Vedolizumab Drug Level Correlation With Clinical Remission, Biomarker Normalization, and Mucosal Healing in Inflammatory Bowel Disease

Al-Bawardy, Badr; Ramos, Guilherme Piovezani; Willrich, Maria Alice V.; Jenkins, Sarah M.; Park, Sang Hyoung; Aniwan, Satimai; Schoenoff, Shayla; Papadakis, Konstantinos A.; Raffals, Laura E.; Loftus, Edward V.

doi:10.1093/ibd/izy272

Cited by 42 publications

(44 citation statements)

References 27 publications

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“…From 12 104 studies identified using the original search strategy, 5655 unique studies were identified. From these, 32 studies focusing on vedolizumab were identified for full text review, and five studies were included in quantitative synthesis (Figure ) . Additionally, data from five studies was qualitatively synthesized to inform vedolizumab concentrations associated with favourable outcomes .…”

Section: Resultsmentioning

confidence: 99%

“…From these, 32 studies focusing on vedolizumab were identified for full text review, and five studies were included in quantitative synthesis ( Figure 1). [8][9][10]19,20 Additionally, data from five studies was qualitatively synthesized to inform vedolizumab concentrations associated with favourable outcomes. 7,[21][22][23][24] Multiple studies were reported using the GEMINI trials and unique aspects of each analyses were used to quantitatively or qualitatively inform evidence on role of TDM with vedolizumab.…”

Section: Re Sultsmentioning

confidence: 99%

“…While TDM has been extensively studied and implemented when using tumour necrosis factor‐α (TNFα) antagonists, it's role in the optimisation of vedolizumab is unclear. Vedolizumab trough concentrations have been variably associated with clinical outcomes in patients with IBD, with some studies suggesting higher vedolizumab trough concentrations in patients responding to therapy, whereas others suggesting no differences in trough concentrations in responding vs nonresponding patients . In in vitro cell‐based assays, complete α 4 β 7 receptor saturation was reached at a vedolizumab serum concentration of approximately 1 μg/mL, a concentration considered subtherapeutic .…”

Section: Introductionmentioning

confidence: 99%

“…Vedolizumab trough concentrations have been variably associated with clinical outcomes in patients with IBD, with some studies suggesting higher vedolizumab trough concentrations in patients responding to therapy, whereas others suggesting no differences in trough concentrations in responding vs nonresponding patients. [6][7][8][9][10] In in vitro cell-based assays, complete α 4 β 7 receptor saturation was reached at a vedolizumab serum concentration of approximately 1 μg/mL, a concentration considered subtherapeutic. 11,12 This suggests that while receptor saturation may be necessary, it is not sufficient for clinical efficacy of vedolizumab.…”

Section: Introductionmentioning

confidence: 99%

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Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Singh

Dulai

Casteele

et al. 2019

Aliment Pharmacol Ther

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SUMMARY Background There has been limited evaluation of the association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases (IBD). Aim To perform a systematic review and meta‐analysis to evaluate the potential role of therapeutic drug monitoring (TDM) for vedolizumab. Methods Through a systematic literature search through 28 February 2019, we identified five cohort studies (558 patients, 42% with ulcerative colitis) reporting the association between vedolizumab trough concentration and clinical outcomes in patients with IBD. We calculated mean difference (MD) in vedolizumab trough concentration in patients achieving vs not achieving clinical outcomes, and qualitatively synthesized thresholds associated with favourable outcomes. Results In patients with UC, median vedolizumab trough concentrations were consistently higher in patients achieving clinical remission (median, 14.3 μg/mL vs 10.5 μg/mL; MD, 5.1 μg/mL, 95% CI, 2.8‐7.4) or endoscopic remission (median, 13.0 μg/mL vs 9.7; MD, 5.1 μg/mL, 95% CI, 2.2‐7.9). In patients with CD, there was no significant difference in median vedolizumab trough concentrations in patients achieving vs not achieving clinical remission (MD, 2.0 μg/mL; 95% CI, −0.5 to 4.5) or endoscopic remission (MD, 3.6 μg/mL; 95% CI, −1.4 to 8.6). In patients with UC, week 6 vedolizumab trough concentrations ≥18.5‐20.8 μg/mL, and maintenance trough concentrations ≥9.0‐12.6 μg/mL were associated with favourable clinical outcomes. Antibodies to vedolizumab were reported in 1.7%‐3.0% patients on maintenance therapy. Conclusion Based on meta‐analysis, patients with UC who achieve endoscopic and clinical remission have significantly higher vedolizumab trough concentration during maintenance therapy. Vedolizumab trough concentration >20 μg/mL at week 6, and >12 μg/mL during maintenance may be associated with better outcomes, though cause‐effect relationship remains unclear. Prospective studies on reactive and proactive therapeutic drug monitoring of vedolizumab (vs empiric dose escalation) are warranted.

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Section: Resultsmentioning

confidence: 99%

Section: Re Sultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Singh

Dulai

Casteele

et al. 2019

Aliment Pharmacol Ther

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“…42 Moreover, there was a trend toward higher rates of deep remission at week 52 with higher vedolizumab trough steady-state serum concentrations. 43 In contrast, a study by Badr Al-Bawardy et al 44 did not observe a correlation between vedolizumab serum concentrations and mucosal healing in either patients with UC or patients with CD. The pooling of different time points in which vedolizumab concentrations were measured could account for the lack of this association.…”

Section: Vedolizumabmentioning

confidence: 90%

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

Berghe

Gils

Thomas

2019

Clin Pharma and Therapeutics

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Biologicals introduced a major shift in the treatment of patients suffering from inflammatory bowel diseases. Despite providing a tight disease control for many patients, a considerable proportion of patients will fail to respond favorably to treatment or will lose response over time. Therapeutic drug monitoring emerged as a valuable tool to guide clinical decision making as serum drug concentrations have been linked to outcomes. Focusing on mucosal healing as the ultimate treatment goal, different drug concentration thresholds to achieve this outcome have been identified in the literature and are summarized in this review. For therapeutic drug monitoring to be successful in guiding clinical decision making, the used assay, the sampling time point, and the outcome that is aimed for should be taken into account when interpreting drug concentration thresholds. Awareness of these essential aspects among clinicians will improve the implementation of therapeutic drug monitoring and aid in making an evidence‐based decision.

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Proactive therapeutic drug monitoring and vedolizumab dose optimization in children with inflammatory bowel disease

Rowland,

McNicol,

Kiel

et al. 2024

J. pediatr. gastroenterol. nutr.

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ObjectivesTherapeutic drug monitoring (TDM) and dose optimization have been shown to improve clinical outcomes with antitumor necrosis factor and recent studies in adults suggest an exposure–response relationship with drug levels associated with improved clinical outcomes. However, these levels are not universally recognized as therapeutic targets for vedolizumab dosing. We aimed to assess the impact of a TDM quality improvement (QI) initiative on 52‐week clinical outcomes and describe proactively obtained vedolizumab levels during the induction period in children with inflammatory bowel disease (IBD).MethodsA QI initiative to proactively obtain TDM levels at Week 6 was implemented in 2019. A retrospective review of pediatric patients with IBD treated with vedolizumab from 2018 to 2022 was performed. Baseline demographic data, medication dosing details, disease characteristics, lab results, and 12‐month clinical outcomes were recorded. For this study, we defined therapeutic target levels (>20 μg/mL at Week 6 and >12 μg/mL during maintenance) based on existing data correlating these levels with improved clinical outcomes.ResultsFifty‐nine patients (31 Crohn disease [CD], 28 ulcerative colitis [UC]/indeterminate colitis [IC]) were included in the study. In total, 68% (40/59) of patients had vedolizumab levels at Week 6 and 90% (53/59) had levels drawn at Week 6 or 14. Thirty‐five percent of Week 6 trough levels were below our defined target of 20 μg/mL. Fifty‐two of 59 patients had available data at 52 weeks. Over 80% (42/52) of patients remained on vedolizumab 52 weeks after initiation (CD 79% [23/29], UC/IC 83% [19/23]). Sixty‐two percent (26/42) of patients that remained on vedolizumab at 52 weeks were treated with an intensified dosing interval of <8 weeks. Thirty‐one of these 42 (74%) were in clinical remission (CR) rate at 52 weeks with 29/42 (69%) in corticosteroid‐free remission. The CR rate for the entire cohort including those who discontinued therapy due to a lack of efficacy before 52 weeks was 60% (31/52).ConclusionProactive TDM and early dose optimization with vedolizumab may improve drug durability and clinical outcomes in pediatric patients with IBD.

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Vedolizumab Drug Level Correlation With Clinical Remission, Biomarker Normalization, and Mucosal Healing in Inflammatory Bowel Disease

Abstract: Our cohort showed a low rate of immunogenicity to VDZ and an association between VTLs and CRP in CD but not in UC patients. No relationship between VTLs and MH was detected. Vedolizumab trough level measurements altered management in approximately three fourths of patients.

Cited by 42 publications

References 27 publications

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

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

Proactive therapeutic drug monitoring and vedolizumab dose optimization in children with inflammatory bowel disease

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