Safety and Efficacy of Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options for adolescents with moderate-to-severe disease. Lebrikizumab, a monoclonal antibody targeting interleukin (IL)-13, demonstrated clinical benefit in previous Phase 3 trials: ADvocate1 (NCT04146363), ADvocate2 (NCT04178967), and ADhere (NCT04250337). We report 52-week safety and efficacy outcomes from ADore (NCT04250350), a Phase 3, open-label study of lebrikizumab in adolescent patients with moderate-to-severe AD. The primary endpoint was to describe the proportion of patients who discontinued from study treatment because of adverse events (AEs) through the last treatment visit. METHODS: Adolescent patients (N = 206) (≥ 12 to < 18 years old, weighing ≥ 40 kg) with moderate-to-severe AD received subcutaneous lebrikizumab 500 mg loading doses at baseline and Week 2, followed by 250 mg every 2 weeks (Q2W) thereafter. Safety was monitored using reported AEs, AEs leading to treatment discontinuation, vital signs, growth assessments, and laboratory testing. Efficacy analyses included Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Body Surface Area (BSA), (Children's) Dermatology Life Quality Index ((C)DLQI), and Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression. RESULTS: 172 patients completed the treatment period. Low frequencies of SAEs (n = 5, 2.4%) and AEs leading to treatment discontinuation (n = 5, 2.4%) were reported. Overall, 134 patients (65%) reported at least one treatment-emergent AE (TEAE), most being mild or moderate in severity. In total, 62.6% achieved IGA (0,1) with ≥ 2-point improvement from baseline and 81.9% achieved EASI-75 by Week 52. The EASI mean percentage improvement from baseline to Week 52 was 86.0%. Mean BSA at baseline was 45.4%, decreasing to 8.4% by Week 52. Improvements in mean change from baseline (CFB) to Week 52 were observed in DLQI (baseline 12.3; CFB - 8.9), CDLQI (baseline 10.1; CFB - 6.5), PROMIS Anxiety (baseline 51.5; CFB - 6.3), and PROMIS Depression (baseline 49.3; CFB - 3.4) scores. CONCLUSIONS: Lebrikizumab 250 mg Q2W had a safety profile consistent with previous trials and significantly improved AD symptoms and quality of life, with meaningful responses at Week 16 increasing by Week 52. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04250350.

Atopic dermatitis is a chronic relapsing inflammatory skin disease that affects up to 15% of adolescents worldwide, with up to 50% suffering from moderate-to-severe disease. Signs and symptoms include dry, cracked skin; redness; itching; and painful lesions, which can negatively affect quality of life and lead to complications, including skin infections. Adolescents also report increased rates of anxiety and stress. Lebrikizumab is a novel monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, the key cytokine in atopic dermatitis, blocking the downstream effects of IL-13 with high potency. Lebrikizumab has been shown previously to improve symptoms of atopic dermatitis, including itch, skin clearance, and quality of life in ADvocate1, ADvocate2 and ADhere. The ADore study aimed to evaluate the safety and efficacy of lebrikizumab in adolescents with moderate-to-severe atopic dermatitis. Investigators recruited patients ≥ 12 to < 18 years old, weighing ≥ 40 kg, from Australia, Canada, Poland, and the US who were diagnosed with moderate-to-severe atopic dermatitis. These patients received a loading dose of 500 mg of lebrikizumab at Weeks 0 and 2, followed by 250 mg every 2 weeks for 52 weeks. The safety profile of lebrikizumab was consistent with previously published reports, with mostly mild or moderate adverse events, which did not lead to treatment discontinuation. Lebrikizumab improved skin clearance; 62.6% of patients had clear or almost clear skin by the end of the trial. Lebrikizumab also improved the patients' quality of life. These safety and efficacy results support lebrikizumab's role in treating adolescents with moderate-to-severe atopic dermatitis. Safety and Efficacy of Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study (MP4 44681 KB).

Long-term Efficacy and Safety of Up to 108 Weeks of Ixekizumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis: The IXORA-PEDS Randomized Clinical Trial.

Importance: About 1% of children and adolescents worldwide are affected by plaque psoriasis. Objective: To evaluate the long-term efficacy and safety of ixekizumab for pediatric patients with moderate to severe psoriasis. Design, Setting, and Participants: This multicenter randomized clinical trial (IXORA-PEDS) evaluated pediatric patients with plaque psoriasis. Participants were aged 6 years to younger than 18 years; had moderate to severe psoriasis, which was defined as Psoriasis Area and Severity Index (PASI) of 12 or higher, static Physician's Global Assessment (sPGA) score of 3 or higher, and psoriasis-affected body surface area of 10% or greater at screening and baseline; were candidates for phototherapy or systemic therapy; or had psoriasis that was not adequately controlled by topical therapies. Data analysis, which followed the intention-to-treat principle, was conducted from May to October 2021. Interventions: Pediatric patients were randomized 2:1 to receive either a weight-based dose of ixekizumab every 4 weeks or placebo. After a 12-week placebo-controlled period, patients entered a 48-week, open-label ixekizumab maintenance period (weeks 12-60), followed by an extension period that lasted through 108 weeks. A substudy evaluated the randomized withdrawal of ixekizumab after week 60. Main Outcomes and Measures: Efficacy outcomes at week 108 included the percentage of patients achieving 75% (PASI 75), 90% (PASI 90), or 100% (PASI 100) improvement from baseline; an sPGA score of 0 or 1 or score of 0; and improvement of 4 points or higher from baseline in the Itch Numeric Rating Scale. Safety outcomes included assessments of adverse events (AEs), including treatment-emergent AEs, serious AEs, and AEs of special interest, as well as improvement from baseline in a range of challenging body areas. Missing data for categorical outcomes were imputed using modified nonresponder imputation. Results: A total of 171 patients (mean [SD] age, 13.5 [3.04] years; 99 female children [57.9%]) were randomized to either ixekizumab (n = 115) or placebo (n = 56). Of 166 patients who entered the maintenance period, 139 (83.7%) completed week 108 of the trial. Primary and gated secondary end points were sustained through week 108, with patients achieving PASI 75 (91.7% [n = 86]), PASI 90 (79.0% [n = 74]), PASI 100 (55.1% [n = 52]), sPGA 0 or 1 (78.3% [n = 74]), and sPGA 0 (52.4% [n = 49]). Fifty-five patients (78.5%) reported an Itch Numeric Rating Scale improvement of 4 points or higher. In patients who received ixekizumab, at week 108, clearance of nail psoriasis was reported in 68.1% (n = 28), clearance of palmoplantar psoriasis was reported in 90.0% (n = 10), clearance of scalp psoriasis was reported in 76.2% (n = 83), and clearance of genital psoriasis was reported in 87.5% (n = 24). There were no new safety findings during weeks 48 to 108 of the trial, including no new cases of inflammatory bowel disease or candida infection. Conclusions and Relevance: Results of this study showed improvements across patient-reported outcomes and objective measures of complete skin clearance of psoriasis among pediatric patients who received ixekizumab, and these response rates were sustained through week 108 of the trial. Safety of ixekizumab was consistent with previously reported findings in this population and the known safety profile of this treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT03073200.

Population pharmacokinetic and exposure-efficacy analysis of ixekizumab in paediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS).

AIMS: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A used in the treatment of adult and paediatric patients with moderate-to-severe psoriasis. This analysis evaluated the pharmacokinetics (PK) of ixekizumab and the exposure-efficacy relationship in paediatric patients aged 6 to <18 years with psoriasis. METHODS: Population PK and exposure-efficacy models were developed. The models used data from paediatric patients with psoriasis participating in the Phase 3 IXORA-PEDS trial in which patients were dosed according to weight categories. The exposure-efficacy model is a Psoriasis Area and Severity Index (PASI) time course model using data up to Week 12, a co-primary efficacy endpoint. RESULTS: A 2-compartment population PK model describes the PK of ixekizumab in paediatric patients with the effect of body weight incorporated on clearance and volume terms using an allometric relationship. The weight category-based dosing ensured that ixekizumab mean trough serum concentrations in paediatric patients with psoriasis (3.20-3.33 µg/mL) were within the range of concentrations observed in adult patients with psoriasis (mean [standard deviation]: 3.48 [2.16] µg/mL) administered an efficacious dosing regimen. The observed PASI response rates at Week 12 in paediatric patients (91.9/81.8/52.5% for PASI75/90/100) are well predicted by the final exposure-efficacy model and response rates are similar or higher than those achieved in adults (86.2/66.6/35.0% for PASI75/90/100). CONCLUSION: This analysis is the first to describe the PK and exposure-efficacy relationship of ixekizumab in paediatric patients with psoriasis. The analyses support the selection of the weight category-based ixekizumab dosing regimens approved for use in paediatric patients with psoriasis.

Higher rates of skin clearance and efficacy in challenging body areas are associated with better health-related quality of life following ixekizumab maintenance treatment in pediatric patients with plaque psoriasis.

BACKGROUND/OBJECTIVES: Information is limited on the relationship between skin clearance, resolution of challenging body areas, and improvement of patient-reported outcomes (PROs) in pediatric psoriasis. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe psoriasis in patients aged 6 to <18 years. This study examines improvement in psoriasis clearance in challenging body areas in pediatric patients relative to health-related quality of life. METHODS: Data from the IXORA-PEDS trial (NCT03073200) were analyzed, and changes from baseline were measured for overall Psoriasis Area and Severity Index (PASI), static Physicians' Global Assessment of psoriasis (sPGA), Psoriasis Scalp Severity Index (PSSI), Palmoplantar Psoriasis Area and Severity Index (PPASI), and Nail Psoriasis Severity Index. Rates of Dermatology Life Quality Index (DLQI), or Children's DLQI (CDLQI), scores of 0 or 1 were evaluated using the Cochran-Armitage trend test. RESULTS: Higher rates of DLQI/CDLQI (0,1) scores were significantly associated with greater PASI and PSSI responses at both Week 12 and Week 48 (p < .0001). A significant association was also observed between DLQI/CDLQI (0,1) and sPGA scores (p < .0001). Significantly higher rates of DLQI/CDLQI (0,1) scores were achieved in patients with greater levels of palmoplantar clearance as measured by PPASI at Week 12 (p = .0139), but significance was not sustained at Week 48 (p = .0896). CONCLUSIONS: Greater skin clearance and scalp resolution are associated with better PROs over a short-term (12-week) and long-term (48-week) period. This demonstrates that greater improvement of skin clearance and scalp resolution may benefit quality of life in pediatric patients with psoriasis.

El tatuaje como factor de riesgo para la transmisión de la infección por el virus de la hepatitis C / The tattooing practice how risk factors for the hepatitis C

Para investigar el tatuaje corporal como factor de riesgo para la hepatitis C, se tomaron muestras de sangre a 88 miembros del personal de la Armada Venezolana, destacados en la base naval "Agustin Armario" en Puerto Cabello. De este personal 76 presentaban tatuajes, 11 de ellos resultaron positivos para el VHC, y dos tenían factores de riesgo conocidos, de los nueve positivos restantes (17,30 por ciento) el único factor de riesgo encontrado fue el tatuaje. Concluimos que la práctica de el tatuaje corporal es un factor de riesgo para la infección por el VHC