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Association of Vedolizumab Level, Anti-Drug Antibodies, and α4β7 Occupancy With Response in Patients With Inflammatory Bowel Diseases Bella Ungar, Uri Kopylov, Miri Yavzori, Ella Fudim, Orit Picard, Adi Lahat, Daniel Coscas, Matti Waterman, Ola Haj-Natour, Noam Orbach-Zingboim, Ren Mao, Minhu Chen, Yehuda Chowers, Rami Eliakim, Shomron Ben-Horin Clinical Gastroenterology and Hepatology Volume 16, Issue 5, Pages e7 (May 2018) DOI: /j.cgh Copyright © 2018 AGA Institute Terms and Conditions
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Figure 1 Association between baseline albumin level quartiles and week 14 vedolizumab trough levels (n = 106). Clinical Gastroenterology and Hepatology , e7DOI: ( /j.cgh ) Copyright © 2018 AGA Institute Terms and Conditions
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Figure 2 (A) Week 6 vedolizumab levels among patients in clinical remission vs clinically active patients at week 6. (B) Vedolizumab trough level quartiles at week 6 in relation to clinical remission rates at the same time point. (C) Correlation between week 6 vedolizumab levels and CRP values. Clinical Gastroenterology and Hepatology , e7DOI: ( /j.cgh ) Copyright © 2018 AGA Institute Terms and Conditions
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Figure 3 Maintenance-phase vedolizumab levels among 60 patients with normal vs increased CRP values. Clinical Gastroenterology and Hepatology , e7DOI: ( /j.cgh ) Copyright © 2018 AGA Institute Terms and Conditions
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Figure 4 (A) Fluorescence-activated cell sorting analysis of free α4β7 integrin on peripheral blood memory T cells (α4β7+CD45RO+CD3+ cells, of total CD45RO+CD3+ T cells), detected by staining with conjugated-vedolizumab at weeks 0, 2, and 14. Exemplary 4 patients are shown with their respective induction’s clinical outcome and drug levels. (B) Graphic summary of the percentage of free α4β7 on memory T cells (α4β7+ CD45RO+CD3+) in peripheral blood of vedolizumab-treated patients (separately presented for responders and nonresponders). Induction and maintenance period observations are shown. Each point denotes a single patient, except during induction when 2 points connected with a line represent a single patient at the 2 designated time points. The color of the connecting line denotes if a patient’s week 14 level vedolizumab was low or high. High vedo, above median, shown as blue line; low vedo, level below the median value at week 14 of entire 106-patient cohort, shown as red line; Vedo, vedolizumab; W, week. (C) Results of experiments (n = 3) of drug concentration α4β7 blockade titration curve. Unstimulated peripheral blood T cells were cultured with graded concentrations of unconjugated vedolizumab in media alone or after polyclonal stimulation by Muromonab-CD3. Staining with conjugated vedolizumab was performed after 5 days in culture to delineate the drug concentration that confers complete receptor occupancy. (D) Flow cytometry and fluorescence-activated cell sorting analysis of intestinal memory LP T cell free α4β7 integrin (α4β7+CD45RO+CD3+ cells, of total CD45RO+CD3+ T cells), determined by staining with conjugated vedolizumab. Two controls were used: an IgG-isotype control and a pre-incubation with unconjugated 50 mcg/mL vedolizumab. Exemplary 3 experiments are shown. (E) Box-and-whisker plot depicting the percentage of α4β7+ on LP memory T cells (α4β7+CD45RO+CD3+ cells, of total CD45RO+CD3+ T cells) in intestinal biopsy specimens of control (n = 14) or vedolizumab-treated patients (n = 15). Clinical Gastroenterology and Hepatology , e7DOI: ( /j.cgh ) Copyright © 2018 AGA Institute Terms and Conditions
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Supplementary Figure 1 Correlation between graded concentrations of exogenously added vedolizumab to unexposed serum and ELISA reading by optical density. Clinical Gastroenterology and Hepatology , e7DOI: ( /j.cgh ) Copyright © 2018 AGA Institute Terms and Conditions
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Supplementary Figure 2 (A) ROC analysis of vedolizumab levels among CD patients, with clinical remission as a classification variable. (B) ROC analysis of vedolizumab levels among UC patients, with clinical remission as a classification variable. Clinical Gastroenterology and Hepatology , e7DOI: ( /j.cgh ) Copyright © 2018 AGA Institute Terms and Conditions
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Supplementary Figure 3 (A) Intra-individual vedolizumab levels during maintenance therapy among responders. (B) Intra-individual vedolizumab levels among patients who lost response to maintenance therapy. Clinical Gastroenterology and Hepatology , e7DOI: ( /j.cgh ) Copyright © 2018 AGA Institute Terms and Conditions
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