Gender perspective in psoriasis: a scoping review and proposal of strategies for improved clinical practice by European dermatologists.

Background: The prevalence of psoriasis is similar between men and women; however, evidence exists of sex- and gender-related differences in disease expression, impact, coping, and needs of patients with psoriasis. These differences are essential and should be considered in clinical practice and research. Objective: To compile available evidence on sex- and gender-related differences in psoriasis, identify the most critical gaps in clinical practice and research, and use it to propose strategies for improved clinical practice. Methods: Six European dermatologists selected the topics to consider according to their relevance in the dermatology setting with the support of methodologists. Evidence on sex- and gender-related differences was obtained by a scoping review based on search strategies in Medline and Cochrane Library from inception to October 2021 using the following terms: arthritis, psoriatic, psoriasis, gender, and sex. The panel discussed the results and proposed strategies by consensus. Results: The scoping review identified broad themes: (1) clinical expression, (2) severity and patient-reported outcomes, (3) psychosocial impact, (4) access to treatments and propensity to treat, (5) comorbidities, and (6) treatment effect. The strategies are based on these broad themes. Limitations: No risk of bias assessment was done due to the scoping nature of the review. Conclusion: This review offers insights into gender differences in psoriasis, providing a foundation for improving clinical practice and patient outcomes.

Improvement of head and neck symptoms in patients with atopic dermatitis treated with baricitinib based on five Phase III clinical trials

Background: In adults with atopic dermatitis (AD), head and/or neck involvement is frequent, bothersome, and impacts quality of life, however, long-term topical corticosteroids (TCS) are contraindicated for this difficult-to-treat region. Baricitinib, an oral, selective, reversible inhibitor of Janus kinase 1/2 has demonstrated efficacy in adult patients with moderate-to-severe AD. Objectives: For this post hoc analysis, data from five Phase III trials were used to investigate the efficacy of baricitinib in patients with head and neck involvement. Materials & Methods: Data were obtained from BREEZE-AD1, -AD2, -AD4, -AD5, and -AD7; Phase III, multicenter, randomized, double-blind, placebo-controlled studies conducted in patients ≥18 years with moderate-to-severe AD. BREEZE-AD1, -AD2, and -AD5 evaluated baricitinib as monotherapy, and BREEZE-AD4 and -AD7 evaluated baricitinib in combination with TCS, topical calcineurin inhibitors, or topical PDE-4 inhibitors, where available. The proportion of patients with improvement of Eczema Area and Severity Index (EASI) total score from baseline of ≥50% (EASI50) and ≥75% (EASI75), as well as head/neck EASI50 and EASI75 and erythema head/neck EASI50 and EASI75 response rates were assessed up to Week 16. Results: Across the studies, 93-98% of patients had head/neck involvement at baseline (EASI head/neck score ≥1). Baricitinib was similarly effective based on EASI total score for the entire body in all studies. In the monotherapy studies, the proportion of patients achieving head/neck EASI50 and EASI75 scores was significantly higher for baricitinib 2-mg and 4-mg versus placebo at Weeks 1 and 16. Conclusion: Baricitinib 2-mg and 4-mg treatment showed rapid and substantial reduction in AD head and neck severity, including erythema.

The PKC inhibitor AEB071 may be a therapeutic option for psoriasis.

PKC isoforms tau, alpha, and beta play fundamental roles in the activation of T cells and other immune cell functions. Here we show that the PKC inhibitor AEB071 both abolishes the production of several cytokines by activated human T cells, keratinocytes, and macrophages in vitro and inhibits an acute allergic contact dermatitis response in rats. To translate these findings into humans, single and multiple ascending oral doses of AEB071 were administered to healthy volunteers and patients with psoriasis, respectively. AEB071 was well tolerated with no clinically relevant laboratory abnormalities. Ex vivo stimulation of lymphocytes from subjects exposed to single doses of AEB071 resulted in a dose-dependent inhibition of both lymphocyte proliferation and IL2 mRNA expression. Clinical severity of psoriasis was reduced up to 69% compared with baseline after 2 weeks of treatment, as measured by the Psoriasis Area Severity Index (PASI) score. The improvement in psoriasis patients was accompanied by histological improvement of skin lesions and may be partially explained by a substantial reduction of p40+ dermal cells, which are known to mediate psoriasis. These data suggest that AEB071 could be an effective novel treatment regimen for psoriasis and other autoimmune diseases, and that AEB071 warrants long-term studies to establish safety and efficacy.