Integrin Calculus: The Predictive Power of Vedolizumab Concentrations in IBD Therapy

Abstract

Although biological therapies, including the monoclonal antibody directed against the α 4 β 7 integrin, vedolizumab, have revolutionized the treatment of patients with inflammatory bowel disease (IBD), response and remission to this therapy are not universal. Up to 30% of patients with Crohn's disease (CD) and ulcerative colitis (UC) do not respond at all, and up to 70% of initial responders only partially respond, with many patients losing response over time. Many of these undesired therapeutic outcomes can be explained by undetectable or low drug concentrations due to antibody formation or an increased non-immune drug clearance rate. Numerous studies suggest that higher serum biological drug concentrations are associated with a greater rate of favorable therapeutic outcomes [1]. Nonetheless, most of these studies relate to therapies directed against tumor necrosis factor (TNF), whereas exposure-outcome relationship studies remain limited for vedolizumab. Consequently, the time to assess drug concentrations and the related therapeutic drug window for vedolizumab remains undefined.In this issue of Digestive Diseases and Sciences, Yarur et al. [2] recently added to knowledge regarding therapeutic drug monitoring (TDM) of vedolizumab. They performed a nicely designed single-center prospective cohort study that reported that serum vedolizumab concentrations obtained shortly after therapy initiation correlated with long-term steroid-free endoscopic remission. This study of 55 patients with IBD (CD, n = 25, and UC, n = 30) and with active endoscopic disease in whom vedolizumab therapy was initiated demonstrated that patients achieving steroid-free endoscopic remission by week 52 of therapy had statistically significant higher serum vedolizumab concentrations at weeks 2 and 6.Additionally, they identified that vedolizumab concentration thresholds ≥ 23.2 μg/ml at week 2 and ≥ 19.8 μg/ml at week 6 were independently associated with endoscopic (odds ratio [OR] 8.8; 95% confidence interval [CI] 2.6-29.7; p < 0.001) and clinical (OR 6.8 [95% CI 1.2-4], p = 0.033) remission at week 52. Furthermore, they demonstrated a positive correlation between serum vedolizumab concentrations and serum albumin and an inverse correlation with C-reactive protein (CRP), fecal calprotectin, and body mass. Finally, immunogenicity was very low as only 3/55 (5.5%) patients had detectable antibodies to vedolizumab through the 52 weeks of follow-up using a drug-tolerant homogeneous mobility shift assay.These results are in line with previous studies, showing that higher vedolizumab concentrations, during both induction and maintenance treatments, are typically associated with superior therapeutic outcomes in patients with IBD (Table 1) [2][3][4][5][6][7][8]. The identification of clinically relevant vedolizumab thresholds is important as this would be the first step for applying both reactive and proactive TDMbased therapeutic algorithms. These algorithms for reactive TDM have been proven useful and cost-effective for clarifying the etiology and m...