April W Armstrong, Melinda Gooderham, Charles Lynde, Catherine Maari, Seth Forman, Lawrence Green, Vivian Laquer, Xinyan Zhang, Nathalie Franchimont, Esha A Gangolli, Jessamyn Blau, Yiwei Zhao, Wenwen Zhang, Bhaskar Srivastava, Graham Heap, Kim Papp
{"title":"用扎索西替尼 (TAK-279) 抑制酪氨酸激酶 2 治疗银屑病：随机临床试验","authors":"April W Armstrong, Melinda Gooderham, Charles Lynde, Catherine Maari, Seth Forman, Lawrence Green, Vivian Laquer, Xinyan Zhang, Nathalie Franchimont, Esha A Gangolli, Jessamyn Blau, Yiwei Zhao, Wenwen Zhang, Bhaskar Srivastava, Graham Heap, Kim Papp","doi":"10.1001/jamadermatol.2024.2701","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>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.</p><p><strong>Objective: </strong>To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Intervention: </strong>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.</p><p><strong>Main outcomes and measures: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions and relevance: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04999839.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"1066-1074"},"PeriodicalIF":11.5000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339701/pdf/","citationCount":"0","resultStr":"{\"title\":\"Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis: A Randomized Clinical Trial.\",\"authors\":\"April W Armstrong, Melinda Gooderham, Charles Lynde, Catherine Maari, Seth Forman, Lawrence Green, Vivian Laquer, Xinyan Zhang, Nathalie Franchimont, Esha A Gangolli, Jessamyn Blau, Yiwei Zhao, Wenwen Zhang, Bhaskar Srivastava, Graham Heap, Kim Papp\",\"doi\":\"10.1001/jamadermatol.2024.2701\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>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.</p><p><strong>Objective: </strong>To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Intervention: </strong>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.</p><p><strong>Main outcomes and measures: </strong>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.</p><p><strong>Results: </strong>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. 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Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis: A Randomized Clinical Trial.
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.
期刊介绍：
JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery.
JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care.
The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists.
JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.
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