Dermatology and Therapy最新文献

Introduction: Risankizumab has demonstrated superior efficacy compared to other psoriasis treatments, including secukinumab, adalimumab, and ustekinumab; switching to risankizumab from other psoriasis treatments has shown superior clinical and quality of life (QoL) outcomes. We evaluated the efficacy and safety of directly switching patients with moderate-to-severe plaque psoriasis and a suboptimal response to interleukin (IL)-17 inhibitors (secukinumab or ixekizumab) to risankizumab.

Methods: This 52-week, phase 3b study enrolled patients (≥ 18 years) with moderate-to-severe plaque psoriasis who had previously been treated with the recommended dose of secukinumab or ixekizumab for ≥ 6 months but did not achieve an optimal response (static Physician's Global Assessment [sPGA] 2/3; body surface are [BSA] 3- < 10%). Patients received subcutaneous risankizumab (150 mg) without washout. The primary endpoint was the proportion of patients achieving sPGA of 0/1 at week 16. Secondary endpoints included sPGA 0/1 at week 52, sPGA 0, Dermatology Life Quality Index (DLQI) 0/1, and Psoriasis Symptoms Scale (PSS) 0 at weeks 16 and 52. Safety was monitored throughout the study.

Results: The study included 244 patients. sPGA 0/1 was achieved by 57.4% and 62.3% at week 16 and 52. At week 16, sPGA 0, DLQI 0/1, and PSS 0 were achieved by 20.5%, 40.2%, and 20.9%, respectively. At week 52, these proportions increased to 27.1% for sPGA 0, 47.2% for DLQI 0/1, and 27.5% for PSS 0. Most frequently reported adverse events (reported in ≥ 5% of patients) in risankizumab-treated patients were COVID-19 infection (8.6%) and nasopharyngitis (5.7%). No new safety signals were observed.

Conclusions: Directly switching to risankizumab improved outcomes and QoL in patients with moderate-to-severe psoriasis who had suboptimal responses to anti-IL-17 inhibitors (secukinumab or ixekizumab). The safety results are consistent with previously reported safety of risankizumab. This study supports the efficacy of risankizumab in patients previously treated with biologics, including IL-17 inhibitors, and suggests a direct switch to risankizumab for improved clinical outcomes and QoL.

Clinical trials: ClinicalTrials.gov identifier: NCT04102007.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease involving complex immune dysregulation, including the OX40-OX40L pathway. Rocatinlimab and amlitelimab, monoclonal antibodies targeting OX40 and OX40L, respectively, have shown promise in treating moderate-to-severe AD. Both therapies have demonstrated significant efficacy in reducing disease severity, with favorable safety profiles and no serious treatment-related adverse events. Both treatments outperformed placebo across key clinical endpoints, including skin clearance and symptom reduction, highlighting their potential as effective AD therapies. Although initial results are promising, further research is needed to evaluate the long-term effects, durability of response, and safety of these treatments. These findings support the therapeutic potential of targeting the OX40-OX40L pathway in AD, providing new options for patients with moderate-to-severe disease, with ongoing trials necessary to confirm their sustained benefits.

Introduction: Topical therapies are used in almost all patients with psoriasis. A novel fixed topical combination cream (GN-037) with a lower concentration (0.0356%) of clobetasol 17-propionate (CP) was developed together with urea, salicylic acid, and retinoic acid to provide a better benefit-risk ratio. The present multicenter randomized double-blind vehicle-controlled parallel group phase 2 study aimed to investigate the efficacy and safety of GN-037 in patients with mild-to-moderate plaque psoriasis (MMPP).

Methods: Patients (n = 190) were randomized (2:2:1) to receive GN-037 or CP or vehicle (V) cream twice daily to a selected target body lesion for 4 weeks. The primary endpoint was treatment success defined as percentage of patients with at least two-grade improvement in Investigator's Global Assessment Score (IGA) and IGA score equal to 0 or 1 evaluated at weeks 2, 4, 6, and 8 in each arm compared with baseline. Treatment-emergent adverse events (TEAEs) and safety were evaluated throughout the study.

Results: GN-037 demonstrated statistically significant superiority over V throughout the study. At week 4, treatment success was achieved in 37.9% of patients in the GN-037 arm compared with 29.2% and 9.1% in the CP and V arms, respectively. At least two-grade improvement compared with baseline was achieved by 57.6%, 72.7%, and 80.3% of the patients in the GN-037 arm for erythema, plaque elevation, and scaling, respectively. The mean changes in affected BSA were -2.1 ± 2.9, -1.8 ± 2.4, and -0.5 ± 1.6 in the GN-037, CP, and V arms, respectively. The TEAEs were similar among the arms and the most frequently observed TEAEs were Psoriasis Area and Severity Index (PASI) increase in all arms.

Conclusions: GN-037 was more effective than V in achieving primary and all secondary endpoints throughout the study. Safety data did not reveal any new safety concerns with the combination cream product. Therefore, 4 weeks of GN-037 treatment demonstrated an excellent efficacy and safety profile in patients with MMPP.

Trial registration number: ClinicalTrials.gov identifier, NCT05706870.

Introduction: There is a lack of objective, accurate, and convenient methods for classification diagnostic hypopigmented dermatoses (HD) and severity evaluation of vitiligo. To achieve an accurate and intelligent classification diagnostic model of HD and severity evaluation model of vitiligo using a deep learning-based method.

Methods: A total of 11,483 images from 4744 patients with HD were included in this study. An optimal diagnostic model was constructed by merging the squeeze-and-excitation (SE) module with the candidate model, its diagnostic efficiency was compared with that of 98 dermatologists. An objective severity evaluation indicator was proposed through weighting method and combined with a segmentation model to form a severity evaluation model, which was then compared with the assessments conducted by three experienced dermatologists using the naked eye.

Results: The improved diagnosis model SE_ResNet-18 outperformed the other 11 classic models with an accuracy of 0.9389, macro-specificity of 0.9878, and macro-f1 score of 0.9395, and outperformed the different categories of 98 dermatologists (P < 0.001). The weighted Kappa test indicated medium consistency between the Indicator_v and the VASI_change (K = 0.567, P < 0.05). The optimal segmented model, HR-Net, had 0.8421 mIOU. The model-based severity evaluation results were not significantly different among the three experienced dermatologists.

Conclusions: This study proposes an objective, accurate, and convenient hybrid model for diagnosing HD and evaluating the severity of vitiligo, providing a method for dermatologists especially in grassroots hospitals, and provides a foundation for telemedicine.

Introduction: Alopecia areata (AA) is an autoimmune disease that causes scalp, face, and/or body hair loss. Recently, oral treatments with kinases inhibition became the first approved therapies for severe AA. An understanding of the use and effectiveness of traditional therapies in real-world treatment settings is needed to guide integration of novel therapies into the treatment paradigm. This study aimed to describe traditional treatment patterns, dermatologists' reasons for therapy choice, and dermatologists' satisfaction with disease control among patients with AA.

Methods: Data were drawn from the 2021-2022 Adelphi Real World AA Disease Specific Programme™, a cross-sectional survey of dermatologists and adult patients with AA, conducted in France, Germany, Italy, Spain, and the UK. For each patient, using data from patient consultation and medical records, dermatologists reported % scalp hair loss (SHL), characteristics of current and prior AA therapies, and satisfaction with disease control.

Results: Overall, 239 dermatologists provided data for 1720 patients with AA. Mean (SD) patient age was 35.8 (11.6) years, and 51% were male. Based on dermatologist perception, among patients with ≤ 10% SHL, 74% were experiencing mild AA, while ≥ 95% of patients with ≥ 50% SHL were experiencing severe/very severe AA. In patients with ≥ 50% SHL, the most common therapies received included systemic immunosuppressants (31%), topical corticosteroids (24%), and oral corticosteroids (24%). Among all patients who had switched therapies, 49%, 26%, and 24% switched because of worsening AA, lack of initial efficacy with prior treatment, and loss of response over time, respectively. Among those with SHL ≥ 50%, dermatologists reported satisfaction with current therapy in < 30% of patients.

Conclusion: Dermatologists reported low satisfaction with traditional AA therapies used in patients with extensive SHL, with some patients discontinuing treatment because of worsening disease. This suggests more effective treatments are needed for patients with severe AA.

Introduction: In adults with moderate-to-severe atopic dermatitis (AD), rocatinlimab demonstrated significant and progressive improvement in clinical measures of disease severity compared with placebo. This post hoc analysis of a phase 2b study was undertaken to understand the disease burden and to assess the impact of rocatinlimab on patient-reported outcomes (PROs).

Methods: This analysis used baseline data from a multicenter, randomized, double-blind study of adults with moderate-to-severe AD, who completed a Worst Pruritus numerical rating scale (NRS), Sleep Disturbance NRS, and the Dermatology Life Quality Index (DLQI). A mixed model for repeated measures was used to estimate changes in PRO scores from baseline; scores were also compared with clinically meaningful change benchmarks.

Results: The analysis included 267 subjects, mean (SD) age 37.9 (14.7) years, 40.8% female; 55.1% grade 3 and 44.9% grade 4 Investigator Global Assessment for AD. Mean (SD) scores were: Worst Pruritus NRS 7.5 (1.9), Sleep Disturbance NRS 5.5 (2.9), DLQI total score 12.6 (7.1). Worst Pruritus and Sleep NRS scores had low positive correlations with SCORing AD (SCORAD) score (r = 0.44, r = 0.45 respectively) and negligible correlations with Eczema Area and Severity Index (EASI) score and area affected (r < 0.30). DLQI score varied by sex, study country, race, age, longer disease duration, disease severity (EASI and SCORAD), presence of asthma, and Worst Pruritus NRS, Sleep disturbance NRS, and DLQI scores. Rocatinlimab showed benefit on all three PROs, with significant improvements from baseline at the end of the double-blind period (week 18) and active treatment extension (week 36). Benefits were maintained over 20 weeks' post-treatment follow-up. The benefit of rocatinlimab treatment on PROs is rapid and maintained for at least 20 weeks following treatment completion.

Conclusion: This analysis demonstrates the importance of characterizing the burden of moderate-to-severe AD from the patient's perspective, alongside clinical disease measures, to develop a fuller picture of treatment benefit.

Trial registration: ClinicalTrials.gov identifier, NCT03703102.

Introduction: The Atopic Dermatitis Control Tool (ADCT) assesses six concepts regarding patient-perceived control of atopic dermatitis (AD) in adults and adolescents with AD. This study aimed to develop two modified ADCT versions, one for children with AD aged 8-11 years and another for caregivers of children with AD aged 6 months to 11 years.

Methods: Following the US Food and Drug Administration patient-reported outcomes guidance, the ADCT was modified to produce draft Child and Caregiver ADCT versions, maintaining the original six concepts. The instruments were refined and finalized through an iterative process using input from children with AD and caregivers of children with AD via qualitative interviews. Inclusion criteria were clinician diagnosis of AD, prescription treatment use in the past 3 months, and itching/scratching or rash in the past month. Interviews consisted of concept elicitation to identify perceptions of AD control and cognitive debriefing to test and refine the ADCT items.

Results: In total, 19 children (mean age 9.2 years, 74% male) and 17 caregivers (mean age 36.3 years, 100% female) were interviewed. During concept elicitation, children and caregivers reported similar symptoms and described the cycling and unpredictability of AD. Most participants reported that daily activities were impacted negatively by AD symptoms. The concept of AD control resonated with children and caregivers, and respondents were able to describe their experiences related to AD symptom severity. Children were unfamiliar with the term AD, so the Child ADCT version was named the Child Eczema Control Tool (ECT). Children and caregivers both reported that the instruments assessed relevant concepts, comprehensively measured AD control, and demonstrated content and face validity.

Conclusions: The Child ECT and Caregiver ADCT were developed and qualitatively validated for assessing AD control in patients aged 6 months to 11 years and may offer simple ways to assess disease control and optimize treatment decisions. Video Abstract.

Introduction: Patients with hidradenitis suppurativa (HS) experience significantly delayed diagnoses of 7-10 years from symptom onset on average, but the reasons for this remain largely unknown. This study investigated drivers of diagnostic delay from the perspective of healthcare system equity.

Methods: A literature review was performed to identify published factors associated with delayed HS diagnosis to inform data analysis. Clinical and demographic data from the Adelphi HS Disease Specific Programme (DSP)™, a real-world cross-sectional survey of dermatologists and their consulting patients in France, Germany, Italy, Spain, the UK and the USA in 2020/2021, were used to model factors influencing delay to diagnosis from onset of symptoms and first consultation.

Results: Factors influencing delay to HS diagnosis in the literature with the most available evidence were misdiagnosis, delay in specialist referral and patient embarrassment. Data analysis revealed that increasing age was associated with reduced diagnostic delay after symptom onset. Patients with HS who were White or in Germany were also more likely to receive a faster diagnosis. Smokers, patients with concomitant conditions, or a family history of HS were slower to be diagnosed. When time to diagnosis following first consultation was assessed, increasing age was associated with quicker diagnosis. Moreover, patients with a family history of HS were diagnosed quicker, whereas those with high body mass index, more concomitant conditions, in employment, managed by multiple physicians or European were more delayed.

Conclusion: On the basis of a thorough analysis of real-world data, multiple factors that potentially influenced the timely diagnosis of HS have been identified. For the first time, this study quantifies the relative impact of these modifiers, providing valuable insights into areas that require attention for faster diagnoses and improved disease outcomes.

Introduction: OBI-858 is a brand-new botulinum Type A complex toxin with a specific molecular weight of 760 kDa intended for development for both aesthetic and therapeutic applications. This is a phase I, dose-escalation study to evaluate the safety and preliminary efficacy of OBI-858 in subjects with moderate to severe glabellar lines.

Methods: Each subject received OBI-858 by intramuscular injections with an assigned dose (10 U, 20 U, and 30 U). The safety and preliminary efficacy were evaluated at each of the in-person visits.

Results: A total of 36 subjects (12 subjects per cohort) were enrolled. The response rates (≥ 1 point) for all groups at maximum frown were assessed at week 4 were 100%. The initial improvement for 30 U occurred at day 3. Response rates revealed benefits lasting 4-6 months or longer. Subject satisfaction at week 4 was high in all groups. Adverse effects were mild and infrequent. Among them, one subject had drug-related AE, and one subject had grade ≥ 3 unrelated AE.

Conclusions: This study demonstrated that OBI-858 is well tolerated and showed preliminary efficacy. Overall, the OBI-858 has a clinically favorable profile of safety and efficacy that warrants proceeding to the next studies.

Introduction: UVA-UVB increases skin matrix metalloproteinases and breaks down extracellular proteins and fibrillar type 1 collagen, leading to photodamage. Topical application of nicotinamide prevents UV-induced immunosuppression. Several studies have demonstrated the importance of protection against UV. This study aims to determine the biological effect of a high broad-spectrum UVB-UVA sunscreen containing nicotinamide and panthenol (SSNP) on photodamaged skin using linear confocal optical coherence tomography (LC-OCT), immunohistochemistry, and RNA profiling.

Methods: Two areas of severely photodamaged forearm skin (L01 and L02) and one less sun-damaged (naturally protected) area on the inner part of the forearm (L03) were identified in 14 subjects. These areas were imaged using LC-OCT and L01 and L03 were biopsied at baseline. After 4 weeks of treatment with SSNP, L02 was reimaged using LC-OCT, and biopsied. Histology, immunostaining with p21, p53, PCNA, and CPD, and RNA sequencing were performed in all samples.

Results: LC-OCT analysis showed that epidermis thickness and the number of keratinocytes is higher in the sun-exposed areas than in the non-exposed areas. Comparing before and after treatment, even though there is a trend towards normalization, the differences were not statistically significant. The expression of p21, PCNA, p53, and CPD increased in severely photodamaged skin compared to less-damaged skin. When comparing before and after treatment, only p21 showed a trend to decrease expression. RNA sequencing analysis identified 1552 significant genes correlating with the progression from non-visibly photodamaged skin to post-treatment and pre-treatment samples; in the analysis comparing pre- and post-treatment samples, 5429 genes were found to be significantly associated. A total of 1115 genes are common in these two analyses. Additionally, nine significant genes from the first analysis and eight from the second are related to collagen. Six of these collagen genes are common in the two analyses. MAPK and cGMP-PKG signalling pathways are upregulated in the progression to photodamage analysis. In the pre- and post-treatment analysis, 32 pathways are downregulated after treatment, the most statistically significant being the ErbB, Hippo, NOD-like receptor, TNF, and NF-kB signalling pathways.

Conclusion: This study demonstrates the role of SSNP in collagen generation, highlights the relevance of the cGMP-PKG and MAPK signalling pathways in photodamage, and shows the ability of SSNP to downregulate pathways activated by UV exposure. Additionally, it deepens our understanding of the effect of SSNP on immune-related pathways.