tbuckley/cabot-search huggingface dataset:
640 - Investigator- and patient-rated local tolerability in phase 3 trials of topical roflumilast in patients with psoriasis, seborrheic dermatitis, and atopic dermatitis
Authors: Christopher G Bunick, Neal Bhatia, James Del Rosso, Zoe D Draelos, Lawrence F Eichenfield, Leon H Kircik, Mark G Lebwohl, Melinda Gooderham, Lawrence J Green, Adelaide A Hebert, Ronald B Vender, Matthew Zirwas, Eric L Simpson, Linda Stein Gold, Melissa Seal, Scott Snyder, David W Osborne, Patrick Burnett, Robert C Higham, David H Chu, David R Berk
Journal: British Journal of Dermatology (2024)

Abstract Background Formulating a topical medication that does not irritate the skin is an important factor contributing to patient treatment adherence and satisfaction. Many topical prescription products use penetration enhancers (including propylene glycol, polyethylene glycol, and ethanol) to overcome barrier properties of the skin. However, these excipients may irritate the skin causing tolerability reactions such as burning and stinging, which can reduce patient treatment adherence. Topical roflumilast is a highly potent (Kd∼0.7 nM) phosphodiesterase 4 inhibitor formulated as a water-based cream or foam that does not contain penetration enhancers or fragrances. Objective We present prospectively assessed investigator- and patient-rated local tolerability from Phase 3 trials of topical roflumilast for patients with psoriasis (DERMIS-1, DERMIS-2, ARRECTOR), seborrheic dermatitis (SD; STRATUM), and atopic dermatitis (AD; INTEGUMENT-1, INTEGUMENT-2). Methods Patients were randomized to apply topical roflumilast (DERMIS: 0.3% cream; ARRECTOR and STRATUM: 0.3% foam; INTEGUMENT: 0.15% cream) or vehicle once daily for 8 weeks (DERMIS, ARRECTOR, and STRATUM) or 4 weeks (INTEGUMENT). Investigators assessed local tolerability on an 8-point scale (0 [no evidence of irritation] to 7 [strong reaction spreading beyond application site]) in the clinic before investigational product (IP) application. Patients reported local tolerability on a 4-point scale (0 [none: no sensation] to 3 [severe: hot, tingling/stinging sensation that has caused definite discomfort]) in the clinic 10-15 minutes after IP application. Tolerability was also assessed by reviewing documented adverse events. Results As assessed by investigators, ≥96.5% of patients in the roflumilast-treated groups had no evidence of irritation at the application site across all trials at all timepoints. Patient-rated local tolerability was favorable and improved with treatment: across all trials, 1% of roflumilast-treated patients reported a score of 3 (severe; defined as a “hot tingling/stinging sensation that has caused definite discomfort”) after the first application (day 1) and &amp;lt;1% at each subsequent assessment. Rates of adverse events, including those at the application site, were low for all trials. Conclusions Roflumilast cream and foam formulations demonstrated favorable local tolerability based on investigator- and patient-rated assessments in patients with psoriasis, SD, and AD, including application to sensitive areas such as the face and intertriginous areas.
634 - Patient-reported outcomes and safety in adolescent and adult atopic dermatitis patients treated with dupilumab: real-world insights one year into the GLOBOSTAD multinational prospective observational study
Authors: Dédée F Murrell, Silvia M Ferrucci, Caterina Foti, Bibiana Perez-Garcia, Hilde Lapeere, Piergiacomo Calzavara-Pinton, Anne-Claire Fougerousse, Jiangming Wu, Marius Ardeleanu, Kwinten Bosman
Journal: British Journal of Dermatology (2024)

Abstract Introduction The GLOBOSTAD study aims to capture long-term dupilumab effectiveness in real-world atopic dermatitis (AD) treatment. Objective To present patient-reported outcomes, that complement clinical AD assessments and guide healthcare decision-making, and a summary of adverse events one year after dupilumab initiation. Methods The GLOBOSTAD five-year, multinational, prospective, observational study (NCT03992417) enrolled patients aged ≥12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N = 955; data cutoff: March 2023) and follow-up (N = 903) populations. Results 758/863/705 patients completed ≥1 follow-up assessment at 3M/6M/12M, respectively. During the study, patients reported rapid improvements in mean (SD) patient-oriented eczema measure from 19.7 (6.4) at baseline to 8.7 (6.6) at 3M to 7.1 (5.8) at end of observation period (12M); pruritus numerical rating scale from 6.3 (2.2) to 2.5 (2.4) to 1.7 (2.0); scoring of atopic dermatitis sleep loss score from 5.6 (3.0) to 1.7 (2.3) to 1.0 (1.8); dermatology life quality index (DLQI) from 13.7 (7.1) to 5.3 (5.1) to 3.9 (4.2); and children’s DLQI from 12.2 (6.2) to 2.7 (2.9) to 4.8 (4.8). Adverse events considered related to dupilumab by the investigator were reported in 187 (19.6%) patients. Adverse events leading to permanent dupilumab discontinuation were reported in 23 (2.4%) patients. Conclusion On initiating dupilumab treatment, patients reported rapid improvements in skin lesions, itch, sleep, and overall quality of life, from severe/very large effect scores to mild/small effect scores, which were sustained for up to one year. Safety data were consistent with previous studies.
623 - Topical steroid withdrawal is a targetable overproduction of nicotinic acid from mitochondrial complex I overexpression
Authors: Nadia Shobnam, Grace Ratley, Sarini Saksena, Manoj Yadav, Prem Prashant Chaudhary, Ashleigh A Sun, Katherine N Howe, Manasi Gadkari, Luis M Franco, Sundar Ganesan, Katelyn J McCann, Amy P Hsu, Kishore Kanakabandi, Stacy Ricklefs, Justin Lack, Weiming Yu, Morgan Similuk, Magdalena A Walkiewicz, Donna D Gardner, Kelly Barta, Kathryn Tullos, Ian A Myles
Journal: British Journal of Dermatology (2024)

Abstract Background Topical glucocorticoids (more commonly termed topical corticosteroids; TCS) are first line therapy for management of numerous skin conditions. Topical Steroid Withdrawal (TSW) is a controversial diagnosis advocated by patients with prolonged TCS exposure who report severe systemic reactions upon treatment cessation. Although the disease may be confused for eczematous disorders or dismissed outright, there have been no systematic clinical or mechanistic studies to either refute or support TSW as molecularly distinct from other dermatopathies. This study aimed to clinically differentiate TSW symptomatology, delineate abnormal molecular pathways, and investigate potential therapeutic agents. Methods A re-analysis of a previous survey encompassing 1,889 patients with eczematous skin disease who either did or did not self-report TSW was performed to evaluate potential TSW distinguishing symptoms. We then conducted a pilot study of 16 patients who fit the proposed diagnostic criteria. We then performed: tissue metabolomics, transcriptomics, and immunostaining on skin biopsies; serum metabolomics and cytokine assessments; shotgun metagenomics on microbiome skin swabs; genome sequencing; followed by functional, mechanistic studies using human skin cell lines. Results Clinically distinct TSW symptoms included thermodysregulation, burning, and flushing. Metabolomic and transcriptomic assessments both implicated elevated NAD+ oxidation stemming from increased expression of mitochondrial complex I and conversion of tryptophan into kynurenine metabolites. These abnormalities were induced by glucocorticoid exposure both in vitro and in a cohort of healthy controls (N=19) exposed to TCS. Targeting complex I via either metformin or the herbal compound berberine improved outcomes in both cell culture and in an open-label case series for patients with TSW. Conclusion Taken together, our results suggest that TSW has a distinct dermatopathology. While future studies are needed to validate these results in larger cohorts, this work provides the first mechanistic evaluation into TSW pathology, and offers insights into clinical identification, pharmacogenomic candidates, and directed therapeutic strategies.
671 - Rapid and early onset of itch relief with tapinarof cream 1% once daily in two pivotal phase 3 trials in adults and children down to two years of age with atopic dermatitis
Authors: Eric Simpson, Jonathan I Silverberg, Robert Bissonnette, Linda Stein Gold, April W Armstrong, Adelaide A Hebert, Rocco T Serrao, Jeannette R Jakus, Philip M Brown, David S Rubenstein, Stephen C Piscitelli, Anna M Tallman, Lawrence F Eichenfield
Journal: British Journal of Dermatology (2024)

Abstract Introduction Itch is the most bothersome symptom for patients with atopic dermatitis (AD), and has a significant negative impact on health-related quality of life. Rapid onset of pruritus relief with sustained efficacy is a key outcome for AD therapies. In ADORING 1 and 2, two identical pivotal phase 3, double-blind, vehicle-controlled trials, tapinarof cream 1% once daily (QD) demonstrated efficacy and was well tolerated in adults and children down to 2 years of age with AD. Objective Here, we evaluate time to onset of itch relief in the pivotal phase 3 trials. Methods In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic DermatitisTM score of ≥3 (moderate or severe), an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5–35% were randomized 2:1 to tapinarof cream or vehicle QD for 8 weeks. Itch relief was assessed by changes in Peak Pruritus Numerical Rating Scale (PP-NRS) score, daily and by visit, from baseline through Week 8. PP-NRS considers itch over the past 24 hours; lower scores indicate less pruritus. Results 407 and 406 patients were randomized in ADORING 1 and 2. At baseline, mean PP-NRS scores were 6.7 and 6.8 in both trials, respectively. For daily evaluations of itch from baseline, greater reductions in mean PP-NRS scores for tapinarof versus vehicle were observed as early as Day 1, 24 hours after initial application in ADORING 1 (–1.2 vs –0.9), and Day 2 in ADORING 2 (–1.6 vs –1.4). Daily itch improvements continued through Week 8 in both trials. Statistically significant reductions in mean weekly PP-NRS scores occurred as early as Week 1 (earliest assessment) with tapinarof versus vehicle (–2.0 vs –1.2 [P&amp;lt;0.0001]) and (–2.0 vs –1.3 [P=0.0010]) in ADORING 1 and 2, respectively. Significantly greater reductions in mean PP-NRS scores with tapinarof versus vehicle were seen for all visits through Week 8 (–4.1 vs –2.6 and –4.1 vs –2.4 [both P&amp;lt;0.0001]). Conclusions Tapinarof cream 1% QD demonstrated rapid, significant, and clinically meaningful pruritus relief from 24 hours after initial application, with improvements increasing through Week 8 in both trials in adults and children down to 2 years with AD.
652 - Tralokinumab real-world use in adults with atopic dermatitis: baseline characteristics of the first 100 patients recruited to the TRACE study in the United States
Authors: April W Armstrong, Cory Rubin, Abel Jarell, Tien Nguyen, Jerry Bagel, John Stinson, Shannon Schneider, Dimitra M Anastasiadou, Adrian Rodriguez
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD) pathogenesis. Numerous clinical studies have established that tralokinumab is an efficacious treatment for patients with moderate-to-severe AD, along with having a favorable safety profile. However, there is a lack of evidence on tralokinumab use in routine clinical practice, where patient management may differ from that defined by clinical trial protocols. Objectives TRACE is a global, real-world study that aims to better understand the effectiveness, safety, and clinical use of tralokinumab in patients with AD in daily practice. Methods TRACE is a global, observational, prospective, single-cohort study of tralokinumab-treated adults with moderate-to-severe AD. Overall, 11 countries across Europe, North America and the Middle East are participating. The primary objective of TRACE is to assess changes in clinical signs and symptoms of AD in patients treated with tralokinumab according to the nationally approved labels. Secondary objectives include safety, quality of life, patient-reported outcomes and treatment adherence. For this interim analysis, the objective was to report the baseline characteristics of the first 100 US patients. Results Overall, 55% of the first 100 US patients initiated on tralokinumab in the TRACE study were female; the majority (54%) were White, followed by 18% Black or African American and 12% Asian. Mean (standard deviation [SD]) age was 46.4 years (18.2) and body mass index was 28.6 kg/m2 (7.7). Patients had a mean disease duration of 13.9 years (SD 16.5), with 46% being biologic-naïve and 54% biologic-experienced. Most patients (88%) had moderate-to-severe AD, with a mean Investigator’s Global Assessment score of 3.2 (SD 0.8); mean Eczema Area and Severity Index was 15.4 (SD 7.9). A heavy symptomatic burden of disease was evident, with a mean eczema-related sleep numerical rating scale (NRS) of 4.2 (SD 3.3) and mean worst daily pruritus NRS of 6.1 (SD 2.6). Patients also reported a substantial impact of AD on quality of life; mean Dermatology Life Quality Index was 13.2 (SD 8.5). Almost one quarter (24%) of patients reported ≥1 atopic comorbidity, with asthma (12%), cardiovascular disease (8%) and autoimmune disease (6%) being the most frequent; 3% of patients had psychiatric illness. Conclusions Initial findings showed that tralokinumab is being prescribed as a first-line biologic treatment option in the US in accordance with the label. Treated patients had a heavy burden of disease with considerable impact on quality of life.
657 - Impact of pruritus on patient fatigue: a case-control study
Authors: Luis F Andrade, Zaim Haq, Parsa Abdi, Michael J Diaz, Gil Yosipovitch
Journal: British Journal of Dermatology (2024)

Abstract Background Pruritus, either as a chronic standalone disease or secondary to inflammatory skin disease, can have a very detrimental effect on the overall quality of life for patients suffering from intense itch, particularly on patients suffering from atopic dermatitis. Symptoms of itching have a reported association with worsened quality of life across various psychological and social domains, including fewer periods of rest and reduced sleep quality. While prior studies have been made to determine the relationship between both fatigue and pruritus combined on systematic disease severity, there is limited data on how the prevalence of pruritus directly correlates with the prevalence of fatigue. Objective We utilized the AoU database to perform a nested case-control study to determine the impact of pruritus on patient-reported fatigue. Methods Within this database, patients experiencing pruritus (chronic pruritus, chronic pruritus of unknown origin (CPUO), prurigo nodularis, psoriasis, and atopic dermatitis) were identified and matched to four controls using nearest neighbor propensity-score matching, with sex, age, and race/ethnicity. Comparative analyses between pruritus cases and controls were performed utilizing the Fisher's exact test for categorical variables and the unpaired t-test for continuous variables. Logistic regression models were developed to calculate the odds ratio (OR) of having pruritus (SNOMED: 279333002, ICD10CM-L29), and developing fatigue (SNOMED: 84229001, ICD10CM-R53.83), with covariates including age, race/ethnicity, sex, income, education, anxiety, and depression. A significance level was set at P&amp;lt;0.05, and 95% confidence intervals were developed using the Wald method. Results From the cohort with accessible electronic health records (EHR) in 91,212 controls and 22,803 cases of pruritus were identified (mean age 59.91 [standard deviation: 15.95], 63.57% female). Patients afflicted with pruritus demonstrated a noticeably elevated prevalence of fatigue (40.81%) compared to the control group (22.06%). After adjusting for demographics and other covariates in multivariable analysis, chronic pruritus remained significantly associated with fatigue, with a multivariable adjusted odds ratio (aOR) of 1.56 (95% CI 1.16-2.07. In-depth analysis revealed that specific pruritic conditions exhibited strong associations with fatigue, namely, CPOU (aOR 2.27, 95% CI 1.35-3.82), prurigo nodularis (aOR 2.21, 95% CI 1.87-2.61), and atopic dermatitis (Aor 2.05, 95% CI 1.97-2.13). Conclusion Our study provides a quantitative measure of pruritus’ impact on the prevalence of patient-reported fatigue across many pruritic conditions, including atopic dermatitis. This two-fold increase in fatigue in patients with itch further emphasizes the clinical importance of understanding the impact of pruritus on patient quality of life.
633 - Physician-assessed effectiveness and safety in adolescent and adult atopic dermatitis patients treated with dupilumab: real-world insights one year into the GLOBOSTAD multinational prospective observational study
Authors: Silvia M Ferrucci, Piergiacomo Calzavara-Pinton, Iva Karlova, Hilde Lapeere, Gregor Holzer, Mona Al-Ahmad, Chia-Yu Chu, Jiangming Wu, Marius Ardeleanu, Kwinten Bosman
Journal: British Journal of Dermatology (2024)

Abstract Introduction Dupilumab demonstrated robust efficacy in patients with moderate-to-severe atopic dermatitis (AD) in randomized controlled trials. Long-term effectiveness of dupilumab in real-world AD treatment is one of the main objectives of the ongoing GLOBOSTAD study. Objective To report dupilumab effectiveness, through physician-assessed AD clinical tools that measure disease severity over time, and a summary of adverse events in patients one year after initiating treatment. Methods The GLOBOSTAD five-year, multinational, prospective, observational study (NCT03992417) enrolled patients aged ≥12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N = 955; data cutoff: March 2023) and follow-up (N = 903) populations. Results 758/863/705 patients completed ≥1 follow-up assessment at 3M/6M/12M, respectively. During the study, mean (SD) eczema area and severity index (EASI; &amp;gt;21 = severe; ≤7 = mild/no disease) score rapidly improved from 25.1 (12.8) at baseline to 6.1 (8.0) at 3M, and was sustained until the end of observation period [12M; 4.2 (8.4)]. Similarly, scoring of atopic dermatitis (SCORAD; &amp;gt;50 = severe; &amp;lt;25 = mild/no disease) score improved from 59.3 (16.6) at baseline to 25.3 (16.4) at 3M, further improving to [17.6 (13.0)] at 12M. Adverse events considered related to dupilumab by the investigator were reported in 187 (19.6%) patients. Adverse events leading to permanent dupilumab discontinuation were reported in 23 (2.4%) patients. Conclusion In a real-world scenario, clinical AD assessments rapidly improved upon initiating dupilumab treatment, and were sustained through the end of the one-year observation period. Safety data were consistent with previous studies.
655 - Long-term safety and efficacy of delgocitinib cream for up to 36 weeks in adults with chronic hand eczema: results of the phase 3 open-label extension DELTA-3 trial
Authors: Melinda Gooderham, Sonja Molin, Robert Bissonnette, Margitta Worm, Marie-Noëlle Crépy, Luca Stingeni, Richard B Warren, Sibylle Schliemann, Cherry Lou Balita-Crisostomo, Marie Louise Oesterdal, Tove Agner
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background In patients with moderate to severe Chronic Hand Eczema (CHE), delgocitinib cream, a topical pan-Janus kinase inhibitor, was well tolerated and demonstrated significant improvement in all efficacy endpoints in DELTA-1 and -2. Objectives The objectives of this study were to evaluate the long-term safety and efficacy of twice-daily applications of delgocitinib cream 20 mg/g as needed for up to 36 weeks in adults with CHE in the Phase 3 open-label DELTA-3 trial (NCT04949841), an extension trial of the 16-week DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101) trials. Methods In DELTA-3, subjects who completed the 16-week (W) treatment period in DELTA-1 and DELTA-2 were treated on an as-needed basis with twice-daily delgocitinib cream 20 mg/g for 36 weeks (n=801). Subjects with Investigator's Global Assessment for CHE (IGA-CHE) ≥2 received delgocitinib cream until symptoms resolved (i.e., IGA-CHE 0/1 [clear/almost clear]). Primary endpoint was number of treatment-emergent adverse events (TEAEs). Key secondary endpoints were IGA-CHE 0/1 and ≥75%/≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) scores; Hand Eczema Symptom eDiary captured patient-reported worst severity of itch/pain over the past 24 hours. Results No safety concerns were identified during delgocitinib cream treatment in DELTA-1 (n=325; R=305.4; PYO=100.9), DELTA-2 (n=313; R=280.6; PYO=95.9) and DELTA-3 (n=801; R=231.1; PYO=535.7). In DELTA-3, the most frequent TEAEs were COVID-19 and nasopharyngitis. In DELTA-3, IGA-CHE 0/1, HECSI-75, HECSI-90 and ≥4-point itch/pain reduction were maintained from baseline (24.6%, 51.8%, 31.8%, and 50.6%/51.9%, respectively) to W36 (30.0%, 58.6%, 36.6%, and 52.4%/55.4%, respectively) among delgocitinib cream-treated subjects in the parent trials. Among those treated with cream vehicle in parent trials, response rates improved from baseline (9.1%, 23.7%, 12.0%, and 26.3%/32.3%, respectively) to W36 (29.5%, 51.5%, 35.7%, and 41.3%/43.3%, respectively). Conclusions Overall, with delgocitinib cream 20 mg/g treatment no safety concerns were identified and efficacy further improved, supporting the benefit of long-term as-needed use of delgocitinib cream in patients with moderate to severe CHE.