For adult patients with moderately to severely active UC or CD when other therapies have not worked well enough.

INDICATIONS: Entyvio (vedolizumab) is indicated for adult patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) who have had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids, or who have had an inadequate response with, lost response to, or were intolerant to an immunomodulator or a tumor necrosis factor (TNF) blocker.1

In UC, Entyvio is indicated for inducing and maintaining clinical response and clinical remission, improving the endoscopic appearance of the mucosa, and achieving corticosteroid-free remission.

In CD, Entyvio is indicated for achieving clinical response, clinical remission, and corticosteroid-free remission.

Clinical Data

CD Study Design

Clinical Data

Long term focus—From the Start

For adult patients with moderately to severely active UC or CD when other therapies have not worked well enough.

INDICATIONS: Entyvio (vedolizumab) is indicated for adult patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) who have had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids, or who have had an inadequate response with, lost response to, or were intolerant to an immunomodulator or a tumor necrosis factor (TNF) blocker.1

In UC, Entyvio is indicated for inducing and maintaining clinical response and clinical remission, improving the endoscopic appearance of the mucosa, and achieving corticosteroid-free remission.

In CD, Entyvio is indicated for achieving clinical response, clinical remission, and corticosteroid-free remission.

Designed to assess 6-week and 52-week remission in CD1,4

CD Trial I

Study design: 2 cohorts with primary end point evaluation at Week 6*

CD Trial III

Study design: Patients receiving Entyvio 300 mg in cohorts 1 and 2 of CD Trial I who had a clinical response (ie, ≥70-point decrease in the CDAI score) at Week 6 were randomly assigned to continue receiving Entyvio 300 mg every 8 weeks, Entyvio 300 mg every 4 weeks, or placebo for up to 52 weeks*

Cohort 1—Blinded

Randomized 3:2 to receive 300 mg Entyvio or placebo intravenously at Weeks 0, 2

Cohort 2—
Open-label

300 mg Entyvio intravenously at Weeks 0, 2 (not included in CD Trial I efficacy analyses)

Crohn's disease trials I and III study design
Baseline characteristics: Cohorts 1 and 2
Overall (N=1115)
Anti-TNFα naïve: ~40%
Anti-TNFα exposed: ~5% Anti-TNFα failure: ~55%
  • ~48% of Entyvio-treated patients from CD Trial I and the open-label cohort qualified for CD Trial III

Designed to assess 6-week and 52-week remission in CD1,4

CD TRIALS I, II, AND III

Three randomized, double-blind, placebo-controlled studies enrolled adult patients with moderately to severely active CD who had failed at least 1 conventional therapy, including corticosteroids, immunomodulators, and/or ≥1 anti-TNFα therapy. Concomitant aminosalicylates, corticosteroids, and immunomodulators were permitted. For CD Trials I and III, corticosteroids were tapered after
Week 6; in the United States, immunosuppressants were discontinued after Week 6.

CD Trial I

Study design: 2 cohorts with primary end point evaluation at Week 6

Cohort 1—Blinded
Randomized 3:2 to receive 300 mg Entyvio or placebo intravenously at Weeks 0, 2

Crohn's disease cohort 1

Cohort 2—Open-label
300 mg Entyvio intravenously at Weeks 0, 2
(not included in CD Trial I efficacy analyses)

Crohn's disease cohort 2
Baseline characteristics: Cohorts 1 and 2
Overall (N=1115)

Anti-TNFα naïve: ~40%
Anti-TNFα exposed: ~5%
Anti-TNFα failure: ~55%

In CD Trial I (N=368), patients were randomized (3:2) to receive Entyvio 300 mg or placebo by intravenous infusion at Weeks 0 and 2. The primary end point for CD Trial I was the proportion of patients with clinical remission (CDAI score ≤150) at Week 6. Another primary end point, the difference in percentage of patients who demonstrated clinical response (≥100-point decrease in CDAI score from baseline), was not statistically significant at
Week 6.

WEEK 6 END POINTS

Co-Primary outcomes
Clinical remission*
Clinical response


CD Trial III

Study design: Patients receiving Entyvio 300 mg in cohorts 1 and 2 of CD Trial I who had a clinical response (ie, ≥70-point decrease in the CDAI score) at Week 6 were randomly assigned to continue receiving Entyvio 300 mg every
8 weeks, Entyvio 300 mg every 4 weeks, or placebo for up to 52 weeks

Patients who achieved clinical response from CD Trial I
In CD Trial III (N=461), patients receiving Entyvio who demonstrated clinical response (≥70-point decrease in CDAI score from baseline) at Week 6 (from CD 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 primary end point for CD Trial III was the proportion of patients achieving clinical remission (CDAI score ≤150) at Week 52.

Clinical Study

~48% of Entyvio-treated patients from CD Trial I and the open-label cohort qualified for CD Trial III

Patients who failed to achieve clinical response from CD Trial I
For patients who did not achieve clinical response (≥ 70-point decrease in the CDAI score from baseline) in cohorts 1 and 2 of CD Trial I, they continued receiving open-label Entyvio
300 mg every 4 weeks up to 52 weeks. Placebo group carried over from cohort 1 of CD Trial I. These findings are not included in the CD Trial III efficacy analysis.

Clinical Study

(Not included in CD Trial III efficacy analyses)

WEEK 52 END POINTS

Primary outcome

Clinical remission*

Secondary outcomes

Clinical response
Corticosteroid-free clinical remission§

CD Trial II

Study design: Patients were randomized in a double-blinded fashion (1:1) to receive either placebo or Entyvio 300 mg intravenously at Weeks 0, 2, and 6

In CD Trial II (N=416), patients were randomized (1:1) to receive either Entyvio 300 mg or placebo at weeks 0, 2, and 6. A majority (76%) of enrolled patients had an inadequate response, loss of response, or intolerance to
≥1 TNF blockers; this was the primary analysis population. The primary end point for CD Trial II was the proportion of patients achieving clinical remission (CDAI score ≤150) at Week 6. Treatment with Entyvio did not result in statistically significant improvement over placebo. Concomitant aminosalicylates, corticosteroids, and immunomodulators were permitted in all trials.

Clinical Study

Assessment done at Week 6
(after doses at Weeks 0 and 2)

WEEK 6 PRIMARY END POINT

Clinical remission* in patients who had an inadequate response, loss of response, or intolerance to one or more TNF blockers

WEEK 10 SECONDARY END POINTS

Including assessment at Week 10 were not tested because the primary end point was not statistically significant

Week 6 end points

Co-Primary outcomes

Week 52 end points

Primary outcome
Secondary outcomes

Clinical remission
Clinical response§

Clinical remission

Clinical response§
Corticosteroid-free clinical remission||

 

CD Trial II
Study design: Patients were randomized in a double-blinded fashion (1:1)
to receive either placebo or Entyvio 300 mg at Weeks 0, 2, and 6*

76% of patients in CD Trial II had an inadequate response,
loss of response, or intolerance to one or more TNF blockers

Crohn's disease trial II study design

 

*

CD Trials I, II, and III were randomized, double-blind, placebo-controlled studies that enrolled adult patients with moderately to severely active CD who had failed at least one conventional therapy, including corticosteroids or immunomodulators and/or ≥1 anti-TNFα therapy. Concomitant aminosalicylates, corticosteroids, and immunomodulators were permitted. For CD Trials I and III, corticosteroids were tapered after Week 6; in the United States, immunosuppressants were discontinued after Week 6.

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.

Clinical remission = Crohn's Disease Activity Index (CDAI) ≤150.

§

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

||

Assessed in the subgroup of patients who were receiving corticosteroids at baseline and who were in clinical response at Week 6 (n=82 for placebo, and n=82 for Entyvio Q8W). Corticosteroid-free clinical remission was defined as the proportion of patients in this subgroup who discontinued corticosteroids by Week 52 and were in clinical remission at Week 52.



Important Safety Information

  • ENTYVIO (vedolizumab) for injection is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.
  • Infusion-related reactions and hypersensitivity reactions including anaphylaxis have occurred. Allergic reactions including dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate have also been observed. If anaphylaxis or other serious allergic reactions occur, discontinue administration of ENTYVIO immediately and initiate appropriate treatment.
  • 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.
  • Although no cases of PML have been observed in ENTYVIO clinical trials, JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death has occurred in patients treated with another integrin receptor antagonist. A risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and 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 a neurologist; if confirmed, discontinue ENTYVIO dosing permanently.
  • 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.
  • 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.
  • Most common adverse reactions (incidence ≥3% and ≥1% higher than placebo): nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities.

Indications

Adult Ulcerative Colitis (UC)

ENTYVIO (vedolizumab) is indicated in adult patients with moderately to severely active UC 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 corticosteroids for inducing and maintaining clinical response, inducing and maintaining clinical remission, improving endoscopic appearance of the mucosa, and achieving corticosteroid-free remission.

Adult Crohn’s Disease (CD)

ENTYVIO (vedolizumab) is indicated in adult patients with moderately to severely active CD who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids for achieving clinical response, achieving clinical remission, and achieving corticosteroid-free remission.

Please see full Prescribing Information, including Medication Guide.

  1. Entyvio [prescribing information]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.
  2. Data on file. Takeda Pharmaceuticals America, Inc. Deerfield, IL.
  3. Feagan BG, Rutgeerts P, Sands BE, et al; for the GEMINI 1 Study Group. N Engl J Med. 2013;369(8):699-710.
  4. Sandborn WJ, Feagan BG, Rutgeerts P, et al; for GEMINI 2 Study Group. N Engl J Med. 2013;369(8):711-721.
  5. Colombel JF, Sands BE, Rutgeerts P, et al. Gut. 2016. doi:10.1136/gutjnl-2015-311079.
  6. Feagan BG, Rubin DT, Danese S, et al. Clin Gastroenterol Hepatol. 2017;15(2):229-239.e5.
  7. Sands BE, Feagan BG, Rutgeerts P, et al. Gastroenterology. 2014;147(3):618-627.e3.
  8. Xavier RJ, Podolsky DK. Nature. 2007;448(7152):427-434.
  9. Briskin M, Winsor-Hines D, Shyjan A, et al. Am J Pathol. 1997;151(1):97-110.

Important Safety Information

  • ENTYVIO (vedolizumab) for injection is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.
  • Infusion-related reactions and hypersensitivity reactions including anaphylaxis have occurred. Allergic reactions including dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate have also been observed. If anaphylaxis or other serious allergic reactions occur, discontinue administration of ENTYVIO immediately and initiate appropriate treatment.
  • 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.
  • Although no cases of PML have been observed in ENTYVIO clinical trials, JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death has occurred in patients treated with another integrin receptor antagonist. A risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and 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 a neurologist; if confirmed, discontinue ENTYVIO dosing permanently.
  • 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.
  • 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.
  • Most common adverse reactions (incidence ≥3% and ≥1% higher than placebo): nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities.

Indications

Adult Ulcerative Colitis (UC)

ENTYVIO (vedolizumab) is indicated in adult patients with moderately to severely active UC 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 corticosteroids for inducing and maintaining clinical response, inducing and maintaining clinical remission, improving endoscopic appearance of the mucosa, and achieving corticosteroid-free remission.

Adult Crohn’s Disease (CD)

ENTYVIO (vedolizumab) is indicated in adult patients with moderately to severely active CD who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids for achieving clinical response, achieving clinical remission, and achieving corticosteroid-free remission.

Please see full Prescribing Information, including Medication Guide.

  1. Entyvio [prescribing information]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.
  2. Data on file. Takeda Pharmaceuticals America, Inc. Deerfield, IL.
  3. Feagan BG, Rutgeerts P, Sands BE, et al; for the GEMINI 1 Study Group. N Engl J Med. 2013;369(8):699-710.
  4. Sandborn WJ, Feagan BG, Rutgeerts P, et al; for GEMINI 2 Study Group. N Engl J Med. 2013;369(8):711-721.
  5. Colombel JF, Sands BE, Rutgeerts P, et al. Gut. 2016. doi:10.1136/gutjnl-2015-311079.
  6. Feagan BG, Rubin DT, Danese S, et al. Clin Gastroenterol Hepatol. 2017;15(2):229-239.e5.
  7. Sands BE, Feagan BG, Rutgeerts P, et al. Gastroenterology. 2014;147(3):618-627.e3.
  8. Xavier RJ, Podolsky DK. Nature. 2007;448(7152):427-434.
  9. Briskin M, Winsor-Hines D, Shyjan A, et al. Am J Pathol. 1997;151(1):97-110.