Dermatology and Therapy最新文献

{"title":"Efficacy of a Multi-lamellar Emulsion Containing a Synthetic Sphingosine Kinase 1 Activator and Pseudoceramide in Patients with Atopic Dermatitis: A Randomized Controlled Trial.","authors":"So Yeon Lee, Jin Seo Park, Daehwan Kim, Wonseok Jeong, Chenghwan Hwang, Hye One Kim, Chun Wook Park, Bo Young Chung","doi":"10.1007/s13555-024-01254-5","DOIUrl":"10.1007/s13555-024-01254-5","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with atopic dermatitis (AD) have impaired barrier function, which decreases skin hydration, weakens their defense against microorganisms, and culminates in increased inflammatory responses. Here, we conducted a clinical trial to evaluate the efficacy of a multi-lamellar emulsion (MLE) containing the pseudoceramide PC-9S and a synthetic sphingosine kinase 1 (SPHK1) activator, Defensamide™, in improving mild-to-moderate atopic dermatitis.</p><p><strong>Methods: </strong>Forty patients aged ≥ 2 years were randomized into a combined-therapy group treated with the MLE containing PC-9S and Defensamide™ plus a topical corticosteroid and a topical-corticosteroid-only group. Assessments based on therapeutic methods included the Eczema Area and Severity Index (EASI), the Investigator Global Assessment (IGA), transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin dryness, a visual analogue scale (VAS) of itchiness, a VAS of sleep disturbance, patient satisfaction, and the Dermatology Life Quality Index (DLQI).</p><p><strong>Results: </strong>Thirty-eight patients completed this study. In the combined-therapy group, significant improvements in clinical and instrumental measures such as EASI scores, skin hydration, and skin dryness were noted at 4 weeks compared to baseline, but such improvements were not noted in the topical corticosteroid-only group. Subjective assessments of itching and sleep disturbance and DLQI scores also showed significant improvements in the combined-therapy group.</p><p><strong>Conclusion: </strong>Combined therapy with the MLE containing Defensamide™ and PC-9S and with topical corticosteroid demonstrated superior clinical outcomes compared with topical corticosteroid monotherapy. Our findings underscore the potential of MLE-containing formulations as effective adjunctive therapies for AD, offering both objective and subjective symptomatic relief and enhancing patients' quality of life.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2591-2605"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Interim Report of a Phase 3, Long-Term, Open-Label Study to Evaluate Efficacy and Safety of Difamilast Ointment in Japanese Infants with Atopic Dermatitis.","authors":"Hidehisa Saeki, Yukihiro Ohya, Naoko Baba, Tomomi Imamura, Daisuke Yokota, Hidetsugu Tsubouchi","doi":"10.1007/s13555-024-01236-7","DOIUrl":"10.1007/s13555-024-01236-7","url":null,"abstract":"<p><strong>Introduction: </strong>Difamilast is the first selective phosphodiesterase 4 inhibitor approved for atopic dermatitis (AD) in Japan. A phase 3, 52-week, open-label study is ongoing to establish efficacy and safety of difamilast ointments in infants with AD aged 3 to < 24 months because a clinical study has not been conducted in this population.</p><p><strong>Methods: </strong>This study consisted of a 4-week primary evaluation period in which difamilast 0.3% ointment was applied twice daily to Japanese infants aged 3 to < 24 months (n = 41) and an ongoing 48-week long-term extension period in which difamilast 0.3% or 1% ointment was applied based on existing symptoms. The data on efficacy and safety of difamilast were obtained as of an interim report in the study period.</p><p><strong>Results: </strong>The response rate in Investigator's Global Assessment score was 45.0% at week 1, which was maintained at 56.1% at week 4 and 63.4% at the interim report. Infants achieved the response rate in Eczema Area and Severity Index 75 (improvement of ≥ 75%) of 47.5% at week 1, which further improved to 82.9% at week 4 and 78.1% at the interim report. Adverse events (AEs) were reported in 22 (53.7%) infants in the primary evaluation period: of those the most frequent AE was nasopharyngitis (19.5%) followed by dermatitis contact (7.3%). As of the interim report, 36 (87.8%) infants experienced AEs: of those, nasopharyngitis (70.7%) and gastroenteritis (22.0%) were most frequently observed. The total AEs were mostly mild or moderate in severity. No investigational medicinal product-related AEs and no AEs leading to discontinuation were reported.</p><p><strong>Conclusion: </strong>Difamilast ointments applied twice daily to Japanese infants with AD aged 3 to < 24 months is effective and well tolerated as of the interim report in the study period. The final results will be reported in the near future.</p><p><strong>Clinical trial registration: </strong>Clinical Trials. gov identifier: NCT05372653.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2443-2455"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct and Indirect Effect of Guselkumab on Anxiety, Depression, and Quality of Life in Patients with Moderate-to-Severe Plaque Psoriasis: A Mediation Analysis.","authors":"April W Armstrong, Peter Foley, Yan Liu, Megan Miller, Rachel E Teneralli, Anthony Bewley, Kenneth B Gordon, Kim A Papp, Chenglong Han","doi":"10.1007/s13555-024-01250-9","DOIUrl":"10.1007/s13555-024-01250-9","url":null,"abstract":"<p><strong>Introduction: </strong>Treating plaque psoriasis (PsO) with guselkumab (GUS) promotes skin clearance and is associated with improvements in health-related quality of life (HRQoL), anxiety, and depression. It is unclear whether improvements in patient-reported outcomes are due to resolution of skin symptoms or the direct result of GUS treatment.</p><p><strong>Methods: </strong>Two phase 3, placebo- and active-comparator-controlled studies randomized patients with moderate-to-severe PsO to GUS, placebo (crossing over to GUS at week 16), or adalimumab. Post hoc mediation analyses examined direct and indirect effects of GUS, versus adalimumab, on Dermatology Life Quality Index (DLQI) or Hospital Anxiety and Depression Scale (HADS) after adjusting for indirect effects mediated by skin clearance, evaluated via Psoriasis Area and Severity Index (PASI), to determine the direct effect of GUS on dermatology HRQoL, depression, and anxiety.</p><p><strong>Results: </strong>Compared with adalimumab, the natural direct effect (NDE) of GUS on change in DLQI from baseline was - 2.04 (P < 0.001), using PASI improvement as a mediator, indicating 89.2% of the total treatment effect was due to direct effects of GUS; using PASI 90 as a mediator, NDE of GUS was - 1.43 (P < 0.001), with 62.2% of the total treatment effect attributed to direct effects of GUS. Compared with adalimumab, 25.5% of change in HADS anxiety score was mediated through PASI improvement (NDE - 0.74; P = 0.002), indicating 74.5% of the total effect was independent of PASI improvement. Similarly, 24% of treatment effect was mediated through PASI 90 (NDE - 0.76; P = 0.002). Comparable proportions of the total improvement in HADS depression scores were due to direct and indirect effects of GUS mediated through PASI improvement (direct, 50.2%; indirect, 49.8%) or PASI 90 (direct, 59.5%; indirect, 40.5%).</p><p><strong>Conclusions: </strong>GUS-mediated improvements in anxiety, depression, and overall HRQoL are not solely mediated by resolution of PsO signs, suggesting GUS use has a potential direct effect on anxiety and depression.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2577-2589"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression of Quality of Life in Patients with Plaque Psoriasis Who Achieved Three or More Years of Complete Skin Clearance with Guselkumab Treatment: a Post hoc Analysis of the VOYAGE 1 Clinical Trial.","authors":"Luis Puig, Antonio Costanzo, Elke M G J de Jong, Tiago Torres, Richard B Warren, Robert Wapenaar, Sven Wegner, Patricia Gorecki, Talia Gramiccia, Maria Jazra, Jozefien Buyze, Curdin Conrad","doi":"10.1007/s13555-024-01245-6","DOIUrl":"10.1007/s13555-024-01245-6","url":null,"abstract":"<p><strong>Introduction: </strong>The interleukin-23p19 subunit inhibitor, guselkumab, has demonstrated improvements in clinical and patient-reported outcome (PRO) measures in patients with moderate-to-severe psoriasis. Understanding the relationship among clinical response, PRO measures and baseline characteristics could help clinicians individualize treatment plans. The objective of this analysis was to examine changes in signs, symptoms and quality-of-life (QoL) PRO measures in patients who maintained complete skin clearance through ≥ 3 years in the phase 3 VOYAGE 1 trial.</p><p><strong>Methods: </strong>A descriptive post hoc analysis of data from VOYAGE 1 was conducted to compare baseline characteristics of patients who maintained complete skin clearance (Psoriasis Area and Severity Index [PASI] = 0 for ≥ 156 consecutive weeks) versus patients who did not. Mean scores for individual domains of the Dermatology Life Quality Index (DLQI) and Psoriasis Symptom and Sign Diary (PSSD) were evaluated in patients who maintained complete skin clearance, and baseline characteristics of patients who achieved PRO scores of DLQI = 0/1 and PSSD = 0 were compared with those who did not.</p><p><strong>Results: </strong>Of the 329 patients included in this post hoc analysis, 73 (22.2%) maintained PASI = 0 for ≥ 156 weeks. This group had a numerically lower proportion of patients at baseline with obesity, depression or previous biologic treatment and a higher proportion who had never smoked. Patients who maintained PASI = 0 generally achieved positive DLQI and PSSD outcomes, though some impact of residual disease was observed, largely related to the DLQI \"Symptoms and feelings\" sub-scale and PSSD components \"Dryness,\" \"Redness\" and \"Itch.\" Patients reporting continued disease impact (despite sustaining PASI = 0) had greater disease severity at baseline versus those achieving DLQI = 0/1 and PSSD = 0.</p><p><strong>Conclusion: </strong>Clinical measures alone do not capture the full patient experience. While both QoL and clinical symptoms are responsive to highly effective treatment, a subset of patients with complete clinical response is still impacted by their psoriasis. Further investigation into this population is warranted.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT02207231.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2539-2558"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Upadacitinib and Dupilumab on Achieving Stringent and Composite Skin and Itch Outcomes: an Indirect Comparison of Adults with Moderate-to-Severe Atopic Dermatitis.","authors":"April W Armstrong, H Chih-Ho Hong, Brian M Calimlim, Marric G Buessing, Marjorie M Crowell, Jonathan I Silverberg","doi":"10.1007/s13555-024-01240-x","DOIUrl":"10.1007/s13555-024-01240-x","url":null,"abstract":"<p><strong>Introduction: </strong>Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 assessed efficacy of upadacitinib 30 mg and upadacitinib 15 mg against placebo, while Heads Up assessed efficacy of upadacitinib 30 mg in a head-to-head trial against dupilumab 300 mg. A head-to-head trial of upadacitinib 15 mg against dupilumab 300 mg has not been conducted. Network meta-analysis has shown that upadacitinib 30 mg and upadacitinib 15 mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated more stringent outcomes.</p><p><strong>Methods: </strong>A population-adjusted indirect comparison was conducted using post hoc individual patient data from Measure Up 1 and 2 and Heads Up to estimate how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates. Absolute response rates at weeks 4, 16, and 24 were estimated for the following outcomes: no/minimal itch [Worst Pruritus Numerical Rating Scale (WP-NRS) score of 0/1], Eczema Area and Severity Index (EASI) score of ≤ 3 (EASI ≤ 3), 100% improvement in EASI (EASI 100), both ≥ 90% improvement in EASI (EASI 90) and WP-NRS 0/1, both EASI ≤ 3 and WP-NRS 0/1, and both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to treat population for the clinical trials, and used non-responder imputation.</p><p><strong>Results: </strong>Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg and then dupilumab. This pattern was observed at week 4, week 16, and week 24.</p><p><strong>Conclusions: </strong>For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining more stringent and composite outcomes across multiple timepoints, followed by upadacitinib 15 mg and then dupilumab 300 mg.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2457-2465"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Participants' Experiences with Vitiligo from Patient Interviews.","authors":"Amit G Pandya, Theresa Amoloja, Kristen Bibeau, Dana DiBenedetti, Katherine Kosa, Kathleen Butler, Deanna Kornacki, Khaled Ezzedine","doi":"10.1007/s13555-024-01241-w","DOIUrl":"10.1007/s13555-024-01241-w","url":null,"abstract":"<p><strong>Introduction: </strong>Vitiligo is an autoimmune disease, causing skin depigmentation. Individuals with vitiligo incur substantial psychosocial burden and have expressed frustration with their treatments. Here, we describe the burden of vitiligo and opinions on what constitutes meaningful change among participants of two qualitative interview studies.</p><p><strong>Methods: </strong>Qualitative interviews were conducted with a subgroup of adolescent and adult participants with vitiligo from two pivotal phase 3 clinical trials of ruxolitinib cream (Study 1) and a real-world panel (Study 2). Participants were asked about their disease burden, treatment goals, importance of facial/body improvement (treatment satisfaction: scale range 0-10), and meaningfulness of change (yes/no).</p><p><strong>Results: </strong>A total of 36 participants from Study 1 and 23 from Study 2 were interviewed. In Study 1, the highest degree of impact was on reduced self-esteem (facial lesions, 62.5%; body lesions, 55.6%), social inhibition (facial lesions, 65.6%; body lesions, 61.1%), and sun sensitivity (facial lesions, 31.3%; body lesions, 55.6%). Most participants (83.3%) reported that facial improvement was equally (36.1%) or more important (47.2%) than body improvement, with mean treatment satisfaction of 8.1 and 6.9, respectively. Meaningful change was reported by 83.3% and 92.9% of participants with 50-74% and ≥ 75% improvement per the facial Vitiligo Area Scoring Index, respectively, and by 82.6% of participants with ≥ 25% improvement per the total Vitiligo Area Scoring Index per Study 1 outcomes at Week 24. In Study 2, most (82.6%) participants felt that the noticeability of their vitiligo affected their behavior. Nearly all (87.0%) said that an ideal treatment would repigment or return natural color to their facial skin; 56.5% considered ≥ 50% facial repigmentation to be the smallest meaningful improvement.</p><p><strong>Conclusions: </strong>Participants from both qualitative interviews expressed substantial psychosocial burden. Repigmentation in both facial and body vitiligo were important, with meaningful change determined to be ≥ 50% facial repigmentation and ≥ 25% body repigmentation.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2467-2478"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality of Life and Burden of Moderate-to-Severe Atopic Dermatitis in Adult Patients Within the Asia-Pacific Region: A Cross-sectional Survey.","authors":"Chia-Yu Chu, Yung Chan, Siriwan Wananukul, Hao Cheng, Nisha Suyien Chandran, Ramesh Bhat, Sang Wook Son, Han-Fang Liao, Sean Gardiner, Qi Qing Ng, See-Hwee Yeo, Sophie Bozhi Chen, Yoko Kataoka","doi":"10.1007/s13555-024-01244-7","DOIUrl":"10.1007/s13555-024-01244-7","url":null,"abstract":"<p><strong>Introduction: </strong>The burden of atopic dermatitis (AD) is significant, with a substantial impact on quality of life (QoL). This cross-sectional study aimed to ascertain the burden of AD, its impact on QoL, and associated costs.</p><p><strong>Methods: </strong>Patients with moderate-to-severe AD were enrolled from eight territories, namely Hong Kong, India, Japan, Mainland China, Singapore, South Korea, Taiwan, and Thailand. After screening was performed and informed consent was obtained, eligible participants were asked to provide responses on their AD symptoms, severity, treatment, and out-of-pocket costs via an online survey. QoL was assessed using EQ-5D-5L and Dermatology Life Quality Index (DLQI), while productivity loss was quantified using the Work Productivity and Activity Impairment (WPAI) questionnaire. Data from completed submissions were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory.</p><p><strong>Results: </strong>Median age of enrolled patients (N = 1103) was 41.0 years (interquartile range, IQR 16.0). The majority of patients reported that their head/neck, trunk, upper limbs, and lower limbs were affected during a flare. Topical (74.2%) and oral steroids (58.7%) were frequently prescribed to manage AD. Common atopic comorbidities were allergic urticaria (64.2%), allergic rhinitis (61.8%), and allergic conjunctivitis (51.5%). Median DLQI score was 13.0 (IQR 11.0), while median EQ-5D-5L (based on China value set) score was 0.8 (IQR 0.4); 87.2% and 77.2% of patients reported pain/discomfort and anxiety/depression on the EQ-5D-5L domains, respectively. Median total annual costs associated with AD were USD 10,128.52 (IQR 12,963.26) per patient, with indirect costs being the largest component. Findings from WPAI indicated that presenteeism is a major contributor to productivity loss.</p><p><strong>Conclusion: </strong>This multinational survey study showed that AD is associated with substantial QoL impairment and economic burden among Asian adult patients with moderate-to-severe AD. To alleviate burden of AD, clinicians should be more proactive in managing other concomitant conditions including psychological issues, and advocate for increased reimbursement for AD treatments.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2479-2493"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transungual Penetration and Antifungal Activity of Prescription and Over-the-Counter Topical Antifungals: Ex Vivo Comparison.","authors":"Ali Elabbasi, Ahmed Kadry, Warren Joseph, Boni Elewski, Mahmoud Ghannoum","doi":"10.1007/s13555-024-01237-6","DOIUrl":"10.1007/s13555-024-01237-6","url":null,"abstract":"<p><strong>Introduction: </strong>Topical antifungals for toenail onychomycosis must penetrate the nail to deliver an inhibitory concentration of free drug to the site of infection. In two ex vivo experiments, we tested the ability of topical antifungals to inhibit growth of Trichophyton rubrum and Trichophyton mentagrophytes, the most common causative fungi in toenail onychomycosis.</p><p><strong>Methods: </strong>Seven topical antifungals were tested: three U.S. Food and Drug Administration-approved products indicated for onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and four over-the-counter (OTC) products for fungal infections (tolnaftate 1% and/or undecylenic acid 25% solutions). The ability to inhibit fungal growth was tested in the presence and absence of keratin. Products were applied either to human cadaverous nails or keratin-free cellulose disks prior to placement on an agar plate (radius: 85 mm) seeded with a clinical isolate of T. rubrum or T. mentagrophytes. After incubation, the zone of inhibition (ZI), defined as the radius of the area of no fungal growth, was recorded.</p><p><strong>Results: </strong>In the nail penetration assay, average ZIs for efinaconazole (T. rubrum: 82.1 mm; T. mentagrophytes: 63.8 mm) were significantly greater than those for tavaborole (63.5 mm; 39.1 mm), ciclopirox (7.4 mm; 3.6 mm) and all OTC products (range: 10.5-34.2 mm against both species; all P < 0.001). In the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal antifungal activity against both species (ZIs = 85 mm); average ZIs against T. rubrum and T. mentagrophytes were smaller for ciclopirox (59.0 and 55.7 mm, respectively) and OTC products (range: 31.2-57.8 mm and 25.7-47.7 mm, respectively).</p><p><strong>Conclusions: </strong>Among all antifungals tested, the ability to penetrate human toenails to inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, suggesting lower keratin binding in the nail.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2495-2507"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Safety of Risankizumab in Patients with Psoriatic Disease: A Comprehensive Analysis from Clinical Trials.","authors":"Kenneth B Gordon, Andrew Blauvelt, Hervé Bachelez, Laura C Coates, Filip E Van den Bosch, Blair Kaplan, Willem Koetse, Doug G Ashley, Ralph Lippe, Ranjeeta Sinvhal, Kim A Papp","doi":"10.1007/s13555-024-01238-5","DOIUrl":"10.1007/s13555-024-01238-5","url":null,"abstract":"<p><strong>Introduction: </strong>Risankizumab has demonstrated a favourable safety profile in patients with psoriatic disease (moderate-to-severe psoriasis [PsO] and psoriatic arthritis [PsA]). We evaluated the long-term safety of risankizumab in psoriatic disease.</p><p><strong>Methods: </strong>Long-term safety was evaluated by analysing data from 20 (phase 1-4) clinical trials for plaque PsO and four (phase 2-3) trials for PsA. Treatment-emergent adverse events (TEAEs) and AEs in areas of special interest were reported among patients receiving ≥ 1 dose of risankizumab. Exposure-adjusted event rates were presented as events (E) per 100 patient-years (PY).</p><p><strong>Results: </strong>The long-term safety data analyses included 3658 patients with PsO (13,329.3 PY) and 1542 patients with PsA (3803.0 PY). The median (range) treatment duration for patients with PsO and PsA was 4.1 (0.2-8.8) years and 2.8 (0.2-4.0) years, respectively. In the PsO population, rates of TEAEs, serious AEs and AEs leading to discontinuation were 145.5 E/100 PY, 7.4 E/100 PY and 1.9 E/100 PY, respectively; in the PsA population, these rates were 142.6 E/100 PY, 8.6 E/100 PY, and 1.8 E/100 PY, respectively. The rates of serious infections (excluding COVID-19-related infections) in the PsO and PsA populations were 1.2 and 1.4 E/100 PY, respectively. The rates of opportunistic infections (excluding tuberculosis and herpes zoster) were low (< 0.1 E/100 PY) in both populations. The rates of both nonmelanoma skin cancer (NMSC) and malignant tumours excluding NMSC were 0.6 and 0.5 E/100 PY in PsO and PsA, respectively, which are within the benchmarks of prior epidemiological studies. Adjudicated major cardiovascular event rates were 0.5 E/100 PY in PsO and 0.3 E/100 PY in PsA, which are within the epidemiologic reference benchmarks for both indications. No additional safety concerns were identified with this long-term exposure.</p><p><strong>Conclusions: </strong>The results support the favourable safety profile of risankizumab for long-term treatment of psoriatic disease with no new safety concerns and similar safety profiles among both PsO and PsA populations.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2523-2538"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Certolizumab Pegol for the Treatment of Plaque Psoriasis in Routine Clinical Practice: One-Year Results from the CIMREAL Study.","authors":"Bernhard Korge, Olivier Vanhooteghem, Charles W Lynde, Alena Machovcova, Marc Perrussel, Elisavet Lazaridou, Claudio Marasca, David Vidal Sarro, Ines Duenas Pousa, Frederik Fierens, Paulette Williams, Saori Shimizu, Tanja Heidbrede, Richard B Warren","doi":"10.1007/s13555-024-01210-3","DOIUrl":"10.1007/s13555-024-01210-3","url":null,"abstract":"<p><strong>Introduction: </strong>Certolizumab pegol (CZP) is an anti-tumor necrosis factor alpha (TNFα) approved for the treatment of moderate to severe plaque psoriasis (PSO). However, data on its real-world use is currently limited. The objective of this study was to describe the 1-year real-world effectiveness of CZP, its impact on health-related quality of life (HRQoL), and safety outcomes in patients with moderate to severe PSO in multi-country settings.</p><p><strong>Methods: </strong>CIMREAL, a prospective, noninterventional study, was conducted across Europe and Canada from August 2019 to December 2022. Patients were followed for 1-year, receiving CZP 400 mg initial doses at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg Q2W maintenance dosing. Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Safety was also evaluated.</p><p><strong>Results: </strong>Overall, 399 patients with moderate to severe PSO were included. Of these, 93.7% (374/399) and 77.9% (311/399) completed months 3 and 12, respectively. Mean age (± standard deviation) was 42.9 ± 13.5 years and body mass index was 28.5 ± 6.8 kg/m², with the majority of patients being female (68.2%). At 12 months, CZP showed substantial effectiveness, achieving PASI 75 and PASI 90 response rates (≥ 75% and ≥ 90% improvement from baseline, respectively) of 77% and 56.5%, respectively. Patients with PASI score of ≤ 3 and ≤ 2 experienced improvement from 3 months (49.8% and 41.1%, respectively) to 12 months (82.0% and 75.3%, respectively). HRQoL considerably improved, with mean DLQI scores decreasing from 12.4 to 2.3 after 12 months of treatment, and the proportion of patients with DLQI 0/1 increased from 28.6% at 3 months to 59.4% at 12 months. The 1-year probability of persistence was approximately 85%. Overall, 30.6% of the patients experienced any adverse events and 9.3% had serious adverse events.</p><p><strong>Conclusion: </strong>In routine clinical practice, CZP exhibited consistent effectiveness, positively impacting both skin psoriasis activity and HRQoL. The 1-year persistence of CZP was high, and no new safety signals were identified.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov Identifier: NCT04053881 https://www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT04053881 .</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":"2077-2092"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}