Serum Eosinophilia Improvement with Ustekinumab vs Adalimumab in IBD Responders

Overview

In patients with inflammatory bowel disease (IBD), clinical responders to ustekinumab showed significant reductions in blood eosinophil counts compared to those treated with adalimumab. Elevated baseline eosinophil counts predicted better clinical response to ustekinumab in both ulcerative colitis (UC) and Crohn’s disease (CD), whereas no such association was observed with adalimumab.

Background

Inflammatory bowel disease, encompassing UC and CD, involves chronic inflammation of the gastrointestinal tract with eosinophils playing a potential pathogenic role. Eosinophils contribute to tissue damage through secretion of inflammatory mediators and are elevated in active IBD. Ustekinumab, targeting IL-12/IL-23, and adalimumab, an anti-TNF agent, are biologics used in moderate to severe IBD. Identifying biomarkers such as eosinophil counts may help predict therapeutic response and guide personalized treatment.

Data Highlights

Key Findings

• Ustekinumab responders with UC had significantly higher baseline eosinophil counts than non-responders (0.21 vs 0.18 ×10⁹/L, P=0.042).
• By week 8, ustekinumab responders showed a greater absolute and percentage decline in eosinophil counts compared to non-responders.
• Similar trends of higher baseline eosinophils and reductions by week 8 were observed in CD patients treated with ustekinumab.
• No significant eosinophil count differences were found among CD patients treated with adalimumab or UC patients treated with vedolizumab.
• Eosinophil reduction may serve as an early biomarker of clinical response to ustekinumab but not to adalimumab.
• Targeting the IL-12/IL-23 pathway may more effectively modulate eosinophil-associated inflammation in IBD.

Clinical Implications

Monitoring blood eosinophil counts could aid in early identification of patients likely to respond to ustekinumab therapy in both UC and CD. This biomarker may help differentiate responders from non-responders, allowing clinicians to optimize treatment strategies. Conversely, eosinophil counts appear less useful for predicting response to adalimumab, highlighting the importance of mechanism-specific biomarkers.

Conclusion

Blood eosinophil count reductions are associated with clinical response to ustekinumab in IBD, supporting their role as a predictive biomarker. These findings underscore the therapeutic relevance of targeting IL-12/IL-23 pathways in eosinophil-driven inflammation.

References

1. UNIFI, SEAVUE, VARSITY Trials -- Ustekinumab and Adalimumab in IBD
2. Janssen Inc. -- UNIFI and SEAVUE Clinical Trial Data
3. Takeda Inc. -- VARSITY Clinical Trial Data