Dermatology

TNF-α inhibitors raise long-term melanoma and NMSC risk without worsening stage

In a 56,209-patient retrospective cohort with chronic inflammatory disease, 13,377 had documented TNF-α inhibitor exposure. TNF-α inhibitor use was significantly associated with higher risk of any cutaneous malignancy, including melanoma, basal cell carcinoma, and squamous cell carcinoma. However, melanoma stage and nonmelanoma skin cancer histopathologic severity at diagnosis did not differ between exposed and unexposed patients. These findings support baseline and periodic total-body skin examinations in TNF-α–treated patients without evidence of more aggressive presentations. 1

Adjuvant pembrolizumab in stage IIB/IIC melanoma improves RFS without extra skin cancers

KEYNOTE-716 randomized 976 patients with completely resected stage IIB/IIC melanoma to pembrolizumab or placebo for up to 17 cycles. New skin cancers developed in 7.6% of pembrolizumab-treated vs 11.5% of placebo-treated participants, with similar new invasive melanoma rates. Recurrence-free survival remained superior with pembrolizumab when new primary melanomas were counted as events (HR 0.65; 95% CI 0.52-0.80). Immune-mediated severe skin reactions were more frequent with pembrolizumab, but overall cutaneous malignancy incidence was not increased. These data support adjuvant pembrolizumab while maintaining, rather than intensifying, routine skin cancer surveillance. 2

Dupilumab improves itch and hive scores in antihistamine-refractory, anti-IgE–naive CSU

LIBERTY-CSU CUPID-C randomized anti-IgE–naive CSU patients uncontrolled on H1-antihistamines to dupilumab or placebo for 24 weeks. Dupilumab significantly improved Itch Severity Score and Urticaria Activity Score versus placebo, with least squares mean differences favoring dupilumab. Pooled CUPID-A and -C data in 289 patients confirmed greater reductions in itch and hive activity compared with placebo. Adverse events were common but similar between dupilumab and placebo and aligned with the established dupilumab safety profile. 3

A 487‑gene expression profile helps choose JAK inhibitor vs Th2 therapy in atopic dermatitis

This prospective study generated a 487-gene expression profile from lesional skin scrapings to predict systemic treatment response in atopic dermatitis. Patients classified with a JAK inhibitor Responder Profile and treated with JAK inhibitors achieved higher EASI-90 rates than those given Th2-targeted therapy. These JAK-profile patients also reached EASI-90 more quickly, reported “no itch” more often, and had higher flare-free rates on JAK inhibitors. Among patients with a Th2 Molecular Profile, EASI-90 rates were similar with Th2-targeted agents and JAK inhibitors. Validation included patients aged 12 years and older, suggesting early feasibility of molecularly guided systemic selection. 4