General Information

Entyvio (vedolizumab) is a humanized monoclonal antibody.Vedolizumab targets a protein called alpha-4-beta-7, an integrin on inflammatory cells that causes these cells to adhere to the gastrointestinal tract.

Entyvio is specifically indicated for adults with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroid. Entyvio is indicated to induce and maintain clinical response/clinical remission, achieve corticosteroid-free remission and improve the endoscopic appearance of the mucosa (UC).

Entyvio is supplied as a lyophilized powder for reconstitution into a solution for intravenous administration. The recommended dose for UC and CD is 300 mg infused intravenously over approximately 30 minutes at zero, two and six weeks, then every eight weeks thereafter.

Mechanism of Action

Entyvio (vedolizumab) is a humanized monoclonal antibody that specifically binds to the a4ß7 integrin and blocks the interaction of a4ß7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. The a4ß7 integrin is expressed on the surface of a discrete subset of memory T-lymphocytes that preferentially migrate into the gastrointestinal tract. MAdCAM-1 is mainly expressed on gut endothelial cells and plays a critical role in the homing of T-lymphocytes to gut lymph tissue. The interaction of the a4ß7 integrin with MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn’s disease.

Side Effects

Adverse events associated with the use of Entyvio may include, but are not limited to, the following:

• nasopharyngitis
• headache
• arthralgia
• nausea
• pyrexia
• upper respiratory tract infection
• fatigue
• cough
• bronchitis
• influenza
• back pain
• rash
• pruritus
• sinusitis
• oropharyngeal pain
• pain in extremities

Clinical Trial Results

Ulcerative colitis
The FDA approval of Entyvio for ulcerative colitis was based on two randomized, double-blind, placebo-controlled trials (UC Trials I and II) in adults with moderately to severely active UC. Enrolled patients in the US had over the previous five-year period an inadequate response or intolerance to immunomodulator therapy and/or an inadequate response, loss of response, or intolerance to a TNF blocker. Outside the US, prior treatment with corticosteroids was sufficient for entry if over the previous five-year period the patients were corticosteroid dependent or had an inadequate response or intolerance to corticosteroids. The primary endpoints was based on clinical response: reduction in complete Mayo score of >3 points and >30% from baseline with an accompanying decrease in rectal bleeding subscore of >1 point or absolute rectal bleeding subscore of <1 point. Clinical remission: complete Mayo score of <2 points and no individual subscore >1 point. Improvement of endoscopic appearance of the mucosa: Mayo endoscopy subscore of 0 (normal or inactive disease) or 1 (erythema, decreased vascular pattern, mild friability).
UC Trial 1
374 subjects were randomized in a double-blind fashion to receive Entyvio 300 mg or placebo by intravenous infusion at Week 0 and Week 2. Efficacy assessments were at Week 6. Concomitant stable dosages of aminosalicylates, corticosteroids and immunomodulators were permitted through Week 6. A greater percentage of patients treated with Entyvio compared to placebo achieved clinical response (26% placebo vs. 47% Entyvio) and achieved clinical remission (5% placebo vs. 17% Entyvio) at Week 6. In addition, a greater percentage of patients treated with Entyvio had improvement of endoscopic appearance of the mucosa at Week 6 (25% placebo vs. 41% Entyvio).
UCTrial 2
In order to be randomized to treatment in UC Trial II, patients had to have received Entyvio and be in clinical response at Week 6. Patients could have come from either UC Trial I or from a group who received Entyvio open-label. 373 patients were randomized in a double-blind fashion to one of the following regimens beginning at Week 6: Entyvio 300 mg every eight weeks, Entyvio 300 mg every four weeks or placebo every four weeks. Efficacy assessments were at Week 52. Concomitant aminosalicylates and corticosteroids were permitted through Week 52. Concomitant immunomodulators were permitted outside the US but were not permitted beyond Week 6 in the US. A greater percentage of patients in groups treated with Entyvio as compared to placebo achieved clinical remission at Week 52, and maintained clinical response (clinical response at both Weeks 6 and 52). In addition, a greater percentage of patients in groups treated with Entyvio as compared to placebo were in clinical remission at both Weeks 6 and 52, and had improvement of endoscopic appearance of the mucosa at Week 52. In the subgroup of patients who achieved clinical response at Week 6 and were receiving corticosteroid medication at baseline, a greater proportion of patients in groups treated with Entyvio as compared to placebo discontinued corticosteroids and were in clinical remission at Week 52. The Entyvio every four week dosing regimen did not demonstrate additional clinical benefit over the every eight dosing week regimen.

Crohn's disease
The FDA approval of Entyvio for Crohn's disease was based on three randomized, double-blind, placebo-controlled clinical trials (CD Trials I, II, and III) in adult patients with moderately to severely active Crohn’s disease (CD). Enrolled patients in the US had over the previous five-year period an inadequate response or intolerance to immunomodulator therapy and/or an inadequate response, loss of response, or intolerance to one or more TNF blockers. Outside the US, prior treatment with corticosteroids was sufficient for entry if over the previous five-year period the patients were corticosteroid dependent or had an inadequate response or intolerance to corticosteroids. The primary endpoint was Clinical Remission: CDAI <150. The primary analysis population for CD Trial II was patients that had an inadequate response, loss of response, or intolerance to one or more TNF blockers (76% of the overall population).
CD Trial 1
368 patients were randomized in a double-blind fashion to receive Entyvio 300 mg or placebo by intravenous infusion at Week 0 and Week 2. Efficacy assessments were at Week 6. A statistically significantly higher percentage of patients treated with Entvio achieved clinical remission as compared to placebo at Week 6 (7% placebo vs. 15% Entyvio).
CD Trial 2
Compared to CD Trial I, CD Trial II enrolled a higher number of patients who had over the previous five-year period had an inadequate response, loss of response, or intolerance to one or more TNF blockers (76%); this was the primary analysis population. In CD Trial II, 416 patients were randomized in a double-blind fashion to receive either Entyvio 300 mg or placebo at Weeks 0, 2 and 6. Efficacy assessments were at Weeks 6 and 10. For the primary endpoint (clinical remission at Week 6), treatment with Entyvio did not result in statistically significant improvement over placebo (12% placebo and 15% Entyvio). Secondary endpoints including assessments at Week 10 were not tested because the primary endpoint was not statistically significant.
CD Trial 3
In order to be randomized to treatment in CD Trial III, patients had to have received Entyvio and be in clinical response (defined as a >70-point decrease in CDAI score from baseline) at Week 6. 461 patients were randomized in a double-blind fashion to one of the following regimens beginning at Week 6: Entyvio 300 mg every eight weeks, Entyvio 300 mg every four weeks or placebo every four weeks. Efficacy assessments were at Week 52. Concomitant aminosalicylates and corticosteroids were permitted through Week 52. Concomitant immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate) were permitted outside the US but were not permitted beyond Week 6 in the US. A greater percentage of patients in groups treated with Entyvio as compared to placebo were in clinical remission (defined as CDAI score <150) at Week 52 (22% placebo vs. 39% Entyvio). A greater percentage of patients in groups treated with Entyvio as compared to placebo had a clinical response (defined as >100 decrease in CDAI score from baseline) at Week 52 (30% placebo vs. 44% Entyvio). In the subgroup of patients who were receiving corticosteroids at baseline and who were in clinical response at Week 6, a greater proportion of patients in groups treated with Entyvio as compared to placebo discontinued corticosteroids by Week 52 and were in clinical remission at Week 52. The Entyvio every four week dosing regimen did not demonstrate additional clinical benefit over the every eight dosing week regimen.