Investigator's Global Assessment Scale Research Articles

Pharmacokinetics, Safety, Tolerability, and Exploratory Efficacy of Upadacitinib in Children with Severe Atopic Dermatitis

PurposeThis study aims to characterize the pharmacokinetics, safety, tolerability, and exploratory efficacy of upadacitinib, an oral Janus kinase inhibitor approved for treating moderate to severe atopic dermatitis (AD) in adults and adolescents, in children with severe AD. MethodsIn an open-label, multiple-dose, Phase 1 study, pediatric patients with severe AD from two age groups (2 to <6 years and 6 to <12 years) received bodyweight-based dosing regimens of upadacitinib using either twice-daily immediate-release (IR) oral solution or once-daily extended-release (ER) tablets. A pharmacokinetic assessment was conducted on Day 7 of the study, which was followed by a long-term safety and exploratory efficacy evaluation for up to 108 weeks. The results reported here are based on an interim analysis when the study had completed enrollment and pharmacokinetic assessment. FindingsA total of 35 patients were enrolled and received upadacitinib. The maximum upadacitinib plasma concentration was attained within a median time of 0.5 to 2 hours and 2 to 2.5 hours for the IR oral solution and ER tablet formulations, respectively. Upadacitinib functional half-life was generally shorter with IR oral solution relative to ER tablets. Upadacitinib apparent oral clearance decreased with decreasing body weight in the pediatric patients enrolled in this study. Upadacitinib was generally safe and well tolerated. The most common (≥3 patients) adverse events were upper respiratory tract infection, COVID-19 infection, headache, abdominal discomfort, vomiting, asthma, and cough. No new safety risks were identified compared to the known safety profile for upadacitinib in adults and adolescents. In the 30 patients with available exploratory efficacy data at Week 12, 36.7% achieved validated Investigator's Global Assessment scale for AD score of 0 or 1 (Validated Investigator Global Assessment for AD 0/1), and 70.0% had Eczema Area and Severity Index (EASI) improvement of at least 75% (EASI 75). ImplicationsThe characterized pharmacokinetic profiles in this study, together with the observed safety and exploratory efficacy results, support further investigation of the current upadacitinib dosing regimen in future confirmatory Phase 3 clinical trials in children with AD.Clinical Trial Number: NCT03646604, registered 2018-08-23

Efficacy of topical treatments for mild‐to‐moderate acne: A systematic review and meta‐analysis of randomized control trials

AbstractAcne is a common skin condition, but little data exist on the comparative efficacy of topical acne therapies. We conducted a systematic review and network meta‐analysis to evaluate the efficacy of topical therapies for mild‐to‐moderate acne. Searches in PubMed/MEDLINE, Cochrane CENTRAL via Ovid, Embase via Ovid and Web of Science were conducted on 29 November 2021. Randomized controlled trials examining ≥12 weeks of topical treatments for acne vulgaris in subjects aged 12 and older were included. Main outcomes were absolute or percent change in acne lesion count and treatment success on the Investigator's Global Assessment scale. Thirty‐five randomized clinical trials with 33,472 participants comparing nine different topical agents were included. Adapalene‐benzoyl peroxide (BPO), clindamycin‐BPO and clindamycin‐tretinoin demonstrated the greatest reduction in non‐inflammatory (ratio of means [RoM] 1.76; 95% CI [1.46; 2.12], RoM 1.70; 95% CI [1.44; 2.02] and RoM 1.87; 95% CI [1.53; 2.30], respectively), inflammatory (RoM 1.56; 95% CI [1.44; 1.70], RoM 1.49; 95% CI [1.39; 1.60] and RoM 1.48; 95% CI [1.36; 1.61], respectively) and total lesion count (ROM 1.67; 95% CI [1.47; 1.90], RoM 1.59; 95% CI [1.42; 1.79] and RoM 1.64; 95% CI [1.42; 1.89], respectively) compared to placebo. All single agents outperformed placebo except tazarotene, which did not significantly outperform placebo for inflammatory and non‐inflammatory lesion count reduction. Most combination agents significantly outperformed their individual components in lesion count reduction and global assessment scores, except for clindamycin‐tretinoin and clindamycin‐BPO, which did not significantly outperform tretinoin (RoM 1.13; 95% CI [0.94; 1.36]) and BPO (RoM = 1.15, 95% CI [0.98; 1.36]), respectively, for non‐inflammatory lesion reduction. There was no significant difference amongst most single agents when evaluating lesion count reduction. Combination agents are generally most effective for mild‐to‐moderate acne; however for non‐inflammatory acne, the addition of clindamycin in topical regimens is unnecessary and should be avoided.

Efficacy and Safety of Q-Switched 1064/532 nm Nd:YAG Lasers on Benign Hypermelanosis in Dark-Skinned Individuals-A Preliminary Study.

Background: Facial hypermelanosis is a major cosmetic issue that causes severe social embarrassment and psychological pain, particularly among Asians and dark-skinned individuals. Aim: This study assesses the safety and effectiveness of Q-switched 1064/532 nm nanosecond/picosecond lasers in removing benign hypermelanosis in dark-skinned individuals, evaluating the possible associated side effects. Material and methods: A total of 30 participants (80% females and 20% males) with Fitzpatrick skin types IV-V-VI who presented superficial benign hypermelanoses on the facial and décolleté area were enrolled. All patients underwent to one to two laser treatment sessions with a 1064/532 nm Q-switched laser system. Three months after the final laser session, results were assessed by comparing before- and after-treatment photos and using a quartile scale for lesion clearance (4-point Investigator Global Assessment scale). Results: All patients observed global improvements in their pigmented lesions: 53% of patients achieved excellent clearance, 30% of patients achieved good to moderate clearance, 10% of patients achieved slight clearance, and 7% of patients did not respond to the therapy. No serious adverse event occurred. Photos showed the clinical improvement achieved at 3 months follow-up. Conclusions: The Q-switched 1064/532 nm laser proved to be a key tool for treating benign hypermelanosis in all skin types, including dark-skinned persons.

524 - Efficacy of upadacitinib and dupilumab on achieving stringent and composite skin and itch outcomes: an indirect comparison of adults with moderate-to-severe atopic dermatitis

Abstract Introduction/Background Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and Measure Up 2 assessed efficacy of upadacitinib 30mg and upadacitinib 15mg against placebo, while Heads Up assessed efficacy of upadacitinib 30mg in a head-to-head trial against dupilumab 300mg. Network meta-analysis has shown that upadacitinib 30mg and upadacitinib 15mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated stringent and composite measures of efficacy. Objectives To indirectly compare upadacitinib and dupilumab on stringent and composite measures of skin clearance and itch resolution. Methods A population-adjusted indirect comparison using covariate adjustment as a treatment effect calibration was conducted using individual patient data from Measure Up 1 and 2 and Heads Up. Specifically, the indirect comparison model estimated how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates (age, gender, race, country, previous use of systemic therapy, disease duration, baseline validated Investigator Global Assessment scale for AD score, and baseline Eczema Area and Severity Index [EASI]). Absolute response rates at weeks 4 and 16 were estimated for the following outcomes: no/minimal itch (Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1), 100% improvement in EASI (EASI 100), achievement of both ≥90% improvement in EASI (EASI 90) and WP-NRS 0/1, and achievement of both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to-treat population for the clinical trials, and utilized non-responder imputation. Results Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg, and then dupilumab. This pattern was observed at week 4 on the achievement of WP-NRS 0/1 (upadacitinib 30 mg: 34.2% | upadacitinib 15 mg: 18.2% | dupilumab: 7.9%), EASI 100 (8.5% | 4.7% | 1.8%), EASI 90 &amp; WP-NRS 0/1 (21.9% | 10.6% | 3.3%), and EASI 100 &amp; WP-NRS 0/1 (6.4% | 3.5% | 1.2%). This ranking was maintained at week 16 for WP-NRS 0/1 (35.4% | 22.5% | 16.2%), EASI 100 (28.4% | 22.2% | 7.9%), EASI 90 &amp; WP-NRS 0/1 (32.2% | 19.6% | 12.4%), and EASI 100 &amp; WP-NRS 0/1 (19.6% | 12.7% | 4.2%). Conclusions For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining stringent and composite outcomes after 4 and 16 weeks, followed by upadacitinib 15 mg, and then dupilumab.

Whey protein and male acne: A double-blind, randomized controlled trial.

Acne vulgaris (AV) exacerbation after whey protein (WP) consumption remains inconclusive among experts. To investigate the association between WP consumption and acne severity in men with acne. A noninferiority trial was conducted in men with mild to moderate facial and/or truncal acne. After randomization, participants in an intervention group took daily WP 30 g with a non-WP nutritional supplement 18 g (WP group, n = 25), while the control group took a non-WP nutritional supplement 46 g (non-WP group, n = 24). At each follow-up appointment, investigators evaluated acne count (total acne lesions, comedonal lesions, and inflammatory lesions) and severity. Forty-nine participants had a mean age of 19.7 years (standard deviation [SD], 0.9) and 20.3 years (SD, 1.4) in the WP and non-WP groups, respectively. The mean differences in the facial and truncal total acne lesions for the WP and non-WP group were -5.99 (95% confidence interval [CI], -13.18 to 1.19, p = 0.09) and -2.18 (95% CI, -11.83 to 7.48, p = 0.65), respectively. For severity changes, only one (4.3%) participant in the non-WP group reported an increase in the Investigator Global Assessment scale of at least two levels. In this 6-month trial, men with acne who undertook WP supplementation showed a noninferior difference in the changes in total acne lesions and severity of facial and truncal acne compared with the non-WP group.

A pilot study examining a double-conjugated, retinoid-based skincare regimen for darker, blemish-prone skin.

Retinoids and alpha- and beta hydroxy acids are common components utilized in regimens for blemish-prone skin. However, balancing efficacy and tolerability is often challenging. This pilot study evaluated a double-conjugated retinoid serum specifically formulated for blemish-prone skin (AHARet-SA) in combination with exfoliating peel pads (double-conjugated retinoid, glycolic, lactic, and salicylic acids), a cleanser, mineral-based sunscreen, and a lightweight moisturizer in female participants with mild-to-moderate blemish-prone skin. Fifty-five percent of participants were Fitzpatrick Skin Type (FST) IV and 27% were FST V. Participants used the exfoliating peel pads (3x/week for 8 weeks; 2x/week for 4 weeks) followed by nightly AHARet-SA and a moisturizer (as needed). Improvements in skin were assessed using the 5-point Investigator Global Assessment Scale, and participant satisfaction and tolerability were assessed over 12 weeks. Significant mean improvement from baseline in skin clarity occurred after 4 weeks (14%; p = 0.04) with progressive improvements through week 12 (52%; p = 0.004). Eighty-eight percent of participants reported improvements in the appearance and texture of their skin and fewer blemishes/breakouts. Mild, transient adverse events were reported. A regimen comprised of a double-conjugated serum and exfoliating peel pads formulated for blemish-prone skin led to significant improvements from baseline in skin clarity after 12 weeks in participants with predominately darker skin tones and mild-to-moderate blemish-prone skin.

Assessment of the efficacy of 595nm pulsed dye laser in the management of facial flat angiomas. Results of a case series.

Studies on pulsed dye laser (PDL) have shown the best efficacy and safety data for treating vascular anomalies among the various lasers used and the 595-nm PDL has been used to treat cutaneous vascular anomalies for about 30 years. The purpose of this study was to assess the efficacy of 595nm Pulsed Dye Laser in the management of facial flat angiomas present in the form of Port-Wine Stain. Seven cases of PWS in Fitzpatrick skin type ranged from I to III and colour ranging from pink to purple, were treated with 595nm pulse Dye Laser. Patients underwent to 6-8 laser sessions at 20-30 days intervals. Results obtained were judged by dermatologist, by comparing pre-treatment and post-treatment photographs, 6 months after the last session and a quartile scale of lesion clearance (4-point Investigator Global Assessment scale): 1=no or low results (0%-25% of the lesion area improved), 2=slight improvement (25%-50% of the lesion area cleared), 3=moderate-good improvement (50%-75%), and 4=excellent improvement (75%-100%) was used. Possible side effects such as blisters, hyper/hypopigmentation, and scarring were monitored. All patients observed global improvements. 71% of patients achieved excellent clearance and 29% patients achieved good-moderate clearance of their angioma. Patients were asked for a subjective evaluation of the results: 57% of patients were very satisfied, 29% were satisfied, and 14% patients were not very satisfied with the results. No patients were dissatisfied. No significant side effects were noted. This research confirms the efficacy of the 595nm PDL for flat angioma management, without considerable side effects.

406 Tapinarof cream 1% once daily for the treatment of extensive atopic dermatitis in adolescents and children: outcomes from the 4-week maximal usage trial

Abstract Tapinarof is a first-in-class, nonsteroidal, topical, aryl hydrocarbon receptor agonist approved by the Food and Drug Administration for the treatment of plaque psoriasis in adults, and under investigation for the treatment of atopic dermatitis (AD) in adults and children. Tapinarof cream 1% once daily (QD) demonstrated significant efficacy vs. vehicle and was well tolerated in adults and adolescents with moderate to severe AD in a previously reported phase 2b trial. The pharmacokinetic (PK) profile of tapinarof across psoriasis and AD trials in adults is characterized by no-to-minimal systemic absorption and decreasing plasma concentrations over the course of treatment. Here, we report PK, tolerability and safety of tapinarof cream 1% QD in adolescents and children down to age 2 years with extensive AD. Adolescents and children with a Validated Investigator Global Assessment scale for Atopic Dermatitis™ (vIGA-AD™) score ≥3 (moderate or worse) and body surface area (BSA) involvement ≥25% (ages 12–17 years) or ≥35% (ages 2–11 years) were enrolled into three age cohorts (2–6, 7–11 and 12–17 years) and were treated with tapinarof cream 1% QD for 4 weeks. Primary endpoints included PK parameters, investigator-assessed Local Tolerability Scale (LTS) scores by visit (overall and for sensitive areas) and treatment-emergent adverse events (TEAEs). Overall, 36 patients (12 per cohort) were enrolled. Patients’ mean age was 8.9 years and 66.7% were male. At baseline, 66.7%, 75% and 91.7% of patients had a vIGA-AD score of 3 for cohorts 2–6, 7–11 and 12–17 years, respectively. Mean BSA (range) affected was 52.4% (36.0–90.0%), 42.0% (35.0–72.0%) and 33.9% (26.0–54.5%) for the three age cohorts, respectively. Mean Eczema Area and Severity Index scores were 30.2, 21.0 and 20.3, respectively. No-to-minimal tapinarof systemic exposure was observed, consistent with previous trials in adults. Mean tapinarof maximum plasma concentration (Cmax) at Day 1 was 2.4 ng/mL, and the median time to Cmax was approximately 3 h, for all patients. Approximately 25% of post-treatment plasma samples were below the quantifiable limit of the highly sensitive assay [&amp;lt;50 pg (10–12)/mL]. There was no correlation between tapinarof exposure (Cmax on Day 1) and baseline %BSA affected. Mean overall investigator-assessed LTS score was 0.1 (no irritation) at Weeks 1 and 4. Investigators assessed that the majority of patients had no irritation (LTS score of 0), including sensitive and intertriginous skin. The TEAEs were reported by eight patients (22%) and were all mild or moderate; one patient discontinued due to two unrelated TEAEs. One case of mild folliculitis and no contact dermatitis occurred. Most patients (87.5%) chose to enroll in the 48-week long-term extension trial. This is the first trial evaluating tapinarof in children down to 2 years of age. Tapinarof cream 1% QD demonstrated no-to-minimal systemic exposure in children with extensive AD, even when measured with a highly sensitive assay. There was a low incidence of TEAEs in patients with up to 90% BSA affected. Tapinarof cream was well tolerated, including sensitive and intertriginous skin areas.

428 Evaluating chronic pruritus prevalence, characteristics and effects on atopic dermatitis patients from a referral university hospital in São Paulo, Brazil: a cross-sectional study

Abstract Chronic pruritus is one of the predominant symptoms of atopic dermatitis (AD), with one study showing that over 90% of patients with AD experience itch at least once a day. A multicenter, retrospective study in southern and southeastern Brazil found that at least 77% of patients had moderate to severe AD, and 55% experienced pruritus. However, this study did not specifically assess the characteristics of the itch associated with AD. Atopic dermatitis is also known to have a significant impact on quality of life, and has a detrimental effect on mental health, school and work performance, and social interactions. A study assessing patients with AD seen at the Dermatology Clinic at the University of Sao Paulo School of Medicine found that AD severely impacted patient scores on the Dermatology Life Quality Index (DLQI). Although the DLQI measures the impact of dermatologic diseases on Health-Related Quality of Life, it is not itch-specific. The itch-specific quality of life (ItchyQoL), a pruritus-specific instrument, was developed in order to better assess the impact of chronic pruritus on patients’ health-related quality of life. It has since been validated in over 22 European countries with a high degree of reliability and internal consistency across multiple languages. Since it is known that AD is phenotypically and molecularly different in ethnic populations, the diverse patient population found in São Paulo, Brazil represents an opportunity to further the understanding of AD in these individuals. Therefore, we conducted a large-scale, prospective study on the prevalence, severity and quality of life impacts of pruritus in patients with AD from a referral university hospital in São Paulo, Brazil to further strengthen the current understanding of this unique disease entity in this diverse patient population. Additionally, the association of itch intensity with the clinical severity of AD measured by objective, validated assessment tools will allow providers to better understand and manage chronic pruritus in this unique patient population. The primary objective of this cross-sectional study is to evaluate the prevalence and severity of itch in patients with Atopic Dermatitis (AD) in São Paulo, Brazil. The secondary objective of this study is to describe the characteristics of itch in this population and its effect on quality of life by using validated itch questionnaires and itch quality of life tools. The third objective of this study is to describe the clinical severity of AD in this patient population and its association to itch intensity. We conducted a cross-sectional study of patients aged 15–65 years old with atopic dermatitis who attended the Atopic Dermatitis Clinic at the Department of Dermatology, University of Sao Paulo Medical School over a 15-month period. Patients who experienced pruritus were asked to complete three validated questionnaires: The Itch Questionnaire, the ItchyQoL questionnaire and the Patient Oriented Eczema Measure. All itchy subjects were also asked to measure their perception of pruritus with a 10-cm NRS scale. The extent of disease was also assessed using the Eczema Area and Severity Index and the Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA). Results will be available to be presented at the conference. Finalized results of the study are pending.

357 The effect of upadacitinib on the genital region in moderate-to-severe atopic dermatitis: an analysis from the Measure Up 1 and Measure Up 2 studies

Abstract Atopic dermatitis (AD) is a chronic, inflammatory skin disease that can be debilitating, impacting all body areas, including the genital region. Genital AD results in impairments in daily activity levels, sexual function and sleep, contributing to impaired quality of life in patients with moderate-to-severe AD. Upadacitinib (UPA) is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 vs. JAK2, JAK3 and tyrosine kinase 2, indicated for the treatment of moderate to severe AD. The SCORing Atopic Dermatitis (SCORAD) measure assesses the extent and severity to which a body area is affected, as well as itch and sleeplessness due to AD. In this post-hoc analysis of the Measure Up 1 and Measure Up 2 studies, we evaluated the proportion of patients whose genital AD resolved with UPA 15 mg or UPA 30 mg compared with placebo. Measure Up 1 and 2 are phase 3 multicenter, randomized, double-blind studies comparing the safety and efficacy of UPA 15 mg and UPA 30 mg to placebo in adolescent and adult patients with moderate-to-severe AD. Patients were randomized to oral once daily UPA 15 mg, UPA 30 mg or placebo. The current study assessed the proportion of patients with genital involvement at baseline who achieved genital AD resolution at week 2 and week 16 based on data collected from the SCORAD. Non-responder imputation was used. Of the 1679 participants, 239 (14.2%) had genital AD at baseline and were randomized to UPA 15 mg (n = 77), UPA 30 mg (n = 86) or placebo (n = 76). More participants with genital involvement vs. those without were male (61.1% vs. 54.1%), ≥18 years old (92.1% vs. 85.5%), and severe according to the Validated Investigator Global Assessment Scale for Atopic Dermatitis (66.9% vs. 47.2%) at baseline. On average, participants with genital involvement at baseline also reported greater disease duration (25.0 vs. 22.8 years) and higher Dermatology Life Quality Index (DLQI) scores (19.2 vs. 16.3). At week 2, the proportion of patients whose genital AD was resolved was 70.1% of the UPA 15 mg group, and 82.6% of the UPA 30 mg group, both of which were greater than the placebo group (31.6%; P &amp;lt; 0.001). At week 16, the proportion of patients whose genital AD was resolved increased in the UPA 15 mg (80.5%) and UPA 30 mg (83.7%) groups, but not in the placebo group (28.9%) which remained lower than both groups (P &amp;lt; 0.001). More patients with moderate-to-severe AD achieved resolution of their genital AD with UPA 15 mg or 30 mg monotherapy daily compared to placebo, with &amp;gt;70% rapidly achieving genital AD resolution after 2 weeks and &amp;gt;80% after 16 weeks of UPA treatment. In addition to overall improvements in moderate-to-severe AD with UPA, resolution of genital AD may correspond to improvements in sexual functioning, reductions in sleeplessness and greater quality of life. These findings underscore the importance of considering genital involvement when assessing the burden of AD to comprehensively inform integrated shared decision-making treatment discussions between patients and physicians.

Determination of key prognostic factors for the development of acne recurrence after systemic isotretinoin therapy

Since the 80s of the last century, the most effective drug for the treatment of acne is systemic isotretinoin (SI). The introduction of SI into practice makes it possible to achieve stable clinical remission or complete recovery in 80% of acne patients, regardless of the severity of the disease, however, 20% of patients may experience relapses in the next 1.52 years.&#x0D; Aim. To establish the factors determining the likelihood of acne recurrence after a course of therapy using the systemic isotrtinoin.&#x0D; Materials and methods. After examining 275 patients, 84 patients (50 women and 34 men) who had previously been treated with SI for acne took part in the study, 54 of them had relapses for at least 4 months and the comparison group consisted of 30 patients out of 221 surveyed who did not have relapses after treatment. As part of the study, a retrospective analysis of outpatient records was carried out, data on the history of life and illness, comorbid hormonal pathology in women, anthropometric characteristics were recorded, and the presence of heredity for acne was also taken into account, the severity of acne was assessed using the Investigator's Global Assessment scale; laboratory examination was performed to exclude insulin resistance.&#x0D; Results. The development of relapses after the first course of acne treatment using SI was registered in 19.63%, however, indications for a second course of treatment were stated in 12.00%. The analysis of the data obtained allowed us to determine the main factors that contributed to the development of relapses: severe acne severity, the presence of rashes on the trunk, body mass index more than 25, the presence of hormonal abnormalities in women, scarification, male sex, daily dose less than 0.5 mg/kg, the presence of heredity for acne in both parents, the course dose of SI120 mg/kg, insulin resistance.&#x0D; Conclusion. The issue of studying the factors that can cause the development of acne recurrence after the end of the course of therapy is an extremely urgent problem, due to the fact that taking them into account at the early stages of treatment of patients will increase the percentage of patients with complete clinical remission or recovery.

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

Baricitinib treatment of severe chronic hand eczema: Two case reports

Baricitinib treatment of severe chronic hand eczema: Two case reports

Combined Therapy with Laser and Autologous Topical Serum for Facial Rejuvenation: A Multiple Case Series Report.

Lasers require several sessions to achieve significant results and may lead to adverse reactions. Platelet-rich plasma (PRP) therapy is a good adjuvant to laser therapies; however, repeated blood extractions and invasive injections are needed. A 100% autologous topical formulation based on the patient's proteins has been recently developed, known as Endoret-Serum (ES). Unlike other PRPs, ES provides a home care, storable, and topical needle-free application. Preliminarily assess the clinical performance of a single session of the combined therapy with nonablative laser and ES in the management of cutaneous pigmented and vasculature lesions. Nine patients with clinical signs of skin aging received a single session of nonablative laser. ES was topically applied twice daily. They were clinically assessed after 1 and 8 weeks. VISIA-CR System was used for high-resolution topographic analysis. Subjects were asked to complete a self-assessment questionnaire and an impression of improvement survey. An investigator's global assessment scale was fulfilled. The combined treatment improved cutaneous spots, wrinkles, and texture after 8 weeks, whereas significant pore reduction was observable at 1 week. Ultraviolet (UV) spots and porphyrins decreased at 1 week, whereas red area improvement was noticeable after 8 weeks. Overall wrinkle amelioration, periorbital hyperpigmentation decrease, softened skin, and tone recovery was observed. Patients referred to be very satisfied and felt that their cutaneous condition was much better. At the end of the study, subjects presented minimal dermatological symptoms like pigmented lesions, redness, or capillaries. No side effects were reported. Results presented herein suggest that one session of laser in combination with ES provides a good clinical outcome.

Investigator's Global Assessment of Chronic Prurigo: A New Instrument for Use in Clinical Trials.

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

What are the best endpoints for Eczema Area and Severity Index and Scoring Atopic Dermatitis in clinical practice? A prospective observational study.

Multiple strategies have been used to evaluate the minimal important change (MIC) of the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD). The meaningfulness of these MICs is not well established across all severities of atopic dermatitis (AD). To determine the MIC of percentage and absolute improvement of EASI and SCORAD scores in adults and children with AD. We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n=826). An anchor-based approach was used to determine thresholds for the percentage and absolute MICs of EASI, SCORAD and objective SCORAD (O-SCORAD) at follow-up from baseline. One-grade improvements of Physician's Global Assessment (PGA) and validated Investigator Global Assessment scale for AD (vIGA-AD) were associated with 50%, 35% and 35% decreases of EASI, SCORAD and O-SCORAD, respectively. The thresholds for percentage MIC of EASI (Kruskal-Wallis test, P=0·61), SCORAD (P=0·07) and O-SCORAD (P=0·09) were similar across baseline AD severities. One-grade improvements of PGA and vIGA-AD were associated with 14·0- and 14·9-point decreases of EASI, 19·9- and 14·9-point decreases of SCORAD, and 15·5- and 17·4-point decreases of O-SCORAD. The thresholds for the absolute MIC of EASI (P<0·001), SCORAD (P<0·001) and O-SCORAD (P<0·001) significantly differed by baseline AD severity. Percentage and absolute MICs for EASI and SCORAD were associated with improvements of AD symptoms and quality of life. EASI 50, SCORAD 35 and O-SCORAD 35 were meaningful percentage MICs regardless of baseline AD severity. The absolute MICs for EASI, SCORAD and O-SCORAD varied by baseline AD severity.

Platelet-rich plasma for male genital lichen sclerosus resistant to conventional therapy: First prospective study.

Ultrapotent topical corticosteroids and circumcision are usually effective for male genital lichen sclerosus (MGLSc); however, refractory cases are often referred to our Male Genital Dermatology Unit. Treatment with autologous platelet-rich plasma (TPRP) has recently been advocated as a safe and effective treatment option, but there have been no prospective studies in men to date. The objective of this study is to assess the safety and efficacy of TPRP for MGLSc resistant to conventional therapy. A prospective, open-label, single-arm, therapeutic study was carried out in this study. Inclusion criteria: resistant to conventional therapy for at least 6 months. Procedure: infiltration of 0.1 mL/cm2 PRP every 8 weeks. Monthly data recording: visual appearance with photographs and external scoring by an expert using Investigator's Global Assessment Scale (IGA scale 0-5), symptoms (scale 0-5), quality of life (QoL; Dermatology Life Quality Index [DLQI]), and complications. No. of patients included was n = 5. No. of patients excluded during treatment was n = 1. Mean initial IGA: 3.6. Mean initial DLQI: 6. TPRP n = 34 (range: 2-9; average: 6.8 per patient). Mean IGA at 18 months: 3.25. Mean DLQI at 18 months: 1.25. All patients reported being completely asymptomatic at 10 months. No. of patients with complications is n = 1 (balanitis). TPRP seems to be safe and effective, regarding symptom control and improvement in QoL; however, visual changes were minimal.

Efficacy and safety of oral dapsone in acne vulgaris – experience of a tertiary care teaching hospital in central Lahore

Background: Acne is the eighth most prevalent disease affecting 9.4% of the population worldwide and its prevalence in our country is estimated to be around 5%. Severe inflammatory acne is most likely to leave scars and in order to prevent facial disfigurement due to acne scarring, early treatment is desirable. Various treatment options have been formulated for acne, and are tailored according to the severity of the disease. Numerous clinical trials have been conducted till now, to determine the usefulness and side effect profile of such therapies, making acne treatment a highly studied area in dermatology. Objective of this study is to highlight the fact that oral Dapsone could be used as a cheaper alternate to isotretinoin in recalcitrant severe acne, especially in females where retinoids are sometimes contraindicated.&#x0D; Patients and methods: 51 patients, suffering from severe nodulocystic acne, fulfilling the criteria, were enrolled from the Department of Dermatology, Sir Ganga Ram Hospital, Lahore. All the study patients were given oral Dapsone 50mg for initial two weeks and then 100mg daily for the next 10 weeks along with oral cimetidine and topical clindamycin application twice daily. Investigator Global Assessment Scale (IGAS) was employed to measure effectiveness. The treatment was considered ʽeffectiveʹ if the patient achieves 2 or more than 2-grade improvement or almost clear or clear skin at the end of 12 weeks according to IGAS scale. The lesion counts were also done before the start of therapy (day 1) and at every two weeks follow up for 12 weeks. The change in lesion count observed between the baseline number and that seen at follow up visits was also used to evaluate the effectiveness of oral Dapsone. Safety was analyzed by fortnightly visits of the patients to look for any undesirable side effects and monitoring of the hematologic profile of the patients. Final follow up was done at the end of 16 weeks.&#x0D; Results: The study was conducted on 51 patients, with a ratio of 1:3 for males and females and a mean age of 25.2 years (SD ±5.81). At 12th week, patients had significant reduction in their acne lesions; with 7 patients (13.7%) showing completely clear skin, 17 patients (33.3%) had almost clear skin, 5 patients (9.8%) had 3-grade improvement. Twelve patients (23.5%) had 2-grade improvement from baseline score and only 2 patients (3.9%) had 1-grade improvement from baseline. Based on percentage reduction of lesions, excellent response was seen in 32 patients (62.7%), good response in 9 patients (17.6%), moderate response in 2 patients (3.9%), while no patient showed poor response. Dapsone was discontinued in 8 patients due to derangement of hematologic profile.&#x0D; Conclusion: Oral Dapsone, when given carefully, is a very effective therapeutic option in severe recalcitrant acne, with limited side effects.

650 usec 1064nm Nd:YAG laser treatment of acne: A double‐blind randomized control study

A variety of energy-based devices have been used to treat acne. However, all studies have been subjective and have not involved double-blind and randomized controlled studies. We undertook a randomized controlled study evaluating the use of a 650 usec 1064nm Nd:YAG laser compared with a sham in the treatment of acne. A total of 20 subjects with moderate-to-severe acne were randomized to receive either 650 usec 1064nm Nd:YAG laser or sham treatment. All subjects received 3 treatments, two weeks apart, plus an additional session undertaken 4weeks after the 3rd treatment. Subjects were evaluated for investigator global improvement, improvement in inflammatory lesions, improvement in comedonal lesions, total porphyrin score, and total sebum score. The laser-treated group showed an Investigator's Global Assessment Scale (IGA) improvement of 26% compared with 7% for the sham group (a 271% improvement over sham treatment group). The treatment group also showed a decrease in the number of inflammatory lesions of 42% compared with 26% in the sham group (a 62% improvement over sham). The laser-treated cohort also experienced a reduction in total number of comedones similar to that seen with inflammatory lesions and a decrease in total porphyrin score. There was also an 18% reduction in sebum production in the treated group, compared with 9% in the sham group (a 100% improvement). This is the first study that has compared laser treatment of acne compared with a sham treatment. A 650 usec 1064nm Nd:YAG laser can effectively treat acne.

The Alopecia Areata Investigator Global Assessment scale: a measure for evaluating clinically meaningful success in clinical trials.

SummaryBackgroundContent‐valid and clinically meaningful instruments are required to evaluate outcomes of therapeutic interventions in alopecia areata (AA).ObjectivesTo develop an Investigator's Global Assessment (IGA) to interpret treatment response in AA treatment studies.MethodsQualitative interviews were conducted in the USA with expert dermatologists and with patients with AA who had experienced ≥ 50% scalp‐hair loss. Thematic data analysis identified critical outcomes and evaluated the content validity of the new IGA.ResultsExpert clinicians (n = 10) judged AA treatment success by the amount of scalp‐hair growth (median 80% scalp hair). Adult (n = 25) and adolescent (n = 5) patients participated. Scalp‐hair loss was the most bothersome AA sign/symptom for most patients. Perceived treatment success – short of 100% scalp hair – was the presence of ~ 70–90% scalp hair (median 80%). Using additional clinician and patient insights, the Alopecia Areata Investigator Global Assessment (AA‐IGA™) was developed. This clinician‐reported outcome assessment is an ordinal, static measure comprising five severity categories of scalp‐hair loss. Nearly all clinicians and patients in this study agreed that, for patients with ≥ 50% scalp‐hair loss, successful treatment would be hair regrowth resulting in ≤ 20% scalp‐hair loss.ConclusionsWe recommend using the Severity of Alopecia Tool to assess the extent (0–100%) of scalp‐hair loss. The AA‐IGA is a robust ordinal measure providing distinct and clinically meaningful gradations of scalp‐hair loss that reflects patients’ and expert clinicians’ perspectives and treatment expectations. What is already known about this topic? The Severity of Alopecia Tool is widely used to assess the extent of scalp‐hair loss in patients with alopecia areata.Guidelines define treatment success as a 50% improvement in scalp hair, and clinical trials have used dynamic thresholds of 50% and 90%.However, there is no clinical consensus on these endpoints, and patient perspectives on treatment success are unknown. What does this study add? Through qualitative interviews with 10 expert dermatologists and 30 patients with alopecia areata who had experienced ≥ 50% scalp‐hair loss, we developed the Alopecia Areata Investigator Global Assessment (AA‐IGA™) to measure five clinically meaningful gradations of alopecia areata scalp‐hair loss that reflects patients’ and clinicians’ perspectives and expectations of treatment success in alopecia areata treatment studies. What are the clinical implications of this work? The AA‐IGA is a robust ordinal measure that can inform clinical evaluation of alopecia areata treatment outcomes.The AA‐IGA can be used to determine clinically meaningful treatment success for alopecia areata, with success defined by patients and clinicians as reaching ≤ 20% scalp‐hair loss. Linked Comment: Blome. Br J Dermatol 2020; 183:609.