Dermatology

Thaçi, D., Strober, B., Gordon, K. B., Foley, P., Gooderham, M., Morita, A., Papp, K. A., Puig, L., Menter, M. A., Colombo, M. J., Elbez, Y., Kisa, R. M., Ye, J., Napoli, A. A., Wei, L., Banerjee, S., Merola, J. F. and Gottlieb, A. B. (2022). “Deucravacitinib in Moderate to Severe Psoriasis: Clinical and Quality-of-Life Outcomes in a Phase 2 Trial.” Dermatol Ther (Heidelb) 12(2): 495-510.

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INTRODUCTION: Deucravacitinib is an oral, selective tyrosine kinase 2 inhibitor that demonstrated therapeutic benefit in a Phase 2 clinical trial of adults with moderate to severe plaque psoriasis. This analysis was designed to evaluate the effect of deucravacitinib on additional clinical and quality-of-life (QoL) outcomes and assess the relationship between these outcomes in adults with psoriasis. METHODS: Post-hoc analysis of a 12-week Phase 2 trial was conducted for the three most efficacious dosage groups (3 mg twice daily, 6 mg twice daily, 12 mg once daily) and placebo. Investigator assessments for efficacy included Psoriasis Area and Severity Index (PASI), body surface area (BSA) involvement, and static Physician’s Global Assessment; QoL was assessed using the Dermatology Life Quality Index (DLQI). Treatment responses and their associations were evaluated over time. RESULTS: Deucravacitinib elicited improvement versus placebo as early as Week 4 for most efficacy measures (including changes in absolute PASI and BSA), with efficacy trends observed from Week 2 to Week 12. Improvements in QoL, assessed by achievement of a DLQI overall score of 0/1 (no effect at all on patient’s life), followed a pattern similar to deucravacitinib-related clinical outcomes over 12 weeks. Overall, patients with greater improvements in psoriasis-related clinical signs and symptoms also reported greater improvement in QoL. However, complete skin clearance was not required for achieving DLQI 0/1. CONCLUSION: Deucravacitinib treatment produced early response and similar trends in improvements across multiple efficacy assessments and QoL in moderate to severe plaque psoriasis. Deucravacitinib has the potential to become a promising new oral therapy for this condition. TRIAL REGISTRATION: ClinicalTrials.gov identifier; NCT02931838.

Farberg, A. S., Fitzgerald, A. L., Ibrahim, S. F., Tolkachjov, S. N., Soleymani, T., Douglas, L. M., Kurley, S. J. and Arron, S. T. (2022). “Current Methods and Caveats to Risk Factor Assessment in Cutaneous Squamous Cell Carcinoma (cSCC): A Narrative Review.” Dermatol Ther (Heidelb) 12(2): 267-284.

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Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, and the number of deaths due to cSCC is estimated to be greater than the number attributed to melanoma. While the majority of cSCC tumors are resectable with clear margins by standard excision practices, some lesions exhibit high-risk factors for which there is evidence of their association with recurrence, metastasis, and disease-specific death. The most commonly used staging systems and guidelines in the USA for cSCC are based on these clinical and pathologic high-risk factors; however, these are limited in their ability to predict adverse events, thus posing a challenge for implementing risk-directed patient management. Since the development of local recurrence and/or metastasis has a profound impact on the survival of patients with cSCC, accurate identification of patients at high risk for poor outcomes is critical, potentially allowing for early and appropriate adjuvant therapy. This review summarizes the current cSCC literature with a focus on how differing clinical assessments within each of the five selected risk factors (perineural invasion, differentiation, depth of invasion, size, and location) can influence the evaluation of patient outcomes, along with summarizing the utility of staging and guidelines, and highlighting the potential for molecular tools to improve upon cSCC risk assessment.

Preston, A., West, C., McCollough, M. and Hosler, G.A. (2021). “Melanocytic Panfolliculoma: A Case Report of a Rare Benign Follicular Tumor.” Am J Dermatopathol Dec 28. [Epub ahead of print].

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Panfolliculomas (PF) are rare, benign, follicular tumors that differentiate toward multiple components of the hair follicle, and several variants have been described. We present a case of a rare pigmented PF presenting on actinically damaged skin in an 83-year-old man, which was clinically concerning for malignancy. This tumor arose near an area of atypical squamous proliferation and has evidence of infundibular, outer root sheath, and matrical differentiation and foci of heavy melanin pigmentation and increased melanocytes. We propose the novel designation of “melanocytic PF,” akin to melanocytic matricoma but with panfollicular differentiation.

Drissi, M., Carr, E. and Housewright, C. (2022). “Sunscreen: a brief walk through history.” Proc (Bayl Univ Med Cent) 35(1): 121-123.

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The sunscreens we see today were paved by our ancestors’ sun protection methods, followed by scientific discovery in the more recent era and the trials and errors of the sunscreen formulations that followed. This history highlights sun protection methods used over the centuries and the varying degrees of agreeable sensorial properties or comforts in these methods.

Reich, K., Mrowietz, U., Menter, A., Griffiths, C.E.M., Bagel, J., Strober, B., Nunez Gomez, N., Shi, R., Guerette, B. and Lebwohl, M. (2021). “Effect of baseline disease severity on achievement of treatment target with apremilast: results from a pooled analysis.” J Eur Acad Dermatol Venereol 35(12): 2409-2414.

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BACKGROUND: Treating to absolute treatment targets rather than relative measures such as Psoriasis Area and Severity Index (PASI)-75 is emerging as an important clinical concept included in psoriasis guidelines and clinical practice. Achieving treatment targets is associated with achievement of long-term outcomes. OBJECTIVE: To evaluate the relationship between psoriasis severity, disease characteristics and achievement of PASI ≤2 with apremilast in a pooled analysis of the phase 3 ESTEEM 1 and 2 (NCT01194219 and NCT01232283), phase 3b LIBERATE (NCT01690299) and phase 4 UNVEIL (NCT02425826) clinical trials. METHODS: Pooled data from patients with moderate-to-severe plaque psoriasis randomized to apremilast 30 mg BID were analysed by baseline PASI quartiles (Q1: 2.4-13.1; Q2: 13.2-15.9; Q3: 16.0-20.0; Q4: 20.1-57.8). Assessments included PASI, Dermatology Life Quality Index (DLQI), Scalp Physician’s Global Assessment (ScPGA; ScPGA ≥1) and target (worst) Nail Psoriasis Severity Index (NAPSI; NAPSI ≥1). RESULTS: Of 1062 patients, 963 had ScPGA ≥1 and 643 had NAPSI ≥1; 771 patients with baseline and Week 32 PASI assessments were included in analyses of Week 32 PASI target achievement. Rates of PASI ≤2 at Week 32 were greater in lower PASI quartiles (Q1: 43.5%; Q2: 31.2%; Q3: 26.8%; Q4: 18.4%). Most patients achieving PASI ≤2 target (83.6%) achieved DLQI ≤5 at Week 32; 59.3% of patients who did not achieve PASI ≤2 target achieved DLQI ≤5. At Week 32, mean improvements in ScPGA and NAPSI were similar with more moderate vs. more severe disease (ScPGA, range: 1.1-1.4; NAPSI, range: 1.6-2.5). In a subgroup analysis, achievement of PASI ≤2 target was higher in the lowest PASI quartile and with disease duration <5 years. CONCLUSIONS: Greater achievement of PASI ≤2 was observed in patients with more moderate vs. more severe skin disease. Apremilast may be particularly beneficial in more moderate disease early in the treatment paradigm.