Ivarmacitinib is associated with rapid clinical improvement and immune remodeling in palmoplantar pustulosis: A multi-center, single-arm clinical trial
Journal of the American Academy of Dermatology, 2026
Xu Z., Chen W., Du J., Tian B., Wang J., Ma S., Yang J., Yu C., Cao T., Liu L., Wang G., Shao S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases Dermatological Diseases | Patient Stratification | Plasma |  Olink Target 96 |
Abstract
Background
Palmoplantar pustulosis (PPP) carries substantial burden with limited treatments. Selective JAK1 inhibition is promising, yet prospective, immune-integrated data remain scarce.
Objectives
To evaluate the efficacy, safety, and immunomodulatory effects of ivarmacitinib in PPP and to explore baseline predictors of response.
Methods
Prospective, single-arm, 12-week study across three centers. Sixty patients received oral ivarmacitinib 4 mg daily; 58 (96.7%) completed follow-up. Primary endpoint: PPPASI change at week 12. Exploratory endpoints included peripheral T lymphocyte subsets, neutrophil phenotypes, and plasma proteomics.
Results
Mean PPPASI decreased from 11.3 (95%CI: 9.9-12.6) to 3.9 (3.4-4.4) (P < 0.001); 85.0% achieved PPPASI50 and 13.3% achieved PPPASI75 after 12 weeks. Pruritus, pain, and quality of life improved by week 2 (all P < 0.05). Treatment partially normalized Th2/Th17-skewed polarization and activated neutrophil phenotypes. Early response correlated with lower baseline CD4/CD8 ratio, Th2/Th1 ratio, and plasma IL10RA/IL2RB; sustained response with lower CD4+ effector memory and CD8+ central memory proportions, and higher GDNF. Twenty-two grade 1-2 adverse events occurred and 2 patients discontinued treatment.LimitationsSingle-arm design.ConclusionsIvarmacitinib achieved rapid improvement with favorable safety and partial immune remodeling in PPP. Baseline immune profiles may stratify response, supporting selective JAK1 inhibition and biomarker-guided patient selection.