Abstract
Vedolizumab, a monoclonal antibody directed against integrin α4β7, is an effective treatment for inflammatory bowel diseases. However, a significant number of patients do not achieve steroid-free clinical remission in the first year of treatment. An early identification of these patients is one of the most important challenges for clinicians and offers the possibility of therapeutic optimization in order to personalize biological therapy. The aim of our study was to test the prediction ability of interleukin (IL)-6 and -8 of clinical response after 12 months of therapy with vedolizumab (T2). We performed a prospective, multicentre study in patients affected by inflammatory bowel disease by analysing cytokines level before starting vedolizumab (T0) and after 10 weeks of therapy (T1). In the overall cohort (n = 54), IL-8 decrease > 2.6 pg/mL in the first 10 weeks of therapy was able to predict clinical response (area under the curve (AUC) = 0.70, sensitivity = 66%, specificity = 75%, p = 0.010), negative C-reactive protein (CRP) (AUC = 0.71, sensitivity = 64%, specificity = 80%, p = 0.009) and calprotectin < 250 mg/kg (AUC = 0.69, sensitivity = 64%, specificity = 78%, p = 0.030) after 44 weeks of therapy. In patients with ulcerative colitis (n = 40), baseline IL-8 values > 8.6 pg/mL and a decrease of IL-6 values > 0.4 pg/mL from T0 to T1 were significant and independent predictors of clinical response after 12 months of vedolizumab therapy (odds ratio (OR) = 6.96, 95% CI 1.27–38.22, p = 0.026 and OR = 7.29, 95% CI 1.42–37.50, p = 0.017, respectively). In patients with Crohn’s disease (n = 14), baseline IL-8 values > 8.6 pg/mL and baseline IL-6 values > 1.6 pg/mL allowed the identification of patients achieving negative CRP at T2 (AUC = 0.75, sensitivity = 74%, specificity = 76%, p < 0.001) and patients with faecal calprotectin values < 250 mg/kg at T2 (AUC = 0.71, sensitivity = 78%, specificity = 63%, p = 0.004). In conclusion, our study highlights a potential clinical role of serum cytokine levels for the prediction of clinical and biochemical steroid-free response in patients treated with vedolizumab.
Highlights
Inflammatory bowel diseases (IBD) are chronic gastrointestinal disorders consisting of two main entities, ulcerative colitis (UC) and Crohn’s disease (CD), both characterized by an immune-mediated pathogenesis and a clinical relapsing course [1,2]
In the last two decades, a more comprehensive understanding of the cytokine pathways involved in the pathogenesis of IBD allowed the development of new treatment strategies that led to reduced use of corticosteroids [3]
In a previous monocentre study involving patients with UC and CD treated with different types of biologics drugs, we observed that IL-6 reduction from baseline to 10 weeks of treatment was able to broadly predict clinical response at 12 months of therapy [17].Here, we aimed at investigating the prediction ability of IL-6 and -8 of clinical response after 10 weeks and after 12 months of therapy with VDZ
Summary
Inflammatory bowel diseases (IBD) are chronic gastrointestinal disorders consisting of two main entities, ulcerative colitis (UC) and Crohn’s disease (CD), both characterized by an immune-mediated pathogenesis and a clinical relapsing course [1,2].In the last two decades, a more comprehensive understanding of the cytokine pathways involved in the pathogenesis of IBD allowed the development of new treatment strategies that led to reduced use of corticosteroids [3]. The most used biomarker in IBD practice is faecal calprotectin, but it reflects only a non-specific anti-inflammatory response [8,9] For this reason, an analysis of cytokine levels in patients with IBD could be useful to predict the pharmacological response to treatment with biological drugs, such as VDZ. An analysis of cytokine levels in patients with IBD could be useful to predict the pharmacological response to treatment with biological drugs, such as VDZ In this perspective, the most relevant cytokines involved in the pathophysiology of IBD [10,11,12] and studied as possible biomarkers of therapeutic response [13,14,15,16] are interleukin (IL)-6 and IL-8. In a previous monocentre study involving patients with UC and CD treated with different types of biologics drugs, we observed that IL-6 reduction from baseline to 10 weeks of treatment was able to broadly predict clinical response at 12 months of therapy [17].Here, we aimed at investigating the prediction ability of IL-6 and -8 of clinical response after 10 weeks and after 12 months of therapy with VDZ
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