bluuebunny/crossref_metadata_2025_split huggingface dataset:
653 - Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema: pooled results of the phase 3 DELTA-1 and -2 trials
Authors: Bissonnette Robert , Worm Margitta , Warren Richard B , Agner Tove , Gooderham Melinda , Schuttelaar Marie Louise , Baranowski Keith , Plohberger Ursula , Soerensen Laura , Schliemann Sibylle 
Published: August 2024

Abstract

Introduction/Background
Chronic Hand Eczema (CHE) is a frequent inflammatory skin disease associated with pain, pruritus, and significant occupational, functional, social, and psychological burden. Delgocitinib is a topical pan-JAK inhibitor which showed a dose-dependent efficacy in adults with CHE in a Phase 2b trial.

Objectives
The objectives of this analysis were to study (1) the efficacy of twice-daily applications of delgocitinib cream 20 mg/g, as assessed by Investigator's Global Assessment for CHE treatment success (primary outcome), and the secondary outcomes ≥75%/≥90% improvement in Hand Eczema Severity Index and ≥4-point improvement in the Dermatology Life Quality Index, and (2) the safety of twice-daily applications of delgocitinib cream 20 mg/g compared with cream vehicle in the treatment of adults with moderate to severe CHE in a pooled analysis of the DELTA-1 and DELTA-2 trials.

Methods
In the Phase 3 DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101) trials, adults with moderate to severe CHE were randomized 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was the Investigator's Global Assessment for CHE (IGA-CHE) treatment success at Week 16, defined as IGA-CHE score of 0/1 (clear/almost clear, i.e., no/barely perceptible erythema and no other signs), with a ≥2-step improvement from baseline. Key secondary endpoints included ≥75%/≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) and ≥4-point improvement in the Dermatology Life Quality Index (DLQI). This DELTA-1 and -2 pooled analysis included 639 patients treated with delgocitinib cream and 321 with cream vehicle.

Results
At Week 16, a significantly greater proportion of delgocitinib-treated patients, versus cream vehicle, achieved IGA-CHE treatment success (24.3% vs. 8.4%; P&lt;0.001), HECSI-75 (49.4% vs. 20.9%; P&lt;0.001), HECSI-90 (30.3% vs. 10.6%; P&lt;0.001), and DLQI ≥4-point improvement (73.3% vs. 47.8%; P&lt;0.001). Most frequent adverse events (occurring in ≥5% of patients) were COVID-19, nasopharyngitis, and headache with similar rates in both treatment groups.

Conclusions
In the DELTA-1 and -2 pooled analysis, delgocitinib cream twice-daily confirmed its clinical efficacy in patient- and clinician-reported efficacy outcomes versus cream vehicle in adult CHE patients and suggests an innovative treatment option in this often difficult-to-treat patient population.
654 - Delgocitinib cream reduces itch and pain in adults with moderate to severe chronic hand eczema: pooled analyses of the phase 3 DELTA-1 and -2 trials
Authors: Bauer Andrea , Schuttelaar Marie-Louise , Baranowski Keith , Plohberger Ursula , Sørensen Laura , Worm Margitta 
Published: August 2024

Abstract

Introduction/Background
Itch and pain are two of the most common and burdensome symptoms of Chronic Hand Eczema. Delgocitinib cream, a topical pan-Janus kinase inhibitor, was well tolerated and demonstrated significant improvement in primary and all secondary efficacy endpoints in DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101).

Objectives
The objectives of this analysis were to assess the effect on itch and pain of twice-daily applications of delgocitinib cream 20 mg/g, including early onset of reductions, compared with cream vehicle in the treatment of adults with moderate to severe CHE in a pooled analysis of the pivotal Phase 3 DELTA-1 and DELTA-2 trials.

Methods
This analysis includes pooled data from DELTA-1 and -2 (delgocitinib cream 20 mg/g [n=639]; cream vehicle [n=321]; twice-daily). The Hand Eczema Symptom eDiary (HESD) captured patient-reported worst severity of itch and pain over the past 24 hours on an 11-point numeric rating scale (0=no itch/pain to 10=severe itch/pain). Changes in itch and pain from baseline were assessed daily during Week (W)1 and weekly from W1-16.

Results
For itch, a significant least square (LS) mean reduction from baseline was detected 1 day after patients first applied delgocitinib 20 mg/g (0.75) versus the cream vehicle group (0.32, P&lt;0.001). For pain, a significant LS mean reduction was detected 3 days after the first application of delgocitinib cream (0.98) versus cream vehicle (0.58, P&lt;0.001). The LS mean itch and pain reductions continued for delgocitinib cream-treated patients up to W16 (P&lt;0.001). A clinically meaningful ≥4-point reduction in itch was achieved by significantly more patients applying delgocitinib cream from W2 (14.2%) versus cream vehicle (6.3%, P&lt;0.001) and onwards to W16 (delgocitinib cream: 47.2%; cream vehicle: 21.5%; P&lt;0.001). Similar results for a ≥4-point reduction in pain were observed.

Conclusions
Early onset of itch and pain reduction was observed within W1 for delgocitinib-treated patients, with reductions remaining significantly greater versus cream vehicle-treated patients from W1 to W16.
665 - Lack of publications assessing patient impact of vitiligo and alopecia areata
Authors: Brown Sarah , Chastain Emily , Suryajaya Kaylen , Feaver Sarah , Harbers Stephanie 
Published: August 2024

Abstract

Introduction/Background
Vitiligo and alopecia areata (AA) are immune-mediated diseases which have unpredictable disease courses.1,2 The profound psychosocial impact of vitiligo and AA is often under recognised despite association with elevated incidence of psychological disorders1,2; the perceived burden frequently remains driven by cosmetic considerations.1,3 Improved awareness and understanding of the burden of vitiligo and AA by healthcare professionals is needed,1,2 however, both have been the subject of limited clinical research.

Objectives
Here, we characterise publications on the disease burden of vitiligo and AA, relative to other major immune-mediated dermatological diseases.

Methods
A PubMed search (limited to English language with available abstract) identified articles on disease burden in vitiligo, AA, psoriasis, atopic dermatitis (AD), systemic sclerosis (SS), and hidradenitis suppurativa (HS) (01JAN2014–31DEC2023). Analysis of cross-indication data was conducted for article type, clinical research phase, and articles behind paywall. Relevant vitiligo and AA abstracts underwent further analysis regarding disease burden and provision of enhanced publication content (EPC)/plain language summary (PLS).

Results
Of 2002 publications, 3% were related to vitiligo (N=68) and 4% to AA (N=78), compared to psoriasis (45%), AD (30%), SS (11%), and HS (7%). A similar proportion of articles across all diseases were clinical trials (vitiligo and AA: 3.4%; other diseases: 4.2%) and behind paywall (38%; 43%). Among the relevant vitiligo (n=21) and AA (n=39) articles on disease burden, 57% and 51% focused on QoL burden, respectively, followed by 19% on psychological comorbidities for vitiligo and 21% on economic impact for AA. Far fewer articles addressed immune-mediated comorbidities, burden of treatment, and physical symptoms. Findings revealed limited PLS/EPC availability.

Conclusions
Compared with other immune-mediated dermatological diseases, vitiligo and AA are underserved with limited published data characterising disease burden. Accessible publications addressing all aspects of disease burden are required to provide a holistic understanding of patient experiences and aid in shifting perceptions of vitiligo and AA.
667 - Maintenance of efficacy and safety with nemolizumab at week 48: results from two global phase 3 pivotal studies (ARCADIA-1 and ARCADIA-2) in patients with moderate-to-severe atopic dermatitis
Authors: Silverberg Jonathan I , Wollenberg Andreas , Legat Franz J , Laquer Vivian T , Armstrong April W , Herranz Pedro , Naldi Luigi , Ahmad Faiz , Ulianov Liliana , Piketty Christophe 
Published: August 2024

Abstract

Background
Atopic dermatitis (AD) is a common, chronic, and flaring itchy inflammatory skin disease requiring long-term treatment. Nemolizumab significantly improved skin lesions, itch, and sleep through Week (W) 16 in two global phase 3 studies (ARCADIA-1 [NCT03985943] and ARCADIA-2 [NCT03989349]) in adolescents and adults with moderate-to-severe AD.1

Introduction/Background
To evaluate the efficacy and the safety of maintenance treatment with nemolizumab with background topical therapy for up to 32 weeks in patients (≥12 years) with moderate-to-severe atopic dermatitis

Methods
This analysis pooled 32-week maintenance data from two double-blind, placebo controlled, phase 3 studies (N=507) in moderate-to-severe AD. Clinical responders (IGA 0/1 [clear/almost-clear] or EASI-75 [75% improvement in EASI score]) to nemolizumab at W16 were re-randomized (1:1:1) to receive nemolizumab 30mg every 4 weeks (Q4W), nemolizumab 30mg Q8W, or placebo (nemolizumab withdrawal) Q4W subcutaneously for further 32 weeks in combination with topical corticosteroids of low/medium potency and/or topical calcineurin inhibitors. Safety was assessed throughout the study.

Results
At W48, the proportion of patients who maintained IGA success (defined as IGA score of 0 [clear] or 1 [almost clear] and a ≥2-point improvement from baseline) was 61.5% (nemolizumab-Q4W), 60.4% (nemolizumab-Q8W), and 49.7% (placebo); EASI-75 was maintained in 76.3% (nemolizumab-Q4W), 75.7% (nemolizumab-Q8W), and 63.9% (placebo); and itch response (≥4 points improvement in weekly average PPNRS) was achieved in 76.2% (nemolizumab-Q4W), 59.7% (nemolizumab-Q8W), and 41.0% (placebo). Similarly, response in sleep and quality of life was well maintained at W48. The safety profile was consistent across treatment arms; most treatment-emergent adverse events were non-serious and mild/moderate in intensity.

Conclusions
Among patients with clinical responses in skin lesions at W16, the majority maintained skin and itch responses at W48 with nemolizumab Q4W/Q8W. Nemolizumab was well-tolerated up to W48, and no safety signals were identified.
668 - Improvements in itch and sleep disturbance are maintained up to week 48 with nemolizumab plus TCS/TCI treatment in patients with moderate-to-severe atopic dermatitis: results from two global phase 3 pivotal studies (ARCADIA 1 and ARCADIA 2)
Authors: Silverberg Jonathan I , Wollenberg Andreas , Legat Franz J , Laquer Vivian T , Ulianov Liliana , Cheong Soo Yeon , Ryzhkova Anna , Piketty Christophe 
Published: August 2024

Abstract

Background
Treatment with nemolizumab plus topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) achieved improvements in itch and sleep (measured using Peak Pruritus Numerical Rating Scale and Sleep Disturbance Numerical Rating Scale) at Week (W) 16 and maintained them up to W48 in patients with moderate-to-severe AD.1,2

Objectives
To evaluate the efficacy of nemolizumab in maintaining itch and sleep responses (using SCORing Atopic Dermatitis (SCORAD) Visual Analog Scale [VAS] Pruritus and SCORAD VAS Sleep) over 48 weeks in patients with moderate-to-severe AD.

Methods
We analyzed 32-week maintenance data pooled from two double-blinded, placebo-controlled, phase 3 studies (ARCADIA-1 and ARCADIA-2). Clinical responders (those achieving IGA 0/1 or EASI-75 at W16) were re-randomized (1:1:1) to receive nemolizumab 30mg every 4 weeks (nemolizumab-Q4W), nemolizumab 30mg every 8 weeks (nemolizumab-Q8W), or placebo Q4W (nemolizumab-withdrawal arm) subcutaneously, all with TCS and/or TCI up to W48.

Results
At W48, response rates for ≥4-point improvement in SCORAD VAS Pruritus were maintained in nemolizumab-Q4W (72.8%, p&lt;0.0001) and nemolizumab-Q8W (66.9%, p≤0.001) vs placebo (49.1%) groups. Similarly, response rates for ≥4-point improvement in SCORAD VAS Sleep were maintained in nemolizumab-Q4W (61.5%, p&lt;0.001) and nemolizumab-Q8W (56.2%, p&lt;0.05) vs placebo (43.2%) groups at W48. Response rates for SCORAD VAS Pruritus-75 (≥75% improvement in VAS Pruritus from initial baseline) were also maintained in nemolizumab-Q4W (63.3%, p&lt;0.0001) and nemolizumab-Q8W (58.6%, p&lt;0.0001) vs placebo (37.3%) groups at W48. Similar maintenance of response rates for SCORAD VAS Sleep-75 (≥75% improvement in VAS Sleep from initial baseline) was noted in nemolizumab-Q4W (60.4%, p&lt;0.01) and nemolizumab-Q8W (56.8%, p&lt;0.05) vs placebo (43.8%) groups at W48.

Conclusions
Treatment with nemolizumab plus TCS/TCI maintained rate of improvements in itch and sleep through W48 in patients who achieved clinical response at W16. The Q8W regimen was similar to Q4W in maintenance of the rate of itch and sleep response.
670 - Tapinarof cream 1% once daily is efficacious for the treatment of atopic dermatitis in patients with skin of color down to 2 years of age in two pivotal phase 3 trials
Authors: Alexis Andrew F , Kircik Leon , Chovatiya Raj , Rice Zakiya P , Bhutani Tina , Brown Philip M , Piscitelli Stephen C , Rubenstein David S , Tallman Anna M , Armstrong April W 
Published: August 2024

Abstract

Introduction
Patients with atopic dermatitis (AD) and skin of color can have heterogeneous presentations and treatment responses. In the pivotal phase 3 ADORING 1 and ADORING 2 trials, tapinarof cream 1% once daily (QD) was significantly efficacious and well tolerated versus vehicle in adults and children down to 2 years of age with AD.

Objective
Here, we report analyses of efficacy by patients’ self-identified race and investigator-assessed Fitzpatrick skin type in ADORING 1 and 2.

Methods
In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic DermatitisTM (vIGA-ADTM) 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. The primary efficacy endpoint was a vIGA-ADTM score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement from baseline at Week 8. Secondary endpoints included proportion of patients with a ≥75% improvement in Eczema Area and Severity Index (EASI75).

Results
Of 407 and 406 randomized patients, 8.8–15.3% were Asian, 26.5–35.0% were Black or African American, 44.8–56.8% were White, and 2.7–5.2% were Other groups (including American Indian or Alaska Native, Native Hawaiian or Pacific Islander, or multiple races) across trials. Patients with Fitzpatrick skin types IV, V, and VI represented 23.8–25.1%, 20.6–22.2%, and 7.6–8.9%, respectively, of participants (&gt;50% in both trials). Across trials, vIGA-ADTM responses (ranges) for tapinarof versus vehicle were: Asian, 39.5–48.9% vs 3.7–18.5%; Black or African American, 43.1–47.0% vs 17.5–24.1%; White, 49.4–52.1% vs 12.2–14.5%; and Other, 26.0–44.8% vs 0.0–40.2%. EASI75 responses for tapinarof versus vehicle were: Asian, 47.6–76.6% vs 17.7–20.2%; Black or African American, 48.9–55.3% vs 25.7–30.0%; White, 61.4–67.8% vs 19.6–20.7%; and Other, 38.3–63.3% vs 0.0–40.6%. Similarly, high and consistent vIGA-ADTM and EASI75 responses were reported with tapinarof compared with vehicle for patients with Fitzpatrick skin types I–III and IV–VI.

Conclusion
Tapinarof cream 1% QD was consistently efficacious among all racial groups and Fitzpatrick skin types, including adults and children down to 2 years of age with skin of color, who comprised approximately 50% of patients in these trials.
673 - Efficacy of nemolizumab in different subgroups of patients with prurigo nodularis in two randomized, placebo-controlled phase 3 trials
Authors: Kwatra Shawn G , Metz Martin , Pink Andrew E , Yosipovitch Gil , Gharib Rola , Sundaram Hema , Chen Xiaoxiao , Noda Aliene , Jabbar Lopez Zarif K , Piketty Christophe , Ständer Sonja 
Published: August 2024

Abstract

Introduction
It is unknown whether baseline demographics and disease characteristics have an influence on efficacy and safety of nemolizumab in adults with moderate-to-severe prurigo nodularis (PN).

Objectives
To report safety and efficacy of nemolizumab in the phase 3 studies (OLYMPIA-1 [NCT04501666]1 and OLYMPIA-2 [NCT04501679]2) for different subgroups.

Materials & Methods
Data were pooled from the pivotal studies in which adults with moderate-to-severe PN were randomized (2:1) to receive nemolizumab (initial 60mg subcutaneous dose, followed by 30mg/60mg [depending on a baseline weight: &lt;90kg/≥90kg] every 4 weeks) or matching placebo.

Results
Comparisons in all subgroups (age, sex, race, weight, disease severity, atopy, prior treatment) identified efficacy of nemolizumab versus placebo consistent with the overall intention-to-treat population. At Week (W) 16, a ≥4-point improvement in weekly average Peak Pruritus Numerical Rating Scale of nemolizumab vs. placebo was found in 18- to 65-year-old/&gt;65-year-old: 58.6%/54.0% vs 20.0%/14.3%; males/females: 54.7%/59.2% vs 21.1%/17.1%; White/Black/Asian/Other race: 60.3%/56.5%/36.4%/40.0% vs 20.8%/11.8%/12.5%/0%, &lt;90kg/≥90kg baseline weight: 55.6%/60.8% vs 17.9%/20.8%, baseline Investigator’s Global Assessment [IGA] score of 3 [moderate]/4 [severe]: 54.9%/60.8% vs 23.6%/11.7%, with/without history of atopy: 53.8%/59.0% vs 20.3%/17.9% and with/without prior systemic treatment for PN: 57.9%/56.8% vs 14.4%/22.7%. An IGA success (score of 0/1 [clear/almost clear skin] with ≥2-point reduction from baseline) was found in 18- to 65-year-old/&gt;65-year-old: 34.8%/24.0% vs 11.0%/2.4%; males/females: 28.0%/34.5% vs 10.5%/8.1%; White/Black/Asian/Other race: 32.2%/26.1%/33.3%/30.0% vs 8.1%/11.8%/18.8%/0%, &lt;90kg/≥90kg baseline weight: 34.3%/27.2% vs 9.0%/9.4%, baseline IGA score of 3 [moderate]/4 [severe]: 34.0%/29.1% vs 12.7%/3.9%, with/without history of atopy: 29.9%/32.8% vs 4.7%/11.4% and with/without prior systemic treatment for PN: 37.2%/26.8% vs 8.9%/9.3%. Similar results were noted for sleep disturbance. No major difference was reported in the safety profile of nemolizumab between the subgroups.

Conclusion
Safety and efficacy of nemolizumab monotherapy in itch, skin lesions and sleep disturbance were consistent between the subgroups.
676 - Dupilumab increases levels of bone growth biomarker irrespective of prior use of systemic corticosteroids in children with moderate-to-severe atopic dermatitis
Authors: Irvine Alan D , Paller Amy S , Hamon Sara , Horowitz Julie , Farrell Annamaria , Hatsell Sarah , Ehmann Peter , Marco Ainara Rodríguez , Bansal Ashish , Chen Zhen , Levy Stephane , Cyr Sonya L 
Published: August 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 &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.
691 - Understanding patient and physician preferences when choosing between biologic and oral systemic treatment options for moderate-to-severe atopic dermatitis: a discrete choice experiment
Authors: Puelles Jorge , Arija Pablo , Durno Nicholas , Pantiri Krystallia , Subramanian Ramkumar , Jack Katrin , Chambenoit Olivier , Boeri Marco , van Hout Ben , Silverberg Jonathan I 
Published: August 2024

Abstract

Background
A growing number of treatment options are becoming available for moderate-to-severe atopic dermatitis (AD), including biologic therapies. As these treatments have different efficacy, safety, and tolerability profiles, it is important to understand patient and physician preferences for informed treatment decision making.

Objective
To discover the importance of different attributes, including efficacy, safety, and mode of administration, and to provide insights into whether patient preferences concur or conflict with those of physicians.

Methods
We conducted a cross-sectional, online discrete choice experiment involving 306 patients with AD and 206 physicians in the UK and Germany. Qualitative interviews identified key attributes influencing treatment preferences, including efficacy (itch relief, sleep disturbance, time-to-itch relief, and total body surface area affected by eczema), safety (special warnings and risks of eye problems and shingles), and treatment administration. Data were analyzed using a random parameters logit model to calculate the conditional relative importance of each attribute.

Results
Both groups placed significant emphasis on efficacy, with reducing sleep disturbance ranking first for patients and second for physicians and itch ranking first for physicians and second for patients. Time to itch relief was the third most important efficacy attribute for both groups, although it was more important for patients. For both groups, the risk of eye problems was the most important safety concern. The mode of administration was not considered of great importance when compared with efficacy and safety attributes.

Conclusions
Our findings suggest patients prioritize sleep disturbance, an attribute not captured in other preference studies in AD, and itch. This emphasizes the importance of addressing sleep-related issues and itching to enhance patients’ well-being. The findings offer insights for prioritization strategies among healthcare providers, aiming to improve patient outcomes amidst a growing number of AD treatments.