Amy S Paller

BACKGROUND: Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, and tyrosine kinase 2. We aimed to assess the efficacy and safety of upadacitinib compared with placebo for the treatment of moderate-to-severe atopic dermatitis.

METHODS: Measure Up 1 and Measure Up 2 were replicate multicentre, randomised, double-blind, placebo-controlled, phase 3 trials; Measure Up 1 was done at 151 clinical centres in 24 countries across Europe, ...

Importance: Adolescents with atopic dermatitis (AD) have high disease burden negatively affecting quality of life, with limited treatment options. The efficacy and safety of dupilumab, a monoclonal antibody, approved for treatment in adolescent patients with inadequately controlled AD, remain unknown in this patient population.

Objective: To assess the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled AD.

Design, Setting, and ...

BACKGROUND: Plaque psoriasis affects children and adults, but treatment options for paediatric psoriasis are limited.

OBJECTIVES: To evaluate the efficacy and safety of ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, for moderate-to-severe paediatric psoriasis.

METHODS: In a randomized, double-blind, placebo-controlled, phase III study (IXORA-PEDS), patients aged 6 to < 18 years with moderate-to-severe plaque psoriasis were randomized 2 : 1 ...

BACKGROUND: Children with severe atopic dermatitis (AD) have limited treatment options.

OBJECTIVE: We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years with severe AD inadequately controlled with topical therapies.

METHODS: In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline ...

BACKGROUND: Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children.

OBJECTIVE: We sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) "polar" CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects.

METHODS: Flow cytometry was ...

The interaction of the urokinase-type plasminogen activator (uPA) receptor (uPAR) with integrins plays a critical role in the regulation of cell adhesion and migration. However, the molecular events underlying the modulation of the interaction of uPAR and integrin are poorly understood. Gangliosides are thought to regulate epithelial cell adhesion and migration by inhibiting alpha(5)beta(1) integrin and epidermal growth factor receptor (EGFR) signaling. We report here that increases in ...

BACKGROUND: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phase II study with concomitant topical corticosteroids.

OBJECTIVES: To evaluate the efficacy and safety of baricitinib in patients with moderate-to-severe AD who had an inadequate response to topical therapies.

METHODS: In two independent, multicentre, double-blind, phase III monotherapy trials, BREEZE-AD1 and BREEZE-AD2, adults with moderate-to-severe AD ...

BACKGROUND: Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis.

METHODS: In this 48-week study, 211 patients with psoriasis (4 to 17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.8 mg of etanercept per kilogram ...

BackgroundAtopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator’s Global Assessment 0/1 at week 16.ObjectiveThe objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of ...

BACKGROUND: Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks.

OBJECTIVE: We sought to assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766; AD-302: NCT02118792).

METHODS: Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an ...

Importance: Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB.

Objectives: To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial ...

The autosomal recessive disorder lipoid proteinosis results from mutations in extracellular matrix protein 1 (ECM1), a glycoprotein expressed in several tissues (including skin) and composed of two alternatively spliced isoforms, ECM1a and ECM1b, the latter lacking exon 7 of this 10-exon gene (ECM1). To date, mutations that either affect ECM1a alone or perturb both ECM1 transcripts have been demonstrated in six cases. However, lipoid proteinosis is clinically heterogeneous with affected ...

Importance: Interleukin 13 (IL-13) is a central pathogenic mediator driving multiple features of atopic dermatitis (AD) pathophysiology.

Objective: To evaluate the efficacy and safety of lebrikizumab, a novel, high-affinity, monoclonal antibody targeting IL-13 that selectively prevents formation of the IL-13Rα1/IL-4Rα heterodimer receptor signaling complex, in adults with moderate to severe AD.

Design, Setting, and Participants: A phase 2b, double-blind, placebo-controlled, dose-ranging ...

The epidermal growth factor receptor (EGFR) can be activated by both direct ligand binding and cross-talk with other molecules, such as integrins. This integrin-mediated cross-talk with growth factor receptors participates in regulating cell proliferation, survival, migration, and invasion. Previous studies have shown that ligand-dependent EGFR activation is inhibited by GM3, the predominant ganglioside of epithelial cells, but the effect of GM3 on ligand-independent, integrin-EGFR ...