bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of a digital exercise programme in health services to prevent falls in older people
Authors: Taylor Morag E , Ambrens Meghan , Hawley-Hague Helen , Todd Christopher , Close Jacqueline C T , Lord Stephen R , Clemson Lindy , Lung Thomas , Berlowitz David , Blennerhassett Jannette , Dayhew Julia , Gluchowski Ashley , Hodge Wendy , Johnson Pamela , Lasrado Reena , Merlene Marita , Miles Lillian , O’Rourke Sandra , Said Catherine M , White Leanne , Wilson Nicola , Zask Avigdor , Delbaere Kim
Published: August 2024

Background

StandingTall uses eHealth to deliver evidence-based balance and functional strength exercises. Clinical trials have demonstrated improved balance, reduced falls and fall-related injuries and high adherence. This study aimed to evaluate the implementation of StandingTall into health services in Australia and the UK.

Methods

Two hundred and forty-six participants (Australia, n = 184; UK, n = 62) were recruited and encouraged to use StandingTall for 2 h/week for 6-months. A mixed-methods process evaluation assessed uptake and acceptability of StandingTall. Adherence, measured as % of prescribed dose completed, was the primary outcome.

Results

The study, conducted October 2019 to September 2021 in Australia and November 2020 to April 2022 in the UK, was affected by COVID-19. Participants’ mean age was 73 ± 7 years, and 196 (81%) were female. Of 129 implementation partners (e.g. private practice clinicians, community exercise providers, community service agencies) approached, 34% (n = 44) agreed to be implementation partners. Of 41 implementation partners who referred participants, 15 (37%) referred ≥5. Participant uptake was 42% (198/469) with mean adherence over 6 months being 41 ± 39% of the prescribed dose (i.e. 39 ± 41 min/week) of exercise. At 6 months, 120 (76%) participants indicated they liked using StandingTall, 89 (56%) reported their balance improved (moderately to a great deal better) and 125 (80%) rated StandingTall as good to excellent. For ongoing sustainability, health service managers highlighted the need for additional resources.

Conclusions

StandingTall faced challenges in uptake, adoption and sustainability due to COVID-19 and a lack of ongoing funding. Adherence levels were lower than the effectiveness trial, but were higher than other exercise studies. Acceptance was high, indicating promise for future implementation, provided sufficient resources and support are made available.

Trial registration

Australian and New Zealand Clinical Trials Registry ACTRN12619001329156.
The role of the World Guidelines for Falls Prevention and Management’s risk stratification algorithm in predicting falls: a retrospective analysis of the Osteoarthritis Initiative
Authors: Ragusa Francesco Saverio , Di Bella Giovanna , Dominguez Ligia J , Veronese Nicola , Smith Lee , Barbagallo Mario
Published: August 2024

Introduction

Recurrent falls are observed frequently among older people, and they are responsible for significant morbidity and mortality. The aim of the present study was to verify sensitivity, specificity and accuracy of World Guidelines for Falls Prevention and Management (WGFPM) falls risk stratification algorithm using data from the Osteoarthritis Initiative (OAI).

Methods

Participants aged between 40 and 80 years were stratified as ‘low risk’, ‘intermediate risk’ or ‘high risk’ as per WGFPM stratification. Data from the OAI cohort study were used, a multi-centre, longitudinal, observational study focusing primarily on knee osteoarthritis. The assessment of the outcome was carried out at baseline and during the follow-up visit at 24 months. Data about sensitivity, specificity and accuracy were reported.

Results

Totally, 4796 participants were initially included. Participants were aged a mean of 61.4 years (SD = 9.1) and were predominantly women (58.0%). The population was divided into three groups: low risk (n = 3266; 82%), intermediate risk (n = 25; 0.6%) and high risk (n = 690; 17.3%). WGFPM algorithm applied to OAI, excluding the intermediate-risk group, produced a sensitivity score of 33.7% and specificity of 89.9% for predicting one or more falls, with an accuracy of 72.4%.

Conclusion

In our study, WGFPM risk assessment algorithm successfully distinguished older people at greater risk of falling using the opportunistic case finding method with a good specificity, but limited sensitivity, of WGFPM falls risk stratification algorithm.
Policies and indicators to operationalize structural racism for quantitative health research
Authors: Ali Talha , Allgood Kristi L , Needham Belinda , Ro Annie , Hirschtick Jana L , Fleischer Nancy L
Published: August 2024

The field of structural racism is developing rapidly, with researchers moving from commentaries and review papers toward empirical research that aims to quantify the impact of exposure to structural racism on racial and ethnic inequities in health. Despite the increasing recognition of the impact of structural racism on health outcomes, its measurement in the empirical literature has focused on a limited set of area-based measures. We propose 2 ways to expand the measurement of structural racism in public health research: first, by situating indicators of structural racism within the broader context of discriminatory policies that gave rise to racial and ethnic inequities; and second, by broadening the range of area-level indicators of structural racism beyond what has been used in the extant literature. We provide practical tools, including an extensive list of discriminatory federal policies, a list of common and novel indicators of structural racism across multiple domains, and an applied example showing how to connect policies and indicators of structural racism. These tools will aid researchers in developing a robust empirical evidence base to examine the role of structural racism in long-standing health inequities and advance quantitative research on the impact of structural racism on health inequities.
Racial disparities in maternal exposure to ambient air pollution during pregnancy and prevalence of congenital heart defects
Authors: Arogbokun Knutson Olufunmilayo C , Luben Thomas J , Stingone Jeanette A , Engel Lawrence S , Martin Chantel L , Olshan Andrew F
Published: August 2024

Air pollution may be a potential cause of congenital heart defects (CHDs), but racial disparities in this association are unexplored. We conducted a statewide population-based cohort study using North Carolina birth data from 2003 to 2015 (n = 1 225 285) to investigate the relationship between air pollution and CHDs (specifically pulmonary valve atresia/stenosis, tetralogy of Fallot [TOF], and atrioventricular septal defect [AVSD]). Maternal exposure to particulate matter ≤ 2.5 μm in diameter (PM2.5) and ozone during weeks 3 to 9 of pregnancy were estimated using the Environmental Protection Agency’s Downscaler Model. Single- and co-pollutant log-binomial models were created for the entire population and stratified by race to investigate disparities. Positive associations between PM2.5 and CHDs were observed. An increasing concentration-response association was found for PM2.5 and TOF in adjusted, co-pollutant models (quartile 4 prevalence ratio: 1.46; 95% CI, 1.06-2.03). Differences in the effect of PM2.5 on CHD prevalence were seen in some models stratified by race, although clear exposure-prevalence gradients were not evident. Positive associations were also seen in adjusted, co-pollutant models of ozone and AVSD. Study results suggest that prenatal PM2.5 and ozone exposure may increase the prevalence of certain CHDs. A consistent pattern of differences in association by race/ethnicity was not apparent.

This article is part of a Special Collection on Environmental Epidemiology.
Site-specific cancer mortality after low-level exposure to ionizing radiation: findings from an update of the International Nuclear Workers Study (INWORKS)
Authors: Richardson David B , Laurier Dominique , Leuraud Klervi , Gillies Michael , Haylock Richard , Kelly-Reif Kaitlin , Bertke Stephen , Daniels Robert D , Thierry-Chef Isabelle , Moissonnier Monika , Kesminiene Ausrele , Schubauer-Berigan Mary K
Published: August 2024

A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309 932 nuclear workers employed in France, the United Kingdom, and the United States were monitored for external radiation exposure. Associations of radiation with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28 089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers. Negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy = 0.65; 95% credible interval [CrI], 0.24-1.07), prostate (ERR per Gy = 0.44; 95% CrI, −0.06 to 0.91), and colon cancer (ERR per Gy = 0.53; 95% CrI, −0.07 to 1.11). The results contribute evidence regarding associations between low-dose radiation and cancer.
Nutritional convergence in plants growing on gypsum soils in two distinct climatic regions
Authors: Muller Clare T , Cera Andreu , Palacio Sara , Moore Michael J , Tejero Pablo , Mota Juan F , Drenovsky Rebecca E
Published: August 2024

Background and Aims

Soil endemics have long fascinated botanists owing to the insights they can provide about plant ecology and evolution. Often, these species have unique foliar nutrient composition patterns that reflect potential physiological adaptations to these harsh soil types. However, understanding global nutritional patterns to unique soil types can be complicated by the influence of recent and ancient evolutionary events. Our goal was to understand whether plant specialization to unique soils is a stronger determinant of nutrient composition of plants than climate or evolutionary constraints.

Methods

We worked on gypsum soils. We analysed whole-plant nutrient composition (leaves, stems, coarse roots and fine roots) of 36 native species of gypsophilous lineages from the Chihuahuan Desert (North America) and the Iberian Peninsula (Europe) regions, including widely distributed gypsum endemics, as specialists, and narrowly distributed endemics and non-endemics, as non-specialists. We evaluated the impact of evolutionary events and soil composition on the whole-plant composition, comparing the three categories of gypsum plants.

Key Results

Our findings reveal nutritional convergence of widely distributed gypsum endemics. These taxa displayed higher foliar sulphur and higher whole-plant magnesium than their non-endemic relatives, irrespective of geographical location or phylogenetic history. Sulphur and magnesium concentrations were mainly explained by non-phylogenetic variation among species related to gypsum specialization. Other nutrient concentrations were determined by more ancient evolutionary events. For example, Caryophyllales usually displayed high foliar calcium, whereas Poaceae did not. In contrast, plant concentrations of phosphorus were mainly explained by species-specific physiology not related to gypsum specialization or evolutionary constraints.

Conclusions

Plant specialization to a unique soil can strongly influence plant nutritional strategies, as we described for gypsophilous lineages. Taking a whole-plant perspective (all organs) within a phylogenetic framework has enabled us to gain a better understanding of plant adaptation to unique soils when studying taxa from distinct regions.
Anatomical Trajectory of the Corrugator Supercilii Muscle in Koreans: Implications for Aesthetic and Clinical Practices
Authors: Park Hyun Jin , Paulsen Friedrich , Kim Hongtae , Hur Mi-Sun
Published: August 2024

Background

Understanding the attachment patterns of the corrugator supercilii (CS) muscle is vital for treatments designed to improve facial symmetry and functionality.

Objectives

The aim of this research was to elucidate the anatomical trajectory and intricate relationships of the CS within the upper face and midface, specifically focusing on its connections with the frontalis (FT) and orbicularis oculi (OOc) muscles.

Methods

The CS was examined in 41 specimens of embalmed adult Korean cadavers with microdissection, histological analyses, and microcomputed tomography, performing an in-depth exploration of its anatomical positioning and the intricate interactions with adjacent muscles.

Results

Some lower fibers of the CS extended to the upper orbital part of the OOc in 59.5% of cases, while the CS interdigitated or blended exclusively with the FT in 40.5% of cases. The fibers of the CS demonstrated diverse extensions toward the upper face and midface, exhibiting varied trajectories and lengths. Additionally, lower fibers of the CS extended to significant anatomical landmarks such as the OOc, malaris muscle, and the superficial musculoaponeurotic system (SMAS).

Conclusions

In this study, we demonstrate that precise understanding of the CS and its relationship with the FT and OOc is crucial for optimizing invasive or noninvasive treatment like botulinum toxin injection, SMAS lifting, and browplasty surgery. The extension of lower fibers of the CS to significant anatomical landmarks indicates complex interactions with adjacent facial structures, highlighting the necessity of detailed anatomical knowledge for clinical applications.
Stochastic EM algorithm for partially observed stochastic epidemics with individual heterogeneity
Authors: Bu Fan , Aiello Allison E , Volfovsky Alexander , Xu Jason
Published: August 2024

We develop a stochastic epidemic model progressing over dynamic networks, where infection rates are heterogeneous and may vary with individual-level covariates. The joint dynamics are modeled as a continuous-time Markov chain such that disease transmission is constrained by the contact network structure, and network evolution is in turn influenced by individual disease statuses. To accommodate partial epidemic observations commonly seen in real-world data, we propose a stochastic EM algorithm for inference, introducing key innovations that include efficient conditional samplers for imputing missing infection and recovery times which respect the dynamic contact network. Experiments on both synthetic and real datasets demonstrate that our inference method can accurately and efficiently recover model parameters and provide valuable insight at the presence of unobserved disease episodes in epidemic data.
603 - Ruxolitinib cream 1.5% twice daily for the treatment of extensive atopic dermatitis in children aged 2–11 years: 52 week results from a maximum-use trial
Authors: Bissonnette Robert , Lee Mark S , Forman Seth B , Gold Linda Stein , Kallender Howard , Angel Brett , Kuo Yutzu , Paller Amy S
Published: August 2024

Background

Eight-week safety and tolerability, efficacy, and limited systemic absorption of ruxolitinib cream 1.5% in an open-label, single-arm, maximum-use trial (MUsT) of children with moderate to severe atopic dermatitis (AD; NCT05034822) were previously described. This is the first report of longer-term data from the same study.

Objectives

Data on tolerability, safety, systemic exposure, and clinical and patient-reported outcomes are presented from the entire 52-week treatment period to assess whether clinical benefits and tolerability observed through Week 8 are sustained during the as-needed treatment long-term safety period through Week 52.

Methods

In this open-label, single-arm MUsT, patients 2-11 years old with AD ≥3 months, ≥35% affected body surface area (BSA), and Investigator’s Global Assessment (IGA) ≥3 applied twice-daily ruxolitinib cream 1.5% for 4 weeks to baseline lesions, then as-needed to active lesions for 4 weeks; patients could continue into the as-needed 44-week long-term safety period.

Results

This MUsT included 29 patients with moderate to severe AD. Treatment-emergent adverse events through Week 52 occurred in 31.0% of patients. One patient (3.4%) had 2 treatment-related application site reactions (paresthesia and folliculitis); no adverse events resulted in treatment interruption/discontinuation; none were serious or suggested systemic Janus kinase (JAK) inhibition. Through the 4-week continuous-use twice-daily treatment period, the mean (SD) application quantity was 8.5 (6.29) g/day, which was associated with a mean steady-state ruxolitinib plasma concentration of 98.2 nM, well below half-maximal concentration of JAK–mediated myelosuppression in adults (281 nM). From Week 8 to Week 52 (as-needed use), mean (SD) application quantity was 3.2 (2.79) g/day, consistent with lower, as-needed use in this long-term safety period. At Weeks 4 and 52 (assessed in n=26 and n=13 patients, respectively), 53.8%/53.8% achieved IGA–Treatment Success (IGA 0/1 with ≥2-grade improvement from baseline). Mean BSA decreased from 58.0% (range, 35.0%–92.0%) at baseline (n=29) to 11.4% at Week 4 and continued to decrease to 2.2% through Week 52 (n=26 and n=14, respectively). Patient-reported outcomes, such as the Patient-Oriented Eczema Measure, Children's Dermatology Life Quality Index, and Infants' Dermatitis Quality of Life Index, were collected through Week 52.

Conclusions

Ruxolitinib cream 1.5% demonstrated consistently good tolerability and safety over 52 weeks in children aged 2 to 11 years with extensive moderate to severe AD. Rapid lesion clearance over 4 weeks with twice-daily therapy, which was sustained with longer-term as-needed use associated with low quantities of ruxolitinib cream being applied, may address application burden concerns.
630 - Efficacy comparison of targeted systemic monotherapies including lebrikizumab for moderate-to-severe atopic dermatitis: a network meta-analysis
Authors: Silverberg Jonathan I , Bieber Thomas , Paller Amy , Beck Lisa A , Kamata Masahiro , Puig Luis , Wiseman Marni , Ezzedine Khaled , Foley Peter , Johansson Erin , Dossenbach Martin , Akmaz Bülent , Casillas Marta , Karlsson Andrei , Chovatiya Raj
Published: August 2024

Introduction

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting 2–7% of adults globally, with 30% experiencing moderate-to-severe disease. Although several treatments for moderate-to-severe AD are available, the efficacy of many treatments has not been compared in head-to-head trials.

Objectives

Using a network meta-analysis (NMA), we evaluated the relative efficacy between lebrikizumab, an emerging biologic, and approved targeted systemic treatments for AD.

Methods

Double-blind, randomized, placebo-controlled clinical trials (systemic monotherapy-only) for moderate-to-severe AD in adults (≥18 years) and adolescents (≥12 years to ≤18 years) published before April 2023 were identified in a systematic literature review. Data were extracted for short-term (12–16 weeks) efficacy outcomes (Investigator’s Global Assessment [IGA] 0/1 with ≥2-point improvement from baseline and the Eczema Area and Severity Index [EASI]) and patient-reported outcomes (Pruritus Numeric Rating Scale [NRS] with ≥4-point improvement from baseline). Bayesian NMAs were performed using random-effects models, with baseline-risk adjustment. Key estimates from the NMAs included pairwise differences between all treatments and absolute response rates for each treatment.

Results

Twenty-two clinical trials were included. For % achieving IGA 0/1, at 12–16 weeks, the estimated response rates (posterior median and 95% credible interval) for each of the treatments were: upadacitinib 30 mg 55.8% (43.7–64.2%), upadacitinib 15 mg 41.3% (30.1–50.0%), abrocitinib 200 mg 39.0% (29.8–47.8%), dupilumab 300 mg 31.8% (23.1–38.7%), lebrikizumab 250 mg 31.4% (24.1–39.2%), abrocitinib 100 mg 24.5% (17.5–32.0%), tralokinumab 300 mg 17.3% (12.8–22.2%), baricitinib 4 mg 16.7% (9.8–25.5%), baricitinib 2 mg 15.5% (9.6–22.0%), and placebo 6.0% (4.3–7.3%). Similar trends were observed for the EASI and pruritus NRS responses at 12–16 weeks.

Conclusions

This 16-week NMA shows that lebrikizumab had a similar response rate to dupilumab, the most widely used targeted systemic therapy for AD, and may represent a valuable treatment option for moderate-to-severe AD.
634 - Patient-reported outcomes and safety in adolescent and adult atopic dermatitis patients treated with dupilumab: real-world insights one year into the GLOBOSTAD multinational prospective observational study
Authors: Murrell Dédée F , Ferrucci Silvia M , Foti Caterina , Perez-Garcia Bibiana , Lapeere Hilde , Calzavara-Pinton Piergiacomo , Fougerousse Anne-Claire , Wu Jiangming , Ardeleanu Marius , Bosman Kwinten
Published: August 2024

Introduction

The GLOBOSTAD study aims to capture long-term dupilumab effectiveness in real-world atopic dermatitis (AD) treatment.

Objective

To present patient-reported outcomes, that complement clinical AD assessments and guide healthcare decision-making, and a summary of adverse events one year after dupilumab initiation.

Methods

The GLOBOSTAD five-year, multinational, prospective, observational study (NCT03992417) enrolled patients aged ≥12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N = 955; data cutoff: March 2023) and follow-up (N = 903) populations.

Results

758/863/705 patients completed ≥1 follow-up assessment at 3M/6M/12M, respectively. During the study, patients reported rapid improvements in mean (SD) patient-oriented eczema measure from 19.7 (6.4) at baseline to 8.7 (6.6) at 3M to 7.1 (5.8) at end of observation period (12M); pruritus numerical rating scale from 6.3 (2.2) to 2.5 (2.4) to 1.7 (2.0); scoring of atopic dermatitis sleep loss score from 5.6 (3.0) to 1.7 (2.3) to 1.0 (1.8); dermatology life quality index (DLQI) from 13.7 (7.1) to 5.3 (5.1) to 3.9 (4.2); and children’s DLQI from 12.2 (6.2) to 2.7 (2.9) to 4.8 (4.8). Adverse events considered related to dupilumab by the investigator were reported in 187 (19.6%) patients. Adverse events leading to permanent dupilumab discontinuation were reported in 23 (2.4%) patients.

Conclusion

On initiating dupilumab treatment, patients reported rapid improvements in skin lesions, itch, sleep, and overall quality of life, from severe/very large effect scores to mild/small effect scores, which were sustained for up to one year. Safety data were consistent with previous studies.
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: Simpson Eric , Boguniewicz Mark , Eichenfield Lawrence , Gonzales Mercedes E , Hebert Adelaide A , Prajapati Vimal H , Gooderham Melinda , Krupa David , Chu David H , Higham Robert C , Berk David R
Published: August 2024

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<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<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<0.0001] and −47.9% vs. −22.9% [P<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.
648 - Response to ritlecitinib with or without narrow band ultraviolet B (nbUVB) add-on therapy in patients with active non-segmental vitiligo (NSV)
Authors: Yamaguchi Yuji , Peeva Elena , Adiri Roni , Ghosh Pranab , Napatalung Lynne , Hamzavi Iltefat , Pandya Amit G , Shore Ronald N , Ezzedine Khaled , Guttman-Yassky Emma
Published: August 2024

Introduction/Background

Ritlecitinib, a JAK3/TEC family kinase inhibitor, demonstrated efficacy in a Phase 2b trial of patients with NSV.

Objectives

To evaluate the efficacy and tolerability of ritlecitinib with or without nbUVB add-on therapy in patients with NSV.

Methods

In a Phase 2b trial, following a 24-week placebo-controlled dose-ranging period, patients with NSV received ritlecitinib 200 mg for 4 weeks then 50 mg for 20 weeks, with or without nbUVB phototherapy 2x/week. Missing data were handled using observed case (OC) and last observation carried forward (LOCF).

Results

43 and 187 patients received ritlecitinib+nbUVB and ritlecitinib-monotherapy, respectively. Nine patients receiving ritlecitinib+nbUVB discontinued due to nbUVB group-specific efficacy criteria requiring >10% improvement in %change from baseline (CFB) in Total-Vitiligo Area Scoring Index (T-VASI) at Week 12. At Week 24, mean (90% CI) %CFB in Facial-VASI (F-VASI) was -69.6 (-79.1, -60.1) vs -55.1 (-59.4, -50.7) (OC; P=0.009) and -57.0 (-65.3, -48.7) vs -51.5 (-55.9, -47.1) (LOCF; P=0.158), for ritlecitinib+nbUVB vs ritlecitinib-monotherapy, respectively. 60.9% (43.1%, 77.2%) vs 29.2% (22.8%, 35.9%) (OC; P=0.007) and 44.4% (30.2%, 59.1%) vs 27.4% (21.7%, 33.4%) (LOCF; P=0.081) of patients, respectively, achieved ≥75% improvement in F-VASI. Mean (90% CI) %CFB in T-VASI at Week 24 was -46.8 (-54.5, -39.2) vs -24.5 (-28.1, -21.0) (OC; P<0.001) and -29.4 (-36.5, -22.2) vs -21.2 (-25.0, -17.4) (LOCF; P=0.043) for ritlecitinib+nbUVB vs ritlecitinib-monotherapy, respectively. 50.0% (33.3%, 66.7%) vs 15.2% (11.1%, 20.3%) (OC; P<0.001) and 32.6% (22.1%, 44.7%) vs 14.4% (10.6%, 19.0%) (LOCF, P=0.014) of patients, respectively, achieved ≥50% improvement in T-VASI. nbUVB addition to ritlecitinib was well-tolerated with no new safety signals.

Conclusions

Ritlecitinib alone and with nbUVB therapy improved facial and total body repigmentation and was well-tolerated. nbUVB may improve ritlecitinib efficacy.
650 - Stability of long-term therapeutic responses to tralokinumab in adults with moderate-to-severe atopic dermatitis
Authors: Blauvelt Andrew , Chih-ho Hong H , Peris Ketty , Katoh Norito , Tauber Marie , Ameen Mahreen , Gooderham Melinda , Øland Christian Bjerregård , Tindberg Ann-Marie , Gjerum Le , Reich Kristian
Published: August 2024

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&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.
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

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<0.001), HECSI-75 (49.4% vs. 20.9%; P<0.001), HECSI-90 (30.3% vs. 10.6%; P<0.001), and DLQI ≥4-point improvement (73.3% vs. 47.8%; P<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

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<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<0.001). The LS mean itch and pain reductions continued for delgocitinib cream-treated patients up to W16 (P<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<0.001) and onwards to W16 (delgocitinib cream: 47.2%; cream vehicle: 21.5%; P<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

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

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

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<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<0.001) and nemolizumab-Q8W (56.2%, p<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<0.0001) and nemolizumab-Q8W (58.6%, p<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<0.01) and nemolizumab-Q8W (56.8%, p<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

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 (>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

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: <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/>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%, <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/>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%, <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.