Introduction
Entyvio (vedolizumab) is a biologic medication developed by Takeda Pharmaceuticals for the treatment of moderate to severe ulcerative colitis and Crohn's disease. It represents a targeted approach to inflammatory bowel disease (IBD) therapy, specifically designed to act locally within the gastrointestinal tract while minimizing systemic immunosuppression.
Mechanism of Action
Vedolizumab is a humanized monoclonal antibody that specifically binds to α4β7 integrin, a protein expressed on the surface of circulating lymphocytes. This binding selectively inhibits the interaction between α4β7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is primarily expressed on gut vascular endothelium. By blocking this interaction, vedolizumab prevents lymphocyte migration into gastrointestinal tissue, thereby reducing inflammation at the site of disease while preserving systemic immune function.
Indications
FDA-approved indications:
- Moderately to severely active ulcerative colitis in adults
- Moderately to severely active Crohn's disease in adults
Dosage and Administration
Standard dosing:- 300 mg administered by intravenous infusion over 30 minutes
- Initial: Dose at weeks 0, 2, and 6
- Maintenance: Every 8 weeks thereafter
- Hepatic impairment: No dosage adjustment required
- Renal impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
- Pediatrics: Safety and effectiveness not established
- Must be administered by healthcare professional
- Requires reconstitution and dilution prior to administration
- Pre-medication with antihistamines, antipyretics, or corticosteroids not required but may be considered for patients with infusion-related reactions
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Steady-state volume of distribution approximately 5.1 L Metabolism: Expected to be degraded via proteolytic enzymes throughout the body Elimination: Terminal half-life approximately 25 days Clearance: Linear pharmacokinetics with clearance of 0.157 L/dayContraindications
- History of severe hypersensitivity reaction to vedolizumab or any of its excipients
- Active severe infections until resolved
Warnings and Precautions
Infusions Reactions: May occur during or within several hours of infusion Infections: Increased risk of infections, including opportunistic infections Hepatotoxicity: Liver injury has been reported; monitor liver enzymes Progressive Multifocal Leukoencephalopathy (PML): Although no cases reported with vedolizumab monotherapy, theoretical risk exists due to mechanism of action Malignancies: Theoretical risk of malignancy; monitor patients accordingly Live Vaccines: Avoid concurrent administration with live vaccinesDrug Interactions
- Concurrent use with other biologics: Increased risk of infections (not recommended)
- TNF blockers: Limited data on concomitant use
- Immunosuppressants: May increase risk of infections
- Natalizumab: Contraindicated due to increased risk of PML
Adverse Effects
Most common (>10%):- Nasopharyngitis
- Headache
- Arthralgia
- Upper respiratory tract infections
- Fatigue
- Cough
- Abdominal pain
- Nausea
- Serious infections (1.4%)
- Infusion-related reactions (1%)
- Hypersensitivity reactions
- Liver injury
Monitoring Parameters
Baseline:- Complete blood count with differential
- Comprehensive metabolic panel (including liver function tests)
- Screening for latent tuberculosis (TB)
- Hepatitis B and C serology
- Pregnancy test if applicable
- Clinical assessment of disease activity
- Monitoring for signs of infection
- Liver function tests periodically
- Regular assessment of treatment response
- Monitoring for infusion reactions during and after administration
Patient Education
- Inform patients about the increased risk of infections and to report any signs of infection promptly
- Advise patients to complete all recommended vaccinations before starting therapy
- Educate patients about the signs and symptoms of infusion reactions
- Instruct patients to report any new neurological symptoms immediately
- Discuss pregnancy planning and contraception if appropriate
- Emphasize importance of adherence to scheduled infusions
- Inform patients that clinical response may be delayed (typically 6-14 weeks)
References
1. Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013;369(8):711-721. 2. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699-710. 3. Entyvio (vedolizumab) [package insert]. Lexington, MA: Takeda Pharmaceuticals America, Inc.; 2021. 4. Colombel JF, Sands BE, Rutgeerts P, et al. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut. 2017;66(5):839-851. 5. US Food and Drug Administration. Entyvio prescribing information. Accessed January 2023. 6. Peyrin-Biroulet L, Danese S, Argollo M, et al. Loss of response to vedolizumab and ability of dose intensification to restore response in patients with Crohn's disease or ulcerative colitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019;17(5):838-846.