Population pharmacokinetics of vedolizumab in Asian and non-Asian patients with ulcerative colitis and Crohn’s disease

Okamoto, Hiroyuki; Dirks, Nathanael L.; Rosario, Maria; Hori, Tetsuharu; Hibi, Toshifumi

doi:10.5217/ir.2019.09167

Cited by 17 publications

(26 citation statements)

References 20 publications

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“…Although vedolizumab clinical efficacy was not explored in this post hoc analysis, real‐world data support the conclusion that ADAs do not appear to play a major role in vedolizumab efficacy, 24 even in patients who discontinue and later restart vedolizumab treatment 25,26 . This is further supported by previously published results 27 and that low‐titer ADA positive status (10‐50 titer values) had minimal effect on the pharmacokinetics of vedolizumab, 18 whereas higher‐titer ADAs (≥250 titer values) affect vedolizumab clearance 28 . Additionally, a recent report suggested that immunogenicity was not a primary driver of vedolizumab treatment failure 24 …”

Section: Discussionsupporting

confidence: 81%

Vedolizumab Immunogenicity With Long‐Term or Interrupted Treatment of Patients With Inflammatory Bowel Disease

Wyant

Yang

Lirio

et al. 2021

The Journal of Clinical Pharma

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Patients in the GEMINI 1 or 2 study (NCT00790933; Eudra CT2008-002784-14) with ulcerative colitis or Crohn disease had low immunogenicity rates after vedolizumab treatment for up to 52 weeks. We report immunogenicity rates from the GEMINI long-term safety (LTS) study using a new drugtolerant electrochemiluminescence assay, including analyses in patients who received continuous vedolizumab induction and maintenance in GEMINI 1 or 2 and long term safety, or vedolizumab induction and placebo maintenance in GEMINI 1 or 2 followed by re-treatment in long term safety (treatment interruption). Patients were enrolled in GEMINI long term safety from GEMINI 1, 2, or 3, or as de novo vedolizumab-treated patients; all received vedolizumab 300 mg intravenously every 4 weeks. Vedolizumab antidrug antibody (ADA) status was determined by electrochemiluminescence assay; ADA-positive samples were characterized by neutralizing activity. Vedolizumab ADA data were available for 1753 patients: 1513 continuously treated with vedolizumab before/during GEMINI long term safety, 240 re-treated after treatment interruption. Among continuously treated patients, 36 (2.4%) were ADA positive (15 persistently, 20 neutralizing ADA positive). Among re-treated patients, 53 (22.1%) were ADA positive (42 persistently, 40 neutralizing ADA positive). Longitudinal immunogenicity rates increased during placebo maintenance (19.4% at week 52), then decreased in GEMINI long term safety to rates (0 at the final visit) similar to continuously treated patients. ADA positivity was 1.1% vs 2.5% (continuous treatment) and 23.1% vs 22.0% (re-treatment) among patients with and without infusion-related reactions, respectively. Long-term vedolizumab treatment was associated with generally low immunogenicity rates; vedolizumab-re-treated patients had higher rates during placebo maintenance, which decreased during re-treatment. No relationship was observed between immunogenicity and infusion-related reactions.

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Section: Discussionsupporting

confidence: 81%

Vedolizumab Immunogenicity With Long‐Term or Interrupted Treatment of Patients With Inflammatory Bowel Disease

Wyant

Yang

Lirio

et al. 2021

The Journal of Clinical Pharma

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“…How long these medications last in the system and effect of low dose detectable levels on post-surgical outcomes is not well understood, but it has been suggested that even low dose can have negative effects on outcomes. 16,17 In our study, however, rates of complications with vedolizumab were still low in this potentially higher risk group of patients.…”

Section: Discussioncontrasting

confidence: 56%

Vedolizumab does not increase perioperative surgical complications in patients with inflammatory bowel disease, cohort study

et al. 2022

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gery have plateaued for both ulcerative colitis (UC) and Crohn' s disease (CD) while significant concerns have been raised about increasing rates of peri-operative complications. [2][3][4] Anti-tumor necrosis factor (anti-TNF) medications, in particular infliximab, have been shown to increase rates or perioperative infectious complications although this data remains controversial. 3,[8][9][10] It has also been suggested that concerns about anti-TNF related surgical complications is at least in part responsible for the increased rate of 3 stage surgery for UC in the United States. 10 Vedolizumab is an α4β7 anti-integrin antibody that has been increasingly used in both UC and CD. The α4β7 inhibi-

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“…The third step involves TDM during the maintenance phase when the measurement of mABs and ADAs may be appropriate for all anti-TNFα agents ( Papamichael et al, 2019a ), while the reactive TDM can be the standard of care for all IBD patients who experienced a loss of response. As presented in previous paragraphs, the titration of ADAs (rather than the notification of their presence or absence) could further improve the segmentation of patients according to their likelihood of response ( Brandse et al, 2017 ; Okamoto et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is worth noting that two independent population pharmacokinetic studies found that the titer of ADAs correlated with the estimated clearance values of infliximab ( Brandse et al, 2017 ) and vedolizumab ( Okamoto et al, 2020 ) better than a simple dichotomic presence/absence result. These findings are likely suggesting that a more accurate segmentation of patients according to the ADA titer could further improve the individualization of therapeutic regimens.…”

Section: Monoclonal Antibodies Used In Inflammatory Bowel Diseasesmentioning

confidence: 99%

Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

Paolo

Luci

2021

Front. Pharmacol.

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The pharmacotherapy of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) has experienced significant progress with the advent of monoclonal antibodies (mABs). As therapeutic proteins, mABs display peculiar pharmacokinetic characteristics that differentiate them from chemical drugs, such as aminosalicylates, antimetabolites (i.e., azathioprine, 6-mercaptopurine, and methotrexate), and immunosuppressants (corticosteroids and cyclosporine). However, clinical trials have demonstrated that biologic agents may suffer from a pharmacokinetic variability that could influence the desired clinical outcome, beyond primary resistance phenomena. Therefore, therapeutic drug monitoring (TDM) protocols have been elaborated and applied to adaptation drug doses according to the desired plasma concentrations of mABs. This activity is aimed at maximizing the beneficial effects of mABs while sparing patients from toxicities. However, some aspects of TDM are still under discussion, including time-changing therapeutic ranges, proactive and reactive approaches, the performance and availability of instrumental platforms, the widely varying individual characteristics of patients, the severity of the disease, and the coadministration of immunomodulatory drugs. Facing these issues, personalized medicine in IBD may benefit from a combined approach, made by TDM protocols and pharmacogenetic analyses in a timeline that necessarily considers the frailty of patients, the chronic administration of drugs, and the possible worsening of the disease. Therefore, the present review presents and discusses the activities of TDM protocols using mABs in light of the most recent results, with special attention on the integration of other actions aimed at exploiting the most effective and safe therapeutic effects of drugs prescribed in IBD patients.

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Population pharmacokinetics of vedolizumab in Asian and non-Asian patients with ulcerative colitis and Crohn’s disease

Cited by 17 publications

References 20 publications

Vedolizumab Immunogenicity With Long‐Term or Interrupted Treatment of Patients With Inflammatory Bowel Disease

Vedolizumab Immunogenicity With Long‐Term or Interrupted Treatment of Patients With Inflammatory Bowel Disease

Vedolizumab does not increase perioperative surgical complications in patients with inflammatory bowel disease, cohort study

Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

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