Dermatology and Therapy最新文献

Introduction: The efficacy and safety of tildrakizumab for the treatment of plaque psoriasis were demonstrated by randomized clinical studies, but the reappraisal of prolonged experiences in the clinical practice helps to optimize the use of this biologic drug. The aim of this study was to evaluate the long-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the real world.

Methods: This is a long-term retrospective observational study in a real-life setting. Overall, 136 adult patients with moderate-to-severe plaque psoriasis and treated with tildrakizumab were included.

Results: One hundred percent reduction of Psoriasis Area Severity Index (PASI100) was reached by 21.7% of patients at 4 weeks of therapy and by 51.2% at week 16, and the proportion of patients with this improvement was between 66.9% and 64.5% from 36 weeks to 3 years. The mean PASI of the cohort progressively improved from 12.6 at baseline to 1.8 at week 36 and was stable at 1 year, 2 years and 3 years. We could not confirm a previous observation that patients naïve to biologic had a better response, but we observed that those with a short history of psoriasis had a higher probability of 90% PASI reduction (PASI90) or PASI 100 within 36 weeks, suggesting that early treatment could be useful.

Conclusion: This long-term observation in the real life of patients with moderate-to-severe plaque psoriasis receiving tildrakizumab 100 mg showed that PASI100 can be obtained in a high proportion of patients by week 36 and be maintained for up to 3 years.

Introduction: Atopic dermatitis (AD), with its hallmark symptoms of pruritus and skin lesions, often impairs patients' quality of life. We assessed time spent with clear/almost clear skin and no/minimal itch during upadacitinib treatment versus placebo or dupilumab among patients with moderate-to-severe AD.

Methods: This analysis consisted of a post hoc analysis of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 were replicate, randomized, double-blind, placebo-controlled phase 3 studies with patients randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 16 weeks. Heads Up was a head-to-head, randomized, double-blind, double-dummy, phase 3b study with patients randomized (1:1) to upadacitinib 30 mg or subcutaneous dupilumab 300 mg for 24 weeks. Skin clearance was assessed with the Eczema Area and Severity Index (EASI) at baseline, weeks 1, 2, and 4, and every 4 weeks thereafter. Itch was assessed using the Worst Pruritus Numerical Rating Scale (WP-NRS) daily over 16 weeks and every 2 weeks thereafter to week 24 in Heads Up.

Results: This analysis included 1683 patients in Measure Up 1 and 2 and 673 patients in Heads Up. Through 16 weeks in Measure Up 1 and 2, patients receiving upadacitinib spent 9.8-13.4 times as many days with an EASI 90 response and 7.0-10.3 times as many days with a WP-NRS 0/1 response versus placebo. In Heads Up, patients receiving upadacitinib spent 2.0 and 1.7 times as many days through 16 and 24 weeks, respectively, with an EASI 90 response versus dupilumab. Through 16 and 24 weeks, patients receiving upadacitinib spent 3.0 and 2.6 times as many days, respectively, with a WP-NRS 0/1 response versus dupilumab.

Conclusions: Patients with moderate-to-severe AD spent more time with clear/almost clear skin and no/minimal itch with upadacitinib versus placebo or dupilumab.

Trial registration: ClinicalTrials.gov identifier, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), Heads Up (NCT03738397).

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase 2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits.

Introduction: Limited evidence is available on real-world management of atopic dermatitis (AD) among Asian adults. This cross-sectional study aimed to assess current approaches in AD diagnosis and management in Asia.

Methods: Practising dermatologists regularly treating patients with moderate-to-severe AD were recruited from eight Asia-Pacific territories, namely Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. A survey was administered to eligible dermatologists after screening and taking informed consent. Data from fully completed submissions were analysed using descriptive statistics. The study was reviewed by the institutional review board in each territory.

Results: Data from 271 dermatologists were included for analysis. About one-third (31.7%) reported that they referred to the Hanifin and Rajka criteria during diagnosis. The majority of dermatologists used clinical impression when assessing AD severity and treatment response. Reduction of eczema and pruritus was the primary treatment objective when managing both acute (98.1%) and chronic (69.1%) AD. More than half of dermatologists preferred adding systemic anti-inflammatory medication for patients who did not respond to maximized topical treatment, while 43.6% would switch to another systemic medication for those failing to respond to maximized systemic treatment. Topical corticosteroids were frequently selected by dermatologists. For systemic therapies, oral corticosteroids were most frequently used, followed by cyclosporin and dupilumab. Narrow-band ultraviolet B was the most common phototherapy reported (84.9%). There was considerable variation in estimated average and maximum durations of therapies used to treat AD.

Conclusion: This study has provided insights on the real-world management of moderate-to-severe AD in the Asia-Pacific region. The diverse approaches in diagnosis and treatment highlight the multifactorial nature of AD, reliance on clinical judgement, and importance of personalized care. To improve outcomes in patients with AD, it will be crucial to develop biomarkers for diagnosis, reduce subjectivity in assessment, as well as promote access to newer and effective therapies.

Introduction: Ultraviolet-free (UV-free) blue light phototherapy has emerged as a promising option due to its reported efficacy and minimal adverse effects. This study aims to evaluate the effectiveness of full-body blue light irradiation in both adult and pediatric patients with atopic dermatitis (AD), assessing its impact on skin condition and mood regulation by investigating serum concentrations of serotonin and kynurenine pathway metabolites.

Methods: 20 patients (age 9-45) with moderate and severe AD were included in the study. Treatment consisted of 10 irradiations with Full Body Blue device (453 nm). Serum concentrations of serotonin, quinolinic acid, kynurenic acid, tryptophan, and kynurenine were measured before and after irradiations.

Results: After 10 sessions of full blue light therapy (453 nm) statistically significant improvements were observed in Eczema Area Severity Index (EASI 13.16 vs. 8.65; p = 0.00016), SCORing Atopic Dermatitis (SCORAD 44.99 vs. 23.73; p < 0.00001), Visual Analogue Scale (VAS 6.53 vs. 3.95; p = 0.00251), 10-item pruritus severity scale (13.32 vs. 7.05; p < 0.00001). Moreover, statistically significant decrease in Dermatology Life Quality Index (DLQI) was noted (14.37 vs. 7.42; p = 0.00351). Additionally, increase in the serum concentration of serotonin was observed after completing 10 irradiation sessions (median 139.77 mg/ml vs. 274.92 mg/ml; p < 0.00001).

Conclusion: Blue light may be a promising and safe treatment in patients with AD. It might also positively influence mood. Further investigations are needed to confirm those findings.

Trial registration: ClinicalTrials.gov identifier, NCT06516783.

Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients' quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980-September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.

Introduction: Knowing the remission duration after biologics discontinuation in patients with psoriasis is important, especially when disease relapse is defined as the restart of systemic agents, because it also reflects the real-world clinical practice when topical treatment alone is not adequate for disease control, and a systemic treatment, including biologic, is needed. Biologics are currently indicated for patients with psoriasis who are candidates for systemic treatments.

Methods: We included 42 patients who were followed up with regularly after the end of risankizumab, guselkumab and mirikizumab trials and investigated the drug-free remission (DFR). A Kaplan-Meier survival analysis and Cox regression model were employed to identify the possible risk factors for relapse.

Results: Overall, 38/42 (90.5%) patients experienced relapses after discontinuing trial biologics during the follow-up period of at least 96 weeks and up to 227 weeks. In all patients with relapse, the median DFR was 104 days. Kaplan-Meier survival analysis revealed a significant 1-year drug-free survival (DFS) difference between risankizumab (Z) and guselkumab (T) + mirikizumab (M) (p = 0.0462). A difference in DFS curves was noted when patients were categorized by disease duration > or ≤ 2 years (p = 0.1577) and maintenance of a psoriasis area and severity index score (PASI) of 90 at the end of trials (p = 0.1177). Univariate Cox regression model identified that age [hazard ratio (HR) = 1.030 (1.000-1.060), p = 0.0467] and disease duration [HR = 1.046(1.009-1.084), p = 0.0134] were significantly associated with relapse risk. A risk model was established on the basis of multivariable Cox regression results. Risk value = 0.021038 * Age + 0.515628 * Biologic_type (Z = 0,T/M = 1) + 0.025048 * Disease_Duration. The validated patients were divided into two groups by median risk value (1.5). The high-risk group (risk value > 1.5) had a non-significant higher relapse risk than the low-risk group (risk value < 1.5), with a hazard ratio of 1.62 [95% confidence interval (CI) = 0.82-3.23, p = 0.1809].

Conclusion: Types of biologics used, disease duration > or ≤ 2 years, and PASI 90 improvement at the end of trial affect the 1-year DFS after biologics discontinuation. Further studies consisting of a larger patient number and longer follow-up period are needed to verify our findings.

Trial registration: ClinicalTrials.gov identifiers NCT02694523, NCT03047395, NCT02207224, NCT02576431, NCT03482011, and NCT03556202.

Advancements in the molecular genetics of epidermolysis bullosa (EB) and ichthyosis, two rare inherited skin conditions, have enabled the identification of genetic variants that cause these diseases. Alongside technological advancements in genetic medicine, the identification of variants causal of these rare skin conditions has led to preclinical research and the clinical development of various in vivo and ex vivo gene and cell therapies for their treatment. Gene and cell therapies are considered to be the most advanced forms of personalized medicine, demonstrating safety and efficacy in numerous rare diseases. Although the orphan drug development boom has resulted in regulatory approval of multiple gene and cell therapies for various rare conditions, the application of these modalities to rare inherited skin conditions remains limited. Nonetheless, there are successful examples of both in vivo gene therapy- and ex vivo cell therapy-based approaches developed to treat EB and ichthyosis. This review highlights preclinical research and the clinical development of gene and cell therapies for multiple subtypes of these two devastating congenital skin conditions, including a gene therapy recently approved by the U.S. Food and Drug Administration for the treatment of recessive dystrophic EB.

Introduction: This pilot study investigated the effects of a 12-week administration of a nutritional supplement containing special collagen peptides on the structural and molecular properties of the collagen fiber network in the human skin. For the assessments, the suction blister method and electron microscopical comparisons were used.

Methods: Three suction blisters were generated on the inner forearm of each test subject before and after the 12-week administration of the nutritional supplement. High-resolution scanning electron microscopy (SEM) was employed to meticulously investigate the structural characteristics of the skin's collagen network, including the length and diameter of collagen fibers within the suction blister roof. Furthermore, the analysis included immunohistochemistry and fluorescence light microscopy to study hyaluronic acid within the extracellular matrix. Additional assessments encompassed changes in various epidermal parameters. Nine female participants within the age range of 43.7-61.8 years (mean: 52.5 ± 5.9 years) completed the study in accordance with the study protocol.

Results: Compared with baseline, the 12-week supplementation regimen led to a statistically significant average increase in the collagen fiber network size of 34.56% (p < 0.0001). Additionally, collagen fiber cross-linking and fiber length were substantially increased. The ingestion of the supplement also resulted in an 18.08% elevation in epidermal hyaluronic acid concentration (p < 0.0001). No adverse events were recorded during the study.

Conclusion: Using an innovative approach, this study demonstrated the ability of a targeted nutritional supplement to effectively restore the ultrastructural integrity of the dermal collagen network, which is typically disrupted by the natural aging process of the skin. These findings not only corroborate existing data regarding the positive effects of oral collagen peptides on skin structure and function but also contribute to our understanding of ultrastructural morphological aspects of changes in the skin's collagen network. Supplementation can induce regeneration of the collagen fiber network in the human skin.

Trial registration number: German Clinical Trials Register, DRKS-ID DRKS00034161- Date of registration: 06.05.2024, retrospectively registered.

Hidradenitis suppurativa (HS) is a chronic skin condition that significantly impacts patients' quality of life. HS is often challenging to treat. In this review, we discuss the unique characteristics of HS in four special populations: children, the elderly, pregnant individuals, and breastfeeding mothers. In children, diagnosis may be delayed due to atypical and early HS disease presentations. HS management plans must take into consideration the lack of rigorous efficacy and safety data of HS treatments in this population. However, it is important to weigh the risk of treatments against the risk of untreated HS and the morbidity and mortality risk that having HS confers. Pregnancy poses unique challenges for women with HS, with their condition possibly worsening during pregnancy and increased risk of fetal death. Management strategies during pregnancy must consider both maternal and fetal safety. Similarly, breastfeeding mothers require thoughtful medication selection to balance symptom management with infant safety. In the elderly, HS may present more severely and is often complicated by comorbidities. Treating HS in this population should safely accommodate patients' additional health conditions. Furthermore, this review highlights the overall paucity of primary literature addressing management in these populations, underscoring the need for further research to optimize HS care across all stages of life.