Demonstrated efficacy

Proven Long-term
remission in
Crohn’s disease

For adults with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD). 

ENTYVIO-treated patients achieved long-term remission vs placebo at Week 521

Study Design1: Crohn's Disease Trials I and III were randomized, double-blind, placebo-controlled studies that enrolled adult patients with moderately to severely active Crohn's disease who had failed at least 1 conventional therapy, including corticosteroids, immunomodulators, and/or ≥1 anti-TNFα therapy. Concomitant aminosalicylates, corticosteroids, and immunomodulators were permitted in both trials. In Crohn's Disease Trial I, patients were randomized (3:2) to receive ENTYVIO 300 mg or placebo by intravenous infusion at Weeks 0 and 2. In Crohn's Disease Trial III, patients receiving ENTYVIO who demonstrated clinical response (≥70-point decrease in CDAI score from baseline) at Week 6 (from Crohn's Disease Trial I or an open-label cohort) were randomized (1:1:1) to receive either ENTYVIO 300 mg every 8 weeks, ENTYVIO 300 mg every 4 weeks, or placebo every 4 weeks. The ENTYVIO Q4W dosing regimen did not demonstrate additional clinical benefit over the Q8W dosing regimen. The Q4W dosing regimen is not the recommended dosing regimen.

GEMINI II full study design: 48% of patients achieved ≥ 70­-point decrease in CDAI.
  • Crohn’s Disease Trials I and III were randomized, double-blind, placebo-controlled studies that enrolled adult patients with moderately to severely active Crohn’s disease who had failed at least one conventional therapy, including corticosteroids or immunomodulators and/or ≥1 TNFα therapy
  • Concomitant aminosalicylates and corticosteroids were permitted through Week 52. Concomitant immunomodulators were permitted outside the US but were discontinued after Week 6 in the US

*Not included in efficacy analysis.

†Clinical response=≥70-point decrease in CDAI from baseline. 

‡The ENTYVIO Q4W dosing regimen did not demonstrate additional clinical benefit over the Q8W dosing regimen and is not the recommended dosing regimen.

CDAI=Crohn’s disease activity index; IV=intravenously; Q4W=every 4 weeks; Q8W=every 8 weeks; TNFα=tumor necrosis factor alpha.

GEMINI II Baseline Characteristics for patients with Crohn’s disease - ENTYVIO® (vedolizumab) vs placebo.

*Plus–minus values are means ± SD. Cohort 1 included patients who were randomly assigned, in a 3:2 ratio, as part of the double-blind trial of induction therapy, to receive intravenous vedolizumab, at a dose of 300 mg, or placebo at Weeks 0 and 2. Cohort 2 included patients who received open-label vedolizumab at a dose of 300 mg at Weeks 0 and 2. There were no significant differences (at P<0.05) between the placebo group and the vedolizumab group in cohort 1.

†Race was determined by the investigator.

‡The Crohn’s Disease Activity Index (CDAI) consists of 8 components, each of which is adjusted by a weighting factor. The components are subsequently added together to yield a composite score; scores range from 0 to approximately 600, with higher scores indicating more severe disease activity.

§Data on fecal calprotectin concentrations were available for 142 patients in the placebo group, 210 in vedolizumab cohort 1, and 719 in vedolizumab cohort 2.

||The glucocorticoids used included prednisone, methylprednisolone, prednisolone, budesonide, hydrocortisone, and triamcinolone. The immunosuppressive agents included azathioprine, mercaptopurine, and methotrexate.

Included in this category were patients who did not have an initial response.

#Loss of response indicates that the patient had a response initially but subsequently did not have a response.

TNFα=tumor necrosis factor alpha.

Gemini II trial primary end points

Overall population compared with placebo

Patients achieved clinical remission
at Week 61-3*

GEMINI II trial data: 15% of patients achieved clinical remission at Week 6 with ENTYVIO® (vedolizumab) vs 7% with placebo.

No significant differences in
clinical response at Week 61-3†

GEMINI II trial data: nonsignificant differences in clinical response at Week 6 with ENTYVIO® (vedolizumab) vs placebo.

ENTYVIO

Placebo

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; NS=not significant.

*Clinical remission=CDAI score ≤150.

†Clinical response=≥100-point decrease in CDAI from baseline.

Patients can achieve

Long-term
remission

with ENTYVIO at
Week 521,2‡

Clinical remission at Week 521,2‡

GEMINI II trial data: 39% of patients achieved clinical remission at Week 52 with ENTYVIO® (vedolizumab) vs 22% with placebo.

ENTYVIO

Placebo

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; Q8W=every 8 weeks.

‡Clinical remission=CDAI score ≤150.

GEMINI II Trial Secondary End Points

Overall population compared with placebo

ENTYVIO-treated patients achieved long-term response at Week 521,2* 

GEMINI II trial data: 44% of patients achieved clinical response at Week 52 with ENTYVIO® (vedolizumab) vs 30% with placebo.

Patients achieved corticosteroid-free clinical remission with ENTYVIO at
Week 521,2†

GEMINI II trial data: 32% of patients achieved corticosteroid-free remission at Week 52 with ENTYVIO® (vedolizumab) vs 16% with placebo.

ENTYVIO

Placebo

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; CS=corticosteroid; Q8W=every 8 weeks.

*Clinical response=≥100-point decrease in CDAI from baseline.

†Corticosteroid-free clinical remission: Assessed in the subgroup of patients who were receiving corticosteroids at baseline and who were in clinical response (defined as ≥70 decrease in CDAI from baseline) at Week 6 (n=82 for placebo and n=82 for ENTYVIO every 8 weeks). Corticosteroid-free clinical remission was defined as the proportion of patients in this subgroup that discontinued corticosteroids by Week 52 and were in clinical remission at Week 52.

Due to rounding, some estimates of treatment difference may not correspond with the mathematical differences shown above.

GEMINI III studied ENTYVIO in an anti-TNFα failure subpopulation

Study Design1: Crohn's Disease Trial II was a randomized, double-blind, placebo-controlled study that enrolled adult patients with moderately to severely active Crohn's disease who had failed at least 1 conventional therapy, including corticosteroids, immunomodulators, and/or ≥1 anti-TNFα therapy. Concomitant aminosalicylates, corticosteroids, and immunomodulators were permitted. Patients were randomized (1:1) to receive either ENTYVIO 300 mg or placebo at Weeks 0, 2, and 6.

GEMINl III was a randomized, double-blind, placebo-controlled study that enrolled adult patients with moderately to severely active Crohn&#39;s disease.
  • Crohn’s Disease Trial II was a randomized, double-blind, placebo-controlled study that enrolled adult patients with moderately to severely active Crohn’s disease who had failed at least one conventional therapy, including corticosteroids or immunomodulators and/or ≥1 anti-TNFα therapies
  • Concomitant aminosalicylates, corticosteroids, and immunomodulators were permitted
  • The primary end point of Crohn’s Disease Trial II was not statistically significant
  • Because the primary outcome was not statistically significant, formal hypothesis testing of ranked secondary outcomes was not performed and considered exploratory
  • Crohn’s Disease Trial II patients were not enrolled in the maintenance study

IV=intravenously; TNFα=tumor necrosis factor alpha.

*Clinical remission=CDAI score ≤150.

Gemini III Trial Primary End Point

Anti-TNFα failure subpopulation

Clinical remission at Week 61*

GEMINI III trial data: nonsignificant difference in clinical remission for anti-TNFa-failure subpopulation at Week 6 with ENTYVIO® (vedolizumab) vs placebo.

ENTYVIO

Placebo

76% of patients in Crohn’s Disease Trial II had an inadequate response, loss of response, or intolerance to one or more anti-TNFα therapies.

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; NS=not significant; TNFα=tumor necrosis factor alpha.

*Clinical remission=CDAI ≤150.

Gemini III Trial Exploratory End Point

Not powered for statistical significance.

Clinical remission at Week 101,4*

GEMINI III trial data: analysis of clinical remission at Week 10 for ENTYVIO® (vedolizumab) vs placebo.

ENTYVIO

Placebo

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; TNFα=tumor necrosis factor alpha.

*Clinical remission=CDAI ≤150.

GEMINI II TRIAL EXPLORATORY SUBGROUP ANALYSES OF PRIMARY END POINTS

Not powered for statistical significance.

Clinical remission at Week 61-3*

GEMINI II trial data: analysis of clinical remission at Week 6 in anti-TNFa-naïve and anti-TNFa-failure subpopulations for ENTYVIO® (vedolizumab) vs placebo.

Clinical remission at Week 521-3*

GEMINI II trial data: analysis of clinical remission at Week 52 in anti-TNFa-naïve and anti-TNFa-failure subpopulations for ENTYVIO® (vedolizumab) vs placebo.

ENTYVIO

Placebo

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; Q8W=every 8 weeks; TNFα=tumor necrosis factor alpha.

*Clinical remission=CDAI score ≤150.

Clinical response at Week 61-3*

GEMINI II trial data: analysis of clinical response at Week 6 in anti-TNFa-naïve and anti-TNFa-failure subpopulations for ENTYVIO® (vedolizumab) vs placebo.

ENTYVIO

Placebo

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; TNFα=tumor necrosis factor alpha.

*Clinical response=≥100-point decrease in CDAI from baseline.

GEMINI II TRIAL EXPLORATORY SUBGROUP ANALYSES OF SECONDARY
END POINTS

Not powered for statistical significance.

Clinical response at Week 521-3*

GEMINI II trial data: analysis of clinical response at Week 52 in anti-TNFa-naïve and anti-TNFa-failure subpopulations for ENTYVIO® (vedolizumab) vs placebo.

ENTYVIO

Placebo

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; Q8W=every 8 weeks; TNFα=tumor necrosis factor alpha.

*Clinical response=≥100-point decrease in CDAI from baseline.

Corticosteroid-free remission at Week 521-3*

GEMINI II trial data: analysis of corticosteroid-free remission at Week 52 in anti-TNFa-naïve and anti-TNFa-failure subpopulations for ENTYVIO® (vedolizumab) vs placebo.

ENTYVIO

Placebo

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; Q8W=every 8 weeks; TNFα=tumor necrosis factor alpha.

*Corticosteroid-free clinical remission: Assessed in the subgroup of patients who were receiving corticosteroids at baseline and who were in clinical response (defined as ≥70 decrease in CDAI from baseline) at Week 6 (n=82 for placebo and n=82 for ENTYVIO every 8 weeks). Corticosteroid-free clinical remission was defined as the proportion of patients in this subgroup that discontinued corticosteroids by Week 52 and were in clinical remission at Week 52.

The CDAI is used to assess severity of Crohn’s disease5

The CDAI consists of 8 factors that are used to assess the severity of Crohn’s disease. The loose stool frequency and abdominal pain subscores are patient-reported outcomes of the CDAI.

Factors that are weighted on the CDAI:

  1. Number of liquid stools
  2. Abdominal pain
  3. General well-being
  4. Extra-intestinal complications
  5. Use of anti-diarrheal medications
  6. Abdominal mass
  7. Hematocrit levels
  8. Body weight

GEMINI II and III Trials Patient-reported outcomes

Overall population compared with placebo

Not powered for statistical significance.

Analysis of abdominal pain subscore6*†‡

GEMINI II and III trial data: Analysis of abdominal pain subscore for ENTYVIO® (vedolizumab) vs placebo.

ENTYVIO

Placebo

CI=confidence interval; TNFα=tumor necrosis factor alpha.

*Data are derived from a post-hoc pooled analysis of Crohn’s Disease Trials I and II and therefore not powered for statistical significance and should be considered exploratory.

†Patients with baseline abdominal pain subscore=0 were excluded from the analysis.

‡Data points represent adjusted % change from baseline mean, where adjustment is for subscore baseline value and treatment.

Analysis of loose stool frequency subscore6*†‡

Exploratory End Point

GEMINI II and III trial data: Analysis of loose stool frequency subscore for ENTYVIO® (vedolizumab) vs placebo.

ENTYVIO

Placebo

CI=confidence interval; TNFα=tumor necrosis factor alpha.

*Data are derived from a post-hoc pooled analysis of Crohn’s Disease Trials I and II and therefore not powered for statistical significance and should be considered exploratory.

†Patients with baseline loose stool frequency subscore=0 were excluded from the analysis.

‡Data points represent adjusted % change from baseline mean, where adjustment is for subscore baseline value and treatment.

See Gemini Safety Results

VISIBLE 2 demonstrated that ENTYVIO offers a consistent clinical profile in Crohn's

PATIENTS WANT
OPTIONS.

ENTYVIO
DELIVERS.

Study Design1,7: VISIBLE 2 was a phase 3, randomized, double-blind, multicenter, placebo-controlled trial that enrolled adult patients with moderately to severely active Crohn’s disease. Patients with clinical response to open-label ENTYVIO 300 mg IV at Week 6 were randomized to maintenance treatment with ENTYVIO SC or placebo SC in a 2:1 ratio with stratification by concomitant use of oral corticosteroids, clinical remission status (defined as CDAI ≤150) at Week 6, and previous treatment failure with or exposure to anti-TNF therapy or concomitant immunomodulator use.

IV=intravenous; SC=subcutaneous.

Phase 3, randomized, double-blind, multicenter, placebo-controlled trial

VISIBLE 2 full study design: 64% of patients achieved clinical response to ENTYVIO IV at Week 6.
  • Eligible patients were adults (aged 18-80 years) with moderately to severely active Crohn’s disease (defined as CDAI 220-450) for ≥3 months who had previously failed treatment with corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate), and/or anti-TNF therapies (including primary nonresponders) 
  • At Week 6, patients were assessed for clinical response, defined as a ≥70-point decrease in CDAI from baseline
  • Patients with clinical response at Week 6 were randomized to maintenance treatment with ENTYVIO SC or placebo SC in a 2:1 ratio with stratification by concomitant use of oral corticosteroids, clinical remission status (defined as CDAI ≤150) at Week 6, and previous treatment failure with or exposure to anti-TNF therapy or concomitant immunomodulator use
  • The proportion of patients who had previous exposure to but had not failed anti-TNF therapy was limited to 10%
  • Patients who did not achieve clinical response at Week 6 (n=192) received a third dose of ENTYVIO IV. Of patients who received a third dose of ENTYVIO IV at Week 6, 65.1% (125/192) achieved clinical response at Week 14 (not randomized to the maintenance phase or included in efficacy analysis)
  • The overall population included all randomized patients who received at least one dose of placebo or ENTYVIO in the maintenance phase
  • All primary and secondary end points were measured at Week 52

CDAI=Crohn’s Disease Activity Index; IV=intravenous; Q2W=every 2 weeks; SC=subcutaneous; TNF=tumor necrosis factor.

VISIBLE 2 Baseline Characteristics for patients with Crohn’s disease - ENTYVIO® (vedolizumab) SC vs placebo.

VISIBLE 2 TRIAL PRIMARY END POINT

Overall population compared with placebo

Significantly more patients treated with ENTYVIO SC achieved clinical remission vs placebo at Week 521,7*

VISIBLE 2 trial data: 48% of patients achieved clinical remission at Week 52 with ENTYVIO® (vedolizumab) SC vs 22% with placebo.

ENTYVIO SC

Placebo

CDAI=Crohn’s Disease Activity Index; CI=confidence interval; SC=subcutaneous.

*Clinical remission=CDAI score ≤150.

VISIBLE 2 TRIAL SECONDARY END POINT

Overall population compared with placebo

Corticosteroid (CS)-free remission at Week 521†​

This result was not statistically significant under the prespecified multiple testing procedure​

45% (43/95) achieved CS-free remission with ENTYVIO SC vs 18% (8/44) with placebo​​

†CS-free remission was defined as patients who were using oral CS at baseline and achieved clinical response at Week 6 but had discontinued oral CS and were in clinical remission at Week 52.

See Visible 2 Safety Results

Explore more topics

Review ENTYVIO's well-studied safety profile based on 4 clinical trials

See the safety data

See ENTYVIO results in
ulcerative colitis
 

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The content on this page has been written and
reviewed by Takeda.

IMPORTANT SAFETY INFORMATION

Contraindications

ENTYVIO is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.

WARNINGS AND PRECAUTIONS

  • Infusion-Related and Hypersensitivity Reactions: Infusion-related reactions and hypersensitivity reactions including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart

IMPORTANT SAFETY INFORMATION

Contraindications

ENTYVIO is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.

Warnings and precautions

  • Infusion-Related and Hypersensitivity Reactions: Infusion-related reactions and hypersensitivity reactions including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate have been reported. These reactions may occur with the first or subsequent infusions and may vary in their time of onset from during infusion or up to several hours post-infusion. If anaphylaxis or other serious infusion-related or hypersensitivity reactions occur, discontinue administration of ENTYVIO immediately and initiate appropriate treatment.
  • Infections: Patients treated with ENTYVIO are at increased risk for developing infections. Serious infections have been reported in patients treated with ENTYVIO, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis. ENTYVIO is not recommended in patients with active, severe infections until the infections are controlled. Consider withholding ENTYVIO in patients who develop a severe infection while on treatment with ENTYVIO. Exercise caution in patients with a history of recurring severe infections. Consider screening for tuberculosis (TB) according to the local practice.
  • Progressive Multifocal Leukoencephalopathy (PML): PML, a rare and often fatal opportunistic infection of the central nervous system (CNS), has been reported with systemic immunosuppressants, including another integrin receptor antagonist. PML typically only occurs in patients who are immunocompromised. One case of PML in an ENTYVIO-treated patient with multiple contributory factors has been reported. Although unlikely, a risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms that may include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. If PML is suspected, withhold dosing with ENTYVIO and refer to neurologist; if confirmed, discontinue ENTYVIO dosing permanently.
  • Liver Injury: There have been reports of elevations of transaminase and/or bilirubin in patients receiving ENTYVIO. ENTYVIO should be discontinued in patients with jaundice or other evidence of significant liver injury.
  • Live and Oral Vaccines: Prior to initiating treatment with ENTYVIO, all patients should be brought up to date with all immunizations according to current immunization guidelines. Patients receiving ENTYVIO may receive non-live vaccines and may receive live vaccines if the benefits outweigh the risks.

Adverse reactions

The most common adverse reactions (incidence ≥3% and ≥1% higher than placebo) were: nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, pain in extremities, and injection site reactions with subcutaneous administration.

Drug interactions

Because of the potential for increased risk of PML and other infections, avoid the concomitant use of ENTYVIO with natalizumab products and with TNF blockers. Upon initiation or discontinuation of ENTYVIO in patients treated with CYP450 substrates, monitor drug concentrations or other therapeutic parameters, and adjust the dosage of the CYP substrate as needed.

INDICATIONS

Adult Ulcerative Colitis (UC):

ENTYVIO is indicated in adults for the treatment of moderately to severely active UC.

Adult Crohn’s Disease (CD):

ENTYVIO is indicated in adults for the treatment of moderately to severely active CD.

Dosage forms & strengths:

  • ENTYVIO Intravenous (IV) Infusion: 300 mg vedolizumab
  • ENTYVIO Subcutaneous (SC) Injection: 108 mg vedolizumab

Please click for Full Prescribing Information.

References:

  1. ENTYVIO (vedolizumab) prescribing information. Takeda Pharmaceuticals.
  2. Sandborn WJ, Feagan BG, Rutgeerts P, et al; for the GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013;369(8):711-721.
  3. Data on file. Takeda Pharmaceuticals.
  4. Sands BE, Feagan BG, Rutgeerts P, et al. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014;147(3):618-627.
  5. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology. 1976;70(3):439-444.
  6. Feagan B, Lasch K, Lissoos T, et al. Rapid response to vedolizumab therapy in biologic-naïve patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2019;17:130-138. Published correction appears in Clin Gastroenterol Hepatol. 2020;18(3):759.7.
  7. Vermeire S, D’Haens G, Baert F, et al. Efficacy and safety of subcutaneous vedolizumab in patients with moderately to severely active Crohn’s disease: results from the VISIBLE 2 randomised trial. J Crohn’s Colitis. 2022;16(1):27-38.
  8. Khanna R, Zou G, D’Haens G, et al. A retrospective analysis: the development of patient reported outcome measures for the assessment of Crohn’s disease activity. Aliment Pharmacol Ther. 2015;41(1):77-86.
  9. Vermeire S, D’Haens G, Baert F, et al. Efficacy and safety of subcutaneous vedolizumab in patients with moderately to severely active Crohn’s disease: results from the VISIBLE 2 randomised trial. J Crohn’s Colitis. 2022;16(1):27-38 (supplemental appendix).