Baseline Assessment of Serum Cytokines Predicts Clinical and Endoscopic Response to Ustekinumab in Patients With Crohn's Disease: A Prospective Pilot Study

Inflamm Bowel Dis. 2024 Dec 5;30(12):2449-2456. doi: 10.1093/ibd/izae133.

Abstract

Background: No biomarkers are currently available to predict therapeutic response to ustekinumab (UST) in Crohn's disease (CD). The aim of this prospective study was to identify 1 or more cytokines able to predict mucosal healing in patients with CD treated with UST.

Methods: We prospectively enrolled consecutive CD patients treated with UST. At weeks 0 (baseline), 24, and 48, a panel of serum cytokines was measured by a fluorescence assay. At the same time points, fecal calprotectin (FC) was assessed. A colonoscopy was performed at baseline and at week 48, where therapeutic outcome was evaluated in terms of mucosal healing.

Results: Out of 44 patients enrolled, 22 (50%) achieved mucosal healing at the end of follow-up. Response was associated with higher interleukin (IL)-23 levels (P < .01). Fecal calprotectin levels decreased over time in responders but did not change in nonresponders (test for the interaction between time and mucosal healing, P < .001).

Conclusions: This pilot study showed that IL-23 and FC could be reliable biomarkers in predicting therapeutic outcome to UST therapy in CD. In particular, the correlation between baseline serum levels of IL-23 and mucosal healing at 48 weeks is particularly strong, paving the way for its use to drive therapeutic decisions.

Keywords: Crohn’s disease; biologics; cytokines; mucosal healing; ustekinumab.

Plain language summary

This prospective pilot study showed that the assessment of IL-23 levels at baseline could predict clinical and endoscopic outcomes to ustekinumab therapy in Crohn’s disease. Testing this biomarker before starting a biological therapy could be useful for a personalized choice.

MeSH terms

  • Adult
  • Biomarkers* / blood
  • Colonoscopy
  • Crohn Disease* / blood
  • Crohn Disease* / drug therapy
  • Cytokines / blood
  • Feces* / chemistry
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-23 / blood
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Leukocyte L1 Antigen Complex* / analysis
  • Leukocyte L1 Antigen Complex* / blood
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Treatment Outcome
  • Ustekinumab* / therapeutic use
  • Young Adult

Substances

  • Ustekinumab
  • Leukocyte L1 Antigen Complex
  • Biomarkers
  • Cytokines
  • Interleukin-23

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