Highly selective tyrosine kinase 2 inhibition with zasocitinib (TAK-279) improves outcomes in patients with active psoriatic arthritis: a randomised phase 2b study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14160%2F25%3A00143929" target="_blank" >RIV/00216224:14160/25:00143929 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0003496725010416?pes=vor&utm_source=clarivate&getft_integrator=clarivate" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0003496725010416?pes=vor&utm_source=clarivate&getft_integrator=clarivate</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ard.2025.05.023" target="_blank" >10.1016/j.ard.2025.05.023</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Highly selective tyrosine kinase 2 inhibition with zasocitinib (TAK-279) improves outcomes in patients with active psoriatic arthritis: a randomised phase 2b study

Popis výsledku v původním jazyce

Objectives: To assess the efficacy, safety, and tolerability of the investigational, oral, allosteric, highly selective, and potent tyrosine kinase 2 inhibitor zasocitinib (TAK-279) in patients with active psoriatic arthritis (PsA). Methods: In this phase 2b, randomised, multicentre, double-blind, placebo-controlled, multiple-dose study, patients (&gt;= 18 years, with PsA symptoms for &gt;= 6 months) received 30 mg, 15 mg, or 5 mg zasocitinib or placebo (1:1:1:1) once daily for 12 weeks, with a 4-week safety follow-up. The primary endpoint was American College of Rheumatology (ACR)20 response at week 12. Secondary efficacy endpoints included ACR50 response, ACR70 response, Psoriasis Area and Severity Index (PASI) 75 response among those with &gt;= 3% body surface area at baseline and minimal disease activity (MDA) at week 12. Results: Overall, 290 patients (mean [SD] age, 49.9 [11.6] years; 57.2% female) received treatment. At week 12, 30 mg or 15 mg zasocitinib treatment resulted in significantly higher ACR20 responses (54.2%; P = .002 and 53.3%; P = .002, respectively) than placebo (29.2%). A numerically higher number of ACR50 responses were achieved at week 12 with 30 mg (26.4%; nominal P = .009) or 15 mg (26.7%; nominal P = .005) zasocitinib than placebo (9.7%). In addition, 30 mg zasocitinib demonstrated a numerically higher number of ACR70 responses (13.9% versus 5.6%, respectively; nominal P = .158), PASI 75 responses (45.7% versus 15.4%, respectively; nominal P = .002), and MDA (29.2% versus 12.5%, respectively; nominal P = .014) at week 12 versus placebo. In this small study of limited duration, most adverse events were mild/moderate and were more frequently observed in the higher dose group. In this small sample size, no new safety signals or clear dose-dependent laboratory parameter changes were identified. Conclusions: Here, 30 mg and 15 mg zasocitinib demonstrated efficacy across core domains in patients with active PsA with no new safety signals. These findings will be confirmed in ongoing larger studies of longer duration.

Název v anglickém jazyce

Highly selective tyrosine kinase 2 inhibition with zasocitinib (TAK-279) improves outcomes in patients with active psoriatic arthritis: a randomised phase 2b study

Popis výsledku anglicky

Objectives: To assess the efficacy, safety, and tolerability of the investigational, oral, allosteric, highly selective, and potent tyrosine kinase 2 inhibitor zasocitinib (TAK-279) in patients with active psoriatic arthritis (PsA). Methods: In this phase 2b, randomised, multicentre, double-blind, placebo-controlled, multiple-dose study, patients (&gt;= 18 years, with PsA symptoms for &gt;= 6 months) received 30 mg, 15 mg, or 5 mg zasocitinib or placebo (1:1:1:1) once daily for 12 weeks, with a 4-week safety follow-up. The primary endpoint was American College of Rheumatology (ACR)20 response at week 12. Secondary efficacy endpoints included ACR50 response, ACR70 response, Psoriasis Area and Severity Index (PASI) 75 response among those with &gt;= 3% body surface area at baseline and minimal disease activity (MDA) at week 12. Results: Overall, 290 patients (mean [SD] age, 49.9 [11.6] years; 57.2% female) received treatment. At week 12, 30 mg or 15 mg zasocitinib treatment resulted in significantly higher ACR20 responses (54.2%; P = .002 and 53.3%; P = .002, respectively) than placebo (29.2%). A numerically higher number of ACR50 responses were achieved at week 12 with 30 mg (26.4%; nominal P = .009) or 15 mg (26.7%; nominal P = .005) zasocitinib than placebo (9.7%). In addition, 30 mg zasocitinib demonstrated a numerically higher number of ACR70 responses (13.9% versus 5.6%, respectively; nominal P = .158), PASI 75 responses (45.7% versus 15.4%, respectively; nominal P = .002), and MDA (29.2% versus 12.5%, respectively; nominal P = .014) at week 12 versus placebo. In this small study of limited duration, most adverse events were mild/moderate and were more frequently observed in the higher dose group. In this small sample size, no new safety signals or clear dose-dependent laboratory parameter changes were identified. Conclusions: Here, 30 mg and 15 mg zasocitinib demonstrated efficacy across core domains in patients with active PsA with no new safety signals. These findings will be confirmed in ongoing larger studies of longer duration.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30226 - Rheumatology

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Annals of the Rheumatic Diseases

ISSN

0003-4967

e-ISSN

1468-2060

Svazek periodika

84

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

15

Strana od-do

1660-1674

Kód UT WoS článku

001588404500001

EID výsledku v databázi Scopus

2-s2.0-105009901501