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

1

Tofacitinib is a JAK inhibitor approved for moderate-to-severe ulcerative colitis, but 40-60% of patients do not respond adequately.
2

Responders to tofacitinib show higher baseline JAK-STAT activity, while non-responders exhibit increased NF-kB pathway activation.
3

Non-responders experience hyperactivation of macrophages and fibroblasts, with significant upregulation of inflammatory markers post-treatment.
4

IL-10-dependent macrophages are identified as a key cellular subset contributing to resistance against tofacitinib treatment.
5

Understanding the mechanisms of refractoriness to tofacitinib is essential for improving therapeutic strategies in ulcerative colitis.

Journal Of Crohn's And Colitis

by Elisa Melón-Ardanaz, Marisol Veny, Ana M Corraliza, Victoria Gudiño, Alba Garrido-Trigo, Ángela Sanzo-Machuca, Marc Buendia, Miriam Esteller, Lisseth Robbins-Moreno, Maite Rodrigo, M Carme Masamunt, Ángel Giner, Marta Gallego, Ingrid Ordás, Agnès Fernández-Clotet, Berta Caballol, Ángel Corbí, Bram Verstockt, Severine Vermeire, Julian Panés, Elena Ricart, Azucena Salas
May 5, 2025

1