tbuckley/cabot-search huggingface dataset:
544 - Cost-per-responder analysis of tralokinumab versus dupilumab in patients with moderate-to-severe atopic dermatitis in the US and Canada
Authors: Jashin J Wu, Sanjeev Balu, Nikolaj Birk Larsen, Ryan Pulleyblank, Liv Strømkjær, Aron Quah, Marni Wiseman
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Biologic treatments such as tralokinumab and dupilumab are therapeutic options for adult patients with moderate-to-­severe atopic dermatitis (AD) who do not achieve adequate control with topical treatments or phototherapy. To date, no trials have been conducted to directly evaluate the relative efficacy of these biologic treatments. Objectives Applying indirect comparison of efficacy, we examined the cost-per-responder of tralokinumab compared to dupilumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-serve AD in the United States (US) and Canada. Methods A cost-per-responder analysis was undertaken considering the Eczema Area and Severity Index 75 (EASI-75) and Investigator’s Global Assessment (IGA-0/1) response criteria over a 32-week period. For each treatment, the cost-per-­responder was computed by multiplying the treatment cost by the number needed to treat (NNT). Efficacy data were derived from an unanchored matching-adjusted indirect comparison (MAIC) utilizing patient-level data from ECZTRA-3 (tralokinumab) and aggregate data from LIBERTY AD CHRONOS (dupilumab). Treatment cost was defined as the drug cost of the biologic treatment with a duration corresponding to 32 weeks. TCS cost was not considered. Treatments were assumed to be administered every 2 weeks (Q2W). The costs were estimated based on Wholesale Acquisition Costs (WAC) from the US and ex-factory prices via the McKesson price list for Canada. All prices were converted to US dollars ($). Sensitivity analyses (SA) were conducted with every 4 week (Q4W) dosing beginning at week 16 for 10% and 20% of patients treated with tralokinumab. Results For the US, the average cost-per-responder was $62,714 (Q4W SA: 10%: $61,239; 20%: $59,763) for tralokinumab versus $63,993 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $82,419 (Q4W SA: 10%: $80,480; 20%: $78,450) for tralokinumab versus $118,835 for dupilumab considering the IGA 0/1 response criteria. For Canada, the average cost-per-responder was $22,846 (Q4W SA: 10%: $22,308; 20%: $21,771) for tralokinumab versus $26,475 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $30,024 (Q4W SA: 10%: $29,317; 20%: $28,611) for tralokinumab versus $49,165 for dupilumab considering the IGA 0/1 response criteria. Conclusions Assessing EASI-75 and IGA-0/1 response criteria at 32 weeks, this analysis indicates that tralokinumab in combination with TCS is associated with lower costs-per-responder compared with dupilumab in combination with TCS in the treatment of moderate-to-severe AD in the US and Canada.
562 - Dupilumab treatment provides long-term improvement in itch in pediatric patients with moderate-to-severe atopic dermatitis over 1 year
Authors: Elaine Siegfried, Eric L Simpson, Mark Boguniewicz, Carsten Flohr, Lawrence F Eichenfield, Andreas Pinter, Michele Ramien, Xing-Hua Gao, Zhen Chen, Lauren Bates, Ana B Rossi
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background As symptoms of atopic dermatitis (AD) can wax and wane over time, disease control is better represented by consistency of response over a long treatment duration rather than at a single time point. Objective To evaluate the proportion of pediatric patients achieving and maintaining mild or no itch (defined by a SCORing Atopic Dermatitis (SCORAD) itch visual analog scale (VAS; 0-10 over last 3 days) score of lower than 4) across 5 visits during a 52-week open label extension trial of dupilumab. Methods Patients who previously participated in 16-week trials and were aged 0.5–5 years (LIBERTY AD PRESCHOOL; NCT03346434), 6–11 years (LIBERTY AD PEDs; NCT03345914), and 12–17 years (LIBERTY AD ADOL; NCT03054428), were subsequently enrolled in the phase 3, open-label extension trial, LIBERTY AD PED-OLE (NCT02612454). Patients were treated with 300 mg q4w or 200/300 mg q2w (body weight &amp;lt;60 or ≥60 kg, respectively). In this analysis, patients with a SCORAD itch VAS score of greater than 4 at OLE baseline, were assessed for the maintenance of SCORAD itch VAS lower than 4, at 5 timepoints: Weeks 4, 16, 28, 40, and 52. Results In 763 patients, 400 patients with a SCORAD itch VAS score of greater than 4 were assessed. Mild or no itch was achieved in at least 4 of 5 timepoints in most patients aged 0.5–5 years (55/110; 50%), 6–11 years (76/148; 51%), and 12–17 years (73/142; 51%). Across these age groups, over 65% maintained this response for at least 3 of 5 timepoints. Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions Most pediatric patients achieved improvement in itch, maintained during 1 year of treatment with dupilumab. Results were consistent for infants/preschoolers, children, and adolescents.
536 - Association between pediatric BMI and vitiligo distribution: an observational cohort study
Authors: Ross O’Hagan, Shira Wieder, Marcel Perl, Jonathan I Silverberg, Nanette B Silverberg
Journal: British Journal of Dermatology (2024)

Abstract Background No articles have ever addressed the relationship of BMI with the location of disease in pediatric vitiligo patients. Objective We aimed to explore the relationship between birthweight, reported BMI classifications, and pediatric vitiligo disease characteristics. Methods We explored 232 consecutive pediatric vitiligo patients. Patients’ parents self-reported height, weight, and disease localization. The body mass index classifications were divided into underweight for body mass index (BMI) &amp;lt;18.5, normal for BMI of 18.5 or greater and &amp;lt;25, and overweight for a BMI of 25. Results Exploring birthweight and age of onset, there was a trend towards decreasing median age of onset with weight increases, but it is not statistically significant when we group the patients by BMI class. There is a trend towards older age for children with higher BMI classes (p-value = 0.06). For kids under the age of 12, duration of disease was 4.6 years, vs. 7.7 years for kids over the age of 12 years (p&amp;lt;0.001). When further broken down into kids under 6 years, &amp;gt;6 and less than 12 years, &amp;gt;12 years, and less than 14 years, and 14-17 years, years of disease jumped from 1.3 to 4, to 6.6, and to 7.5 years respectively, demonstrating increased years of disease burden (P&amp;lt;0.001). There is a positive trend in locations and age when looked at for self-reported BSA of 1-25% vs. &amp;gt;25%: (p-value = 0.044). Wrists, hands, hips, legs, ankles, and feet were statistically more likely to be involved by 14-17 years, over 0-6 years (p&amp;lt;0.05 for each site). BSA was 1-25% in 79% of kids under 12 years of age and 75% for kids&amp;gt; 12 years of age. For those with a BSA of 26%+ all anatomical regions explored were statistically significant (p&amp;lt;0.05) other than the specific locations of the scalp, eyelids, lips or mouth. Limitations The cohort does not address long-term weight fluctuations. There are some limitations to self-reported data. Conclusion and Relevance Long-term disease in children and adolescents is associated with increasing years of disease burden and extension of disease to highly visible acral locations. BMI was not directly associated with disease extent in this cohort.
493 - Lebrikizumab does not impact vaccine-induced immune responses: results from a phase 3 study in adult patients with moderate-to-severe atopic dermatitis
Authors: Jennifer Soung, Vivian Laquer, Joseph F Merola, Seth Forman, Hany Elmaraghy, Eric Meskimen, Chaoran Hu, Chitra R Natalie, Evangeline Pierce, Hitoe Torisu-Itakura, Esther Garcia Gil, Abel D Jarell
Journal: British Journal of Dermatology (2024)

Abstract Introduction Lebrikizumab (LEB) is a monoclonal antibody (Ab) that has shown efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) in Phase 2/3 trials. LEB targets IL-13 and inhibits signaling of the IL-4Rα/IL-13Rα1 complex. The potential immunomodulator effect of LEB necessitates investigating its impact on immune responses. Objectives To report the seroresponses to the Tdap (Diphtheria/Tetanus Toxoids/Pertussis) and MCV (Meningococcal (Groups A, C, Y, and W-135)) vaccines in LEB-treated and placebo (PBO)-treated adult patients (aged 18-15 years) with moderate-to-severe AD; and to compare the efficacy of LEB vs PBO in the treatment of AD. Methods ADopt-VA was a US Phase 3, 16-week (W) randomized, double-blind, placebo-controlled study to assess LEB impact on vaccine immune responses in adult patients with moderate-to-severe AD. The primary endpoint was the immune response to 2 vaccines, the Tdap and MCV . LEB was given as a 500 mg loading dose at baseline and W2, followed by 250 mg LEB Q2W. At W12, both vaccines (Tdap and MCV) were administered to all patients, LEB group N=107, Placebo (PBO) group N=81. Immune responses were determined by Ab level differences between W12 and W16. Secondary efficacy endpoints at W16 were Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI 75) scores. Results For Tdap, 73.6% of LEB patients had a positive Ab response vs 73.4% for PBO, 90% CI, 0.3 (-10.2, 11.2). For MCV, LEB patients had an 86.9% positive Ab response vs 75.0% for PBO, 90% CI, 12.2 (2.5, 22.0). IGA (0,1) was achieved by 40.6% of LEB patients vs 18.9% receiving PBO (p=&amp;lt;0.001); EASI 75 was achieved by 58.0% and 32.7% (p&amp;lt;0.001), respectively. The safety profile was consistent with previous LEB trials. Conclusions These data show that LEB does not negatively impact immune responses for Tdap or MCV vaccines in adults with moderate-to-severe AD.
557 - 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.
495 - Lebrikizumab reduces systemic inflammation in serum of patients with moderate-to-severe atopic dermatitis
Authors: Emma Guttman-Yassky, Angela Okragly, Zhe Sun, Laura Rebeca Mena, Nathan Hahn, Brian J Nickoloff, Kimberly Siu, Gaia Gallo, Eric Wolf, Kilian Eyerich, Monica Aparici, Robert J Benschop
Journal: British Journal of Dermatology (2024)

Abstract Introduction Lebrikizumab is an interleukin (IL)-13 inhibitor that has completed phase 3 studies. It demonstrated statistical superiority vs. placebo in patients with moderate-to-severe atopic dermatitis (AD) across all primary and key secondary endpoints at week 4 and week 16 of ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Objectives The objective of this analysis is to determine lebrikizumab’s impact on AD-relevant serum biomarkers in patients from these studies through week 16. Methods Protein biomarkers were determined in available serum samples from patients receiving lebrikizumab 250 mg every 2 weeks (n=72) or placebo (n=36) from both ADvocate1 and ADvocate2. Pre- and post-treatment biomarkers were compared to healthy controls (HC, n=30) which were age, sex, race, and ethnically matched. The analysis included biomarkers known to be elevated in AD. IL-13 was only measured at baseline because of lebrikizumab’s known interference with IL-13 measurement. Results At baseline, CCL13, CCL17, CCL22, total IgE, IL-5, IL-13, and periostin were elevated in patients with AD (p&amp;lt;0.001) with IL-13 measuring approximately 7-fold greater in the AD population vs. HC. In patients with AD, IL-4, CCL11, CXCL10, CCL2, and CCL4 were not elevated at baseline vs. HC. At week 4, lebrikizumab significantly reduced levels of the key type 2 biomarkers, CCL13, CCL17, and periostin vs. placebo (p&amp;lt;0.01) with a trend toward levels consistent with HC (within 1.5-fold). At week 16, CCL13, CCL17, and periostin levels remained consistent with HC levels with CCL13 and periostin retaining statistically significant reductions vs. placebo (p&amp;lt;0.01). Conclusions In sum, selective targeting of IL-13 with lebrikizumab monotherapy reduced known molecular biomarkers of systemic type 2 inflammation in patients with moderate-to-severe AD.
565 – Safety and pharmacokinetic profiles of a humanized monoclonal antibody TQH2722 targeting interleukin 4 receptor alpha (IL-4Rα) in health adult subjects
Authors: Pingping Lin, Feifei Sun, Yi Xu, Rongxin Ban, Xin Jiang, Yao Fu, Xiaomeng Gao, Yu Cao
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background TQH2722 is a humanized monoclonal antibody targeting interleukin 4 receptor alpha (IL4Rα) which leads to the dual-blockade of interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, inhibiting the T-helper cell type 2 immune pathway. Th2 inflammation is implicated in the pathobiology of diseases such as asthma and atopic dermatitis. We describe the safety and pharmacokinetic results from a first-in-human study in healthy subjects. Objectives To evaluate the safety, tolerability, pharmacokinetic characteristics, and immunogenicity of TQH2722 injection in healthy adult subjects. Methods This randomized, double-blind, placebo-controlled, ascending-dose phase I study (NCT05409326) was conducted in China. Each adult subject received a single subcutaneous (sc.) TQH2722 dose or placebo in single ascending-dose (SAD) cohorts, and 4 doses of TQH2722 or placebo administrated Q2W in multiple ascending-dose (MAD) cohorts. Pharmacokinetic samples were collected prior to first dose administration through 56 days after initial dosing in SAD cohorts. In the MAD cohorts, samples were collected before every administration until 56 days after last dosing. Results As of 28 September 2023, all subjects had completed the study, with the database locked while remaining unblinded. Sixty-six (66) healthy subjects were enrolled in this study. The SAD cohorts consisted of single doses of TQH2722 of 50 mg (n-4), 150 mg (n=10 active, 2 placebo), 300, 600, and 1200 mg cohorts, each receiving TQH2722 (n=8) or placebo (n=2). Ten subjects were enrolled in each of the 150 and 600 mg MAD cohorts receiving TQH2722 (n=8) or placebo (n=2). No dose-limiting toxicities or SAEs were observed and only 3 subjects experienced a grade 3 AE including 1 subject of increased triglycerides, 1 subject with increased creatine kinase and 1 subject with decreased blood potassium). All other AEs were of grade 1 or 2. The incidence and severity of AEs were not dose dependent. No SAEs or AEs led to treatment discontinuation. The pharmacokinetics of TQH2722 were indicative of an anti-receptor mAb in that TQH2722 exhibited nonlinear target-mediated clearance. Maximum serum concentration was reached after 2.78-6.75 days with the half-life of a single sc. administration of TQH2722 increasing by dose level, ranging between 4 and 18 days. Conclusions TQH2722 was safe and well tolerated in healthy volunteers. Injection site reactions and laboratory abnormalities were the most reported AEs, with grade 1-2 as the major severity. Most AEs resolved on their own. Single dosing showed non-linear increases of the drug exposure as the dosage increased. These data support further clinical development of TQH2722 as a therapeutic treatment for patients with Atopic Dermatitis and other related diseases mediated by Th2 inflammation.
541 - Real-world effectiveness of dupilumab in adult and adolescent patients with atopic dermatitis: 3-year data from the PROSE registry
Authors: Eric L Simpson, Ben Lockshin, Lara Wine Lee, Liyang Shao, Bengisu Ozarslan, Andrew Korotzer
Journal: British Journal of Dermatology (2024)

Abstract Background Dupilumab has shown efficacy in the treatment of atopic dermatitis (AD) in clinical trials, but there is a need for long-term data on patients starting dupilumab treatment for atopic dermatitis in a real-world setting. Methods PROSE (NCT03428646) is an ongoing 5-year, prospective, observational study of patients aged ≥12 years who initiated commercially available dupilumab treatment for AD per country-specific prescribing information. Patients received a loading dose of dupilumab at baseline, without restrictions on post-baseline dosing changes or concomitant medication and were encouraged to stay in the study if they discontinued dupilumab. Data presented are descriptive, from a 3-year interim analysis. Results 857 patients were enrolled. In these patients, mean (SD) age was 40.1 (17.9) years, AD duration 17.4 (16.2) years, and dupilumab treatment duration 23.1 (13.7) months (M). Mean (SE) baseline EASI total score was 16.2 (0.4), Pruritus Numerical Rating Scale (NRS) 7.1(0.1), Dermatology Life Quality Index (DLQI) 13.3 (0.3), and skin pain NRS 5.4 (0.1). 189 (22.1%) patients had withdrawn by data cut-off; the most common reasons for discontinuation were withdrawal of consent in 76 patients and loss to follow-up in 30. Mean (SE) EASI total score was 5.6 (0.4) at 3M, 2.9 (0.2) at 12M, 2.7 (0.4) at 24M, and 1.7 (0.3) at 36M. Mean (SE) change from baseline in Peak Pruritus NRS was −3.5 (0.2) at 3M, −4.2 (0.2) at 12M, −4.7 (0.2) at 24M, and −5.1 (0.3) at 36M. Mean (SE) change from baseline in DLQI was −7.4 (0.3) at 3M, −8.3 (0.7) at 12M, −9.2 (0.9) at 24M, and −8.8 (1.5) at 36M. Mean (SE) change from baseline in skin pain NRS was −3.3 (0.3) at 3M, −3.8 (0.2) at 12M, −4.0 (0.3) at 24M, and −4.6 (0.3) at 36M. Safety findings were consistent with the previously described safety profile of dupilumab. Conclusion In this interim analysis of the PROSE registry, sustained disease control was observed in patients with moderate-to-­severe AD for up to 3 years after initiating dupilumab treatment.
505 - Once-daily roflumilast cream 0.15% for atopic dermatitis: pooled results from INTEGUMENT-1/2 phase 3 trials
Authors: Lawrence F Eichenfield, Mark Boguniewicz, Eric L Simpson, Andrew Blauvelt, Melinda Gooderham, Edward Lain, David H Chu, Robert C Higham
Journal: British Journal of Dermatology (2024)

Abstract Introduction Roflumilast cream 0.15% is a selective, highly potent phosphodiesterase 4 inhibitor under investigation as a non-steroidal, once-daily treatment for atopic dermatitis (AD). Objectives Here, pooled results from two identical Phase 3 randomized controlled trials (INTEGUMENT-1: NCT04773587 and INTEGUMENT-2: NCT04773600) are presented. Methods Patients with AD aged ≥6 years with baseline Eczema Area and Severity Index (EASI) score ≥5 and Validated Investigator Global Assessment-AD (vIGA-AD) score of Mild or Moderate were randomized 2:1 to apply roflumilast (n=884) or vehicle (n=453) once daily for 4 weeks. Results A significantly greater percentage of roflumilast- versus vehicle-treated patients achieved the primary endpoint, vIGA-AD Success (Clear or Almost Clear vIGA-AD plus ≥2-grade improvement from baseline) at Week 4 (31.3% vs. 14.1%; P&amp;lt;0.0001). Significant differences favoring roflumilast were observed for multiple secondary endpoints at Week 4: percentage of patients achieving vIGA-AD of Clear or Almost Clear (41.1% vs. 21.4%; P&amp;lt;0.0001), percentage achieving 75% reduction in EASI (42.7% vs. 20.6%; P&amp;lt;0.0001), and percentage with baseline Worst Itch-Numeric Rating Scale ≥4 achieving a 4-point reduction (31.9% vs. 16.6%; P&amp;lt;0.0001). Improvement in itch was reported as early as 24 hours. Both groups had low incidences of treatment-emergent adverse events (TEAE), serious adverse events, and TEAEs leading to discontinuation. Local tolerability was favorable, with &amp;gt;90% of patients reporting no or mild sensation across both treatment groups at all timepoints. Conclusions Once-daily roflumilast cream 0.15% provided improvement across multiple efficacy endpoints by Week 4 with favorable safety and tolerability in patients aged ≥6 years with AD in two Phase 3 trials.