Entyvio

Entyvio is available as a powder to be made up into a solution for infusion (drip) into a vein and as a prefilled syringe or pen for injection under the skin. It can only be obtained with a prescription and treatment should be started and supervised by a specialist who has experience in the diagnosis and treatment of ulcerative colitis, Crohn’s disease or pouchitis.

The recommended dose by infusion into a vein is 300 mg given at the start and weeks two and six, and then every eight weeks after that in patients who respond to treatment. The infusion lasts 30 minutes; all patients are monitored for any reactions during the infusion and for at least one to two hours after the end of the infusion.

Patients with ulcerative colitis or Crohn’s disease who have responded to initial treatment by infusion may be switched to treatment by injection under the skin. The recommended dose is 108 mg. The first dose by injection under the skin replaces the next scheduled infusion, and subsequent doses are then given every 2 weeks. Patients or their caregivers can inject the medicine themselves once they have been properly trained.

For more information about using Entyvio, see the package leaflet or contact your doctor or pharmacist.

Patients who receive Entyvio must be given a special alert card that summarises the safety information about the medicine.

The active substance in Entyvio, vedolizumab, is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a specific structure (called an antigen) in the body. Vedolizumab has been designed to attach to ‘alfa-4-beta-7 integrin’, a protein mostly found on the surface of certain white blood cells in the gut. In ulcerative colitis, Crohn’s disease and pouchitis these cells are involved in causing inflammation in the gut. By blocking alfa-4-beta-7 integrin, vedolizumab reduces the inflammation in the gut and the symptoms of these diseases.

Ulcerative colitis

Entyvio for infusion into a vein has been investigated in a main study in patients with moderate to severe active ulcerative colitis in whom conventional therapy or TNF-alfa antagonists were ineffective or could not be tolerated. Patients received either Entyvio or placebo (a dummy treatment) and the main measure of effectiveness was the proportion of patients whose symptoms improved after 6 weeks of treatment. Entyvio was shown to be more effective than placebo: 47% (106 out of 225) of patients who received Entyvio showed an improvement in symptoms, compared with 26% (38 out of 149) of patients who received placebo. In addition, the study also showed that Entyvio maintained the effect up to 52 weeks more effectively than placebo.

In results involving 216 patients who had responded to initial Entyvio infusion in a second study, injection under the skin every 2 weeks was as effective in maintaining control of the disease over a year as infusion every 8 weeks. After 52 weeks, around 46% of those given injection under the skin (49 of 106) and 42% of those given the medicine by infusion (23 of 54) still had their symptoms controlled.

Crohn’s disease

Entyvio was also shown to be more effective than placebo at improving symptoms of Crohn’s disease. In one main study in adult patients with moderate to severe active Crohn’s disease in whom conventional therapy or TNF-alfa antagonists were ineffective or could not be tolerated, 15% (32 out of 220) of patients receiving Entyvio showed improved symptoms after 6 weeks of treatment, compared with 7% (10 out of 148) of patients on placebo. Similarly, in this study the maintenance of the effect up to 52 weeks with Entyvio was more effective than with placebo.

Data from another study involving patients who had responded to Entyvio infusion showed that injection under the skin every 2 weeks could maintain control of the disease: after 52 weeks around 48% of those treated in this way (132 of 275) still had their symptoms controlled.

Pouchitis

Entyvio was also shown to be more effective than placebo at improving symptoms of chronic pouchitis using the Pouchitis Disease Activity Index (PDAI) and the modified PDAI (mPDAI). The mPDAI and PDAI are 12 and 18 point scales of disease severity, with higher scores corresponding to worse disease severity.

In one main study in 102 adult patients with active chronic pouchitis in whom conventional antibiotic therapy was ineffective, around 31% (16 out of 51) of patients receiving Entyvio were in clinical remission after 14 weeks of treatment, compared with 10% (5 out of 51) of patients on placebo. Remission was defined as an mPDAI score less than 5 and a reduction in total mPDAI score of equal or more than 2 points from baseline.

The most common side effects with Entyvio (which may affect more than 1 in 10 people) are nasopharyngitis (inflammation of the nose and throat such as a cold), headache and arthralgia (joint pain). For the full list of side effects of Entyvio, see the package leaflet.

Entyvio must not be used in people with active serious infections such as tuberculosis, sepsis (infection in the blood), listeriosis (infection with bacteria called Listeria) or opportunistic infections (those seen in patients with a weakened immune system) such as progressive multifocal leukoencephalopathy (PML, a rare brain infection that usually leads to severe disability or death). For the full list of restrictions, see the package leaflet.

The European Medicines Agency decided that Entyvio’s benefits are greater than its risks and it can be authorised for use in the EU. In ulcerative colitis, the Agency considered that the benefit of Entyvio has been clearly demonstrated, which is relevant for patients who do not respond to TNF-alfa therapy. Furthermore, the risks are considered manageable, despite the lack of long-term safety data, if recommendations in place are followed.

In Crohn’s disease, the Agency considered that although the time required for improvement of symptoms may be longer and the size of the effect limited when compared with anti-TNF-alfa therapy, Entyvio still offers a benefit for patients because of its different mechanism of action and safety profile.

In pouchitis, Entyvio led to better rates of remission compared with placebo. Its safety profile was similar to the other uses and the Agency considered that the benefits are greater than its risks.

The company that markets Entyvio will provide educational material to all healthcare professionals expected to prescribe the medicine to remind them of the need to monitor patients for signs of neurological disease or PML, in particular those treated with certain biological medicines which may potentially cause PML.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Entyvio have also been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Entyvio are continuously monitored. Side effects reported with Entyvio are carefully evaluated and any necessary action taken to protect patients.

Entyvio received a marketing authorisation valid throughout the EU on 22 May 2014.