The European Commission has granted marketing authorization for the intravenous ( IV ) formulation of Entyvio ( Vedolizumab ) for the treatment of adult patients with moderately to severely active chronic pouchitis, who have undergone proctocolectomy and ileal pouch-anal anastomosis ( IPAA ) for ulcerative colitis ( UC ), and have had an inadequate response with or lost response to antibiotic therapy.
Entyvio is the first treatment indicated for active chronic pouchitis across the European Union.
The European Commission approval was based on the EARNEST trial that has assessed the safety and efficacy of Vedolizumab IV in the treatment of active chronic pouchitis.
Furthermore, information from a number of retrospective studies indicating that Vedolizumab can have a positive impact on patients with inflammation of the pouch was also included in the application.
IPAA, also known as J-pouch surgery, is a procedure used to help patients who have had their colon and rectum removed ( proctocolectomy ) pass stools normally.
Pouchitis is a complication after proctocolectomy with IPAA in patients with ulcerative colitis with a reported incidence rate between 23% and 59%, and can have a significant impact on quality of life.
Chronic pouchitis, which affects 10-15% of patients with pouchitis globally, does not adequately respond to antibiotic therapy, and can cause fecal urgency, incontinence, straining during defecation, bleeding, abdominal or pelvic discomfort, fever and malaise.
EARNEST is a randomized, double-blind, placebo-controlled multicenter study that evaluated the efficacy and safety of Vedolizumab IV in the treatment of 102 adult patients with ulcerative colitis who had undergone a proctocolectomy and IPAA, and had developed active chronic pouchitis, defined as patients who had inadequate response with or lost response to antibiotics therapy.
The EARNEST study met its primary endpoint of clinical remission at week 14.
Measured using the modified Pouchitis Disease Activity Index ( mPDAI ), clinical remission rates were 31.4% ( 95% CI: 19.1% - 45.9% ) in patients in the Vedolizumab IV arm ( n=51 ), compared with 9.8% ( 95% CI: 3.3% - 21.4% ) in the placebo arm ( n=51 ) ( p=0.013 ).
Safety findings were in line with general use of Vedolizumab.
Adverse events were reported in 47 ( 92.2% ) and 44 ( 86.3% ) of patients treated with Vedolizumab and placebo, respectively. Treatment-related adverse reactions ( as assessed by the investigator ) were reported in 12 ( 23.5% ) and 11 ( 21.6% ) of patients treated with Vedolizumab and placebo, respectively. Serious adverse effects were reported in 3 ( 5.9% ) and 4 ( 7.8% ) patients treated with Vedolizumab and placebo, respectively.
Vedolizumab is a gut-selective biologic and is approved in both intravenous ( IV ) and subcutaneous ( SC ) formulations.
The SC formulation is currently approved in Europe, Canada, Australia, and Switzerland only.
Vedolizumab is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 ( MAdCAM-1 ), but not vascular cell adhesion molecule 1 ( VCAM-1 ).
MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.
The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.
These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis and Crohn’s disease. By inhibiting alpha4beta7 integrin, Vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.
Vedolizumab is approved for the treatment of adult patients with moderately to severely active ulcerative colitis and Crohn’s disease, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha ( TNFα ) antagonist. ( Xagena )
Source: Takeda, 2022