Impact of Selective Tyrosine Kinase 2 Inhibition With Zasocitinib ( <scp>TAK</scp> ‐279) on Molecular Pathways and Correlated Clinical Response in Patients With Active Psoriatic Arthritis
ACR Open Rheumatology, 2026
Choudhury A., Cheng J., Tang J., Kumar S., Saha B., Arunachalam V., Hong T., Mark E., Wennbo H., McInnes I.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases Dermatological Diseases | Pathophysiology | Plasma |  Olink Target 48  Olink Explore HT |
Abstract
Objective
This post hoc analysis evaluated the effect of zasocitinib, an investigational, oral, allosteric, highly selective, and potent tyrosine kinase 2 (TYK2) inhibitor in late‐stage clinical development, on TYK2 signaling response and disease‐related biomarkers and the association of these changes with clinical response in patients with active psoriatic arthritis from a phase 2b trial (NCT05153148).
Methods
Blood samples were collected predose from patients receiving zasocitinib 15 mg, 30 mg, or placebo once daily on Day 1 (baseline), Week 4, and Week 12. Plasma biomarkers related to TYK2 signaling response, inflammation, skin and joint pathogenesis, cartilage/bone turnover, and bone formation were measured using Olink Explore HT, Olink Target 48, or Nordic BioScience platforms.
Results
As early as Week 4 and through Week 12, in patients receiving zasocitinib 15 or 30 mg, reductions in analyzed biomarkers were observed. Among American College of Rheumatology 20% improvement criteria (ACR20) and Psoriasis Area and Severity Index 75% improvement criteria (PASI 75) responders, reductions in TYK2‐ and skin‐joint‐related biomarkers occurred following zasocitinib treatment from baseline to Week 12. Maintenance of baseline bone formation biomarkers was observed in ACR20 responders receiving zasocitinib. Patients with high baseline levels (≥ median) of TYK2‐ and skin‐joint‐related biomarkers receiving zasocitinib achieved greater ACR20 and PASI 75 response rates than those receiving placebo.
Conclusion
Reductions in biomarkers related to TYK2 signaling response, inflammation, skin and joint pathogenesis, and cartilage/bone turnover, along with maintenance of bone formation biomarkers at Week 4, occurred following zasocitinib treatment; associations with clinical response (ACR20 and PASI 75) were observed.
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