Scholarly Activity

OBJECTIVES: Understanding patient priorities in nonsegmental vitiligo is essential for developing therapies that address unmet needs. This study used a modified Outcome-Driven Innovation approach to quantify unmet need by considering patients' perspectives on the importance of, and their satisfaction with, treatment attributes.

METHODS: A cross-sectional survey of 522 patients with nonsegmental vitiligo in the United States quantified the relative importance participants placed on 26 treatment attributes. Participants also rated their satisfaction with how well available treatments performed on those attributes. K-means clustering was used to segment participants based on priorities.

RESULTS: Three segments, focusing on efficacy, administration and dosing, or safety, were identified. The two most underserved attributes, identified by >10% of participants as important for which satisfaction was low, were improvement in emotional well-being from repigmentation (15.6% of participants) and access to systemic therapy (15.1% of participants). Participants with ≥5% body surface area affected, including the face, more often identified efficacy and systemic treatment that targets the entire body as unmet needs than did those reporting facial involvement only.

CONCLUSIONS: These findings highlight substantial unmet needs in nonsegmental vitiligo treatment, underscoring the importance of developing systemic therapies that align with patients' priorities to deliver meaningful repigmentation that improves emotional well-being.

Vitiligo is a chronic autoimmune depigmenting disease characterized by loss of pigment in the skin, hair, or both. As treatment options evolve, particularly with the emergence of oral Janus kinase inhibitors and dual Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, it is essential to assess population-level safety events in patients with vitiligo. This retrospective cohort study examined patients aged ≥ 12 years with vitiligo in the United States, comparing them with age-, sex-, and race-matched controls to evaluate patient demographics, baseline comorbidities, medication histories, vitiligo prevalence and incidence across demographic groups, and incidence rates of safety events following vitiligo diagnosis. This study used records dated 1 January 2016 to 30 September 2023 from the Optum Market Clarity United States Electronic Health Record database. This study included 15 047 patients with vitiligo and 75 231 matched controls. In both cohorts, the median age was 51 years and 56.3% of patients were female. Compared with controls, patients with vitiligo had a higher baseline proportion of autoimmune and inflammatory diseases (e.g., autoimmune thyroiditis, psoriasis, alopecia areata, and atopic dermatitis), infections, malignancies, hypothyroidism, allergic rhinitis, and hearing loss; they were also more likely to have used treatments for dermatologic conditions and immunosuppressive medications. Post diagnosis, higher incidence rates of autoimmune and inflammatory conditions (e.g., alopecia areata, systemic sclerosis, pernicious anemia, autoimmune thyroiditis, and psoriasis), infections, hearing-related events, and skin cancer were observed in the vitiligo cohort compared with the non-vitiligo cohort. Furthermore, vitiligo incidence and prevalence rates were numerically higher in Asian and Hispanic populations than in other racial and ethnic groups. However, the observed results should be interpreted with caution considering the limitations of the dataset. These findings provide valuable insight into the epidemiology of and safety considerations for patients with vitiligo in the United States, informing future clinical and therapeutic strategies.

Psoriasis is an immune-mediated inflammatory disease (IMID) impacting more than 40 million people globally and characterized by skin plaques, elevated systemic levels of inflammatory cytokines, and psychosocial burden. Many patients remain undertreated. Available topical and oral treatments are typically less effective than biologic therapies and have safety considerations that may limit long-term use. Tyrosine kinase 2 (TYK2), a Janus kinase (JAK) enzyme, is a validated target in psoriasis and is also being investigated for other IMIDs. TYK2 mediates signaling of interleukin (IL)-23 and IL-17, central proinflammatory cytokines whose dysregulation contributes to chronic inflammation associated with psoriasis, and IL-12 and type I interferons (IFNs). Therefore, selective inhibition of TYK2 offers more targeted immunomodulation vs. broader immunosuppression associated with JAK 1/2/3 inhibition. Envudeucitinib (formerly ESK-001) is a next-generation, oral, allosteric TYK2 inhibitor under investigation for the treatment of psoriasis and systemic lupus erythematosus. Envudeucitinib selectively binds to the unique regulatory domain (JAK homology 2 [JH2]) of TYK2 to induce a conformational change that prevents ATP from binding the catalytic domain (JAK homology 1 [JH1]), thereby inactivating TYK2. This approach avoids adverse events associated with classic JAK inhibition. In preclinical and phase 1 studies, oral administration of envudeucitinib twice daily achieved maximal (90% inhibitory concentration [IC(90)]) TYK2 inhibition over 24 h, highlighting a level of sustained target engagement that distinguishes envudeucitinib from other oral immunomodulators. Envudeucitinib decreased type I IFN gene signatures in whole blood and pSTAT1 in T cells. These findings were corroborated in a phase 2 study in adults with moderate-to-severe plaque psoriasis; envudeucitinib showed maximal TYK2 inhibition at higher doses (40-80 mg daily), patients demonstrated significant and increasing efficacy responses through week 52, and the safety profile was favorable. The efficacy and safety of envudeucitinib are being further evaluated in the ongoing phase 3 ONWARD studies. Psoriasis, an inflammatory disease that develops when the immune system is overactive in the skin, impacts more than 40 million people globally. Patients with psoriasis have red, scaly, itchy skin plaques and high levels of inflammatory molecules in the blood. Many patients do not receive adequate treatment, highlighting the need for more effective and safer oral therapies. We describe how a new potential oral medicine for psoriasis, envudeucitinib, works. Envudeucitinib targets the tyrosine kinase 2 (TYK2) protein that is involved in the inflammation process associated with psoriasis. When taken twice daily, envudeucitinib achieved strong and sustained inhibition of TYK2 for a full 24 h, which is a distinguishing feature of this therapy. Selective reduction of TYK2 activity, while avoiding effects on other related proteins, may allow for more targeted adjustment of inflammatory signaling associated with psoriasis and may translate to clinical benefit. In early studies, envudeucitinib taken orally twice daily markedly reduced TYK2 activity and the levels of other inflammatory molecules over a 24-h period. These findings were confirmed in a phase 2 study in patients with psoriasis, where envudeucitinib again reduced TYK2 activity. Patients with psoriasis taking envudeucitinib had significant improvements in their skin after 12 weeks of treatment, and these improvements were sustained or continued to improve through 52 weeks of treatment without notable side effects. In summary, envudeucitinib is a new potential oral medication for psoriasis that reduces inflammation with an acceptable safety profile.

BACKGROUND: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy.

OBJECTIVE: The 52-week, phase 3b/4 PSORIATYK SCALP (NCT05478499) trial evaluated deucravacitinib efficacy and safety in scalp psoriasis, including patients with more limited overall psoriasis. Here, we report week 16 results.

METHODS: Adults with moderate to severe scalp psoriasis and body surface area involvement ≥ 3% were randomized 1:2 to placebo (n = 51) or deucravacitinib 6 mg once daily (n = 103) through week 16. The primary efficacy endpoint was scalp-specific Physician Global Assessment score of 0/1; key secondary endpoints were Psoriasis Scalp Severity Index 90, scalp-specific numeric rating scale itch score, and static Physician Global Assessment (sPGA) 0/1.

RESULTS: In the overall population, scalp-specific Physician Global Assessment score of 0/1 (48.5% vs 13.7%; P < .0001), Psoriasis Scalp Severity Index 90 (38.8% vs 2.0%; P < .0001), and mean change from baseline in scalp-specific numeric rating scale itch (-3.2 vs -0.7; P < .0001) were superior with deucravacitinib versus placebo. In the sPGA ≥ 3 subpopulation, sPGA 0/1 was superior with deucravacitinib (51.0% vs 4.3%; P < .0001). Adverse events were comparable between groups.

LIMITATIONS: 16-week analysis.

CONCLUSION: Deucravacitinib was efficacious and well tolerated in patients with moderate to severe scalp psoriasis.

BACKGROUND AND OBJECTIVES: Vitiligo is challenging to treat and may have a substantial impact on quality of life. Despite the exponential growth in the development of new "traditional" vitiligo treatments, many vitiligo patients choose to employ medical products and practices that are used with or instead of standard medical care (complementary and alternative medicine or CAM). In this study, CAMs and camouflage were discussed together and referred to as over-the-counter products (OTCs). Using an observational cross-sectional study, we aimed to investigate the motivations and demographic factors of individuals with vitiligo who use OTCs, to identify the most utilized OTCs in this population, and to assess side effects and perceived efficacy of the utilized OTCs.

METHODS: We performed an international observational cross-sectional study between July 2021 and June 2022. An anonymous digital questionnaire was distributed to adults (aged ≥ 18 years) who had been diagnosed with vitiligo by a healthcare provider via e-mails from the Global Vitiligo Foundation to vitiligo support groups and through postings on the MyVitiligoTeam social media network. Participants were presented with a predefined list of OTC products and an open-ended option was also provided.

RESULTS: Of the 224 respondents, half were aged 45-64, most were female (69.6%), and the majority were White (56.3%). A total of 41.1% of participants used OTCs, either exclusively (19.2%) or with prescribed therapies (22%), while 58.9% used only prescribed therapies. The top reasons for using OTCs were dissatisfaction with conventional therapy, concerns about side effects, inconvenience, and cost. The most commonly used OTCs were camouflage, Vitamin B12, Vitamin D, zinc, ginkgo biloba, and vitamin C. Camouflage was reported as the most helpful OTC. Mild side effects were reported by 6.3% of users.

CONCLUSION: This study highlights the widespread use of OTCs in managing vitiligo, emphasizing the need for healthcare providers to be familiar with commonly used OTCs. Patients using OTCs raised concerns about conventional treatments, which should be considered in management discussions and drug development. Camouflage was the most beneficial OTC in this study, and it should be included in management plans. A better understanding of OTCs could improve treatment strategies and patient satisfaction.

IMPORTANCE: There is no international consensus on defining vitiligo severity or relapse. Current measures (such as body surface area) quantify depigmentation but do not fully capture the broader clinical and psychosocial effects of the disease.

OBJECTIVE: To develop internationally agreed-upon definitions and criteria for vitiligo severity and relapse as part of the International Consensus on Definition of Severity and Relapse in Vitiligo study.

EVIDENCE REVIEW: This global, mixed-methods consensus study used a multistep approach, including comprehensive literature review, qualitative study, 2 rounds of electronic Delphi surveys, and a final consensus meeting. To ensure adequate diversity and inclusivity and to capture a broad range of experiences, perspectives, social contexts, and representation, a recruitment framework (encompassing variation in age, sex, and skin phototypes) was predefined.

FINDINGS: In total, 91 people from 5 continents expressed interest in participating. Experts (dermatologists, trialists, methodologists, nurses, psychologists, journal editors, and researchers) and people with vitiligo from diverse ethnic backgrounds and skin phototypes took part. During the first electronic Delphi survey round, 85 people participated and 81 participated in round 2 (response rate of 95% in each survey round). Consensus was reached that even though measurement of body surface area remains a necessary and adequate starting point for assessing vitiligo severity, this measure alone is insufficient to capture disease burden. The final consensus meeting included 44 participants (response rate of 54%). Twelve criteria for upgrading severity were recommended, encompassing both clinical aspects of vitiligo and its psychosocial effects. The major criteria for vitiligo include spread or active disease, involvement of highly visible or high-impact areas, psychological distress, stigmatization, lack of self-acceptance, and overall burden. The minor criteria for vitiligo include darker skin tones, younger age, involvement of scalp/facial hair, increased risk of sunburn, impact on career or school, and perceived loss of personal or cultural identity. No consensus was reached on the extent of pigment loss. Relapse was defined as loss of pigmentation in previously repigmented lesions (repigmentation had occurred either spontaneously or with treatment).

CONCLUSION AND RELEVANCE: This global, mixed-methods consensus study established internationally agreed-upon severity criteria for vitiligo. This consensus aims to bridge the gap between physician assessment and patient experience; improve the relevance and consistency of the severity classification in clinical care, research, and regulatory frameworks; and help close the remaining gaps in the diagnosis and classification of vitiligo.

Conventional type 1 dendritic cells (cDC1s) are specialized for cross-presenting tumor antigens and determining the efficacy of immunotherapies, including immune checkpoint blockade and adoptive cell therapy. However, their rarity and tumor-induced dysfunction severely limit CD8 T cell priming and represent a central bottleneck to therapeutic efficacy. While strategies such as anti-DEC-205-mediated antigen delivery and Flt3L-driven DC expansion can enhance host DC function, their reliance on functional cDC1s remains a significant constraint. We developed Tim-3-targeted vaccines by conjugating tumor antigens or neoantigens to anti-Tim-3 antibodies. These vaccines delivered antigens to both cDC1s and cDC2s, and elicited robust, durable CD8 T cell responses. Remarkably, Tim-3-targeted vaccines endowed cDC2s with efficient cross-presentation capacity that matched that of cDC1s. In tumor-bearing mice or in CD11c-β-catenin(active) mice, which model β-catenin-driven DC dysfunction, Tim-3-targeted vaccination restored cross-priming and counteracted tumor- and DC-mediated immunosuppression. In Batf3(-/-) mice lacking cDC1s, anti-Tim-3-based vaccines still elicited significant CD8 T cell cross-priming and tumor control-albeit both were reduced compared to wild-type mice- demonstrating that cDC1s contribute to but are not essential for Tim-3-targeted vaccine-induced CD8 T cell priming and anti-tumor efficacy. Strikingly, a single dose of anti-Tim-3-neoantigen vaccination eradicated large established MC38 tumors in a CD8 T cell-dependent manner. Together, these data identify Tim-3-targeted vaccines as a next-generation cancer vaccine platform that broadens DC engagement, reduces reliance on cDC1s, and overcomes tumor- and DC-mediated immunosuppression, addressing key limitations of current DC-based cancer vaccines.

BACKGROUND: Vitiligo is a multi-factorial autoimmune skin disorder often triggered by environmental exposures. Although the exposome has gained attention, no systematic review has fully assessed its role in vitiligo.

OBJECTIVE: We aimed to evaluate evidence linking exposomal factors to vitiligo onset and progression, focusing on quantifiable associations and study quality.

METHODS: A systematic search of PubMed and Embase (inception to 25 August, 2024) followed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines and was registered in PROSPERO (CRD42024529828). Eligible studies reported associations between environmental exposures and vitiligo onset, flares, or progression. Observational studies, case series, clinical trials, and pharmacovigilance reports were included. Findings were synthesized narratively.

RESULTS: Of 8377 records, 496 studies met inclusion criteria. Drug-associated vitiligo, particularly from immune checkpoint inhibitors, was the most robustly supported association (7-25% in patients with melanoma). Phenol-based chemicals were consistently linked to melanocyte toxicity. Coronavirus disease 2019 infection modestly increased risk (hazard ratio ≈ 1.11), while vaccination did not. Other factors such as stress (n = 113), trauma, sunburn, smoking, diet, and sleep were frequently cited but supported by lower-level evidence. Study heterogeneity, a lack of standardized outcomes, and the predominance of observational designs limited meta-analysis and causal inference.

CONCLUSIONS: These findings highlight the environmental triggers of vitiligo onset and progression. Drugs, chemicals, and infections are key triggers; lifestyle factors require further study.

The loss of major histocompatibility complex class I (MHC-I) molecules has been proposed as a mechanism for cancer immune evasion. Nevertheless, the mechanism is poorly understood. We report here that membrane-associated RING-CH-type finger 8 (MARCHF8), upregulated by human papillomavirus (HPV), ubiquitinates and degrades MHC-I in HPV-positive head and neck cancer (HPV+ HNC). Inhibiting MARCHF8 restores MHC-I levels on HPV+ HNC cells, suppresses tumor growth, and increases the infiltration of natural killer (NK) and T cells in the tumor microenvironment. Furthermore, Marchf8 knockout markedly increases cross talk between cytotoxic NK cells and CD8(+) T cells with macrophages and enhances the tumor-killing activity of CD8(+) T cells. Interestingly, Marchf8 knockout, in combination with anti-PD-1 treatment, further enhances tumor suppression and increases NK and T cell infiltration in mice bearing immune checkpoint inhibitor-refractory tumors. Our findings suggest that MARCHF8 could be a promising target for immunotherapy for HPV+ HNC patients.

Introduction: Protective hairstyles (PHS) for Afro-textured hair require minimal manipulation and are worn to prevent damage.1 However, there is a dearth of literature regarding risks of PHS.1 As many rely on social media for education, it is imperative to understand the quality of information being shared.2,3 This study aims to analyze the quality of YouTube videos discussing risks of PHS. Methods: A cross-sectional analysis of YouTube videos was performed in December 2024 using a previously validated method.4 Eligibility included being posted January 2020–December 2024, in English, 4–20 minutes, ≥ 1,000 views, and discussed PHS for natural hair. Two reviewers assigned DISCERN scores (DS) from a 16-item validated tool to assess quality of consumer health information.5 DS range from 16–29 (very poor), 30–40 (poor), 41–51 (fair), 52–63 (good), and 64–80 (excellent). Discrepancies were resolved by two additional reviewers. Results: Twenty-six videos were included, mostly by laypersons (n=20) and beauticians (n=2). Discussed styles included box braids, twists, faux locs, wigs, and crochet braids. Risks included breakage, tension, hair loss, dryness, and scalp buildup. The mean DS was 40.8, indicating videos were of poor to fair quality. Nonparametric testing demonstrated no significant difference in DS between personal and educational videos (W=43, p=0.972) or poster types (χ 2 =5.74, df=3, p=0.125). Conclusion: PHS were linked to various types of hair damage in the videos analyzed. The low DS highlights a need for more accurate, high-quality social media content to educate about risks of protective hairstyles and promote safer haircare practices.

Seborrheic dermatitis (SD) is a chronic inflammatory skin condition commonly affecting the scalp, face, and intertriginous areas. It has been reported as a frequent comorbidity among patients with scarring alopecia (SA), a group of disorders characterized by permanent hair loss due to follicular destruction and fibrous replacement. Using the TriNetX US Collaborative Network, which includes approximately 65 million deidentified patients, we evaluated the association between SD and subsequent SA. Patients with SD were identified using ICD-10 code L21 and compared with a control cohort without SD. SA was identified using ICD-10 code L66, which includes pseudopelade, lichen planopilaris, folliculitis decalvans, perifolliculitis capitis abscedens, folliculitis ulerythematosa reticulata, and other nonspecified cicatricial alopecias. A 1:1 greedy nearest-neighbor propensity score matching algorithm controlled for baseline demographics including age, sex, and race/ethnicity. Statistical analyses included chi-square tests and odds ratios (OR) with 95% confidence intervals (CI). After matching, 878,678 patients with SD were compared to 881,049 controls. The mean age was 34.0 years, with most patients female (51%), White (57%), and non-Hispanic/Latino (70%). Patients with SD had significantly greater odds of developing SA (OR 2.674, 95% CI 2.571–2.781, p < 0.001). Findings suggest SD may be a risk factor for SA, potentially through Malassezia-associated inflammation leading to follicular damage and fibrosis. Limitations include diagnostic coding variability, inability to assess disease severity, and lack of subtype specificity. These results highlight the importance of recognizing SD as a possible precursor to SA, warranting further mechanistic and clinical investigation.

Introduction: Lutikizumab, an interleukin-1α/1β antagonist, improved International Hidradenitis Suppurativa Severity Score System (IHS4) in patients with moderate-to-severe hidradenitis suppurativa (HS) who failed anti-TNF therapy in a phase 2b study. Here, we dynamically characterized IHS4 responses to lutikizumab in biologic-naïve adults with moderate-to-severe HS. Methods: In this multicenter, phase 2, open-label study, 47 biologic-naïve adults with moderate-to-severe HS received lutikizumab 300 mg every week (EW) for 16 weeks. Post-hoc efficacy assessments included improvement from baseline in IHS4, percent change from baseline in IHS4 among patients with IHS4 score ≥ 4 at baseline, percent change from baseline in abscess and inflammatory nodule (AN) count ( ≥ 3 AN at baseline), and percent change from baseline in draining tunnels ( ≥ 3 draining tunnels at baseline). Mixed model for repeated measures was used to handle missing data for continuous endpoints. Results: Overall, 47 patients (70.2% female; mean [SD] age 34.4 [9.1] years; mean [SD] IHS4 24.4 (26.26) were enrolled across 20 sites. At Week 16, patients receiving lutikizumab showed improvement from baseline in IHS4 (-19.3) and improvement in percent change from baseline in IHS4 (-71.3%). The proportion of patients with severe HS (IHS4 ≥ 11) decreased from 74.5% at baseline to 22.5% at Week 16. At Week 16, patients receiving lutikizumab showed improvement in percent change from baseline in AN count (-70.8%) and draining tunnels (-84.8%). Conclusions: In biologic-naïve adults with moderate-to-severe HS, lutikizumab 300 mg EW improved IHS4, as well as AN and draining tunnel counts over 16 weeks. These results support further investigation of lutikizumab in HS.

Background: Delgocitinib, a non-steroidal topical pan-JAK inhibitor for moderate to severe CHE, has been shown to improve patients’ HRQoL within 16 weeks. Methods: In the phase 3 open-label DELTA 3 (NCT04949841), patients completing the 16-week DELTA 1 and 2 trials were treated on an as-needed basis with twice-daily delgocitinib cream for an additional 36 weeks. EQ-5D-5L, Dermatology Life Quality Index (DLQI), Hand Eczema Impact Scale (HEIS) and the Work Productivity and Activity Impairment (WPAI) questionnaire were assessed over a total of 52 weeks. Data was reported as observed in patients receiving delgocitinib in the parent trials. Change from baseline in parent trials was reported in those that completed the 52 week trials. Results: Patients (n=560) had a mean age of 45.8 years (SD 14.4), and 63.4% were female. At baseline in the parent trial, average scores for EQ-5D-5L, DLQI, and HEIS were 0.64 (SD 0.23), 12.6 (6.1), and 2.49 (0.76), respectively. At end of parent trials, these scores had improved to 0.83 (0.18), 4.5 (5.0), and 0.89 (0.88), respectively. At week 36, improvements remained stable; 0.86 (0.16), 3.9 (4.1), and 0.81 (0.82), respectively. For patients who completed the study, mean improvements from baseline were significant (P< .0001): EQ-5D-5L improved by 0.20 (95% CI: 0.18, 0.22), DLQI improved by 8.5 (-9.1, -7.9), and HEIS improved by -1.66 (-1.75, -1.57). Furthermore, work productivity loss and daily activity impairment scores improved: -25.4 (-29.0, -21.9) and -33.3 (-35.8, -30.7), respectively. (P< .0001). Conclusion: Improvements in HRQoL, work productivity and daily activity impairment demonstrated after 16 weeks of continuous twice-daily treatment with delgocitinib cream were maintained after an additional 36 weeks of as-needed treatment. Acknowledgements: The DELTA 3 (NCT04949841) trial and analyses were sponsored by LEO Pharma A/S.

Sarecycline, a narrow-spectrum oral antibiotic approved for treatment of inflammatory lesions in moderate-to-severe acne vulgaris (AV), has been evaluated in three phase 3 trials that have been reported separately. This pooled analysis of results from these trials provided information from a cohort of patients with moderate-to-severe facial AV (Investigators’ Global Assessment [IGA] 3 or 4) treated with this agent. Each trial had a 12-week duration and followed a randomized (1:1 sarecycline vs placebo in two studies and 2:1 in one study) double-blind design in which patients received sarecycline (1.5 mg/day) or placebo. Endpoints assessed included IGA success (score of 0 [clear] or almost clear [1] and a reduction from baseline >/=2), percent reduction in inflammatory lesions, and absolute reduction in the number of non-inflammatory lesions. The trials enrolled 2,393 patients (9-45 years old, 57.4% female; 64.9% white, 12.6% black, 19.0% Asian, 2.2% multiracial, and 1.3% other). At Week 12, IGA success was achieved by 25.9% of patients treated with sarecycline vs 13.3% for placebo (P<0.0001). Percent reductions in inflammatory lesions were –58.5% vs –41.2% (P<0.0001), respectively; and those for non-inflammatory lesions were –40.4% vs –29.2% (P<0.01). Pooled results from the three studies indicated a rapid onset of action for sarecycline. At 3 weeks after treatment initiation (first post-baseline evaluation), percent reductions in inflammatory lesions were –30.5% for sarecycline and –22.4% for placebo (P=0.0001). This pooled analysis demonstrates that sarecycline improves IGA and inflammatory lesions in moderate-to-severe AV, with improvements evident as early as week 3 and sustained over time.

CAB gel—the only approved triple-combination acne topical—was efficacious/safe in 12-week clinical trials and in a 24-week study.1-4 Acne presentation and sequelae vary by skin type, requiring long-term management strategies to account for differences in skin pigmentation.5,6 This post hoc analysis assessed long-term CAB use in participants with darker Fitzpatrick skin phototypes IV-VI. Data were pooled from 2 identical, 24-week, single-center, open-label studies of once-daily CAB in 50 participants ≥ 12 years with moderate/severe acne (Investigator’s Global Assessment [IGA] score=3/4). Endpoints included changes from baseline in IGA score and inflammatory/noninflammatory lesions. Skin appearance (dryness, postinflammatory hyperpigmentation [PIH], postinflammatory erythema [PIE]), tolerability (itching, burning, redness, swelling), scarring, and adverse events were evaluated. Of 24 participants with Fitzpatrick skin types IV-VI, 22 completed the studies. At week 24, 73% of participants achieved treatment success ( ≥ 2-grade reduction from baseline in IGA score and clear/almost clear skin), with reductions in inflammatory and noninflammatory lesions of 90% and 66%, respectively. PIH, PIE, and scarring improved from baseline by 71%, 87%, and 32%, respectively. No participants reported tolerability issues at week 24 and all had skin dryness scores of 0 (none). One treatment-related adverse event (BPO allergy) occurred, leading to study discontinuation. In participants with darker skin phototypes, 6 months of once-daily CAB use led to 73% treatment success and inflammatory lesion reductions of 90%. These improvements are higher than those seen at week 12 in the pivotal trials and support the long-term use of CAB in patients with darker skin phototypes.

Background: Gene Expression Profiling (GEP), like the integrated 31-GEP by Castle Biosciences, and clinicopathologic nomograms, like the Melanoma Institute Australia (MIA) and Memorial Sloan Kettering Cancer Center (MSKCC), were developed to assess risk of sentinel lymph node biopsy (SLNB) positivity in patients with thin-melanomas. Direct head-to-head comparisons of their performance remain limited. Methods: We retrospectively reviewed charts of all melanoma patients who underwent i31-GEP testing at a single institution and calculated MIA and MSKCC nomogram scores. Sensitivity, specificity, AUC, and Net Reclassification Index (NRI) were calculated for SLN positivity prediction at 5% and 10% risk thresholds. Recurrence discrimination was evaluated using AUROC for MIA prognostic score and GEP. Results: Among 20 patients (18 SLN–, 2 SLN+) with results from all tools, MIA and MSKCC achieved perfect sensitivity for SLN positivity at 5% threshold, but low specificity (0.17 and 0.22). i31-GEP showed lower sensitivity (0.50) and moderate specificity (0.44). Among 31 patients (7 recurrences) with MIA and i31-GEP results (MSKCC does not calculate recurrence), the MIA prognostic score (AUROC 0.87, 95% CI 0.74–1.00) demonstrated stronger discrimination for recurrence than i31-GEP (AUROC 0.82, 95% CI 0.66–0.99). i31-GEP positivity was significantly associated with recurrence in non-T1a tumors (Fisher’s exact p = 0.0238; OR = ∞ [ 1.06–∞]) but showed no significant link in T1a tumors (p = 0.111; OR = ∞ [ 0.21–∞]). Conclusions: Clinicopathologic nomograms outperform i31-GEP at predicting SLN sensitivity and disease recurrence. Larger prospective studies are needed to validate these findings.

Introduction: Access to pathologic review by a trained dermatopathologist is an integral component of skin disease diagnosis management. [1,2] There is currently no worldwide assessment of access to dermatopathology. [3]. Methods: The Global Access to Skin Health Observatory (SkinObservatory) Study is a cross-sectional, Delphi-developed, survey of national-level dermatologic leaders in all 194 WHO member states. Participants reported number of dermatopathologists, presence of specialty board, training programs, and access to dermatopathology slide review. Responses were compared across World Bank Income (WBI) levels with Chi-squared and Kruskal-Wallis analyses. Results: Out of 157 countries responding, 139 reported on dermatopathology. Presence of dermatopathologists is associated with WBI level (p=0.024), with dermatopathologists present in 80% of high-income and 41% of low-income countries. Seventy-five percent of lower-income countries rank their access to dermatopathology as either “extremely poor” or “inadequate,” while 67% of higher-income countries report their access as “adequate” to “excellent.” Dermpatopathologist density is significantly associated with WBI (p=0.0001), with median dermatopathologists per 1,000,000 people of 0.0318 in low-income, 0.222 in lower-middle-income, 0.376 in upper-middle-income, and 2.45 in high-income countries. The presence of dermatopathology boards (p=0.026) and training programs (p=0.013) is more common in higher-income countries. Forty-seven countries have no dermatopathologists. In areas without dermatopathologists, dermatopathology is primarily done by: 1) general/surgical pathologists, 2) dermatologists, and 3) referrals to regional/national centers. Conclusion: Our data illustrates a global dearth of access to dermatopathology that disproportionately burdens lower-income countries. By providing a granular assessment of global access to dermatopathology, we aim to define avenues to improve access to this vital resource.

Introduction: Among adults with moderate-to-severe plaque psoriasis in ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604), the targeted oral peptide icotrokinra (ICO) demonstrated significantly higher rates of skin clearance vs placebo (PBO) at Week (W)16 and vs deucravacitinib (Deucra) at W16&W24, with adverse event (AE) rates similar to PBO and numerically lower than Deucra.1 Here, ICO findings through W52 of ICONIC-ADVANCE 1&2 are reported. Methods: ICONIC-ADVANCE 1&2 participants (pts) were randomized (2:1:2/4:1:4) to once-daily oral ICO 200mg, PBO (PBO→ICO at W16), or Deucra 6mg (Deucra→ICO at W24). Investigator’s Global Assessment (IGA)/Psoriasis Area and Severity Index (PASI) responses and AEs were assessed through W52. Results: In ICONIC-ADVANCE 1&2, 774/731 pts with moderate-to-severe psoriasis received ICO (311/322), PBO (156/82 [PBO→ICO=141/74]), or Deucra (307/327 [Deucra→ICO=283/301]). Skin clearance rates achieved with ICO through W24 of ICONIC-ADVANCE 1&2 (IGA0/1: 74/68%, PASI90: 66/65%, IGA0: 48/40%, PASI100: 41/33%) were maintained or increased through W52 (IGA0/1: 74/73%, PASI90: 69/71%, IGA0: 52/50%, PASI100: 49/48%). PBO→ICO pts achieved consistent rates of skin clearance at W52 (IGA 0/1: 75/80%, PASI 90: 71/74%, IGA0: 56/47%, PASI100: 50/43%). In Deucra→ICO pts, skin clearance rates at W24 (IGA0/1: 52/55%, PASI90: 41/43%, IGA0: 21/21%, PASI100: 16/16%) increased substantially after transitioning to ICO (W52 IGA 0/1: 75/79%, PASI 90: 71/77%, IGA0: 45/56%, PASI100: 42/51%). ICO safety through W52 was consistent with that observed through W16/W24. Conclusion: ICO provided robust and durable skin response rates through 1 year of treatment; skin clearance rates increased in Deucra-randomized pts after transitioning to ICO. No ICO safety signals were identified.