Letter: addition of methotrexate neither restores clinical response nor improves the pharmacokinetic profile of vedolizumab‐treated patients

Gouynou, Célia; Peyrin–Biroulet, Laurent

doi:10.1111/apt.14320

Cited by 12 publications

(11 citation statements)

References 5 publications

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“…Combination therapy at initiation did not lead to higher early vedolizumab through levels, nor was it predictive of mucosal healing within the first year of treatment. These results are in line with our previous finding that addition of methotrexate neither restored clinical response nor improved the pharmacokinetic profile of vedolizumab‐treated patients . Potential explanation is the low immunogenicity of vedolizumab.…”

Section: Discussionsupporting

confidence: 91%

Early vedolizumab trough levels predict mucosal healing in inflammatory bowel disease: a multicentre prospective observational study

Yacoub

Williet

Pouillon

et al. 2018

Aliment Pharmacol Ther

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102

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Summary Background The correlation between vedolizumab trough levels during induction therapy and mucosal healing remains unknown. Aim To compare early vedolizumab trough levels in patients with and without mucosal healing within the first year after treatment initiation. Methods We prospectively collected vedolizumab trough levels in all inflammatory bowel disease patients at weeks 2, 6 and 14 of vedolizumab treatment in three French referral centres between 1 June 2014 and 31 March 2017. Results of every patient that underwent mucosal assessment by magnetic resonance imaging and/or endoscopy in the first year after treatment initiation were analysed. Results Median vedolizumab trough levels in the overall population (n = 82) were 27 μg/mL (interquartile range, IQR 21.2‐33.8 μg/mL) at week 2, 23 μg/mL (IQR 15‐34.5 μg/mL) at week 6 and 10.7 μg/mL (IQR 4.6‐20.4 μg/mL) at week 14. Only median vedolizumab trough levels at week 6 differed between patients with and without mucosal healing within the first year after treatment initiation (26.8 vs 15.1 μg/mL, P = 0.035). A cut‐off trough level of 18 μg/mL at week 6 predicted mucosal healing within the first year after the start of vedolizumab with an area under the receiver operating curve of 0.735 (95% confidence interval 0.531‐0.939). A vedolizumab trough level above 18 μg/mL at week 6 was the only independent variable associated with mucosal healing within the first year of treatment (odds ratio 15.7, 95% confidence interval 2.4‐173.0, P = 0.01). Conclusion Early therapeutic drug monitoring might improve timely detection of vedolizumab‐treated patients in need for an intensified dosing regimen.

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Section: Discussionsupporting

confidence: 91%

Early vedolizumab trough levels predict mucosal healing in inflammatory bowel disease: a multicentre prospective observational study

Yacoub

Williet

Pouillon

et al. 2018

Aliment Pharmacol Ther

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102

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“…Synergy on efficacy or prevention of immunogenicity may both concur to these positive outcomes. The impact of combotherapy on patients with VDZ has been evaluated in real-world experience cohort studies, but with opposite conclusions [15,21,37,38]. Our study suggested that the use of concomitant IMM did not alter the pharmacokinetics of VDZ either at induction or during maintenance, confirming the results of other studies [15,21].…”

Section: Discussionsupporting

confidence: 73%

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

Liefferinckx

Minsart

Cremer

et al. 2019

European Journal of Gastroenterology &Amp; Hepatology

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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

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“…This has been confirmed in all available real-world data so far, even when using a drug-resistant assay [23, 24]. It might explain why adding an immunomodulator to vedolizumab therapy seems neither to enhance drug levels nor to restore therapeutic response [14, 25].…”

Section: Immunogenicitymentioning

confidence: 82%

Vedolizumab trough level monitoring in inflammatory bowel disease: a state-of-the-art overview

Pouillon

Vermeire

Bossuyt

2019

BMC Med

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Background Therapeutic drug monitoring involves therapeutic modifications based on the measurement of drug levels and antidrug antibodies. The viability of therapeutic drug monitoring in vedolizumab-treated patients with inflammatory bowel disease remains questioned. Main body Accumulating evidence from clinical trials and real-world data suggests that an exposure–efficacy relationship may exist for vedolizumab in inflammatory bowel disease, but results are not as straightforward as they are for anti-tumour necrosis factor-α therapy. Robust target vedolizumab trough levels are currently missing, since available data are heterogenous and prospective, interventional pharmacokinetic–pharmacodynamic studies are lacking. The positioning of vedolizumab drug monitoring in therapeutic algorithms is yet to be defined. Conclusion Therapeutic drug monitoring has the potential to improve the outcome parameters of vedolizumab-treated patients with inflammatory bowel disease. Before the therapeutic drug monitoring of vedolizumab can be implemented in a widespread fashion, prospective studies are needed to evaluate the effect of vedolizumab dose optimisation. These studies should focus on objective disease markers and vedolizumab drug levels, and define thresholds for optimal drug exposure.

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Letter: addition of methotrexate neither restores clinical response nor improves the pharmacokinetic profile of vedolizumab‐treated patients

Abstract: Linked Content This article is linked to Strik et al paper. To view this article visit https://doi.org/10.1111/apt.13994.

Cited by 12 publications

References 5 publications

Early vedolizumab trough levels predict mucosal healing in inflammatory bowel disease: a multicentre prospective observational study

Early vedolizumab trough levels predict mucosal healing in inflammatory bowel disease: a multicentre prospective observational study

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

Vedolizumab trough level monitoring in inflammatory bowel disease: a state-of-the-art overview

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