The Effect of Etrasimod on Fecal Calprotectin and High-sensitivity C-reactive Protein: Results From the ELEVATE UC Clinical Program

Inflamm Bowel Dis. 2025 Apr 10;31(4):923-934. doi: 10.1093/ibd/izae111.

Abstract

Background: Biomarkers offer potential alternatives to endoscopies in monitoring ulcerative colitis (UC) progression and therapeutic response. This post hoc analysis of the ELEVATE UC clinical program assessed potential predictive values of fecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) as biomarkers and associated responses to etrasimod, an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC, in 2 phase 3 clinical trials.

Methods: In ELEVATE UC 52 and ELEVATE UC 12, patients were randomized 2:1 to 2 mg of etrasimod once daily or placebo for 52 or 12 weeks, respectively. Fecal calprotectin/hsCRP differences between responders and nonresponders for efficacy end points (clinical remission, clinical response, endoscopic improvement-histologic remission [EIHR]) were assessed by Wilcoxon P-values. Sensitivity and specificity were presented as receiver operating characteristics (ROC) curves with area under the curve (AUC).

Results: In ELEVATE UC 52 and ELEVATE UC 12, 289 and 238 patients received etrasimod and 144 and 116 received placebo, respectively. Baseline fCAL/hsCRP concentrations were generally balanced. Both trials had lower week-12 median fCAL levels in week-12 responders vs nonresponders receiving etrasimod for clinical remission, clinical response, and EIHR (all P < .001), with similar trends for hsCRP levels (all P < .01). For etrasimod, AUCs for fCAL/hsCRP and EIHR were 0.85/0.74 (week 12; ELEVATE UC 52), 0.83/0.69 (week 52; ELEVATE UC 52), and 0.80/0.65 (week 12; ELEVATE UC 12).

Conclusions: Fecal calprotectin/hsCRP levels decreased with etrasimod treatment; ROC analyses indicated a prognostic correlation between fCAL changes during induction and short-/long-term treatment response.

Keywords: biomarker; etrasimod; phase 3 clinical trial; sphingosine 1-phosphate; ulcerative colitis.

Plain language summary

We show associations between fecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) levels with efficacy outcomes among patients receiving 2 mg of etrasimod once daily, and that fCAL levels may be an early indicator of the achievement of long-term efficacy end point achievement.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis
  • C-Reactive Protein* / analysis
  • C-Reactive Protein* / metabolism
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / metabolism
  • Double-Blind Method
  • Feces* / chemistry
  • Female
  • Follow-Up Studies
  • Humans
  • Leukocyte L1 Antigen Complex* / analysis
  • Leukocyte L1 Antigen Complex* / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • ROC Curve

Substances

  • Leukocyte L1 Antigen Complex
  • C-Reactive Protein
  • Biomarkers

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