Publications by authors named "Paola Facheris"
Psoriasis is a chronic skin disease driven by immune system dysfunction and associated with increased cardiovascular risk and metabolic disorders. Risankizumab is an anti-interleukin-23 humanized monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis. We conducted a 3-year retrospective study to evaluate the effectiveness and the safety of risankizumab in patients with moderate-to-severe psoriasis, comparing those with and without the presence of at least one cardiometabolic comorbidity (CMD).
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- A study assessed the efficacy and safety of ritlecitinib, a JAK3/TEC inhibitor, in treating nonsegmental vitiligo among patients with different skin types over 24 weeks, involving 247 patients with light skin and 117 with dark skin.
- Results showed significant improvement in facial vitiligo scores after 24 weeks for both skin types, with a 15.2% change for light skin and 37.4% for dark skin, alongside continuous repigmentation through week 48.
- Additionally, the study noted variations in immune response markers related to skin type, suggesting that dark-skinned patients may respond to the treatment faster than those with light skin
Article Synopsis
- A phase 2b trial evaluated the effectiveness of ritlecitinib, a JAK3/TEC kinase inhibitor, in treating patients with active non-segmental vitiligo, comparing different dosages against a placebo over 24 weeks.
- Active vitiligo lesions showed higher levels of inflammatory markers compared to stable lesions, and patients with more active lesions had elevated serum levels of specific biomarkers.
- After 24 weeks, the 50 mg dose of ritlecitinib significantly reduced depigmentation and increased repigmentation in stable lesions, while also influencing immune response markers in both active and stable lesions.
Article Synopsis
- - The text discusses rare skin infections caused by gram-negative bacteria, which are often difficult to diagnose.
- - It presents a unique case that differs from typical presentations regarding where the infection occurred, the absence of known risk factors, and the duration of the illness.
- - The case highlights the challenges in recognizing and treating these atypical infections.
The autoantigens LL37 and ADAMTSL5 contribute to induce pathogenetic T-cells responses in a subset of psoriatic patients. Whether the presence of LL37-and/or ADAMTS5-reactive T-cells influences the clinical response to treatment is still unknown. The aim of the study is to evaluate the clinical responses to the anti-IL-23 risankizumab in LL37 and/or ADAMTSL5-reactive patients in comparison with non-reactive ones and to assess whether genetics (HLA-Cw06.
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- - The Pharmacovigilance Risk Assessment Committee (PRAC) recommends caution when using Janus kinase inhibitors (JAKi) in older patients or those with high cardiovascular, cancer, or venous thromboembolism risks, favoring alternatives when possible.
- - A study involving 21 specialists assessed the appropriateness of JAKi through a two-round survey, finding that while initial uncertainty existed, discussions helped clarify and reduce disagreement regarding best practices.
- - The study highlights the importance of personalized patient evaluations rather than relying solely on regulatory guidelines, emphasizing active management of modifiable health risks and continued concerns over the link between JAKi and cancer risk.
Background: This is the first report on the effects of abrocitinib, a Janus kinase 1-selective inhibitor, on the expression of skin biomarkers in patients with moderate-to-severe atopic dermatitis (AD).
Methods: JADE MOA (NCT03915496) was a double-blind Phase 2a trial. Adults were randomly assigned 1:1:1 to receive monotherapy with once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks.
Background: RPT193 is an orally administered small molecule antagonist of the human C-C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T-helper Type 2 (Th2) cells. We investigated single- and multiple-ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate-to-severe atopic dermatitis (AD).
Methods: This was a first-in-human randomized, placebo-controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate-to-severe AD.
Sclerotic-type cutaneous chronic graft-versus-host disease is a severe complication of allogeneic hematopoietic stem cell transplantation, with profound morbidity. A dearth of effective, targeted treatment options necessitates further investigation into the molecular mechanisms underlying this T-cell-mediated disease. In this study, we compared the transcriptome in skin biopsies from pediatric and young adult (aged <25 years) patients with sclerotic-type cutaneous chronic graft-versus-host disease (n = 7) with that in demographically matched healthy controls (n = 8) and patients with atopic dermatitis (n = 10) using RNA sequencing with RT-PCR and immunohistochemistry validation.
View Article and Find Full Text PDFBackground: Pruritus is the most common and burdensome symptom of atopic dermatitis (AD). Pruritus-targeted treatments in AD are lacking, particularly for patients with milder skin disease.
Objective: We sought to evaluate the impact of the selective κ-opioid receptor agonist difelikefalin (DFK) on pruritus intensity and pruritus- and immune-related biomarkers in subjects with moderate to severe AD-related pruritus.
Targeting type 2 immune activation beyond atopic dermatitis.
Ann Allergy Asthma Immunol
February 2024
Background: Safe and effective long-term topical treatments for atopic dermatitis (AD) remain limited.
Objective: In this phase 2a, single-center, intrapatient, and vehicle-controlled study, we examine the mechanism of action of crisaborole 2% ointment, a topical nonsteroidal PDE4 (phosphodiesterase-4) inhibitor, in a proteomic analysis of 40 adults with mild to moderate AD and 20 healthy subjects.
Methods: Within the AD cohort, 2 target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days.
Article Synopsis
- The study investigates the differences between adult-onset atopic dermatitis (AOAD) and pediatric-onset atopic dermatitis persisting into adulthood (POAD), focusing on their unique characteristics to aid in targeted therapy development.
- Skin biopsies and blood samples from adults with AOAD, POAD, and healthy controls were analyzed using various techniques, revealing distinct immune responses and dysregulations in both conditions.
- Results indicated that while POAD showed more severe inflammation and epidermal barrier issues, AOAD had different immune marker expressions and a greater number of dysregulated proteins in serum, suggesting the need for diverse therapeutic strategies that go beyond just targeting Th2 pathways.
Atopic dermatitis (AD) is the most common inflammatory skin disease, and it is considered a complex and heterogeneous condition. Different phenotypes of AD, defined according to the patient age at onset, race, and ethnic background; disease duration; and other disease characteristics, have been recently described, underlying the need for a personalized treatment approach. Recent advancements in understanding AD pathogenesis resulted in a real translational revolution and led to the exponential expansion of the therapeutic pipeline.
View Article and Find Full Text PDFBackground: Patients with atopic dermatitis (AD) have systemic biomarker dysregulation that differs by age group; however, the proteomic characteristics of these age-based changes are unknown.
Objective: To profile blood proteins of patients with AD across different age groups versus age-appropriate controls.
Methods: Using the Olink high-throughput proteomic platform, we profiled 375 serum proteins of 20 infants (age, 0-5 years), 39 children (age, 6-11 years), 21 adolescents (age, 12-17 years), and 20 adults (age, ≥18 years) with moderate-to-severe AD and 83 age-appropriate controls.
Atopic dermatitis (AD) is one of the most common, chronic inflammatory skin diseases with a significant physical, emotional and socioeconomic burden. In recent years the understanding of AD pathogenesis has expanded from the Th2-centred perspective, with the recognition of the involvement of other immune axes. In different AD endotypes, influenced by environment, genetics and race, transcriptomic profiles have identified differing contributions of multiple immune axes such as, Th17, Th22 and Th1.
View Article and Find Full Text PDFBackground: The mechanisms driving alopecia areata (AA) are still unclear, hindering development of targeted therapeutics. Specific Th2 targeting with dupilumab in AA provides a unique opportunity to dissect its pathogenesis and explore the role of Th2 pathway.
Methods: We evaluated changes in scalp biomarkers in AA patients (with and without concomitant atopy) randomized to weekly dupilumab or placebo for 24 weeks, followed by open-label dupilumab for 24 weeks.