Dermatology and Therapy最新文献

Introduction: Guselkumab, a human monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), has shown efficacy in psoriasis and psoriatic arthritis. However, long-term real-world data on its effectiveness in patients with inadequate response to ustekinumab are limited. This study investigates guselkumab's long-term effectiveness and safety in patients with psoriasis with partial response to ustekinumab.

Methods: We performed a retrospective multicentric study analyzing data of patients with psoriasis from seven Italian hospitals between January 2021 and May 2024. The study included 169 patients who switched from ustekinumab to guselkumab. Primary endpoints were Psoriasis Area and Severity Index (PASI) 75, PASI 90, PASI 100, and absolute PASI ≤ 2. Site-specific Physician Global Assessment (PGA) scores were also collected for difficult-to-treat areas.

Results: The study included 169 patients. After 3 years of treatment, PASI 75, PASI 90 and PASI 100 were achieved by 88.4%, 55.8%, and 32.6% of patients, respectively. Site-specific PGA showed significant improvements, especially in the scalp and genital areas. After 3 years of treatment, no significant impact of higher body mass index (BMI) or cardiometabolic comorbidities on guselkumab effectiveness was detected. No severe adverse events were reported during the study period.

Conclusions: In our study, guselkumab provided significant long-term effectiveness and safety in patients partially responsive to ustekinumab, improving both PASI score and site-specific PGA and confirming its potential use for patients with psoriasis switching from ustekinumab.

Introduction: Alopecia areata (AA) is an autoimmune disease causing non-scarring hair loss, with both genetic and environmental factors implicated. Recent research highlights a possible role for scalp microbiota in influencing both local and systemic inflammatory responses, potentially impacting AA progression. This study examines the link among scalp microbiota imbalances, AA severity, and systemic inflammation.

Methods: We conducted a cross-sectional study with 24 participants, including patients with AA of varying severities and healthy controls. Scalp microbial communities were analyzed using swab samples and ion torrent sequencing of the 16S rRNA gene across multiple hypervariable regions. We explored correlations among bacterial abundance, microbiome metabolic pathways, and circulating inflammatory markers.

Results: Our findings reveal significant dysbiosis in the scalp microbiota of patients with AA compared to healthy controls. Severe AA cases had an increased presence of pro-inflammatory microbial taxa like Proteobacteria, whereas milder cases had higher levels of anti-inflammatory Actinobacteria. Notable species differences included abundant gram-negative bacteria such as Alistipes inops and Bacteroides pleibeius in severe AA, contrasted with Blautia faecis and Pyramydobacter piscolens predominantly in controls. Significantly, microbial imbalance correlated with AA severity (SALT scores) and systemic inflammatory markers, with elevated pro-inflammatory cytokines linked to more severe disease.

Conclusion: These results suggest that scalp microbiota may play a role in AA-related inflammation, although it is unclear whether the shifts are a cause or consequence of hair loss. Further research is needed to clarify the causal relationship and mechanisms involved.

Introduction: Developing automatic acne vulgaris grading systems based on machine learning is an expensive endeavor in terms of data acquisition. A machine learning practitioner will need to gather high-resolution pictures from a considerable number of different patients, with a well-balanced distribution between acne severity grades and potentially very tedious labeling. We developed a deep learning model to grade acne severity with respect to the Investigator's Global Assessment (IGA) scale that can be trained on low-resolution images, with pictures from a small number of different patients, a strongly imbalanced severity grade distribution and minimal labeling.

Methods: A total of 1374 triplets of images (frontal and lateral views) from 391 different patients suffering from acne labeled with the IGA severity grade by an expert dermatologist were used to train and validate a deep learning model that predicts the IGA severity grade.

Results: On the test set we obtained 66.67% accuracy with an equivalent performance for all grades despite the highly imbalanced severity grade distribution of our database. Importantly, we obtained performance on par with more tedious methods in terms of data acquisition which have the same simple labeling as ours but require either a more balanced severity grade distribution or large numbers of high-resolution images.

Conclusions: Our deep learning model demonstrated promising accuracy despite the limited data set on which it was trained, indicating its potential for further development both as an assistance tool for medical practitioners and as a way to provide patients with an immediately available and standardized acne grading tool.

Trial registration: chinadrugtrials.org.cn identifier CTR20211314.

Background: Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor.

Objective: To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris.

Methods: This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris.

Results: A total of 1617 patients were enrolled. At week 12, patients in the adapalene-clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (- 66.85%), compared with adapalene alone (- 50.82%) or clindamycin gel alone (- 57.61%). The difference in the least square means of the adapalene-clindamycin gel group and adapalene group, or clindamycin gel group was - 16.08% (95% CI - 19.95% to - 12.21%) and - 9.38% (95% CI - 13.25% to - 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene-clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups.

Conclusion: Adapalene 0.1%-clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris.

Trial registration: ClinicalTrials.gov identifier NCT03615768.

Introduction: For some patients with atopic dermatitis (AD), topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), and systemic therapies are inadequate to control disease or are associated with adverse events (AEs). Ruxolitinib cream monotherapy demonstrated anti-inflammatory and anti-pruritic effects among patients enrolled in two pivotal phase 3 studies (TRuE-AD1/TRuE-AD2); most patients had long-term disease control with as-needed use during the 44-week long-term safety (LTS) period. This post hoc analysis explored efficacy and safety of 1.5% ruxolitinib cream by previous medication use.

Methods: Patients aged ≥ 12 years enrolled in TRuE-AD1/TRuE-AD2 were randomized 2:2:1 to twice-daily 0.75% or 1.5% ruxolitinib cream or vehicle cream for 8 weeks, followed by a 44-week LTS period; patients initially on vehicle were re-randomized 1:1 to either ruxolitinib cream strength.

Results: Within 12 months of enrollment (N = 1249), previous AD therapies were used by 89.4% of efficacy-evaluable patients applying vehicle or ruxolitinib cream (n = 725); of these, 80.4% received TCS (n = 583), 22.2% TCI (n = 161), 20.3% TCS + TCI (n = 147), and 18.9% systemic therapies (n = 137). Across previous medication subgroups, achievement of Investigator's Global Assessment (IGA)-treatment success (IGA 0/1 with ≥ 2-grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index from baseline, and ≥ 4-point improvement in Itch numerical rating scale score from baseline at Week 8 did not substantially differ among patients who applied ruxolitinib cream. Outcomes were similar to those in the overall study population. At all study visits during the LTS period, > 70% of patients in each subgroup had IGA 0/1 and a low percentage (generally < 3%) of affected body surface area. Treatment-related AEs across subgroups were reported in 7.3% (n = 35/481) to 17.4% (n = 19/109) of patients.

Conclusions: Continuous-use ruxolitinib cream monotherapy for 8 weeks followed by as-needed use was effective and well tolerated, regardless of previous topical or systemic therapy, with outcomes similar to those achieved in the overall study population.

Trial registration: ClinicalTrials.gov Identifier, NCT03745638/NCT03745651.

Introduction: Poor persistence to biologics can result in suboptimal health outcomes and increased economic burden for chronic conditions, including psoriasis (PsO). In Japan, studies evaluating factors responsible for biologic treatment persistence in patients with PsO are limited. We assessed biologic treatment persistence (median treatment duration and overall treatment survival) and associated factors in patients with PsO in a real-world setting.

Methods: This retrospective analysis of insurance claims records from the Japan Medical Data Center (JMDC) database included patients with PsO [International Classification of Diseases (ICD) code: L40.x] ≥ 18 years of age who had received biologic treatment. Treatment persistence was analyzed using data from 2016 to 2020 by biologic class and by individual biologics (infliximab, adalimumab, ustekinumab, guselkumab, secukinumab, ixekizumab, and brodalumab) in bio-naïve (who initiate first biologic at index) and bio-experienced patients. Kaplan-Meier survival (treatment persistence), and multivariate Cox proportional hazard regression (predictive factors) analyses were used.

Results: Overall, 1528 patients with PsO were included (mean age 47.4 years). Infliximab had the longest median treatment duration (33.6 months), while brodalumab had the shortest (9.7 months) among biologics evaluated. Of the biologics evaluated, 1-year treatment survival was highest with guselkumab (83%), and lowest with brodalumab (45%). Bio-experienced patients showed slightly longer median treatment duration than bio-naïve patients (22.8 versus 18.1 months). Factors predictive of treatment persistence were sex [male; hazard ratio (HR) 0.84, p = 0.016] and specific PsO diagnostic codes, such as L40.0 (PsO vulgaris; HR 0.69; p = 0.006), L40.1 (generalized pustular PsO; HR 0.75; p = 0.034), and L40.9 (PsO unspecified; HR 0.72; p = 0.001). Meanwhile, age and Charlson Comorbidity Index score were significantly associated with adalimumab and infliximab treatment persistence, respectively.

Conclusion: Among biologics evaluated, infliximab had the longest median treatment duration, and guselkumab had the highest 1-year treatment survival. Sex and specific PsO diagnostic codes influenced overall treatment persistence. These findings could inform long-term treatment plans for PsO in real-world clinical settings.

Introduction: Seborrheic dermatitis (SD) is a common, chronic inflammatory skin disease, but the physical and emotional burden of patients with SD experience has not been well characterized.

Methods: The Harris Poll conducted online surveys of US patients and healthcare providers (HCPs) from December 2021 to January 2022.

Results: Almost half of patients reported that SD negatively impacts their emotional and physical well-being "a lot/a great deal"; HCPs underestimate the level of impact on patients. Most patients with SD reported a significant mental health impact, including anxiety, depression, anxiety about interacting with other people, and isolation. Two-thirds of patients said they did not know anyone else who had been diagnosed with SD, and even after diagnosis, less than half of patients still said they did not know anyone else with SD. Nearly all patients and HCPs agreed that it was challenging to hide SD symptoms, and most patients felt embarrassed when people commented on their SD symptoms. Most patients agreed that they would be further along in their career if they did not have SD, and SD symptoms made them less confident at work and less likely to want to interact with people at work. Almost half of patients reported ever missing work as a result of SD symptoms.

Conclusion: These insights emphasize the physical and emotional patient burden associated with SD, impacting all aspects of patients' lives. Graphical abstract available for this article.

Introduction: Difamilast has proven to be an effective treatment for the treatment of atopic dermatitis (AD) in Japan, but its cost-effectiveness remains unknown. Therefore, the objective of the current study was to determine the cost-effectiveness of difamilast 1% compared with delgocitinib 0.5% in Japanese adult patients with moderate-to-severe AD and compared with placebo in Japanese adult patients with all-severity AD from a Japanese public health-care perspective.

Methods: The analysis was conducted using a cost-effectiveness model from the Japanese public health-care perspective. This model had four health states ("clear," "mild," "moderate," and "severe") defined according to the Eczema Area and Severity Index score. The time horizon of the analysis was 1 year. Because the analysis period was short, no discount rate was applied. The proportions of patients previously estimated by the anchored matching-adjusted indirect comparison were implemented in the model. The model was further populated with data from the literature. The main model outcomes were quality-adjusted life-years (QALY), costs, and outcomes, including the incremental cost-effectiveness ratio. All prices were stated in JPY at the price level from 2018 April to 2019 March. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of the results.

Results: In the base case, the cost-effectiveness of difamilast 1% compared with delgocitinib 0.5% and placebo was JPY 827,054/QALY and JPY 1,518,657/QALY, respectively. The PSA showed that the cost-effectiveness of difamilast 1% compared with delgocitinib 0.5% and placebo had a 66.6% and 99.6% probability of being below the JPY 5 million/QALY threshold, respectively.

Conclusion: The results suggest that difamilast 1% is a more cost-effective treatment option compared with delgocitinib 0.5% in Japanese adult patients with moderate-to-severe AD and compared with placebo in adult patients with all-severity AD from a Japanese public health-care perspective.