tbuckley/cabot-search huggingface dataset:
641 - Pooled efficacy, patient-reported outcomes, and safety of roflumilast cream 0.15% from the INTEGUMENT-1 and INTEGUMENT-2 phase 3 trials of adults and children with atopic dermatitis
Authors: Eric Simpson, Mark Boguniewicz, Lawrence Eichenfield, Mercedes E Gonzales, Adelaide A Hebert, Vimal H Prajapati, Melinda Gooderham, David Krupa, David H Chu, Robert C Higham, David R Berk
Journal: British Journal of Dermatology (2024)

Abstract Introduction Roflumilast is a selective, highly potent phosphodiesterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). Methods We present pooled results from two identical phase 3 randomized controlled trials (INTEGUMENT-1: NCT04773587; INTEGUMENT-2: NCT04773600) of roflumilast cream 0.15%. Patients aged ≥6 years with mild to moderate AD were randomized 2:1 to apply roflumilast (n=884) or vehicle (n=453) cream once-daily for 4 weeks. The primary endpoint was validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success (Clear/Almost Clear vIGA-AD plus ≥2-grade improvement from baseline) at Week 4. Patient-reported outcomes (PROs) were evaluated using the Worst Itch-Numeric Rating Scale (WI-NRS), SCORing AD (SCORAD), Patient-Oriented Eczema Measure, Dermatology Life Quality Index/Children’s Dermatology Life Quality Index, and the Dermatitis Family Impact questionnaire. Safety and tolerability were also evaluated. Results At Week 4, more roflumilast- than vehicle-treated patients achieved vIGA-AD Success (31.3% vs. 14.1%, P&amp;lt;0.0001), WI-NRS Success (≥4-point improvement on WI-NRS in patients aged ≥12 years with baseline WI-NRS ≥4; 31.9% vs. 16.6%, P&amp;lt;0.0001); and WI-NRS of 0/1 (in patients with baseline WI-NRS ≥2; 28.8% vs 18.5%, P=0.0087). At Week 4, roflumilast-treated patients improved more than vehicle-treated on the pruritus and sleep components of SCORAD (least squares mean percentage change −48.2% vs. −27.8%; [P&amp;lt;0.0001] and −47.9% vs. −22.9% [P&amp;lt;0.05], respectively). Differences favoring roflumilast were also seen for other secondary endpoints, including quality of life of the patient and family. Safety and local tolerability were favorable. Conclusion Once-daily, nonsteroidal roflumilast cream 0.15% improved PROs in patients with AD.
701 - Dupilumab efficacy and safety up to 2 years in children aged 6 months to 5 years with atopic dermatitis
Authors: Amy S Paller, Eric L Simpson, Elaine C Siegfried, Michael J Cork, Peter D Arkwright, Andreas Pinter, Ariane Dubost-Brama, Elizabeth Laws, Zhen Chen, Ashish Bansal, Randy Prescilla, Tien V Nguyen
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background While previous studies into continuous long-term dupilumab treatment for adults with moderate-to-severe atopic dermatitis (AD) demonstrated sustained efficacy, further study into long-term safety and efficacy data regarding dupilumab in children is needed. Objectives To evaluate the impact of treatment with dupilumab and low-potency topical corticosteroids (TCS) for up to 2 years on efficacy and safety measures in children aged 6 months to 5 years with moderate-to-severe AD. Methods Children aged 6 months to 5 years with moderate-to-severe AD, who had participated in prior dupilumab pediatric AD studies were enrolled in a phase 3 open label extension (OLE) study. Patients received subcutaneous dupilumab every 4 weeks; 200 mg for children weighing 5 to &amp;lt;15 kg, 300mg for 15 to &amp;lt;30 kg. Topical AD treatments were allowed. Efficacy outcomes assessed include the proportion of patients who achieved 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) score and the proportion of patients who achieved an Investigator Global Assessment (IGA) score of 0/1 as observed from OLE baseline to 2 years. Safety was also evaluated. Results A total of 180 patients were included in the 6 month to 5 years cohort; mean (±SD) age at OLE baseline was 3.9 (1.3) years with mean (SD) duration of AD of 3.5 (1.3) years. At OLE baseline, 29.4% of patients achieved EASI-75, improving to 85.1% at 52 weeks and 92.1% at 104 weeks. Similarly, 12.8% of patients achieved IGA 0/1 at OLE baseline, improving to 36.0% at Week 52 and 40.6% at Week 104. Total treatment-emergent adverse events (TEAEs) were observed in 87.8% of patients (intensity: mild 24.4%, moderate 52.2%, severe 11.1%). TEAEs assessed as related to dupilumab by the study investigators were reported in 18.3% of patients; the most prevalent were conjunctivitis (2.8%), allergic conjunctivitis (1.7%), nasopharyngitis (1.7%) and urticaria (1.7%). Serious TEAEs assessed as related to dupilumab by the study investigators were observed in 0.6% of patients. Conclusions Treatment with dupilumab for up to 2 years in young children with moderate-to-severe AD demonstrated efficacy outcomes, with sustained improvement in clinical signs reported in a large proportion of patients. Results are consistent with the known safety profile for dupilumab.
578 - Cost per responder in Brazil (EASI-75, EASI90 and ΔNRS ≥4) of biologics and JAK inhibitors based on a network-meta-analysis of therapies for atopic dermatitis
Authors: Guilherme Muzy
Journal: British Journal of Dermatology (2024)

Abstract Background Atopic dermatitis (AD) poses a significant global health burden, affecting a substantial percentage of both pediatric and adult populations. Conventional systemic therapies exhibit limited efficacy and undesirable side effects, emphasizing the urgent need for more effective and economically viable treatment options. Objective This study aims to provide an updated analysis of the cost per response ratio for different systemic medications in monotherapy for moderate-to-severe AD, considering the unique Brazilian healthcare context. Additionally, it explores the number of successfully treated patients across various clinically meaningful endpoints. Methods The study includes biological therapies and JAK inhibitors approved by ANVISA up to January 2024. Efficacy was assessed using EASI and pruritus-NRS scores, aligning with HOME's Core Outcome Set for clinical trials. Costs were calculated based on each specific outcome, considering the factory price with an 18% increment for ICMS. Dosages and costs were derived from prescribing information and network meta-analyses. Results Upadacitinib 15 mg emerged as the most cost-effective therapy for achieving EASI-90, providing a substantial cost reduction compared to other medications. All JAK inhibitors demonstrated superior cost per response values for pruritus △NRS ≥ 4 compared to dupilumab. Study limitations This analysis was limited to the endpoints presented in the meta-analyses and other endpoints might offer different perspectives results. Conclusion This research contributes valuable insights into the cost-effectiveness of systemic therapies for AD in the Brazilian context. Despite not being obligatory, JAK inhibitors showcase notable cost-efficacy, providing an alternative to biological treatments. Decision-makers should leverage cost-effectiveness analyses for informed resource management and prioritize treatments that maximize clinical benefits and minimize costs.
722 - Efficacy of povorcitinib for the treatment of vitiligo by patient demographics and baseline clinical characteristics: week 52 subgroup analysis from a randomized, placebo-controlled, phase 2b clinical trial
Authors: Amit G Pandya, Thierry Passeron, Andrew Blauvelt, Nanja van Geel, Kurt Brown, Lois Erskine, Zhenyi Xue, Khaled Ezzedine
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Povorcitinib—an oral, small-molecule, selective Janus kinase 1 inhibitor—was statistically superior to placebo at Week 24 in patients with nonsegmental vitiligo in a phase 2b clinical trial (NCT04818346). Objectives To evaluate the efficacy of povorcitinib in subgroups of patients with nonsegmental vitiligo defined by demographics and baseline clinical characteristics. Methods Adults with nonsegmental vitiligo affecting ≥0.5%/≥8% facial/total body surface area (F-BSA/T-BSA) were randomized 1:1:1:1 to once-daily povorcitinib 15/45/75 mg or placebo for 24 weeks; subsequently, patients received povorcitinib 45/75 mg for an additional 28 weeks. The percentage of patients achieving ≥50% reduction from baseline in total Vitiligo Area Scoring Index (T-VASI50) and ≥50% and ≥75% reduction in facial-VASI (F-VASI50 and F-VASI75, respectively) were assessed by demographics and baseline characteristics. Data were analyzed using descriptive statistics; missing values were considered nonresponders. Results In total, 171 patients were randomized; at baseline, median (range) age was 50 (23–74) years, mean (SD) disease duration was 19.4 (14.0) years, and mean (SD) T-VASI was 25.5 (19.1). Subgroup analyses were conducted among the 103 patients who received any dose of povorcitinib from Day 1. At Week 52, 35/103 (34.0%) evaluable patients who received povorcitinib 15/45/75 mg achieved T-VASI50, 63/103 (61.2%) achieved F-VASI50, and 47/103 (45.6%) achieved F-VASI75. T-VASI50 responses were consistent within subgroups defined by age (≤40/&amp;gt;40 years, 42.9%/30.7%), sex (male/female, 23.8%/41.0%), race (White/Non-White, 31.6%/41.7%), Fitzpatrick skin type (I–III/IV–VI, 31.4%/39.4%), F-BSA (≤1.5%/&amp;gt;1.5%, 30.4%/41.2%), T-BSA (≤20%/&amp;gt;20%, 35.4%/32.7%), autoimmune comorbidities (Yes/No, 37.9%/32.4%), disease duration (≤10/10–20/&amp;gt;20 years, 41.7%/13.0%/38.6%), and previous therapy (Yes/No, 34.4%/30.0%). Similar findings were observed for F-VASI50 and F-VASI75. Conclusions Patients receiving povorcitinib achieved T-VASI50, F-VASI50, and F-VASI75 responses regardless of demographics or baseline clinical characteristics. Results should be confirmed in larger populations.
639 - Efficacy and safety of once-daily roflumilast cream 0.05% in pediatric patients 2 to 5 years of age with mild to moderate atopic dermatitis (INTEGUMENT-PED): a phase 3 randomized controlled trial
Authors: Lawrence Eichenfield, John Browning, Tracy Funk, Mercedes E Gonzalez, Adelaide A Hebert, Mark Lee, Vimal H Prajapati, Rocco Serrao, Lisa Swanson, Robert Higham, David Berk
Journal: British Journal of Dermatology (2024)

Abstract Background Roflumilast is a highly potent phosphodiesterase 4 inhibitor under investigation as a non-steroidal, once-daily cream for atopic dermatitis (AD). Methods INTEGUMENT-PED (NCT04845620) was a Phase 3 parallel-group, double-blind, vehicle-controlled trial. Children aged 2 to 5 years with mild to moderate AD were treated with roflumilast cream 0.05% (n=437) or vehicle (n=215) once-daily for 4 weeks. The primary efficacy endpoint was validated Investigator Global Assessment-Atopic Dermatitis (vIGA-AD) Success (defined as a score of 0 [clear] or 1 [almost clear] with 2-grade improvement from baseline) at Week 4. Secondary endpoints included 75% improvement in Eczema Area and Severity Index (EASI-75). Worst-Itch-Numeric Rating Score (WI-NRS) Success (≥4-point improvement in patients with baseline ≥4), safety, and tolerability were also assessed. Results At Week 4, significantly more roflumilast-treated than vehicle-treated patients achieved vIGA-AD Success (25.4% vs 10.7%; P&amp;lt;0.0001), EASI-75 (39.4% vs 20.6%; P&amp;lt;0.0001), and WI-NRS Success (35.3% vs 18.0%; nominal P=0.0002). Improvement in pruritus was observed by 24 hours after first application (nominal P=0.0014 versus vehicle). Incidence of treatment-emergent adverse events (AEs) was low in both arms, with 98.9% assessed as mild to moderate. AEs occurring in &amp;gt;2% of patients and greater in the roflumilast-treated group were upper respiratory tract infection, diarrhea, and vomiting. For local tolerability, &amp;gt;92% of roflumilast-treated patients reported no or mild sensation across arms at any timepoint. Conclusion In this phase 3 trial, once-daily roflumilast cream 0.05% improved AD in pediatric patients (2 to 5 years of age), while demonstrating favorable safety and tolerability.
650 - Stability of long-term therapeutic responses to tralokinumab in adults with moderate-to-severe atopic dermatitis
Authors: Andrew Blauvelt, H Chih-ho Hong, Ketty Peris, Norito Katoh, Marie Tauber, Mahreen Ameen, Melinda Gooderham, Christian Bjerregård Øland, Ann-Marie Tindberg, Le Gjerum, Kristian Reich
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background To ensure minimal residual disease and to prevent relapses, recently published consensus reports have defined optimal long-term treatment targets for atopic dermatitis (AD).1,2 Tralokinumab, a monoclonal antibody specifically neutralizing interleukin-13, is approved for the treatment of moderate-to-severe AD. ECZTEND (NCT03587805) is an ongoing open-label, 5-year extension trial investigating the long-term safety and efficacy of tralokinumab 300 mg every other week (Q2W) plus optional topical corticosteroids (TCS). Objectives To determine the proportion of patients treated for up to 4 years with tralokinumab in AD clinical trials who: 1) exhibit stable improvement, with no or minimal fluctuations, in lesion extent and severity long-term (ie, response in ≥80% of attended visits), and 2) exhibit a stable long-term composite response (ie, up to 4 years of tralokinumab treatment and response in ≥80% of attended trial visits) in signs and symptoms of AD, and quality of life based on recent treat-to-target recommendations (EASI ≤7 and either DLQI ≤5 or Itch NRS ≤4). Methods This post hoc analysis included 347 patients who were continuously treated with tralokinumab for 52 weeks in the identically designed phase 3 monotherapy trials ECZTRA 1&amp;2 and subsequently for up to 152 weeks in ECZTEND as of the April 30, 2022 data cutoff. Stability of long-term response, with no or minimal fluctuations, was defined as meeting the target endpoints at ≥80% of attended visits between Weeks 16-152 in ECZTEND. Endpoints analyzed were EASI ≤7, EASI ≤2, and a composite long-term treatment target: EASI ≤7 and either DLQI ≤5 or worst weekly pruritus NRS ≤4. Results A stable EASI ≤7 response (at ≥80% of attended visits) was observed in 70.2% (233/332) of tralokinumab-treated patients over Weeks 16-152 of ECZTEND. A stable EASI ≤2 response was observed in 34.0% (113/332) of patients, and a long-term optimal composite target, EASI ≤7 and either DLQI ≤5 or Itch NRS ≤4, was observed in 60.5% (201/332) of patients. Conclusions High proportions of clinical trial patients maintained stable responses, with no or minimal fluctuations in efficacy, with continued tralokinumab 300 mg Q2W plus optional TCS for up to 4 years of treatment.
637 - ARQ-234: a high affinity CD200-Fc fusion protein for the treatment of atopic dermatitis
Authors: Joseph Sheridan, Jonathan Heal, David R Berk, Patrick Burnett, David J Blackbourn, Philip Huxley, Rebecca Ashfield
Journal: British Journal of Dermatology (2024)

Abstract Background Human CD200 receptor (CD200R, CD200R1), originally OX2R, is an inhibitory immune checkpoint receptor expressed on many myeloid cells, and lymphocyte populations including CD4 T and ILC2 cells, signaling via DOK2 and Erk/MAP kinases to inhibit the NFkB pathway and cytokine secretion. Its ligand, CD200, is expressed on the surface of tissues including endothelium, epithelia and neurons, where it moderates immune activation particularly at barrier sites including lung, skin and the GI tract. Published evidence, including GWAS studies, implicates dysregulation of the CD200 axis in many allergic, autoimmune and inflammatory diseases. Furthermore, a CD200R agonist antibody has demonstrated efficacy in an early phase clinical trial of moderate to severe atopic dermatitis patients. Methods We have engineered high affinity soluble CD200R agonists, comprising human CD200-Fc proteins with substantially increased (up to 130-fold) monomeric binding affinity for CD200R. Results High affinity human CD200-Fc a) out-performs wild type in inhibiting IL-6 release from a cell line expressing high levels of human CD200R, b) has superior potency to a CD200R agonist antibody in a humanized mouse model of contact hypersensitivity, and c) substantially reduces cell infiltrate in bronchoalveolar lavage fluid in a non-human primate model of airway inflammation. A high affinity murine CD200-Fc has been engineered for additional proof-of-concept studies, and is more potent than wild type in an in vivo model (collagen-induced arthritis). Finally, we describe ARQ-234, a high affinity CD200-Fc protein with antibody-like serum half-life in NHP, due to the introduction of mutations in the Fc domain which increase relative binding to the neonatal Fc receptor at low (endosomal) pH. ARQ-234 is currently in pre-clinical development as a therapeutic for atopic dermatitis.
676 - Dupilumab increases levels of bone growth biomarker irrespective of prior use of systemic corticosteroids in children with moderate-to-severe atopic dermatitis
Authors: Alan D Irvine, Amy S Paller, Sara Hamon, Julie Horowitz, Annamaria Farrell, Sarah Hatsell, Peter Ehmann, Ainara Rodríguez Marco, Ashish Bansal, Zhen Chen, Stephane Levy, Sonya L Cyr
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Children with moderate-to-severe atopic dermatitis (AD) are at increased risk of lower bone mineral density (BMD) and fractures. Peak bone mass achieved during prepubescence is a major determinant of lifetime risk of fractures and osteoporosis. Bone alkaline phosphatase (BALP) promotes bone mineralization and contributes to density and linear growth in children. Systemic corticosteroids (SCS) negatively impact growth and bone health. Objectives To describe the impact of dupilumab treatment on BALP in children aged 6–11 years with moderate-to-severe AD and prior history of SCS use. Methods BALP levels in sera from participants receiving dupilumab 300 mg every 4 weeks (q4w) or placebo in LIBERTY AD PEDS (NCT03345914) and dupilumab 300 mg q4w in LIBERTY AD PED-OLE (NCT02612454) were analyzed at baseline and at 8, 12, 16 (PEDS), and 52 weeks (PED-OLE). Serum BALP levels (mcg/L) were stratified by prior use (with SCS; n = 42) or with no prior use of SCS (without SCS; n = 203), as captured in PEDS patient history at baseline. Results Regardless of prior SCS use, dupilumab treatment led to significant increase in BALP levels in children with moderate-to-severe AD at Week 16 compared with the placebo group (with SCS: 300 mg q4w [n = 25] vs placebo [n = 17], mean change [standard deviation] in BALP levels of 15.1 mcg/L [16.5] vs −5.5 mcg/L [16.0], P = 0.0099; without SCS: 300 mg q4w [n = 97] vs placebo [n = 106], 11.8 mcg/L [18.8] vs 2.2 mcg/L [16.3], P = 0.0074). By Week 52, BALP levels further increased vs baseline regardless of prior SCS use and were comparable with reference intervals (with SCS: 24.5 mcg/L [16.8], P = 0.0044; without SCS: 13.4 mcg/L [19.4], P = 0.0002). Patients in the placebo group who switched to dupilumab in PED-OLE had improved to levels similar to those of patients continuing treatment by Week 52 (with SCS: 23.3 mcg/L [19.3], P = 0.0067 [vs baseline]; without SCS: 18.4 mcg/L [20.4], P &amp;lt; 0.0001 [vs baseline]). Conclusions Dupilumab treatment increased BALP levels in children aged 6-11 years with moderate-to-severe AD irrespective of prior history of SCS use. These results add to the body of evidence that moderate-to-severe AD can negatively impact BALP levels, and that this effect may be improved with dupilumab in this age group, regardless of history of SCS use. The increase in BALP levels suggests that dupilumab may help improve bone mineralization in children with moderate-to-severe AD when treated during prepubescence.
651 - 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/Background 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 H&amp;N 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.