Pharmacokinetics and Exposure-response Relationship of Golimumab in Patients with Moderately-to-severely Active Ulcerative Colitis: Results from Phase 2/3 PURSUIT Induction and Maintenance Studies

Detrez, Iris; Gils, Ann

doi:10.1093/ecco-jcc/jjw141

Cited by 5 publications

(6 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Real word experience with VDZ in IBD has been recently reported in a systematic review and pooled analysis of nine adult studies comprising 571 patients with UC and 994 patients with CD. 12 It is important to note that significant heterogeneity in study design, patient population and definition of response and remission were observed between studies. Data for response to induction at week 6 among patients with UC were reported from four studies totalling 288 patients.…”

Section: Clinical Data Supporting the Role Of Vedolizumab In Inflammamentioning

confidence: 99%

“…On ROC analysis a VDZ cutoff level of 5.1 μg/ml during maintenance therapy best predicted deep remission (AuROC: 0.713, p = 0.03). 36 …”

Section: Vedolizumab Drug Levels and Clinical Outcomesmentioning

confidence: 99%

“… 7 Most abstracts from observational studies report rates of AVAs of less than 5% with drug-sensitive assays, with rates being higher when a drug-tolerant assay is used. 33 , 34 , 36 Immunogenicity data from full manuscripts are now briefly reviewed. In the French observational cohort already described, no patients developed AVAs using a drug-sensitive assay.…”

Section: Immunogenicity: Anti-vedolizumab Antibodiesmentioning

confidence: 99%

See 2 more Smart Citations

Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease: current data and future directions

Ward

Sparrow

Roblin

2018

Therap Adv Gastroenterol

View full text Add to dashboard Cite

The introduction of vedolizumab, a lymphocyte adhesion inhibitor, has expanded the relatively limited therapeutic armamentarium available for Crohn’s disease and ulcerative colitis. Despite its effectiveness, both primary nonresponse and secondary loss of response to vedolizumab do occur, as is observed with the use of anti-tumour necrosis factor (TNF) therapy. Further, in a proportion, onset of efficacy may be relatively slow. A large body of data support an exposure–response relationship with anti-TNF drug levels, which has led to therapeutic drug monitoring becoming incorporated into everyday clinical management. The influence of patient and disease factors on the pharmacokinetics of anti-TNF levels, including immunogenicity, has also been examined. The role of therapeutic drug monitoring with vedolizumab is less clear. This review summarizes the available evidence on the pharmacokinetics and pharmacodynamics of vedolizumab in inflammatory bowel disease and how drug levels, immunogenicity and other factors influence clinical outcomes. Vedolizumab clearance is increased with very high body weight and hypoalbuminaemia, but is not influenced by the addition of an immunomodulator. Immunogenicity is uncommon. α4β7 receptor saturation occurs at low serum vedolizumab drug levels, and measuring it alone is insufficient to predict clinical outcomes. Using quartile analysis of vedolizumab drug levels, there appears to be a modest exposure–response relationship during induction. Drug levels at week 6 of approximately >20 μg/ml have been shown to be associated with improved clinical outcomes, including subsequent mucosal healing rates during maintenance and avoiding the need to dose escalate due to lack of response. There are currently insufficient data to support the routine use of therapeutic drug monitoring during maintenance therapy. Further studies to elucidate the role of therapeutic drug monitoring of vedolizumab are needed.

show abstract

Section: Clinical Data Supporting the Role Of Vedolizumab In Inflammamentioning

confidence: 99%

“…On ROC analysis a VDZ cutoff level of 5.1 μg/ml during maintenance therapy best predicted deep remission (AuROC: 0.713, p = 0.03). 36 …”

Section: Vedolizumab Drug Levels and Clinical Outcomesmentioning

confidence: 99%

Section: Immunogenicity: Anti-vedolizumab Antibodiesmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease: current data and future directions

Ward

Sparrow

Roblin

2018

Therap Adv Gastroenterol

View full text Add to dashboard Cite

show abstract

“…These factors include patient demographics such as body size, serum albumin concentration, C-reactive protein (CRP), formation of anti-drug antibodies (ADAs), endogenous IgG concentration, expression/turnover of antibody target, mAb saturation of target, and drug-drug interactions. Many mAbs and biologics including certolizumab pegol (16)(17)(18), which is indicated only for CD, and golimumab (19,20), which is indicated only for UC, reported the same factors as influencing PK and showed that observed variability can negatively impact patient outcomes.…”

Section: Mab Pharmacokinetic Variation In Ibdmentioning

confidence: 99%

“…a Such as patients not responsive or with low sensitivity to the mechanism of action of the drug respect to the treatment duration. Work to identify appropriate concentrations for certolizumab pegol (16,17) and golimumab (19,20) has also been published. Several recent retrospective investigations on proactive dose optimization (52,56) were published.…”

Section: Defining Desired Systemic Exposure (Range)mentioning

confidence: 99%

Individualized Dosing of Therapeutic Monoclonal Antibodies—a Changing Treatment Paradigm?

Strik

Wang

Ruff

et al. 2018

AAPS J

View full text Add to dashboard Cite

The introduction of monoclonal antibodies (mAbs) to the treatment of inflammatory bowel disease (IBD) was an important medical milestone. MAbs have been demonstrated as safe and efficacious treatments of IBD. However, a large percentage of patients either fail to respond initially or lose response to therapy after a period of treatment. Although there are factors associated with poor treatment outcomes in IBD, one cause for treatment failure may be low mAb exposure. Consequently, gastroenterologists have begun using therapeutic drug monitoring (TDM) to guide dose adjustment. However, while beneficial, TDM does not provide sufficient information to effectively adjust doses. The pharmacokinetics (PK) and pharmacodynamics (PD) of mAbs are complex, with numerous factors impacting on mAb PK and PD. The concept of dashboard-guided dosing based on Bayesian PK models allows physicians to combine TDM with factors influencing mAb PK to individualize therapy more effectively. One issue with TDM has been the slow turnaround of assay results, either necessitating an additional clinic visit for a sample or reacting to TDM results at a subsequent, rather than the current, dose. New point-of-care (POC) assays for mAbs are being developed that would potentially allow physicians to determine drug concentration quickly. However, work remains to understand how to determine what target exposure is needed for an individual patient, and whether the combination of POC assays and dashboards presents a safe approach with substantial outcome benefit over the current standard of care.

show abstract

Laparoscopic Intervention in Acute Crohn's Disease Involving an Ovary

Gawron

Chmura

Adamek

et al. 2017

Journal of Minimally Invasive Gynecology

View full text Add to dashboard Cite

Pharmacokinetics and Exposure-response Relationship of Golimumab in Patients with Moderately-to-severely Active Ulcerative Colitis: Results from Phase 2/3 PURSUIT Induction and Maintenance Studies

Cited by 5 publications

References 8 publications

Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease: current data and future directions

Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease: current data and future directions

Individualized Dosing of Therapeutic Monoclonal Antibodies—a Changing Treatment Paradigm?

Laparoscopic Intervention in Acute Crohn's Disease Involving an Ovary

Contact Info

Product

Resources

About