Differential effects of tofacitinib on macrophage activation contribute to lack of response in ulcerative colitis patients.

ABSTRACT:

Background and aims

Tofacitinib, a Janus kinase inhibitor, is approved for the treatment of moderate-to-severe ulcerative colitis. Nonetheless, 40-60% of patients will not respond adequately. The mechanisms underlying responses to tofacitinib remain unknown.

Methods

We applied single-cell and/or bulk RNA analysis to biopsies (n = 23 and 63, respectively) from ulcerative colitis patients (n = 31) before and after tofacitinib treatment. Response was assessed using endoscopic and clinical criteria. In vitro-derived macrophages and primary intestinal fibroblasts were used to validate our findings.

Results

Forty percent of patients responded to tofacitinib. Responders exhibited higher baseline JAK-STAT activity, while non-responders had increased baseline NF-kB pathway act

SUBMITTER: Melon-Ardanaz E 

PROVIDER: S-EPMC12137895 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature