Pharmacokinetics, Safety, Tolerability, and Exploratory Efficacy of Upadacitinib in Children with Severe Atopic Dermatitis.

Purpose: This study aims to characterize the pharmacokinetics, safety, tolerability, and exploratory efficacy of upadacitinib, an oral Janus kinase inhibitor approved for treating moderate to severe atopic dermatitis (AD) in adults and adolescents, in children with severe AD.

Methods: In an open-label, multiple-dose, Phase 1 study, pediatric patients with severe AD from two age groups (2 to <6 years and 6 to <12 years) received bodyweight-based dosing regimens of upadacitinib using either twice-daily immediate-release (IR) oral solution or once-daily extended-release (ER) tablets. A pharmacokinetic assessment was conducted on Day 7 of the study, which was followed by a long-term safety and exploratory efficacy evaluation for up to 108 weeks.

Advances on MXene-Based Memristors for Neuromorphic Computing: A Review on Synthesis, Mechanisms, and Future Directions.

Neuromorphic computing seeks to replicate the capabilities of parallel processing, progressive learning, and inference while retaining low power consumption by drawing inspiration from the human brain. By further overcoming the constraints imposed by the traditional von Neumann architecture, this innovative approach has the potential to revolutionize modern computing systems. Memristors have emerged as a solution to implement neuromorphic computing in hardware, with research based on developing functional materials for resistive switching performance enhancement.

Rapid and sustained improvements in itch and quality of life with upadacitinib plus topical corticosteroids in adults and adolescents with atopic dermatitis: 52-week outcomes from the phase 3 AD Up study.

Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks. In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS.

Refinement of the rKLi8.3-Based Serodiagnostic ELISA Allows Detection of Canine Leishmaniosis in Dogs with Low Antibody Titers.

The diagnosis of canine leishmaniasis (CanL) still represents a challenge due to the variable clinical manifestations and the large number of asymptomatic dogs. Serological tests are most commonly used to detect infected animals, revealing anti- antibodies, mainly of the IgG isotype. Recently, a new diagnostic antigen, rKLi8.

Abdominal Wall Sinus and Recurrent Abscess Formation Due to a Foreign Body Following Surgical Intervention.

The sinus tract, a tubular structure with no outlet connecting deep tissues to the skin, is a rare entity, especially in patients undergoing abdominal surgeries. The pathophysiology involves factors such as liquefaction of adipose tissue, infection, and retention of foreign bodies. Inadequate surgical drainage can lead to chronicity, culminating in the formation of an infectious sinus in the abdominal wall, clinically known as a sinus.

Aggregate Response Benefit in Skin Clearance and Itch Reduction With Upadacitinib or Dupilumab in Patients With Moderate-to-Severe Atopic Dermatitis®.

In patients with moderate-to-severe atopic Dermatitis® (AD), greater skin clearance and itch reduction are associated with more pronounced improvements in quality of life (QoL). To characterize the aggregate response benefit with upadacitinib versus dupilumab or placebo in patients with moderate-to-severe AD. Degree of skin clearance and itch response in 3 phase 3 studies (Heads Up [NCT03738397] and Measure Up 1/2 [integrated; NCT03569293/NCT03607422]) were assessed by the Eczema Area and Severity Index (EASI) and Worst Pruritus Numerical Rating Scale (WP-NRS), respectively, using mutually exclusive categories.

Upadacitinib treatment withdrawal and retreatment in patients with moderate-to-severe atopic dermatitis: Results from a phase 2b, randomized, controlled trial.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic eczematous lesions. The effect of treatment withdrawal after response to upadacitinib oral treatment is not fully characterized.

Objectives: Assess the effect of upadacitinib withdrawal on skin clearance and itch improvement in adult patients with moderate-to-severe AD and evaluate the kinetics of recovery on rescue treatment.

Population pharmacokinetic and exposure-response modelling to inform upadacitinib dose selection in adolescent and adult patients with atopic dermatitis.

Aims: First, population pharmacokinetic analyses were used to characterize upadacitinib pharmacokinetics in adolescent and adult participants with atopic dermatitis (AD) and to identify patient covariates that may impact upadacitinib pharmacokinetics. Second, the exposure-response relationship for upadacitinib with efficacy and safety endpoints, and the effect of age and concomitant use of topical corticosteroids (TCS) on the exposure-response relationship and dose selection for patients with AD were evaluated.

Methods: A two-compartment model with combined first- and zero-order absorption adequately characterized the upadacitinib concentration-time profiles in 911 healthy volunteer adolescent and adult participants with AD who received upadacitinib 15 or 30 mg orally once daily (QD) as monotherapy or in combination with TCS for 16 weeks.

Efficacy and safety of switching from dupilumab to upadacitinib versus continuous upadacitinib in moderate-to-severe atopic dermatitis: Results from an open-label extension of the phase 3, randomized, controlled trial (Heads Up).

Background: Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed.

Objective: To evaluate the long-term safety and efficacy of continuous upadacitinib 30 mg and switching to upadacitinib after 24 weeks of dupilumab.

Methods: Adults who completed the phase 3b clinical trial of oral upadacitinib 30 mg vs injectable dupilumab 300 mg (Heads Up) and entered a 52-week open-label extension (OLE) (NCT04195698) were included.

Development of a Novel Enzyme-Linked Immunosorbent Assay and Lateral Flow Test System for Improved Serodiagnosis of Visceral Leishmaniasis in Different Areas of Endemicity.

Visceral leishmaniasis (VL) is caused by protozoan parasites of the Leishmania donovani complex and is one of the most prominent vector-borne infectious diseases with epidemic and mortality potential if not correctly diagnosed and treated. East African countries suffer from a very high incidence of VL, and although several diagnostic tests are available for VL, diagnosis continues to represent a big challenge in these countries due to the lack of sensitivity and specificity of current serological tools. Based on bioinformatic analysis, a new recombinant kinesin antigen from Leishmania infantum (rKLi8.

Safety and Efficacy of Upadacitinib for Atopic Dermatitis in Japan: 2-Year Interim Results from the Phase 3 Rising Up Study.

Introduction: Upadacitinib, an oral, selective Janus kinase inhibitor, is approved in Japan for the treatment of moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous morphology and intense itch.

Methods: Rising Up is an ongoing phase 3, randomized, multicenter study evaluating the long-term safety and efficacy of upadacitinib in Japan. Patients with moderate-to-severe AD were randomized 1:1:1 to topical corticosteroids plus upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or placebo at baseline; at week 16, placebo patients were rerandomized 1:1 to UPA15 or UPA30 (plus topical corticosteroids per investigator discretion).

Comparative Efficacy of Targeted Systemic Therapies for Moderate to Severe Atopic Dermatitis without Topical Corticosteroids: Systematic Review and Network Meta-analysis.

Introduction: The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD.

Methods: The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region.

A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysis.

Background: Systemic atopic dermatitis treatments that have acceptable safety are needed.

Objective: To evaluate the safety of the oral Janus kinase inhibitor upadacitinib in combination with topical corticosteroids (TCSs) for the treatment of atopic dermatitis.

Methods: In this phase 3, double-blind study (Rising Up), Japanese patients (12-75 years) with moderate-to-severe atopic dermatitis were randomized in a 1:1:1 ratio to receive 15 mg of upadacitinib + TCS, 30 mg of upadacitinib + TCS, or a placebo + TCS (rerandomized in a 1:1 ratio to receive either 15 or 30 mg of upadacitinib + TCS at week 16).

Serum IgA Antibodies Specific to Antigens as Biomarkers for Leprosy Detection and Household Contact Tracking.

Leprosy remains endemic in several developing countries, such as India and Brazil, in part due to delayed diagnosis that facilitates ongoing transmission. Although immunoglobulins against several antigens have been indicated for the early diagnosis, and IgA participates in the early stages of leprosy and in subclinical infection, relatively little research has examined anti-M. leprae IgA responses.

Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement.

Objective: To assess the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD.

Design, Setting, And Participants: Heads Up was a 24-week, head-to-head, phase 3b, multicenter, randomized, double-blinded, double-dummy, active-controlled clinical trial comparing the safety and efficacy of upadacitinib with dupilumab among 692 adults with moderate-to-severe AD who were candidates for systemic therapy.