Mucosal Eosinophilia Is an Independent Predictor of Vedolizumab Efficacy in Inflammatory Bowel Diseases

Abstract

Background Peripheral and mucosal eosinophilia may be associated with more aggressive disease in inflammatory bowel disease (IBD) patients. Vedolizumab blocks T lymphocytes, eosinophil adhesion, and extravasation in the gastrointestinal tract. It is not known if mucosal eosinophilia is a predictor for the therapeutic efficacy of vedolizumab. Methods This was a retrospective cohort study of IBD patients with ileal or colonic biopsies who were off steroids before starting vedolizumab. Biopsies were rereviewed by pathologists, and mean eosinophil density was quantified. Patient characteristics and steroid-free clinical response 6 months after beginning vedolizumab were determined. Features were compared between nonresponders and responders, and multivariable logistic regression was performed to identify predictors of clinical response. Results Of 251 IBD patients starting vedolizumab therapy, 65 patients (48% Crohn’s disease, 52% ulcerative colitis) met inclusion criteria. All IBD patients not responding to vedolizumab were more likely to have a higher baseline mean eosinophil count (340 ± 156 vs 236 ± 124; P = 0.004), be previously exposed to an anti-TNF (96% vs 56%; P = 0.001), and be male (58% vs 28%; P = 0.02). Mean eosinophil counts were significantly increased in colonic biopsies in UC nonresponders (438 ± 149 vs 299 ± 145; P = 0.01). A similar trend was seen in CD nonresponders. On multivariable analysis, colonic eosinophil density and prior anti-TNF exposure—and the combination of both—were independent predictors of response. Conclusion In ulcerative colitis, colonic eosinophilia and prior anti-TNF exposure were independent predictors of 6-month clinical nonresponse to vedolizumab. Mucosal eosinophil density as a novel biomarker should be explored in larger patient cohorts. Aside from the previous anti-TNF exposure, eosinophil density in the colon of patients with UC is a negative predictor for a steroid-free long-term response to vedolizumab. The degree colonic eosinophilia may be a novel biomarker that should be further explored.

Extent of Mucosal Inflammation in Ulcerative Colitis Influences the Clinical Remission Induced by Vedolizumab

“…These data are in line with those of a recent study showing that distal/left-sided colitis was associated with a higher percentage of clinical remission at week 14 as compared to extensive colitis following vedolizumab treatment [14]. However, other studies failed to document an association between extent of UC and response to vedolizumab [22,23,52]. Although, it remains unclear why such studies have generated divergent results, it is conceivable that discrepancies can rely on differences in the selection of the objectives, study population, and statistical analysis adopted.…”

Role of Eosinophils in Intestinal Inflammation and Fibrosis in Inflammatory Bowel Disease: An Overlooked Villain?

“…Non-responders to vedolizumab treatment had higher baseline colonic mucosal mean eosinophil counts. Whether this increased baseline eosinophil count could be used as a predictor for non-response to the humanized antibody vedolizumab should be further investigated ( 192 ). While no effects of infliximab treatment on eosinophil presence and activation status have been described, infliximab has been suggested to be effective in the early stages of fibrosis development.…”

Importance of Eosinophilic Infiltration of the Colonic Mucosa in Ulcerative Colitis Patients who are Refractory to Maintenance Therapy

“…Therefore, it is possible to use steroids for a short duration in refractory UC patients who are Th2-dominant, leading to stable maintenance treatment thereafter. Eosinophilic in ltration of the colonic mucosa has also been reported to be an indicator of resistance to treatment with vedolizumab [7] , and α4β7, the target molecule of vedolizumab, is expressed on the surface of eosinophils [29] . Therefore, one treatment strategy may be to control in ammation more e ciently by rst eliminating eosinophils in the local mucosal area by administering steroids, and simultaneously inhibiting the migration of eosinophils from blood to the mucosal in ammatory area by administering vedolizumab.…”

“…However, in recent years, it has been reported that the pathophysiology of refractory UC is associated with interleukin (IL) -33 produced by damaged colonic epithelial cells and eosinophils induced by IL-33 [4,5] . Recent studies have reported that the mucosa of intractable UC lesions has a large amount of eosinophilic in ltration [6] , and the eosinophilic in ltration of the colonic mucosa is an indicator of treatment resistance to vedolizumab [7] .…”