Improvement in serum eosinophilia is observed in clinical responders to ustekinumab but not adalimumab in inflammatory bowel disease

INTRODUCTION: In inflammatory bowel disease (IBD), the number of eosinophils increases in the lamina propria of the intestinal tract, but their specific patho-mechanistic role remains unclear. Elevated blood eosinophil counts in active IBD suggest their potential as biomarkers for predicting response to biological therapies. This study evaluates blood eosinophil count trends and their predictive value for clinical response and endoscopic improvement in patients with IBD receiving ustekinumab or adalimumab induction therapy. METHODS: Participant-level data from phase 3 and 4 clinical trials (UNIFI, SEAVUE, VARSITY) evaluating ustekinumab and adalimumab for moderate-severe Crohn's disease (CD) and ulcerative colitis (UC) were used. The primary outcome was clinical response, defined by reductions in disease activity scores. Eosinophil counts were compared between responders and non-responders at multiple time points using t-tests. Logistic regression assessed the odds of achieving a clinical response based on baseline eosinophil counts. RESULTS: Among patients treated with ustekinumab for UC, responders had significantly higher baseline eosinophil counts compared to non-responders (0.21 × 109/L vs 0.18 × 109/L, P = .042). By week 8, responders showed a greater absolute (-0.07 × 109/L vs -0.01 × 109/L, P < .001) and percent decline (-33.33% vs -5.55%, P = .027) in eosinophil counts. In CD, ustekinumab responders also had higher baseline eosinophil counts and showed significant reductions by week 8. However, no significant differences in eosinophil counts were observed among CD patients treated with adalimumab or UC patients treated with vedolizumab. CONCLUSION: Eosinophil reduction was identified as a marker for early response to ustekinumab in both UC and CD, but not adalimumab. No difference was observed among UC patients treated with vedolizumab either. Targeting the IL-12/IL-23 pathway may be more effective in managing eosinophil-associated inflammation in IBD.