tbuckley/cabot-search huggingface dataset:
679 - Rocatinlimab significantly improves clinical responses in patients with moderate-to-severe atopic dermatitis by week 2 in a randomized double-blind placebo-controlled phase 2b study
Authors: Emma Guttman-Yassky, Ehsanollah Esfandiari, Hirotaka Mano, Takahiro Arai, Kenji Kabashima
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Moderate-to-severe atopic dermatitis (msAD) can cause chronic cycles of pruritus and scratching, impacting quality of life. Objectives To evaluate rocatinlimab for the treatment of msAD To investigate the onset of action of rocatinlimab on pruritis Numerical Rating scale (pNRS) and Eczema Area and Severity Index (EASI) in adults with msAD Methods A multicenter, randomized, double-blind, placebo-controlled Phase 2b trial (NCT03703102) evaluated rocatinlimab (anti-OX40 monoclonal antibody) for msAD. Primary endpoint achievement (Percent change from baseline to week 16 in EASI) has been presented. Randomized patients (1:1:1:1:1) received subcutaneous rocatinlimab 150mg/600mg every 4 weeks (Q4W) or 300mg/600mg every 2 weeks (Q2W) for 36 weeks, or placebo (Weeks 0–18) followed by rocatinlimab (600mg Q2W Weeks 18–36). All cohorts had 20-week off-treatment follow-up. Results Clinical response onset with rocatinlimab was evaluated post-hoc (N=267; rocatinlimab: n=210; placebo: n=57) by investigating pNRS and EASI between baseline and Week 16. Difference in least squares mean of percent change from baseline between rocatinlimab cohorts and placebo were assessed. Pruritus was significantly improved with rocatinlimab by Week 2 in all cohorts (−18.40% to −21.96%; p≤0.018) except 600mg Q4W (−9.66%; p=0.208), and in all cohorts by Week 4 (−15.70% to −27.19%; p≤0.045); EASI improvements were significant in all rocatinlimab cohorts by Week 6 (−20.50% to −32.13%; p≤0.001) compared with placebo, and the 300mg and 600mg Q2W cohorts by Week 2 (−13.27% and −13.66%; p≤0.028). Further improvements with rocatinlimab continued to Week 16 compared with placebo; improvements from baseline continued in all active cohorts to Week 36 and were maintained for 20 weeks off-treatment, suggesting rocatinlimab may have potential for disease modification in adults with msAD. Conclusion Rocatinlimab improved pNRS and EASI by Week 2; improvements continued and were maintained off-treatment until the end of study.
719 - Modulating Nav1.8-expressing neurons offers promising direction to address symptoms of atopic dermatitis
Authors: Madeline C Scoles, Jacqueline C Wang, Winnie Sung, Mason Olivarez, Ellen Liu, Emmy Lev, Rishi B Shah, Seongmin Kim, Nihal Kaplan, Amy S Paller
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Atopic dermatitis (AD) is an inflammatory skin condition characterized by eczematous lesions, itch and pain. The inflammation and itch associated with AD are caused in part by dysregulation of neuroimmune circuits. Understanding these circuits is crucial for comprehending the pathophysiology of AD. Nav1.8 is a sodium channel expressed on C afferent fibers in the dorsal root ganglia (DRG). Knockdown of signaling pathways in Nav1.8+ nerves has been previously shown to reduce severity of AD in mice. Objectives We hypothesized that ablating Nav1.8 receptor-expressing neurons would lead to reduced severity of AD symptoms including itch and pain, and decreased expression of AD-related genes in a mouse model for AD. Methods Mice expressing iDTR (diphtheria toxin receptor) under the control of Nav1.8-Cre were used. Diphtheria toxin (DTX) was injected to ablate Nav1.8+ nerves and phosphate-buffered saline (PBS) was injected as a control. We achieved AD-like symptoms in both Nav1.8-ablated mice and control mice using topically-applied MC903 to mouse shaved nape skin. Results We noted no obvious clinical differences between Nav1.8-ablated mice and control mice skin. We found that Nav1.8+ ablation resulted in a ∼70% (p&amp;lt;0.05) reduction in scratching behavior and ∼40% (p=0.05) reduction in pain-related behaviors compared to control mice with intact Nav1.8. Nav1.8-nerve ablation similarly resulted in reduced expression of Tac1 (substance P – a neuropeptide known to mediate itch signaling) (p&amp;lt;0.05) and Il31ra (an itch-related cytokine receptor) (p&amp;lt;0.05) in Nav1.8-ablated mouse DRG tissue. However, we see no changes in expression of AD-related cytokines in Nav1.8-ablated nape skin tissue compared to control skin, including Il4, Il13, Il31, and Tslp. Conclusions These results suggest that Nav1.8-expressing neurons play a key role in the itch and pain associated with AD, but may have no effect on AD-induced cutaneous inflammation. These findings could offer a promising new direction for further research into treatments targeting the itch and pain caused by AD.
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: Jonathan I Silverberg, Andreas Wollenberg, Franz J Legat, Vivian T Laquer, April W Armstrong, Pedro Herranz, Luigi Naldi, Faiz Ahmad, Liliana Ulianov, Christophe Piketty
Journal: British Journal of Dermatology (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.
725 - The TCS/TCI-free rate remains high and stable while on lebrikizumab for treatment of moderate-to-severe atopic dermatitis over 1 year
Authors: James Del Rosso, Audrey Nosbaum, Alexandra Golant, Takeshi Nakahara, Jenny E Murase, Andrew Pink, Sonia Montmayeur, Meihua Qiao, Sherry Chen, Ignasi Pau-Charles, Thomas Bieber
Journal: British Journal of Dermatology (2024)

Abstract Background The ADvocate1 and ADvocate2 phase 3 trials investigated lebrikizumab (LEB), a monoclonal antibody selectively targeting interleukin-13, for the treatment of patients with moderate-to-severe atopic dermatitis (AD). Topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) are commonly used as concomitant treatment for AD. However, long term use can result in side effects. Thus, remaining free of TCS/TCI usage is important for evaluating the benefit of systemic AD therapies. Objectives To summarize and assess the proportion of patients without TCS or TCI usage over the course of the maintenance period based on pooled ADvocate1 and ADvocate2 studies. Methods This study consisted of pooled ADvocate1 and ADvocate2 data for patients responding to LEB at week 16 (induction period). Responders (N = 291) were re-randomized in a 2:2:1 ratio to receive 250 mg LEB every 2 weeks (Q2W; N = 113), 250 mg LEB every 4 weeks (Q4W; N = 118), or placebo every 2 weeks (LEB withdrawal/PBO; N = 60) for 36 weeks (maintenance period). Lack of TCS/TCI use was interpreted as an advantageous outcome of LEB treatment. Data are presented as observed data. Results Across the maintenance period, high proportions of patients in all groups (Q2W – 90.3%; Q4W – 88.1%; PBO – 86.7%) did not use TCS. Higher proportions (Q2W – 96.5%; Q4W – 98.3%; PBO – 95%) did not use TCI. Importantly, 88.5% of Q2W, 86.4% of Q4W, and 81.7% of PBO, did not use either TCS or TCI. This high TCS/TCI free rate remained stable over the course of the maintenance period. Conclusions Most patients with moderate-to-severe AD responding to LEB remained free of TCS, TCI, and TCS/TCI use throughout the first year of treatment.
728 - Evaluation of risk factors for dupilumab-associated ocular sequelae in the treatment of atopic dermatitis
Authors: Varsha Reddy, Alexa Lum, Katerina Kitsios, Swarna Shil, Alanna Nattis
Journal: British Journal of Dermatology (2024)

Abstract Background Dupilumab is a monoclonal antibody that inhibits IL-4 and IL-13 signaling. It is used in the treatment of moderate-to-severe atopic dermatitis in those 6 months or older who are uncontrolled on or cannot tolerate topical treatments. Ocular surface disease is a recognized adverse effect of dupilumab use that has been highlighted in previous studies. Few studies describe the risk factors for developing such ocular adverse effects. Objectives This study aims to highlight the risk factors associated with the development of dupilumab-associated ocular surface disease (DAOSD) described in the literature. Methods The PubMed and ScienceDirect databases were searched in April 2024 using key search terms including “dupilumab”, “demographics”, “risk factors”, “ocular”, “keratitis”, “conjunctivitis”, “side effects”, and “atopic dermatitis”. Nine articles were included after deduplication, title/abstract screening, full-text review, and quality appraisal. Studies were included if they were written in English and discussed risk factors for ocular side effects of dupilumab. Studies were excluded if they discussed other biologic agents or ocular conditions of other origins. Results Out of the nine studies analyzed, six described prior history of ocular disease as a risk factor for developing DAOSD. Severe atopic dermatitis was highlighted as a risk factor in five out of nine studies. Elevated total IgE levels and eosinophil count were described as risk factors in four out of nine studies. Three studies cited facial or eyelid eczema and two studies highlighted family history of atopy as having an association with the development of DAOSD. One study described high levels of chemokines, as well as personal history of other atopic conditions. At least one patient needing to discontinue treatment with dupilumab due to ocular side effects was mentioned in six out of nine studies. Seven out of nine studies included a recommendation for ophthalmological evaluation prior to or during treatment with dupilumab. Conclusions While the etiology of DAOSD is not fully understood, past studies have elucidated potential risk factors for its development. Patients being treated with dupilumab for atopic dermatitis have higher severity or refractory disease, and the discontinuation of treatment due to ocular side effects may have implications on the quality of life of these patients. Additional studies are needed to better understand the risk factors for DAOSD and prevent further complications. Limitations include small sample size and lack of control group in some studies, inclusion of studies in non-US countries, and lack of gender and racial representation in some studies.
628 - Clinical measures of improvement in atopic dermatitis are correlated with reductions in relevant biomarkers in patients treated with lebrikizumab
Authors: Emma Guttman-Yassky, Angela Okragly, Zhe Sun, Brian J Nickoloff, Chitra R Natalie, Gaia Gallo, Eric Wolf, Kilian Eyerich, Monica Aparici, Robert J Benschop
Journal: British Journal of Dermatology (2024)

Abstract Introduction In ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), lebrikizumab demonstrated statistical superiority vs. placebo in patients with moderate-to-severe atopic dermatitis (AD). The objective of this analysis is to test for correlations between improvements in clinical outcomes and reductions in AD-relevant serum biomarkers during ADvocate1 and ADvocate2. Objectives To assess the correlation between clinical measures of atopic dermatitis (AD) and AD-specific biomarkers at baseline; and to assess the correlation between clinical measures of AD and changes in AD-specific biomarkers after treatment with lebrikizumab. Methods Full details of these studies were previously reported. Protein biomarkers were determined in available serum samples from patients receiving lebrikizumab 250 mg every 2 weeks (n=72) or placebo (n=36). Tested biomarkers included: IL-13 (baseline only), CCL2, CCL4, CCL11, CCL13, CCL17 (TARC), CCL22, CCL26 (eotaxin-3), CXCL10, total IgE, IL-4, IL-5, and periostin. Baseline biomarker levels and baseline clinical endpoints were compared using a Spearman correlation. A repeated measures correlation analysis was used to characterize paired measurement of within-patient biomarker levels and clinical endpoints at baseline, week 4, week 16, and week 52. Clinical measures of AD included Investigator’s Global Assessment (IGA), Eczema Area and Severity Index (EASI), and Pruritus Numeric Rating Scale (NRS). Results At baseline, EASI score was positively correlated with IL-13, periostin, IL-5, IgE, CCL13, CCL17, CCL22 and CCL26 (correlation coefficient&amp;gt;0.3, p&amp;lt;0.05), but not IL-4. During the studies, improvements in EASI, IGA, and Pruritus NRS were each correlated with reductions in periostin, CCL13, CCL17, CCL22, and CCL26 (correlation coefficient&amp;gt;0.3, p&amp;lt;0.05). Improvement in IGA was also correlated with a reduction in IgE (correlation coefficient&amp;gt;0.3, p&amp;lt;0.05). Conclusions Clinical measures of improvement in the signs and symptoms of AD are correlated with reductions in AD biomarkers in patients treated with lebrikizumab.
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: Jorge Puelles, Pablo Arija, Nicholas Durno, Krystallia Pantiri, Ramkumar Subramanian, Katrin Jack, Olivier Chambenoit, Marco Boeri, Ben van Hout, Jonathan I Silverberg
Journal: British Journal of Dermatology (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.
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: Robert Bissonnette, Mark S Lee, Seth B Forman, Linda Stein Gold, Howard Kallender, Brett Angel, Yutzu Kuo, Amy S Paller
Journal: British Journal of Dermatology (2024)

Abstract 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.
731 - Quality of life in atopic dermatitis: the patient perspective
Authors: Victoria Jiminez, Michaela Crawford, Tiffany Mayo
Journal: British Journal of Dermatology (2024)

Abstract Introduction Atopic Dermatitis (AD) is a cutaneous disease affecting all ages and demographics. Even in an era of biological treatments, many patients continue to struggle with disease factors that influence their overall quality of life. Objectives This study aims to highlight perceived influential factors related to QOL in atopic dermatitis from patient-reported experiences. Methods This study is an IRB-approved cross-sectional survey of patients with a diagnosis of atopic dermatitis at a single academic institution. The survey was conducted via phone calls. Patients were asked to self-report information related to their diagnosis, comorbidities, residential community, and factors that contribute to quality of life. Statistical analysis was performed with SPSS. Results Sixty-four patients agreed to participate in the survey, with a response rate of 78%. Responders were mostly female (55%) with a mean age of 41 and were racially diverse (White/Caucasian) 48%, Black or African American 36%, and Asian or Asian American 16%). Self-reported disease severity was labeled as mild (17%), moderate (33%), or severe (50%). Many patients had psychiatric comorbidities (anxiety 39%, depression 22%). Subjective feelings of being less attractive or less confident due to AD were significant on logistic regression in those with severe disease (p=0.048, OR 2.78, CI (1.0-7.6) and female gender (p=0.007). The severe group also reported experiencing prior judgment or discrimination (63%) and felt their work or school performance had been affected by their AD (47%), more commonly in males (p=0.026). Differences in race were not significant. Most patients reported itch as being the most bothersome symptom (66%). When asked to choose the top factors contributing to their quality of life related to their AD, symptom burden was the most common (88%) followed by time spent obtaining medical care (45%), and treatment regimen difficulty (39%). More than one in every ten patients (16%) reported that their life goals or dreams had been affected by their disease. Conclusion The psychosocial implications of atopic dermatitis remain a significant barrier to patient-perceived quality of life. While symptomatic management remains a large proponent of barriers to QOL improvement, perceived stigmatization anecdotally affects those with AD to a significant degree. Further studies and interventions are needed to discern specific areas of improvement for QOL in atopic dermatitis.