ENTYVIO

What it is

Entyvio contains vedolizumab, a humanised monoclonal antibody that binds to the α4β7 integrin. The intravenous formulation is supplied as a powder for injection containing 300 mg of vedolizumab per vial. The subcutaneous formulation is supplied as a pre-filled syringe or pre-filled pen containing 108 mg of vedolizumab in 0.68 mL of sterile solution.

Approved indications

— Treatment of adult patients with moderate to severe ulcerative colitis who have had an inadequate response with, lost response to, or are intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist. — Treatment of adult patients with moderate to severe Crohn's disease who have had an inadequate response with, lost response to, or are intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist. — Treatment of adult patients with moderate to severe chronic pouchitis, who have undergone proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis, and have had an inadequate response with or lost response to antibiotic therapy.

Dosing overview

For ulcerative colitis and Crohn's disease, the intravenous dose regimen is 300 mg administered by intravenous infusion at 0, 2 and 6 weeks and then every 8 weeks thereafter. Subcutaneous vedolizumab maintenance treatment, following at least 2 intravenous infusions, is 108 mg administered by subcutaneous injection once every 2 weeks, with the first subcutaneous dose administered in place of the next scheduled intravenous dose. For pouchitis, the intravenous dose regimen is 300 mg administered by intravenous infusion at 0, 2, and 6 weeks and then every 8 weeks thereafter. Intravenous infusions are administered over 30 minutes.

Key safety warnings

Infusion-related reactions and hypersensitivity reactions have been reported in clinical studies, with the majority being mild to moderate in severity. If severe infusion-related reaction, anaphylactic reaction, or other severe reaction occurs, administration of Entyvio must be discontinued immediately and appropriate treatment initiated. Vedolizumab is a gut-selective integrin antagonist that has not been shown to cause systemic immunosuppressive activity, although systemic infections including septic shock have occurred in patients receiving vedolizumab, and physicians should be aware of the potential increased risk of opportunistic infections or infections for which the gut is a defensive barrier. Entyvio treatment is not to be initiated in patients with active, severe infections until the infections are controlled, and physicians should consider withholding treatment in patients who develop a severe infection while on chronic treatment with Entyvio. Some integrin antagonists and some systemic immunosuppressive agents have been associated with progressive multifocal leukoencephalopathy, a rare and often fatal opportunistic infection caused by the John Cunningham virus; vedolizumab has no known systemic immunosuppressive activity, and while no cases were identified among patients with at least 24 months of exposure in clinical trials, a risk cannot be ruled out. Patients should be monitored for any new onset, or worsening, of neurological signs and symptoms.

Contraindications

Entyvio is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients. Entyvio is contraindicated in patients with active severe infections such as sepsis, tuberculosis, opportunistic infections, and serious abscesses.

PBS listing

The 300 mg powder for injection is listed on the PBS with 8 items under authority required restriction, with an ex-manufacturer price of A$2802.43. The 108 mg subcutaneous injection in pre-filled pen is listed on the PBS with 6 items under authority required restriction, with an ex-manufacturer price of A$1522.23.

Regulatory history

Entyvio 300 mg powder for injection was first listed on the ARTG on 27 June 2014. In November 2014, the PBAC did not recommend vedolizumab for either Crohn's disease or ulcerative colitis, citing uncertain clinical benefit and unacceptable cost-effectiveness compared to currently listed biological disease-modifying anti-rheumatic drugs. In November 2017, the PBAC recommended an amendment to the PBS listing to allow vedolizumab to be used as a first-line biological disease-modifying anti-rheumatic drug for ulcerative colitis. The 108 mg subcutaneous formulations in pre-filled pen and pre-filled syringe were first listed on the ARTG on 12 May 2020.