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

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

  • 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

  • 0 min

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Objective:

To investigate the mechanisms underlying the inadequate responses to tofacitinib in ulcerative colitis patients, emphasizing the significance for treatment optimization.

Key Findings:
  • 40% of patients responded to tofacitinib treatment.
  • Responders had higher baseline JAK-STAT activity, while non-responders exhibited increased NF-kB pathway activation.
  • Response was associated with significant changes in the abundance and/or activation of immune, epithelial, and stromal cells.
  • Non-responders showed hyperactivation of macrophages and fibroblasts post-treatment, with upregulation of inflammatory markers.
  • IL-10-dependent macrophages were identified as a key subset contributing to resistance against tofacitinib.
Interpretation:

The variability in macrophage activation and the role of IL-10 signaling may explain the insufficient responses to tofacitinib in a significant proportion of ulcerative colitis patients, highlighting the need for tailored treatment strategies.

Limitations:
  • The study did not consider sex as a biological variable.
  • Sample size may limit the generalizability of findings, particularly regarding the diversity of patient responses.
Conclusion:

Resistance to tofacitinib in ulcerative colitis is linked to the hyperactivation of myeloid cells, particularly IL-10-dependent macrophages, underscoring their role in treatment resistance.

Original Source(s)

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

  • 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

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