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

Share

Clinical Scorecard: Variability in Macrophage Activation by Tofacitinib May Explain Insufficient Responses in Ulcerative Colitis Patients

At a Glance

CategoryDetail
ConditionModerate-to-severe ulcerative colitis
Key MechanismsDifferential activation of JAK-STAT and NF-kB pathways; IL-10-dependent macrophage hyperactivation mediates resistance
Target PopulationUlcerative colitis patients treated with tofacitinib
Care SettingInflammatory bowel disease specialty units with endoscopic and clinical monitoring

Key Highlights

  • 40% of UC patients respond to tofacitinib; non-responders show increased baseline NF-kB activity and macrophage hyperactivation.
  • Responders exhibit higher baseline JAK-STAT signaling and downregulation of inflammatory macrophage markers post-treatment.
  • Tofacitinib inhibits IL-10 signaling in LPS-activated macrophages, leading to hyperactivation and treatment resistance.

Guideline-Based Recommendations

Diagnosis

  • Assess baseline JAK-STAT and NF-kB pathway activity via molecular profiling to predict tofacitinib response.
  • Use endoscopic Mayo score and clinical criteria to evaluate disease activity before and after treatment.

Management

  • Administer tofacitinib 10 mg twice daily as standard-of-care for moderate-to-severe UC.
  • Maintain treatment in non-responders at least until week 16 with follow-up endoscopy to assess response.
  • Consider alternative therapies for patients exhibiting macrophage hyperactivation and poor response.

Monitoring & Follow-up

  • Perform endoscopic and clinical assessments at baseline, week 8, and week 16 (or later if needed).
  • Collect colonic biopsies and blood samples for molecular and histologic evaluation of treatment effect.
  • Monitor macrophage and fibroblast activation markers (e.g., MMP9, IL1B, IL6, CXCL1, CXCL8, S100A9) post-treatment.

Risks

  • Potential for macrophage hyperactivation due to IL-10 signaling inhibition leading to treatment resistance.
  • Non-response associated with increased NF-kB pathway activity and inflammatory macrophage expansion.

Patient & Prescribing Data

Patients with moderate-to-severe ulcerative colitis eligible for tofacitinib therapy

Approximately 40% respond to tofacitinib; non-responders show distinct immune activation profiles, suggesting need for personalized therapeutic strategies.

Clinical Best Practices

  • Incorporate molecular profiling of JAK-STAT and NF-kB pathway activity to guide tofacitinib use.
  • Use single-cell RNA sequencing or equivalent methods to monitor immune cell subsets during treatment.
  • Recognize IL-10-dependent macrophage hyperactivation as a mechanism of resistance to optimize patient management.

References

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

Related Content

Refining Vancomycin Use in Early CDI

A modified dosing approach could reshape recurrence prevention strategies.

Exploring Comorbidity Patterns in Inflammatory Bowel Disease: Insights from the All of Us Research Program

Link Between Blastocystis Subtypes 3 and 4 and Intestinal Inflammation as Well as Metronidazole Efficacy in Symptomatic Individuals