Early vedolizumab trough levels at induction in inflammatory bowel disease patients with treatment failure during maintenance

Abstract

Background Vedolizumab (VDZ) is effective as an induction and maintenance treatment for Crohn's disease and ulcerative colitis, but, as observed with antitumour necrosis factor-α (anti-TNFα) agents, some patients are nonetheless experiencing loss of response.Objective The aim of this study was to investigate the impact of the pharmacokinetics of VDZ during induction on long-term treatment response. Patients and methods This study focused on a single cohort of 103 inflammatory bowel disease patients treated with VDZ. VDZ trough levels (TLs) were measured by enzyme-linked immunosorbent assay (n = 536 samples), and thereafter correlated to clinical, biological, endoscopic and serological data. For patients exposed previously to infliximab, antibodies to infliximab were measured at baseline. On the basis of the outcome at the end of follow-up, patients were then categorized into long-term response, optimized and treatment failure groups. Results During VDZ induction, at week 6, inflammatory bowel disease patients with long-term response had higher TLs compared with patients in the treatment failure group (33 vs. 24 µg/ml, P = 0.02). A cut-off TL of 28 µg/ml predicted a sustained response in the follow-up with an area under curve of 0.723 (95% confidence interval = 0.567-0.878, P = 0.02). Patients with mucosal healing in maintenance had higher TLs at week 6 (41.65 µg/ml) compared with patients with mild (26 µg/ml) or severe endoscopic activity (20.8 µg/ml), P = 0.009. Positive perinuclear antineutrophil cytoplasmic antibody serology was associated with lower TLs. Patients previously exposed to anti-TNFα had lower TLs than naive patients (22.5 vs. 36 µg/ml, P = 0.03) without any impact of detectable antibodies to infliximab. Finally, the presence of an immunomodulator at induction did not impact on VDZ TLs at induction. Conclusion We confirmed that a drug exposure-efficacy association was found early on at induction. This study emphasizes that previous exposure to anti-TNFα and positive perinuclear antineutrophil cytoplasmic antibody serology are important factors influencing VDZ TLs at induction. Eur J Gastroenterol Hepatol 31:478-485

Achieving Mucosal Healing in Inflammatory Bowel Diseases: Which Drug Concentrations Need to Be Targeted?

“…A threshold of 18 μg/mL was identified as the optimal vedolizumab concentration at week 6 to reach mucosal healing. A similar concentration–response relationship was observed in a study by Liefferinckx et al . with overall higher vedolizumab concentrations.…”

“…A threshold of 18 μg/mL was identified as the optimal vedolizumab concentration at week 6 to STATE of the ART reach mucosal healing. A similar concentration-response relationship was observed in a study by Liefferinckx et al 46 with overall higher vedolizumab concentrations. At week 6, patients achieving mucosal healing between weeks 14 and 54 had a higher vedolizumab concentration (41.7 μg/mL) compared with patients with mild (26 μg/mL) or severe endoscopic activity (20.8 μg/mL).…”

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

“…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 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.…”

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

“…More recent studies have shown that, at least in UC, patients achieving and maintaining clinical and endoscopic remission have significantly higher vedolizumab trough concentration during maintenance therapy than patients who do not respond [32][33][34][35][36][37][38][39]. Nevertheless, it remains plausible that further clinical and biological factors can influence the response to the drug.…”