INTRODUCTION: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the USA and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. In POETYK PSO-1 and PSO-2, deucravacitinib was superior to placebo and apremilast and well tolerated in patients with plaque psoriasis. Patients who completed PSO-1/PSO-2 could enroll in the POETYK long-term extension (LTE) trial. This analysis evaluates the effects of deucravacitinib on laboratory parameters.

METHODS: POETYK PSO-1 and PSO-2 were 52-week, phase 3, double-blinded trials that randomized patients 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At week 52, eligible patients enrolled in POETYK LTE and received open-label deucravacitinib. Mean changes from baseline in laboratory parameters, laboratory adverse events (AEs), and laboratory AEs resulting in discontinuation were evaluated over 3 years.

RESULTS: A total of 1519 patients received one or more doses of deucravacitinib across trials. Total exposure over 3 years was 3294.3 person-years. No clinically relevant mean changes were observed in laboratory parameters. Grade ≥ 3 laboratory AEs were infrequent during the 1-year period, with incidence rates remaining stable in patients treated with deucravacitinib through 3 years. Most laboratory AEs remained at the same grade; shifts to higher grades were infrequent, with most increases being to grade ≤ 2. Discontinuations due to laboratory AEs were rare.

CONCLUSIONS: Deucravacitinib did not result in clinically meaningful changes in laboratory parameters over 3 years, including changes seen with Janus kinase (JAK) 1,2,3 inhibitors. Grade ≥ 3 laboratory AEs and discontinuations were rare.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, POETYK PSO-1 (NCT03624127), POETYK PSO-2 (NCT03611751), POETYK LTE (NCT04036435).

INTRODUCTION: A cell harvesting device for preparing non-cultured autologous skin cell suspension (ASCS) at the point-of-care is FDA-approved for repigmentation of stable depigmented vitiligo lesions in patients 18 years and older. The pivotal RSVP trial showed ≥80% repigmentation at Week-24 in 36% of lesions treated with laser ablation, ASCS, and narrowband ultraviolet B phototherapy compared to 0% with phototherapy alone (p = 0.012). The objective of this analysis was to evaluate the potential economic impact of laser ablation plus ASCS with phototherapy versus phototherapy alone for repigmentation of stable vitiligo lesions from a US payer perspective.

METHODS: A 5-year decision-tree model was developed reflecting clinical pathways of adults with stable vitiligo lesions who had an inadequate response to prior topicals and phototherapy. Patients entering the model were treated with ASCS plus phototherapy or phototherapy alone and assessed for treatment response at Weeks-24 and 52 based on the RSVP trial's effectiveness endpoints. Durable response for Year-2 onwards was proxied by melanocyte-keratinocyte transplantation data. Model outcomes included per-patient total and incremental healthcare costs, treatment costs and total costs, cost per-patient per-month (PPPM), and cost per-patient per-year (PPPY). One-way sensitivity analyses assessed model result robustness.

RESULTS: The cumulative total per-patient cost for ASCS plus phototherapy increased from $28,177 to $92,779 between Year-1 and Year-5. Phototherapy alone increased from $21,146 to $101,518 over the same period. Compared to phototherapy alone, ASCS plus phototherapy incurred $7,030 more total per-patient cumulative costs in Year-1 and $8,738 less by Year-5 (-$146 PMPM; -$1,748 PPPY). Breakeven occurred between Years 2-3. Results were most sensitive to changes in ASCS response at Weeks-24 and 52 and healthcare costs.

CONCLUSION: Among adults with stable vitiligo with prior inadequate response to topicals or phototherapy, ASCS treatment may lead to lower all-cause direct medical costs over 5 years compared to phototherapy alone.

INTRODUCTION: A low-dose modified formulation of minocycline hydrochloride, DFD-29, is under evaluation for treating papulopustular rosacea (PPR).

OBJECTIVE: To determine the efficacy and safety of DFD-29, 40 mg, compared with doxycycline, 40 mg, and placebo for treating PPR.

DESIGN, SETTING, AND PARTICIPANTS: This study included data from 2 double-blind, placebo-controlled, phase 3 randomized clinical trials (MVOR-1 and MVOR-2) conducted between March 2022 and May 2023 at 61 centers in the US and Germany. Healthy adults 18 years and older with moderate to severe PPR were included.

INTERVENTIONS: Participants were randomized 3:3:2 to oral DFD-29 (minocycline hydrochloride capsules), 40 mg; doxycycline, 40 mg; or placebo once daily for 16 weeks.

MAIN OUTCOMES AND MEASURES: The coprimary efficacy outcomes were (1) proportion of participants with Investigator's Global Assessment (IGA) treatment success with DFD-29 vs placebo and (2) total inflammatory lesion count reductions with DFD-29 vs placebo. Secondary outcomes included comparisons between DFD-29 and doxycycline in coprimary outcomes and between DFD-29 and placebo in erythema reduction.

RESULTS: Of 653 participants enrolled, 323 were randomized in MVOR-1 (247 [76.5%] women; mean [SD] age, 47.2 [13.7] years) and 330 were randomized in MVOR-2 (249 [75.5%] women; mean [SD] age, 51.6 [14.0] years). DFD-29 demonstrated superior efficacy in IGA success rates compared with placebo (MVOR-1: treatment difference [TD], 32.9%; 95% CI, 19.6-46.2; P <  .001; MVOR-2: TD, 34.1%; 95% CI, 21.3-46.8; P <  .001) and compared with doxycycline (MVOR-1: TD, 18.0%; 95% CI, 5.0-31.1; P = .01; MVOR-2: TD, 28.3%; 95% CI, 17.4-39.3; P <  .001). DFD-29 also showed superior efficacy in least-squares mean reductions in total inflammatory lesions vs placebo (MVOR-1: TD, -9.2; 95% CI, -11.5 to -6.9; P <  .001; MVOR-2: TD, -6.8; 95% CI, -8.9 to -4.8; P <  .001) and doxycycline (MVOR-1: TD, -4.7; 95% CI, -6.7 to -2.8; P <  .001; MVOR-2: TD, -3.5; 95% CI, -5.4 to -1.6; P <  .001). Adverse events with DFD-29, doxycycline, and placebo were reported in 32 of 121 (26.4%), 25 of 116 (21.6%), and 27 of 76 (35.5%), respectively, in MVOR-1 and 51 of 122 (41.8%), 40 of 121 (33.1%), and 30 of 82 (36.6%), respectively, in MVOR-2. The most common adverse events with DFD-29, doxycycline, and placebo were nasopharyngitis, reported in 4 of 121 (3.3%), 2 of 116 (1.7%), and 3 of 76 (3.9%), respectively, in MVOR-1 and 13 of 122 (10.7%), 10 of 121 (8.3%), and 13 of 82 (15.9%), respectively, in MVOR-2, and COVID-19, reported in 4 of 121 (3.3%), 3 of 116 (2.6%), and 4 of 76 (5.3%) in MVOR-1 and 7 of 122 (5.7%), 8 of 121 (6.6%), and 5 of 82 (6.1%) in MVOR-2.

CONCLUSIONS AND RELEVANCE: In this study, DFD-29 was superior in efficacy to both doxycycline and placebo and demonstrated a favorable risk-benefit profile in the treatment of PPR.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT05296629 and NCT05343455.

INTRODUCTION: Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the only fixed-dose, triple-combination approved for acne. In phase 2 and 3 studies, CAB demonstrated superior efficacy to vehicle and component dyads. This post hoc analysis examined efficacy/tolerability of CAB in 147 self-identified Hispanic/Latino participants (referred to as Hispanic).

METHODS: Data were pooled from one phase 2 (NCT03170388) and two phase 3 (NCT04214652, NCT04214639) double-blind, 12-week studies. Eligible participants aged ≥9 years with moderate to severe acne were randomized to once-daily CAB or vehicle. Endpoints included ≥2-grade reduction from baseline in Evaluator's Global Severity Score with clear/almost clear skin (treatment success) and inflammatory/noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were assessed.

RESULTS: At week 12, 56.2% of CAB-treated participants achieved treatment success vs 18.4% with vehicle (p <  0.001). Reductions in inflammatory/noninflammatory lesions were 77.1%/76.2% with CAB vs 56.4%/45.0% with vehicle, respectively (p <  0.001, all). CAB TEAE rates were similar to overall study populations (27.0% vs 24.6%-36.2%). Baseline hyperpigmentation scores decreased from 0.6 to 0.3 (1 = mild) at week 12 with CAB. CAB gel was efficacious, safe, and well tolerated in Hispanic participants. Limitations include lack of Fitzpatrick skin phototype and short study duration.

CONCLUSIONS: This study provides support for acne treatment with CAB in ethnically diverse populations.

BACKGROUND: Abrocitinib has a manageable long-term safety profile for patients with moderate-to-severe atopic dermatitis. Identifying populations at higher risk of adverse events will help optimize dose selection.

OBJECTIVE: To evaluate abrocitinib long-term safety by age.

METHODS: Data (cutoff: September 25, 2021) from JADE clinical trials were pooled in a consistent-dose cohort (patients who received the same abrocitinib dose throughout exposure) or a variable-dose cohort (patients who received abrocitinib 200 mg [12 wk], were randomly assigned later to receive abrocitinib 200 mg, 100 mg, or placebo [up to 40 wk], and assigned to receive abrocitinib 200 mg or 100 mg in the long-term study). Data were stratified post hoc by age at baseline (12 to < 18 y; 18 to < 40 y, 40 to < 65 y, and ≥65 y). Incidence rates of treatment-emergent adverse events (TEAEs) of special interest were assessed.

RESULTS: Analysis included 3,802 patients (exposure: 5,214 patient-years). The incidence rates for serious adverse events, TEAEs leading to study discontinuation, serious infections, herpes zoster, thrombocytopenia, lymphopenia, nonmelanoma skin cancer, malignancies (excluding nonmelanoma skin cancer), major cardiovascular events, and venous thromboembolism were numerically higher in patients aged 65 years or older than in younger patients. Overall, adolescents had the lowest rates for TEAEs of special interest.

CONCLUSIONS: Abrocitinib has a manageable long-term safety profile. TEAEs of special interest were lower in adolescents and higher in the 65-years-old or older age group. Risk of specific TEAEs was numerically higher in patients aged 65 years or older treated with abrocitinib 200 mg and underscores the importance of dose selection in older patients.

INTRODUCTION: The mental health burden associated with vitiligo can significantly impact patients' quality-of-life. Although successful for repigmentation of stable vitiligo, adoption of surgical melanocyte transplantation remains limited due to time and skilled-expertise requirements. A cell harvesting device prepares autologous skin cell suspension (ASCS) at point of care, simplifying the process.

OBJECTIVE: To confirm early and favorable repigmentation response and evaluate health-related quality-of-life changes following ASCS treatment of stable vitiligo.

METHODS: In this large (N = 107), prospective, multicenter study, vitiligo lesions were laser-ablated and received ASCS treatment followed by at-home phototherapy.

RESULTS: All Fitzpatrick skin types and major vitiligo subtypes were represented. Excellent repigmentation response (≥80%) was observed by week 4. By week-24, all lesions demonstrated improvement; 67% achieved >50% repigmentation, 42% achieved ≥80% repigmentation, and 8% achieved complete repigmentation. Vitiligo Noticeability Scale response was attained by 27.7% of lesions; 72.3% of patients reported treatment satisfaction. Significant improvement from baseline in Vitiligo Quality-of-Life Instrument (P < .05) was observed at week-24.

LIMITATIONS: No control.

CONCLUSIONS: The cell harvesting device provides a simplified, more accessible technique for melanocyte transplantation. ASCS is highly effective for repigmentation of stable vitiligo lesions, with positive patient-reported outcomes and improvement in quality-of-life, as demonstrated in this large, diverse population.

OBJECTIVE: To evaluate the awareness of and attitudes toward various aspects of sun-exposure risks and protection methods among Canadians.

METHODS: An online survey conducted from September 28 to October 18, 2021, included 17,001 participants aged 18 years and above from 17 countries across 5 continents; the data presented are those of the Canadian population (n = 1,000). The survey focused on demographics, sun-exposure habits, comprehension of risks, and knowledge of photoprotection. The results were analyzed using descriptive statistics to identify prevalent trends and discrepancies in sun-protective behaviours among Canadians.

RESULTS: The majority of Canadian respondents (93%) acknowledged the health risks associated with sun exposure. While 81% of Canadians reported using some form of sun protection, only 10% systematically implemented all recommended protective measures, highlighting a gap in knowledge translation. Misconceptions regarding the safety of tanned skin and the effectiveness of sunscreens were widespread, particularly in younger demographics and in individuals with darker skin. Knowledge and preventive behaviours were markedly better among individuals who regularly consult dermatologists.

CONCLUSIONS: This study highlights general awareness of sun-protective behaviours but a lack of universal and comprehensive implementation among Canadians. Given the knowledge gaps in younger demographics and darker skin phototypes, targeted educational initiatives are essential to correct prevalent misconceptions about sun exposure and tanned skin. Dermatologists and other health care professionals can play a pivotal role in education and primary prevention strategies for skin cancer and other sun-related comorbidities.

Photodynamic therapy (PDT) is a versatile treatment with diverse applications in dermatology. PDT combines photosensitizers, most commonly 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL), and a light source, such as light-emitting diodes (LEDs), fluorescent bulbs, lasers, flash lamps, or sunlight, in the presence of molecular oxygen to induce therapeutic effects primarily through singlet oxygen and reactive oxygen species generation. Downstream cellular and physiological effects include apoptosis, necrosis, and immune modulation. PDT efficacy depends on photosensitizer parameters, including photosensitizer type, concentration, dosing, temperature, and incubation time, and light source parameters such as light source, power density, wavelength, and fluence. PDT is generally safe and well tolerated; potential adverse effects such as pain and erythema are typically mild and self-limiting. Part I of this Continuing Medical Education (CME) provides a foundational overview of PDT principles, including mechanisms of action, photosensitizers, and light sources.