Importance: New, effective, and well-tolerated oral therapies are needed for treating psoriasis. Zasocitinib, a highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor, is a potential new oral treatment for this disease.
Objective: To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis.
Design, setting, and participants: This phase 2b, randomized, double-blind, placebo-controlled, multiple-dose randomized clinical trial was conducted from August 11, 2021, to September 12, 2022, at 47 centers in the US and 8 in Canada. The study included a 12-week treatment period and a 4-week follow-up period. Key eligibility criteria for participants included age 18 to 70 years; a Psoriasis Area and Severity Index (PASI) score of 12 or greater; a Physician's Global Assessment score of 3 or greater; and a body surface area covered by plaque psoriasis of 10% or greater. Of 287 patients randomized, 259 (90.2%) received at least 1 dose of study treatment.
Intervention: Patients were randomly assigned (1:1:1:1:1) to receive zasocitinib at 2, 5, 15, or 30 mg or placebo orally, once daily, for 12 weeks.
Main outcomes and measures: The primary efficacy end point was the proportion of patients achieving 75% or greater improvement in PASI score (PASI 75) at week 12. Secondary efficacy end points included PASI 90 and 100 responses. Safety was also assessed.
Results: In total, 259 patients were randomized and received treatment (mean [SD] age, 47 [13] years; 82 women [32%]). At week 12, PASI 75 was achieved for 9 (18%), 23 (44%), 36 (68%), and 35 (67%) patients receiving zasocitinib at 2, 5, 15, and 30 mg, respectively, and 3 patients (6%) receiving placebo. PASI 90 responses were consistent with PASI 75. PASI 100 demonstrated a dose response at all doses, with 17 patients (33%) achieving PASI 100 with zasocitinib, 30 mg. Treatment-emergent adverse events occurred for 23 patients (44%) receiving placebo and 28 (53%) to 31 (62%) patients receiving the 4 different doses of zasocitinib, with no dose dependency and no clinically meaningful longitudinal differences in laboratory parameters.
Conclusions and relevance: This randomized clinical trial found that potent and selective inhibition of TYK2 with zasocitinib at oral doses of 5 mg or more once daily resulted in greater skin clearance than placebo over 12 weeks.
Trial registration: ClinicalTrials.gov Identifier: NCT04999839.
Importance: US veterans may be at an increased risk of developing various dermatologic conditions compared with nonveterans.
Objectives: To compare the prevalence and the odds of dermatologic conditions (eg, skin cancers, dermatitis/eczema/rash, psoriasis) between veterans and nonveterans.
Design, setting, and participants: This population-based cross-sectional study leveraged nationally representative data from the National Health and Nutrition Examination Survey (NHANES). Three questionnaires (demographics, medical conditions, and dermatology) were merged from 1999-2018 for analysis. Participants were nonveterans and veterans from NHANES data. Data were analyzed from August 2023 to April 2024.
Main outcomes and measures: The prevalence and odds ratios (ORs) comparing veterans and nonveterans were examined for various dermatologic conditions, including self-reported skin cancer history (any skin cancer, melanoma, nonmelanoma and unknown subtypes), dermatitis/eczema/inflamed rash, and psoriasis.
Results: In a total of 61 307 participants (54 554 nonveterans and 6753 veterans), there was a higher prevalence of any skin cancer history among US veterans compared with nonveterans (9.0% vs 2.9%; P < .001) as well as a higher prevalence of melanoma history (2.2% vs 0.6%; P < .001). Adjusted for demographic factors, veterans had higher odds of any skin cancer history (OR, 1.72; 95% CI, 1.23-2.40) and higher odds of a melanoma history (OR, 2.27; 95% CI, 1.17-4.39) compared with nonveterans. Veterans had a higher prevalence of a psoriasis diagnosis compared with nonveterans (4.5% vs 2.9%; P = .002) and a 61% higher odds of a psoriasis diagnosis (OR, 1.61; 95% CI, 1.05-2.46) compared with nonveterans.
Conclusions and relevance: This cross-sectional study found that veterans have higher prevalence and odds of various dermatologic conditions compared with nonveterans. Efforts aimed at improving health care quality among veterans must investigate the underlying causes of worsened skin health in this population.
Importance: There is a burgeoning interest in therapeutic development for cutaneous neurofibromas (cNFs), a major cause of morbidity in persons with neurofibromatosis type 1 (NF1). To determine meaningful clinical trial outcomes, deeper understanding is needed regarding how cNFs are associated with quality of life (QoL). However, this understanding has been hampered by challenges in recruiting participants with this rare genetic disease.
Objective: To develop a large, crowdsourced validated registry of persons with NF1 and determine the association of specific cNF features with QoL, pain, and itch.
Design, setting, and participants: From May 2021 to December 2023, a decentralized platform was developed and recruited persons 40 years or older with NF1 and at least 1 cNF from 49 states and 12 countries, who provided clinical survey data, detailed photographs, and genetic sequencing data. Photographs from 583 participants were scored on 12 features of cNFs, including general severity, number, size, facial severity, color, and subtypes.
Exposure: cNF features derived from participant-supplied photographs.
Main outcomes and measures: Total Skindex scores and subdomain scores (symptoms, emotion, function, pain, and itch).
Results: Of 583 participants, 384 (65.9%) were female, and the mean (range) age was 51.7 (40.0-83.0) years. Female sex, general severity, number, size, and facial severity of cNFs were negatively associated with QoL, as demonstrated by increased total Skindex scores. QoL had the largest association with the number of cNFs and presence of facial cNFs. Increasing number of cNFs was associated with worse QoL, and even individuals with a low cNF burden (<10 total cNFs) experienced a decrease in QoL.
Conclusions and relevance: The results of this study suggest that reducing cNF number, particularly on the face, may be associated with improved QoL in individuals with NF1. In addition, early intervention before the development of numerous tumors may lead to the highest benefit in QoL. These data potentially provide insight into which individuals and cNF tumors may benefit most from therapy and highlights the utility of a completely decentralized, photograph-validated and age-controlled study for rare genetic disease. This cohort will allow analysis of disease and tumor heterogeneity after full phenotypic expression is achieved in NF1 and potentially serves as an example in its design for other rare diseases that struggle from poor recruitment.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：