tbuckley/cabot-search huggingface dataset:
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: Andrew F Alexis, Leon Kircik, Raj Chovatiya, Zakiya P Rice, Tina Bhutani, Philip M Brown, Stephen C Piscitelli, David S Rubenstein, Anna M Tallman, April W Armstrong
Journal: British Journal of Dermatology (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 (&amp;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.
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: Andrea Bauer, Marie-Louise Schuttelaar, Keith Baranowski, Ursula Plohberger, Laura Sørensen, Margitta Worm
Journal: British Journal of Dermatology (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&amp;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&amp;lt;0.001). The LS mean itch and pain reductions continued for delgocitinib cream-treated patients up to W16 (P&amp;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&amp;lt;0.001) and onwards to W16 (delgocitinib cream: 47.2%; cream vehicle: 21.5%; P&amp;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: Sarah Brown, Emily Chastain, Kaylen Suryajaya, Sarah Feaver, Stephanie Harbers
Journal: British Journal of Dermatology (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.
711 - Prolonged half-life and sustained inhibition of key inflammatory biomarkers: a phase 1 study of APG777, a high-affinity humanized IgG1 monoclonal antibody targeting IL-13
Authors: Xiu Qin Lim, Erica Winter, Kristine Nograles, Sai Thankamony, Lukas Dillinger, Carl Dambkowski
Journal: British Journal of Dermatology (2024)

Abstract Introduction APG777 is a high-affinity humanized anti-IL-13 IgG1 monoclonal antibody (mAb) that blocks formation of the IL-13/IL-13Rα1/IL-4Rα complex, preventing receptor heterodimerization and downstream signaling. APG777 contains a triple amino acid modification, YTE, in the Fc region that extends half-life (t1/2) by increasing binding to neonatal Fc receptor. Objectives This is a report of initial results of the first study of APG777 in humans, including safety, pharmacokinetics (PK), and pharmacodynamics (PD). Methods This first-in-human, randomized, double-blind, placebo (PBO)-controlled trial evaluated safety, tolerability, PK, and PD of APG777 in healthy participants. The study was conducted in Australia and consisted of single ascending dose (SAD) and multiple dose (MD) cohorts. Participants received single subcutaneous (SC) doses up to 1200 mg in the SAD and repeat doses of 300 mg SC in the MD. Each cohort consisted of 8 participants randomized 6:2 to APG777 or PBO. Safety assessments were conducted throughout the study and blood draws for PK and PD were obtained at multiple timepoints. Results Forty participants were enrolled. To date, adverse events (AEs) were mild and generally unrelated to study drug. There were no serious AEs or dose-dependent trends. APG777 pharmacokinetics were dose proportional, with t1/2 of approximately 75 days. Single doses of APG777 resulted in sustained inhibition of pSTAT6 and TARC for 12 weeks, the longest available follow-up. Conclusions APG777 was well-tolerated at doses up to 1200 mg, similar to other IL-13-targeted mAbs. The t1/2 of APG777, due to its YTE modification, is approximately 3 times longer than currently available mAbs and PD assessments confirm sustained inhibition of key biomarkers of atopic dermatitis. The favorable safety profile and optimized PK of APG777 support the initiation of a phase 2 study in adults with moderate-to-severe atopic dermatitis where every 3- to 6-month maintenance dosing will be evaluated.
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: Jonathan I Silverberg, Andreas Wollenberg, Franz J Legat, Vivian T Laquer, Liliana Ulianov, Soo Yeon Cheong, Anna Ryzhkova, Christophe Piketty
Journal: British Journal of Dermatology (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&amp;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&amp;lt;0.001) and nemolizumab-Q8W (56.2%, p&amp;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&amp;lt;0.0001) and nemolizumab-Q8W (58.6%, p&amp;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&amp;lt;0.01) and nemolizumab-Q8W (56.8%, p&amp;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.
712 - Positive 52-week maintenance data observed with rademikibart in patients with moderate-to-severe atopic dermatitis (S<u>EASI</u>DE CHINA)
Authors: Jianzhong Zhang, Jonathan I Silverberg, Jiawang Guo, Jili Yun, Wuban Pan, Zheng Wei, Raúl Collazo
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Rademikibart (formally, CBP-201) is a next-generation optimized monoclonal antibody targeting the IL-4Rα subunit. Rademikibart achieved all Week 16 primary and secondary endpoints in a global Phase 2 atopic dermatitis (AD) trial (WW001; NCT04444752) and a pivotal trial in China (SEASIDE CHINA or CN002; NCT05017480)1 in patients with moderate-to-severe AD. Objectives Long-term treatment of atopic dermatitis is essential for continued symptom management, prevention of complications, and improvments in the patient's quality of life. In this report, we now report Stage 2, long-term 52-week data from the SEASIDE CHINA pivotal trial. Methods Adults (n=318) and adolescents (n=12) (IGA ≥3, EASI ≥16, BSA ≥10%, PP-NRS ≥4) were randomized (2:1) to rademikibart (300mg Q2W) or placebo for 16 weeks (Stage-1). EASI-50 responders, regardless of Stage-1 treatment, were re-randomized to Q2W (n=113) or Q4W rademikibart (n=112). Non-responders received open-label Q2W rademikibart (n=86). Results Initial baseline mean EASI was 29.3 (range, 16.0–72.0) with 54.7% IGA4 for Stage 1 responders and 23.7 (16.0-66.6) with 51.2% respectively for non-responders. In patients who achieved IGA 0/1, 76.0% (Q2W) and 87.2% (Q4W) maintained their response at Week 52. Similarly, 91.7% (Q2W) and 91.9% (Q4W) maintained their EASI-75 response. From Week 16 to Week 52, 28.2% (Q2W/Q2W; n=91) and 20.8% (Q2W/Q4W; n=91) additional patients achieved IGA 0/1, and 16.3% (Q2W/Q2W) and 11.0% (Q2W/Q4W) additional patients achieved EASI-75. Of patients with ≥4-point reduction in PP-NRS, 81.6% (Q2W) and 95.2% (Q4W) maintained that response at Week 52. A ≥5-point reduction on the DLQI was maintained by 93.4% (Q2W) and 90.0% (Q4W). For 26 rademikibart non-responders (Stage-1), EASI scores improved by 45% with 51.4% acheiving EASI-75 by Week 52. Treatment with rademikibart was generally well tolerated. Conclusion Maintenance data with rademikibart are compelling and build upon strong results shown in Stage 11. High rates of maintained efficacy with Q4W dosing, additional gains in efficacy with continued treatment, and maintenance of ciniically meaningful changes in pruitis and QOL were observed.
658 - IMG-007, a novel nondepleting anti-OX40 monoclonal antibody with Fc bioengineering, exhibited reduced safety risks: evidence from nonclinical studies
Authors: Chongtian Guo, Xiaotong Wu, Zi Lin, Yufang Lu
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Inflammatory T cell response is promoted by OX40, whose expression is increased in atopic dermatitis (AD). Targeting OX40 is a rational therapeutic strategy in treating AD. We hypothesized that an anti-OX40 monoclonal antibody (mAb) with a silenced antibody-dependent cell-mediated cytotoxicity (ADCC) function would have minimal T cell toxicities, thereby minimizing safety risks. IMG-007 is a novel nondepleting anti-OX40 mAb, bioengineered in its Fc region with a N297A mutation to abolish the ADCC function. Objectives To characterize the effects of a N297A mutation on the pharmacodynamic effect of IMG-007 in non-clinical studies. Methods The kinetics of IMG-007’s binding to recombinant human Fcg receptors was measured using surface plasmon resonance (SPR) Biacore 8K. The ADCC function was evaluated by measuring cytotoxicity to HEK293-OX40-Luc cells cocultured with primary human NK cells and antibody and quantified by flow cytometry. The cytokine release potential was assessed by incubating human peripheral blood mononuclear cells (PBMCs) with antibody under both solid and solution phases from 10 donors, followed with measurement of 10 cytokines in the culture supernatant using the Meso Scale Discovery (MSD) Proinflammatory Panel 1. Results IMG-007 exhibited a minimal binding affinity to Fcg receptors, including FcgRs I, IIA, IIIA (V176), IIIA (F176), IIB and IIIB. At up to the highest concentration tested, IMG-007 did not induce any antibody induced cytotoxicity to the OX40+ HEK293-Luc cells. Furthermore, it did not induce the release of all 10 proinflammatory cytokines tested in human PBMCs under both solid and solution testing formats. Conclusions Silencing ADCC function in IMG-007 via bioengineering resulted in minimal binding to the Fcg receptors and diminished cytotoxicity to OX40+ cells. IMG-007 represents a promising drug candidate for potentially treating AD.
673 - Efficacy of nemolizumab in different subgroups of patients with prurigo nodularis in two randomized, placebo-controlled phase 3 trials
Authors: Shawn G Kwatra, Martin Metz, Andrew E Pink, Gil Yosipovitch, Rola Gharib, Hema Sundaram, Xiaoxiao Chen, Aliene Noda, Zarif K Jabbar Lopez, Christophe Piketty, Sonja Ständer
Journal: British Journal of Dermatology (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 &amp; 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: &amp;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/&amp;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%, &amp;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/&amp;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%, &amp;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.
692 - Dupilumab reduces atopic dermatitis lesion severity and extent in children &amp;lt;12 years of age with moderate-to-severe AD: interim results from the PEDISTAD real-world registry
Authors: Lara Wine Lee, Alan D Irvine, Michele Ramien, Danielle Marcoux, Eulalia Baselga, Marlies de Graaf, Martti Antila, Nelson A Rosario Filho, Irene Lara-Corrales, Joel C Joyce, Rajan Gupta, Patrick Redman, Annie Zhang
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background In clinical trials, dupilumab has consistently improved disease severity in children with moderate-to-severe atopic dermatitis (AD). Objectives To investigate the impact of systemic treatments on the individual anatomical regions that comprise the Eczema Area and Severity Index (EASI). Methods PEDISTAD (NCT03687359) is an international, longitudinal, observational 10-year registry study of patients aged &amp;lt; 12 years with moderate-to-severe AD. This interim analysis reports mean Eczema Area and Severity Index (EASI) scores of the head and neck and upper limbs at therapy start and last observation. Results A total of 207 patients received dupilumab, 127 received methotrexate and 139 received cyclosporine. The mean observation period was 17.0 months, 18.7 months, and 14.3 months for dupilumab, methotrexate and cyclosporine respectively. Mean (SD) EASI scores for the head and neck area of dupilumab patients improved from 2.0 (0.2) at therapy start to 0.7 (0.1) at last observation. Improvement was also seen in patients receiving methotrexate (therapy start: 2.0 [0.2]; last observation: 1.0 [0.2]) and cyclosporine (therapy start: 2.2 [0.2]; last observation: 1.6 [0.2]. A numerically greater improvement in mean (SD) EASI scores of the upper limbs was observed in patients receiving dupilumab (therapy start: 4.5 [0.2]; last observation: 1.5 [0.2]) than methotrexate (therapy start: 3.8 [0.2]; last observation: 2.1 [0.2]) and cyclosporine (therapy start: 4.1 [0.2]; last observation: 2.9 [0.3]). Adverse events were experienced by 23.7%, 30.5% and 32.6% of patients receiving dupilumab, methotrexate and cyclosporine, respectively. Conclusion Children with moderate-to-severe AD receiving dupilumab, methotrexate, or cyclosporine had improvement in AD lesion severity and extent in individual anatomical regions, with the greatest numerical improvement observed in those receiving dupilumab.