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.

Safety Profile

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.

Clinical trials evaluated safety in more than 3300 adults1,2

Including more than 800 patients who received Entyvio for more than 2 years

UC Trials I and II and CD Trials I and III

INFECTIONS

  • Infection rates with Entyvio were 0.85 per patient-year vs 0.7 for placebo
    • Infections consisted primarily of nasopharyngitis, upper respiratory tract infection, sinusitis, and urinary tract infection
    Infections per patient-year
    • 2% of patients discontinued Entyvio due to infections
  • Serious infection rates with Entyvio were 0.07 per patient-year vs 0.06 for placebo
    • Serious infections included anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis
    Serious infections per patient-year
Infections per patient-year Serious infections per patient-year

ADVERSE REACTIONS

  • Adverse reactions were reported in 52% of patients treated with Entyvio (N=1434) and 45% of patients treated with placebo (N=297)
    • Over 52 weeks, 7% of patients treated with Entyvio experienced serious adverse reactions compared to
      4% treated with placebo
  • Malignancies (excluding dysplasia and basal cell carcinoma) were reported in 0.4% (6 of 1434)
    of patients treated with Entyvio and in 0.3% (1 of 297) of patients treated with placebo
    • The number of malignancies in clinical trials was small; however, long-term exposure was limited

The table lists adverse reactions that occurred in ≥3% of Entyvio-treated patients and ≥1% higher than in placebo (UC Trials I and II* and CD Trials I and III*).

Adverse reactions table
*

Data from patients receiving open-label Entyvio treatment at Weeks 0 and 2 (prior to entry into UC Trial II and CD Trial III) and from Weeks 6 to 52 (nonresponders at Week 6 of UC Trial I and CD Trial I) are included.

Patients who received Entyvio for up to 52 weeks.

Patients who received placebo for up to 52 weeks.

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

  • In clinical trials, no cases of PML were reported
  • Since the 2014 launch of Entyvio through mid-May 2017, no cases of PML have been reported through postmarketing surveillance
  • The risk of PML cannot be ruled out:
    • John Cunningham (JC) virus infection resulting in PML and death has occurred in patients treated with a different integrin antagonist. No comparative safety claims regarding other integrin antagonists can be made based on these data

INFUSION-RELATED REACTIONS (IRRs)

  • 4% of patients treated with Entyvio experienced an IRR, including anaphylaxis (1 of 1434), vs 3% of patients on placebo. Allergic reactions included dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate
  • Most frequently observed IRRs: nausea, headache, pruritus, dizziness, fatigue, pyrexia, urticaria, and vomiting. Observed IRRs generally occurred within the first 2 hours after the infusion and resolved with no treatment or following antihistamine and/or IV hydrocortisone treatment
Infusion-related reactions

LIVER INJURY

  • Entyvio should be discontinued in patients with jaundice or other evidence of significant liver injury
  • Three patients reported serious adverse reactions of hepatitis with Entyvio. One additional case of serious hepatitis was seen in the open-label trial
    • These adverse reactions occurred following 2 to 5 Entyvio doses; however, it is unclear if the reactions indicated drug-induced or autoimmune etiology
    • There have been reports of elevations of transaminases and/or bilirubin in patients receiving Entyvio
    • All patients recovered following discontinuation of therapy with or without treatment with corticosteroids

IMMUNOGENICITY

  • The rate of detectable anti-vedolizumab antibodies at any time during the 52 weeks of continuous treatment with Entyvio was 4% (56 of 1434 patients)
    • The frequency of antibodies detected in patients who received Entyvio was 13% at 24 weeks after the last dose of study drug
    • 9 of 56 patients were persistently positive (at 2 or more study visits) for anti-vedolizumab antibody, and 33 of 56 patients developed neutralizing antibodies to vedolizumab. Among 8 out of these
      9 subjects, 6 had undetectable vedolizumab concentrations, and 2 had reduced vedolizumab concentrations. None of the
      9 subjects with persistently positive anti-vedolizumab antibody achieved clinical remission at Weeks 6 or 52 in the controlled trials

5-year integrated safety1,5

  • The cumulative long-term safety of Entyvio was assessed in a 5-year interim analysis (median exposure 365 days, range 1—1977 days) of patients with UC or CD who participated in 6 double-blind or open-label trials. The overall safety population was comprised of 2932 patients.
    • 2830 patients were exposed to 1 or more doses of Entyvio, contributing a total of 4811 patient-years of Entyvio exposure

  • 5-year continuation data was consistent with other studies across safety parameters

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.