL at week 24, participant self-assessed improvement, Investigator’s Global Assessment (IGA) and adverse effects. Of 1267 women assessed, 410 were randomized (201 intervention, 209 control) and 342 were included in the primary analysis. Baseline mean (SD) age was 29.2 (7.2) years, 7.9% (n = 28/356) were of a non-White background, 46% had mild acne, 40% moderate acne and 13% severe acne (IGA classified). Eighty-three per cent used topical treatments. Over 95% of patients in both groups tolerated treatment and increased dosage. Mean (SD) Acne-QoL symptom scores at baseline and week 12 were 13.2 (4.9) and 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo, respectively {difference favouring spironolactone 1.27 [95% confidence interval (CI) 0.07–2.46]}. Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo [difference 3.45 (95% CI 2.16–4.75)]. Secondary outcomes also favoured spironolactone at week 12, with greater differences at week 24. More participants on spironolactone reported acne improvement than those on placebo. At week 12, this difference was not statistically significant [72.2% vs. 67.9%; odds ratio (OR) 1.16, 95% CI 0.70–1.91], but at week 24, it was significant (81.9% vs. 63.3%; OR 2.72, 95% CI 1.50–4.93). Treatment success (IGA classified) at week 12 was 31/201 on spironolactone and 9/209 on placebo (OR 5.18, 95% CI 2.18–12.28). Adverse reactions were not serious and were similar between groups, although more headaches were reported by those on spironolactone (20.4% vs. 12.0%; P = 0.02). Spironolactone improved outcomes vs. placebo, with greater differences at week 24 than at week 12. This study supports spironolactone as a potential alternative to oral antibiotics for acne in adult women.

BH04 Review of a dermatology nurse-led hair service

Abstract In 2017, our department was faced with a significant delay in new patient waiting times for the tertiary hair and nails clinic. A nurse-led service was developed to relieve this pressure. Within 18 months, the waiting list was much more manageable at less than 12 weeks, an improvement that has been maintained. The nurse-led service was designed predominantly to see and treat patients with alopecia areata. We present details of the nurse training and clinic setup. Three years after the setup of the nurse-led hair clinic, we reviewed this service. The aims of this review were to assess the capacity of the nurse-led hair clinic, the clinical outcome and the psychological impact. A review of all patients seen between November 2021 and October 2022 is presented. The total number of patients seen was 130. The majority had focal alopecia areata (90%). Clinical outcome measures were recorded using the Severity of Alopecia Tool score and Alopecia Areata Investigator Global Assessment. Psychological outcome measures were assessed using the Dermatology Life Quality Index and a patient questionnaire. The majority (72%) were treated with intralesional triamcinolone; 5% received a wig. The aim is to treat and discharge, while enabling easy access back into the service. It was hoped that this pathway would alleviate patient anxiety on discharge. All patients reported that they found it easy/very easy to be referred correctly by their general practitioner. The majority of returning patients had been given a clear explanation of the rereferral process on discharge. All reported an excellent or good service. More than 90% answered positively when asked whether the nurse listened, addressed fears/concerns and provided adequate verbal and written information. Sixty-two per cent remember being signposted to a relevant support group and all were satisfied with their treatment. We will present written information provided by the patients on what they found most useful about the clinic and how the clinic could be improved. We show the success of a nurse-led service that has addressed capacity issues and clinical management and provides emotional support. The detail presented will be sufficient to guide other departments on training and clinic setup when developing such a service.

Upadacitinib for moderate-to-severe atopic dermatitis: stratified analysis from three randomized phase 3 trials by key baseline characteristics.

Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics, and prior treatment) in patients with moderate-to-severe AD. Data from phase 3 studies (Measure Up 1, Measure Up 2, and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate-to-severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate-to-severe AD through week 16. These results support upadacitinib as a suitable treatment option in a variety of patients. ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up).

Prevalence and Characteristics of Itch and Pain in Patients Suffering from Chronic Hand Eczema.

Hand eczema (HE) is a frequent chronic inflammatory dermatosis. Itch and pain are considered two of the most common and burdensome symptoms of the disease. Yet, the data related to these symptoms are still limited. The aim of this study was to evaluate characteristics of itch and pain in adults suffering from HE. The study group comprised 100 adult HE patients. An original questionnaire designed by the authors was used to survey the patients. It included questions regarding demographic characteristics such as the duration of the disease, exacerbation count, past diagnostics and treatment, as well as atopic predispositions. Additionally, the itch and pain intensity (numerical rating scale-NRS) during '3 days prior to the study' and the 'entire disease' period was implemented. The clinical assessment of the disease severity was performed according to two specific measurement instruments: Investigator Global Assessment for Chronic Hand Eczema (IGA-CHE) scale and Hand Eczema Severity Index (HECSI). To assess patient quality of life (QoL), the DLQI tool was used and to determine the level of stigmatization and for its impact on patients' life the 6-Item Stigmatization Scale (6-ISS) was employed. Within the period of 3 days prior to the examination, itch was reported by 81.0% of patients (n = 81), whereas 53.0% (n = 53) of them experienced pain. Both symptoms were reported more frequently in females (itch: p = 0.022; pain: p = 0.033). When sexes were compared, females reached higher scores in both IGA-CHE and HECSI. Itch and pain intensity correlated positively with disease severity. The intensity of itch and pain significantly influences HE patients' QoL. A positive correlation between the 6-ISS score and the intensity of itch in the 'last 3 days' period was revealed (r = 0.221; p = 0.027). Itch and pain are common symptoms in HE patients, significantly contributing to the feeling of stigmatization. Providing characteristics of itch and pain may improve HE management. Symptom-decreasing treatment would definitely have a positive influence on patients' well-being.

380 Patients maintain stable response with no or minimal fluctuations during treatment with lebrikizumab up to Week 52

Abstract Lebrikizumab is a monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) are identically designed phase 3, randomized, double-blinded, placebo-controlled trials evaluating lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD). At Week 16 of both studies, lebrikizumab 250 mg every 2 weeks (Q2W) showed statistically significant improvements in measures of skin clearance and patient reported outcomes. Patients treated with lebrikizumab achieved clinically meaningful improvements in the signs and symptoms of AD with fewer AD flares across multiple definitions than patients treated with placebo. In patients who met the protocol-defined criteria for response to lebrikizumab at Week 16, most patients treated with lebrikizumab Q2W and lebrikizumab every 4 weeks (Q4W) maintained an Investigator’s Global Assessment (IGA) 0/1 response (71% and 77%, respectively) and a 75% improvement in the Eczema and Severity Index from baseline (EASI 75; 78% and 82%, respectively) up to Week 52. The objective of this analysis is to determine the proportion and the individual efficacy trajectory of lebrikizumab-treated patients who exhibited a stable response with no or minimal fluctuations of efficacy from Week 16 to Week 52 in Week 16 responders. Patients who responded to lebrikizumab at the end of the 16-week induction period were rerandomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab Q4W or placebo Q2W (withdrawal) for 36 additional weeks. Week 16 responders were defined as those achieving an EASI 75 or IGA 0/1 with a ≥2-point improvement and without rescue medication use. We defined no or minimal fluctuations as maintaining EASI 75 for at least 80% of the 10 study visits from Week 16 to Week 52. Separately, we analysed EASI 90 with the same criteria. We also analysed the proportion of patients who achieved each endpoint at all 10 maintenance period study visits. ADvocate2 analyses were performed on a modified population, excluding 17 patients who entered the maintenance period (from a single study site) and whose eligibility could not be confirmed. Therefore, analyses were performed on the modified pooled population of ADvocate1 and ADvocate2 patients. All analyses were performed post hoc. If patients used rescue medication, discontinued treatment or transferred to the escape arm, data collected at or after the event was imputed as nonresponse. In ADvocate1 and ADvocate2, 291 patients met the criteria for response at Week 16 (EASI 75 or IGA 0/1 with a ≥2-point improvement and without rescue medication use) and were rerandomized to receive lebrikizumab Q2W (n = 113), lebrikizumab Q4W, (n = 118) or withdrawal (n = 60) from Week 16 to Week 52. The proportions of patients who maintained EASI 75 for at least 80% of the maintenance period were 71% (lebrikizumab Q2W), 71% (lebrikizumab Q4W) and 60% (withdrawal). The proportions of patients who maintained EASI 75 at all study visits were 53% (lebrikizumab Q2W), 55% (lebrikizumab Q4W) and 38% (withdrawal). The proportions of patients to achieve and maintain the more stringent response of EASI 90 for at least 80% of study visits were 45% (lebrikizumab Q2W), 51% (lebrikizumab Q4W) and 35% (withdrawal). In ADvocate1 and ADvocate2, approximately 7 out of 10 of patients who continued treatment with lebrikizumab maintained at least an EASI 75 response with no or minimal fluctuations. These individual patient data show that most patients treated with monotherapy lebrikizumab Q2W and Q4W maintain a stable response with no or minimal fluctuations of efficacy up to Week 52.

408 Dupilumab treatment in patients with atopic hand and foot dermatitis: results from a phase 3, randomized, double-blind, placebo-controlled trial

Abstract Atopic dermatitis (AD) of the hands and/or feet is often chronic, difficult to treat and substantially impacts patient quality of life. This study aims to report the effect of dupilumab treatment on signs, symptoms and quality of life in patients with atopic hand and foot dermatitis using dedicated clinical and patient reported instruments. The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients ≥12 years with moderate-to-severe [Investigator’s Global Assessment (IGA) 3/4] atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg q2w in adults; 200/300 mg every 2 weeks in adolescents, or placebo for 16 weeks. The primary endpoint was hand and foot IGA 0/1 score at Week 16. Safety/tolerability was assessed. The 133 patients enrolled were randomized to dupilumab (n = 67) or placebo (n = 66). At Week 16, the primary and all secondary endpoints were met. Significantly more patients in the dupilumab vs. placebo group achieved hand and foot IGA 0/1 (40.3% vs. 16.7%; P = 0.003; primary endpoint) and ≥4-point improvement in the hand and foot Peak Pruritus Numerical Rating Scale (52.2% vs. 13.6%; P &amp;lt; 0.0001; a key secondary endpoint). Dupilumab-treated patients experienced significant improvement in percent change from baseline in the modified Total Lesion Sign Score for hand and foot lesions vs. placebo [LS mean (SE) −69.4 (5.8) vs. −31.0 (5.9); P &amp;lt; 0.0001] and Hand Eczema Severity Index [HECSI; LS mean (SE) −74.8 (6.3) vs. −39.9 (6.2); P &amp;lt; 0.0001]. At Week 16, treatment with dupilumab also significantly increased the proportion of patients achieving a 75% improvement in HECSI (46.9% vs. 21.5%; P = 0.0028) and improved Quality of Life in Hand Eczema Questionnaire scores [LS mean (SE) −40.3 (4.0) vs. −16.2 (4.2); P &amp;lt; 0.0001]. The most common TEAEs (≥10%) were nasopharyngitis (16% vs. 11%) and dermatitis atopic (5% vs. 18%). Dupilumab significantly improved signs, symptoms and quality of life in patients with moderate-to-severe atopic hand and foot dermatitis and had an acceptable safety profile.

388 Efficacy and safety of roflumilast foam 0.3% in patients with seborrheic dermatitis in a phase 3 trial: assessment of pruritus

Abstract Itch is a major complaint among patients with seborrheic dermatitis (SD). Roflumilast is a selective, nonsteroidal, highly potent phosphodiesterase-4 inhibitor under investigation as a once-daily foam for treatment of SD. This phase 3 randomized, parallel-group, double-blind, vehicle-controlled trial (NCT04973228) was conducted in patients ≥9 years old with at least moderate SD affecting scalp and/or nonscalp areas. Patients were randomized 2 : 1 to apply once-daily roflumilast foam 0.3% (n = 304) or vehicle (n = 153) for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) success (IGA of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. Secondary efficacy endpoints included Worst Itch Numeric Rating Scale (WI-NRS), which was completed daily by patients. Safety and local tolerability were also evaluated. Overall, significantly more roflumilast-treated patients than vehicle-treated patients achieved IGA success (79.5% vs. 58.0%; P &amp;lt; 0.0001) and IGA status of Clear (50.6% vs. 27.7%; P &amp;lt; 0.0001) at Week 8. Significantly greater percentages of roflumilast- than vehicle-treated patients had ≥4-point improvement on WI-NRS at Weeks 2 (32.7% vs. 15.5%; P = 0.0016), 4 (47.6% vs. 29.1%; P = 0.0007) and 8 (62.8% vs. 40.6%; P = 0.0001). Greater improvement in itch was observed among roflumilast-treated patients as early as 48 h after the first application (mean percent change from baseline: −27.87% vs. −13.11%; nominal P = 0.0024). Local tolerability and safety were favorable. Once-daily roflumilast foam provided improvement across multiple efficacy endpoints including rapid itch improvement, while demonstrating favorable safety and tolerability.