Project description:A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis (AD).
Project description:Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). The mechanism of action (MOA) of crisaborole and its effects on lesional measures of disease severity are not yet well-defined. This phase 2a, single-center, vehicle-controlled, intrapatient study was designed to further characterize the MOA of crisaborole through evaluation of clinical efficacy and changes in skin biomarkers in adults (N = 40) with mild-to-moderate AD.
Project description:This phase 1b, single-center, double-blind study evaluated safety, efficacy, and effect on molecular profiles of a topical Janus kinase/spleen tyrosine kinase (JAK/Syk) inhibitor, cerdulatinib gel 0.37%, in ten adults with mild-to-moderate atopic dermatitis (AD).
Project description:Background: Chronic hand eczema (CHE) is a debilitating skin condition characterized by pain, itch, and chronic inflammation, with a complex multifactorial origin. Its diverse presentations, including overlapping traits of atopic dermatitis, contact dermatitis, and psoriasis, make diagnosis and treatment particularly challenging. The underlying immune mechanisms of CHE still need to be investigated.Methods: Here we conducted a comprehensive molecular profiling of CHE patients, enrolled without prior selection on etiology and morphology, and performed a phase 2b randomized, multicenter, double-blind, placebo-controlled clinical trial comparing dupilumab to placebo over 16 weeks.Results: We demonstrated that CHE patients may benefit from IL4Rα-blockade, regardless of etiological factors or clinical presentation. Skin transcriptomic and serum profiles of CHE patients closely resemble those seen in both atopic dermatitis and psoriasis, with dysregulated genes affecting keratinocyte differentiation, leucocyte-mediated immunity, cytokine signaling, and mixed type 1, 2, and 3 immunity. The clinical trial included 94 adults with moderate to severe CHE persisting for at least six months and resistant to potent topical corticosteroids. Compared to placebo control, 16-week dupilumab treatment significantly improved clinical severity and quality of life of all CHE patients while largely restoring appropriate transcriptomic and proteomic programs related to skin barrier and immune homeostasis.Conclusion: These findings confirmed the involvement of not only type 2 but also type 1 and type 3 immunity across all CHE patients, and demonstrate that IL-4Rα blockade may offer effective therapeutic perspectives for this highly burdensome condition, independent of an atopic dermatitis background.
Project description:This phase 2a study of atuzabrutinib (PRN473/SAR444727), a Bruton tyrosine kinase inhibitor, comprised of a double-blind placebo-controlled treatment period and an open-label uncontrolled treatment period and evaluated safety and efficacy of atuzabrutinib 5% gel vs placebo (in double-blind period) in patients with mild-to-moderate atopic. dermatitis (AD). Patients aged 18–70 years diagnosed with mild-to-moderate AD (N=39) for at least 6 months were included in the study. During the double-blinded Period (Days 1–14), two target lesions with a difference ≤1 point in total sign score (TSS) were randomized 1:1 to atuzabrutinib or matching placebo twice daily. During open-label period (Days 15–42), patients continued to treat the assigned areas and other AD-affected lesions (except scalp, palms, soles and genitals) with atuzabrutinib BID. The objective is to evaluate the safety, tolerability, PK and preliminary efficacy of atuzabrutinib in patients with mild to moderate AD. RNA sequencing analysis was performed to understand the target immune cell expression in lesional skin biopsies versus normal skin and the effect of atuzabrutinib.
Project description:mRNA array analysis of total RNA from primary kertinocytes from three healthy controls, three atopic dermatitis patients and three psoriasis patients was carried out
Project description:Clinical overlaps between psoriasis and atopic dermatitis are sometimes undiscernible, and there is no consensus whether to treat the overlap phenotype as psoriasis or atopic dermatitis. We enrolled patients diagnosed with either psoriasis or atopic dermatitis, and clinically re-stratified them into classic psoriasis, classic atopic dermatitis, and the overlap phenotype between psoriasis and atopic dermatitis. We compared gene expression profiles of lesional and nonlesional skin biopsy tissues between the three comparison groups. Global mRNA expression and T-cell subset cytokine expression in the skin of the overlap phenotype were consistent with the profiles of psoriasis and different from the profiles of atopic dermatitis. Unsupervised k-means clustering indicated that the best number of distinct clusters for the total population of the three comparison groups was two, and the two clusters of psoriasis and atopic dermatitis were differentiated by gene expression. Our study suggests that clinical overlap phenotype between psoriasis and atopic dermatitis has dominant molecular features of psoriasis, and genomic biomarkers can differentiate psoriasis and atopic dermatitis at molecular levels in patients with a spectrum of psoriasis and atopic dermatitis.