tbuckley/cabot-search huggingface dataset:
535 - Exploring the Intersectionality of Being Deaf and Black while Accessing Dermatological Care
Authors: Diamond Guy, Jason M Rotoli
Journal: British Journal of Dermatology (2024)

Abstract In 2021, Deaf or hard of hearing (DHH) persons made up ∼3.4% of the United States population however, there was no sub-categorical data about race. This dearth of data makes it challenging to quantify the health disparities amongst Black DHH individuals. This paper aims to identify trends and disparities to improve health outcomes for DHH and Black patients seeking dermatologic care. Black patients utilize less preventative service, have lower post-trauma survival, and a 3-fold higher risk of maternal mortality than White patients. DHH patients experience delayed cancer treatment, more emergency department visits, and higher intimate partner violence than hearing patients. Black DHH patients have a higher likelihood of cancer, diabetes, hypertension, and lung disease than Black-hearing patients. Black patients have lower survival rates with certain cutaneous neoplasms and poorer disease control than White counterparts. The literature lacks dermatologic care outcomes for Black DHH patients. Shared themes impacting Black and DHH patients’ care include audism and racism, medical mistrust, and poor communication with clinicians. Unfortunately, the dermatological experiences of Black DHH patients are poorly documented. To minimize disparities for this population, clinicians must acknowledge them and partner with the community to investigate them.
552 - Improvement of the head and neck regions with continuous tralokinumab treatment for up to 4 years in adults with moderate-to-severe atopic dermatitis
Authors: Raj Chovatiya, Andreas Wollenberg, Simone Ribero, Hidehisa Saeki, Christian B Øland, Louise A Steffensen, Ann-Marie Tindberg, Jacob P Thyssen, Andrew Blauvelt
Journal: British Journal of Dermatology (2024)

Abstract Introduction Atopic dermatitis (AD) is a chronic, inflammatory disease that can affect multiple regions of the body, but can be particularly burdensome on exposed areas of skin, such as the head and neck (H&amp;N).Tralokinumab, a high-affinity monoclonal antibody that specifically neutralizes interleukin-13, is approved in multiple countries for adults with moderate-to-severe AD. Phase 3 trials showed tralokinumab provided significant improvements in AD severity and was well-tolerated up to 52 weeks of treatment. The ongoing open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses the safety and efficacy of tralokinumab after the completion of parent trials (PT). Objective To assess tralokinumab efficacy in the head and neck region. Methods This post hoc analysis included adult patients with moderate-to-severe AD initially randomized to tralokinumab 300mg Q2W in the phase 3 PTs ECZTRA 1 (NCT03131648) or ECZTRA 2 (NCT03160885). Patients on active tralokinumab treatment were followed for up to 52 weeks in PTs and for up to 152 weeks in ECZTEND as of data cutoff April 30, 2022. Patients re-randomized to placebo at Week (Wk) 16 were not included beyond that timepoint. For this analysis, overall EASI and H&amp;N regional EASI (H&amp;N EASI) were evaluated. H&amp;N EASI (0-7.2) was calculated based on the severity of erythema, induration/papulation, excoriation, lichenification and area of involvement. All data were analyzed and presented as observed. Results At baseline, 87.8% (1047/1192) of patients had H&amp;N involvement (H&amp;N EASI&amp;gt;1), and 49.9% (591/1192) of patients exhibited severe AD (IGA 4). Baseline median H&amp;N EASI for the pooled PTs was 3.0 (IQR 1.8; 4.5). In the pooled PTs, 48.2% (542/1125) and 71.2% (558/784) of patients achieved H&amp;N EASI≤1, at Wk16 and Wk52, respectively. After 3 years additional treatment (Wk152 in ECZTEND), the proportion of patients with H&amp;N EASI≤1 was 87.2% (232/266) and the median H&amp;N EASI was 0.2 (IQR 0.0; 0.5). In the subgroup of patients (n=301) with severe AD (IGA 4) and high H&amp;N involvement (H&amp;N EASI≥4), median H&amp;N EASI improved from 5.4 at baseline to 2.4 and 0.8 at Wk16 and Wk52, respectively, and 0.4 at Wk152. Improvements in H&amp;N region were comparable to overall EASI improvement. Conclusions Tralokinumab provided sustained improvements in the H&amp;N regions in patients with moderate-to-severe AD for up to 4 years. Sustained improvements were also seen in patients with severe disease and substantial H&amp;N involvement at baseline.
526 - Efficacy of upadacitinib vs dupilumab for moderate-to-severe atopic dermatitis: analysis of time spent in itch response state from the Heads Up study
Authors: Andrew Blauvelt, Marjolein de Bruin-Weller, Shawn G Kwatra, Melinda J Gooderham, Brian Kim, Yingyi Liu, Alvina D Chu, Sarah Ofori, Andrew Platt, Brian M Calimlim, Jonathan I Silverberg
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Atopic dermatitis is a chronic inflammatory skin disease characterized by intense and debilitating pruritus – its most burdensome symptom – and requires long-term control. Results from the Heads Up trial (NCT03738397) found that upadacitinib (UPA) 30 mg was superior to dupilumab (DUPI) 300 mg for improving itch as indicated by increases in the percent of improvement from baseline for Worst Pruritus NRS scores (WP-NRS). Objective This analysis compared the proportion of days patients treated with UPA or DUPI spent in itch response states indicated by WP-NRS. Methods Heads Up was a 24-week head-to-head phase 3b multicenter, randomized, double-blind study comparing UPA 30 mg to DUPI 300 mg in adults with moderate-to-severe AD. We compared the proportion of days patients treated with UPA or DUPI spent in an improved-itch state (WP-NRS improvement ≥4 relative to baseline; among patients with baseline WP-NRS ≥4) or a state of no/minimal itch (WP-NRS 0/1; among patients with baseline WP-NRS &amp;gt;1). Results Participants included 673 patients randomized into two groups: those taking UPA (N=342) or DUPI (N=331). At 4 and 16 weeks, patients treated with UPA vs DUPI spent a greater proportion of days in an improved-itch state (week 4: 50.0% vs 19.3%; week 16: 60.4% vs 35.7%), and in a state of no/minimal itch (week 4: 22.1% vs 4.3%; week 16: 34.4% vs 11.4%). Conclusions Treatment of moderate-to-severe AD with UPA 30 mg daily resulted in a greater proportion of days spent with meaningful itch improvement (WP-NRS improvement ≥4) and more time with no/minimal itch (WP-NRS 0/1) compared to treatment with DUPI over 4 and 16 weeks.
507 - Dupilumab demonstrates greater improvement in disease activity than standard-of-care H1-antihistamines in CSU
Authors: Lisa A Beck, Thomas B Casale, Eric Mortensen, Elizabeth Laws, Ryan B Thomas, Chien-Chia Chuang
Journal: British Journal of Dermatology (2024)

Abstract IntroductionChronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by wheals and/or angioedema recurring for &amp;gt;6 weeks. Cumulative distribution function (CDF) curves compare cumulative probabilities of response between treatments across responder definition spectrums. Methods LIBERTY-CSU CUPID Study A (NCT04180488) was a randomized, placebo-controlled, phase 3 trial of dupilumab treatment for 24 weeks in patients with CSU remaining symptomatic despite standard-of-care (SOC) H1-antihistamines. Patients were randomized to receive add-on dupilumab (dupilumab/SOC) or placebo (placebo/SOC) subcutaneously every 2 weeks. CDF curves were plotted for the distribution of possible within-patient response for Urticaria Activity Score over 7 days (UAS7), Itch Severity Score over 7 days (ISS7), and Hives Severity Score over 7 days (HSS7) for dupilumab/SOC and placebo/SOC arms. Results In CDF analysis at Week 24, more patients experienced UAS7, ISS7, and HSS7 improvements with dupilumab/SOC than placebo/SOC; 74.2% vs 50.0% of patients (dupilumab/SOC vs placebo/SOC) achieved ≥11-point reductions (minimal important difference [MID] threshold) in UAS7. Similarly, 78.8% vs 51.7% of patients (dupilumab/SOC vs placebo/SOC) reached ≥5-point reductions (MID threshold) in ISS7 and HSS7. The responder proportion was ≥20% greater for dupilumab/SOC vs placebo/SOC for response thresholds of 9.5- to 22-point reductions for UAS7, 4.5- to 11-point reductions for ISS7, and 5- to 11-point reductions for HSS7. Conclusion Irrespective of within-patient responder thresholds, greater proportions of patients experienced improvement in UAS7, ISS7, and HSS7 with dupilumab/SOC vs placebo/SOC at Week 24. Overall safety was consistent with the known dupilumab safety profile.
Manganese Porphyrin‐Containing Polymeric Micelles: A Novel Approach for Intracellular Catalytic Formation of Per/Polysulfide Species from a Hydrogen Sulfide Donor (Adv. Healthcare Mater. 4/2024)
Authors: Kemper Young, Setsuko Yamane, Elmira Abbasi GharehTapeh, Shingo Kasamatsu, Hideshi Ihara, Urara Hasegawa
Journal: Advanced Healthcare Materials (2024)
568 - Persistent inadequate disease control and therapeutic inertia in moderate-to-severe atopic dermatitis: a 12-month longitudinal analysis of real-world outcomes from TARGET-DERM registry
Authors: Lawrence F Eichenfield, Ayman Grada, Keith D Knapp, Breda Munoz, Julie M Crawford, Jonathan I Silverberg
Journal: British Journal of Dermatology (2024)

Abstract Background Therapeutic inertia refers to the delay or failure to escalate treatment in patients who are not achieving adequate disease control and poses a challenge in the management of moderate-to-severe atopic dermatitis (AD). Despite the availability of conventional (CST) and advanced systemic therapies (AST) currently utilized for the treatment of moderate to severe AD, many patients do not achieve treatment success. However, the extent of this inadequacy in real-world clinical practice remains underexplored. Objectives This study aims to evaluate the occurrence therapeutic inertia (assessed as non-escalation of therapy despite limited disease control) and the proportion of patients with moderate-to-severe AD who continue to show an inadequate response after receiving systemic therapies for a duration ranging from 3 to 12 months. Methods We conducted a longitudinal analysis of patients with moderate-to-severe AD (vIGA-AD≥3) from the TARGET-DERM AD registry, including 3,457 participants from 39 centers in the U.S. and Canada. Eligible patients had documented outcomes at the initiation of systemic therapy and after 3 months up to 12 months of follow up. We assessed clinician- and patient-reported outcomes to identify the proportion of patients not meeting pre-defined targets based on expert consensus. An inadequate response was defined as not achieving a validated Investigator Global Assessment (vIGA-AD) score ≤2, a 50% improvement in Body Surface Area (BSA), and a ≥4-point reduction in the Worst Pruritus Numeric Rating Scale (WP-NRS). An optimal response was defined as a vIGA-AD score ≤1 (clear or almost clear skin), BSA ≤2%, and WP-NRS itch score of 0/1 (complete or almost complete skin resolution). Results Out of 2,107 patients with moderate-to-severe AD, 445 met the inclusion criteria. The majority were adults (63.8%), female (62.0%), and Non-Hispanic White (45.4%), with an average age of 31 years. Most patients (88.8%) initiated treatment with AST, with dupilumab being the most common (86.5%). The mean vIGA-AD was 3.3 for AST and 3.6 for CST at initiation (P&amp;lt;0.01). At 6 months, 37% and 67% of AST-treated patients had inadequate responses in terms of skin clearance and itch outcomes, respectively, while 82% and 79% did not achieve optimal responses. At 12 months, these figures were approximately 30% and 66% for inadequate responses and 85% and 88% for not achieving optimal responses, respectively. CST-treated patients showed a similar trend. Conclusions The study reveals a significant portion of moderate-to-severe AD patients fail to achieve adequate disease control with systemic therapies over 12 months, indicating a substantial presence of therapeutic inertia. These findings suggest a need for more proactive management strategies in AD treatment.
Peptide Amphiphiles as Biodegradable Adjuvants for Efficient Retroviral Gene Delivery (Adv. Healthcare Mater. 4/2024)
Authors: Kübra Kaygisiz, Lena Rauch‐Wirth, Aysenur Iscen, Jan Hartenfels, Kurt Kremer, Jan Münch, Christopher V. Synatschke, Tanja Weil
Journal: Advanced Healthcare Materials (2024)

Gene therapy requires additives to efficiently deliver therapeutic viruses to cells.However, these additives typically rely on the formation of potentially harmful aggregates.In article 2301364, Jan Münch, Christopher V. Synatschke, Tanja Weil, and co-workers develop peptide amphiphiles that promote the uptake of viruses while drastically reducing the formation of aggregates.Thereby peptide amphiphiles have great potential for therapeutic gene delivery, such as CAR-T cell therapy.
549 - Laboratory parameters in adolescent patients aged 12–17 with moderate-to-severe atopic dermatitis treated with tralokinumab up to week 52: results from the phase 3 ECZTRA 6 trial
Authors: Amy Paller, Michael Cork, Chih-ho Hong, Weily Soong, Shannon Schneider, Hannah Lo, Line Rosendahl Meldgaard Pedersen, Emilia Vacko, Andreas Wollenberg
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Tralokinumab, a high-affinity, monoclonal antibody that targets IL-13, is approved in the EU and Canada for adolescents (aged ≥12 years) with inadequately controlled moderate-to-severe atopic dermatitis (AD), and it does not require laboratory monitoring. The phase 3 ECZTRA 6 (NCT03526861) clinical trial demonstrated efficacy and safety up to 52 weeks in that population. Objectives To further characterize the safety profile of tralokinumab by evaluating laboratory parameters of adolescents in the ECZTRA 6 trial. Methods ECZTRA 6 subjects received tralokinumab 150mg (n=98), 300mg (n=97) or placebo (n=94) every 2 weeks (Q2W) from week 0–16 after a loading dose at week 0 (twice the subsequent dose), and then randomized to maintenance [original tralokinumab dose either Q2W or every 4 weeks (Q4W) or placebo Q2W] or open-label (tralokinumab 300mg Q2W) until week 52. Laboratory parameters included hematology, serum biochemistry, and urinalysis throughout the trial (weeks 0, 8, 16, 28, and 52). Results Overall (n= 289 subjects), laboratory baseline parameters were similar across treatment groups. Mean and median changes of most hematology parameters showed minor fluctuations within the normal ranges through week 52, except for eosinophils. At baseline, elevated mean eosinophil counts (&amp;gt;0.5 109/L) were observed for 40.8% (tralokinumab 150mg), 48.5% (tralokinumab 300mg), and 43.6% (placebo) of subjects in each respective treatment group. Some tralokinumab-treated patients had small transient increases in eosinophils (maximum mean change from baseline 0.2×109/L) before week 16. Continued treatment with tralokinumab or placebo did not correspond with further increase in eosinophil levels over time, and no adverse events of eosinophilia were reported. Mean levels of most biochemistry parameters, including electrolytes, renal and liver function parameters, and lipid panel, were within normal range at baseline, and mean and median changes showed minor fluctuations within normal ranges in all treatment arms. Mean lactate dehydrogenase levels were around or above the upper limit of normal at baseline and decreased to within the normal ranges during the trial across all groups. Overall, no clinically meaningful differences were observed in hematology, biochemistry, or urinalysis parameters between active treatment groups or placebo. Conclusions Similar to findings in adult trials, no meaningful changes in laboratory parameters were observed in adolescents through week 52 with tralokinumab treatment. No routine laboratory monitoring is needed for adult or adolescent AD patients treated with tralokinumab.
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
Authors: April W Armstrong, H Chih-Ho Hong, Brian M Calimlim, Marric G Buessing, Marjorie M Crowell, Jonathan I Silverberg
Journal: British Journal of Dermatology (2024)

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.
503 - Visualizing 3-year treatment outcome trajectories of dupilumab in adults with moderate-to-severe atopic dermatitis in real world practice
Authors: Zhixiao Wang, Bruno Martins, Marius Ardeleanu, Min Yang, Gaëlle Bégo-Le-Bagousse, Debra Sierka, Bruce Strober
Journal: British Journal of Dermatology (2024)

Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with high global prevalence and profound negative impact on the quality of life of children and adults. RELIEVE-AD, a prospective, longitudinal cohort study, included adults with moderate-to-severe AD who initiated dupilumab in real-world clinical practice. Results from RELIEVE-AD showed significant improvements in patient-reported disease control, quality of life, and treatment satisfaction in the overall study population that were sustained through 3 years of dupilumab treatment. Objective To report on response to dupilumab treatment over time at the individual patient-level in adults with moderate-to-­severe AD, using 3-year data from RELIEVE-AD. Methods RELIEVE-AD is a single-arm, prospective, observational study of adults with moderate-to-severe AD prescribed dupilumab and enrolled in the US dupilumab patient support program, who agreed to participate in online surveys at baseline and Months 1, 2, 3, 6, 9, 12, and 30–36. Post hoc analysis of the RELIEVE-AD 3yr data, describing changes from baseline through all post-dupilumab initiation time points at individual patient level, using Sankey plots to assess variability of individual patient response over time for the following patient-reported outcomes: Atopic Dermatitis Control Tool (ADCT) total score-based disease control status, AD-related health status, and AD treatment satisfaction. Results Of 698 patients who completed the baseline survey, 425 completed the Months 30–36 survey. Disease control (as measured by the ADCT) increased rapidly from 5.9% at baseline to 61.0% at Month 1, further increasing to 80.7% at Months 30–36. Patients reported improved AD-related health status at Month 30–36, with 70.9% reporting “Excellent” or “Very Good”, compared to 2.8% at baseline. At Months 30–36, 86.8% of patients reported being “Extremely Satisfied/Very Satisfied/Somewhat Satisfied” with their AD treatment, compared to 17.7% at baseline. All endpoints were significant vs baseline (P &amp;lt; 0.001). Sankey plots of the three outcomes indicated that the majority of patients maintained response over time after achieving the initial response. Conclusion The majority of patients who completed the survey reported benefits of dupilumab, such as AD control, treatment satisfaction, and health status, which remained stable or significantly improved during long-term treatment up to 36 months.
566 - Efficacy of dupilumab treatment in atopic hand and foot dermatitis across morphological subtypes: results from a phase 3, randomized, double-blind, placebo-controlled trial
Authors: Margitta Worm, Eric L Simpson, Golara Honari, Weily Soong, Andreas Pinter, Koji Masuda, Liyang Shao, Ariane Dubost-Brama, Ashish Bansal, Andrew Korotzer, Ana B Rossi
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Dupilumab has previously shown to significantly improve signs, symptoms, and quality of life in patients with moderate-to-severe atopic hand and foot dermatitis. Objective To investigate the efficacy of dupilumab across morphological subtypes in patients with moderate-to-severe atopic hand and foot dermatitis. Methods The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients aged ≥12 years with moderate-to-severe (Investigator’s Global Assessment [IGA] score of 3/4) atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg every 2 weeks (q2w) in adults; 200/300 mg q2w in adolescents, or placebo for 16 weeks. This analysis reports the percent change from baseline in modified total lesion sign score (mTLSS) by hand and foot morphological subtypes: chronic dry fissured, hyperkeratotic (palmar/plantar), and other. Results 133 patients enrolled into this study and were randomized to dupilumab (n = 67) or placebo (n = 66). Atopic hand and foot morphologies were reported in 3 categories: chronic dry fissured (n = 63), hyperkeratotic (palmar/plantar; n = 37), and other (n = 33) In the “other” category, dyshidrotic was the most frequent morphology (n = 13). mTLSS values were similar at baseline for all morphological subtypes. At Week 16, greater improvements were seen in the percent change from baseline (SE) in mTLSS for patients receiving dupilumab vs placebo in all categories: chronic dry fissured (−65.6% [5.1] vs −31.5% [6.2]), hyperkeratotic (palmar/plantar; −58.2% [7.6] vs −11.8% [7.7]), and other (−64.5% [11.6] vs −29.9% [9.0]). Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions The efficacy of dupilumab remains consistent across different hand and foot dermatitis morphologies and shows higher treatment benefit across subtypes compared with placebo.