Clinical Information

Drug and target:

Vedolizumab (VDZ, Entyvio) is a humanized IgG1 kappa monoclonal antibody directed against integrin alpha-4 beta-7 integrin expressed on lymphocytes. VDZ blocks the interaction between the alpha-4 beta-7 integrin and MAdCAM-1, preventing lymphocytes from migrating across the endothelium into inflamed gastrointestinal tissue, thereby reducing inflammation.

Indications:

Vedolizumab is US Food and Drug Administration-approved for the treatment of adult patients with moderately to severely active ulcerative colitis or Crohn disease.(1,2) The standard dosing is 300 mg intravenously (IV) at weeks 0, 2, and 6 (induction), and then every 8 weeks for maintenance. It may be given every 4 weeks in certain cases of partial response.

Pharmacokinetic highlights:

Steady-state trough concentrations are typically achieved after the first few maintenance doses (around 14-22 weeks into therapy). Another option is subcutaneous injection with 108 mg every 2 weeks for maintenance after initial IV induction at weeks 0 and 2. The reported median steady state trough serum concentrations range from 19 to 48 mcg/mL, with multiple studies demonstrating an increase of at least 10 mcg/mL after transition from IV to subcutaneous administration.(3-9)

Immunogenicity:

Patients on VDZ may develop antibodies to VDZ (ATV) over time. In clinical trials, approximately 4% of patients treated with VDZ were positive for ATV at any time and 1% or less had samples that were persistently positive. ATV formation may increase drug clearance in treated patients and/or neutralize the drug effect, thereby potentially contributing to the loss of response. ATV could also cause adverse events such as serum sickness and hypersensitivity reactions. VDZ drug level quantitation is commonly performed in conjunction with immunogenicity assessment for ATV.

Evidence for therapeutic drug monitoring:

Optimal therapeutic concentrations of VDZ associated with clinical remission and mucosal healing range between 12 and 28 mcg/mL, depending on the stage of therapy (induction or maintenance).(10-13) Most often, testing is ordered for patients on therapy who are experiencing loss of response (reactive monitoring). In the setting of loss of response to therapy, testing for ATV may be performed as a reflex after the drug quantitation shows subtherapeutic levels of VDZ (VEDOL / Vedolizumab Quantitation with Reflex to Antibodies, Serum) or as a panel where drug quantitation and ATV are performed simultaneously (this test). Results from drug quantitation combined with ATV testing play an important role in patient management.(10,12,13)

Proactive monitoring of ATV in a patient who is responding to therapy with VDZ is not recommended by the American Gastroenterology Association.