Why Prescribe Entyvio?

Entyvio is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis or moderately to severely active Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.

Proven Efficacy in Clinical Trials

The efficacy and safety of Entyvio (vedolizumab) are supported by a wealth of clinical and real world data.1-10 See below for evidence to show why you should choose Entyvio as first biologic for superior rates of remission vs anti-TNFα treatment, for early disease control, long-term remission and mucosal healing.3-10

Click to expand and view individual study details below.

For a full list of possible adverse effects, contraindications and special warnings and precautions for use, please refer to the Entyvio Summary of Product Characteristics or visit Prescribing Entyvio.

Design5

The first double-blind, double-dummy, randomised, prospective, head-to-head study evaluating the efficacy and safety of vedolizumab vs. adalimumab over 52 weeks in patients with moderately to severely active UC.

Treatment5

Intravenous vedolizumab 300 mg at weeks 0, 2, 6, and then at 8-week intervals until week 46, or subcutaneous adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and then 40 mg at 2-week intervals until week 50.

Outcome measures5

Primary endpoint:

  • Clinical remission at Week 52 (complete Mayo score ≤2 and no individual sub score >1)

Secondary endpoints:

  • Mucosal healing at Week 52 (Mayo endoscopic subscore≤1)
  • Corticosteroid-free remission at Week 52 (among those with baseline corticosteroid use)

Results5

Clinical remission and mucosal healing, but not corticosteroid-free clinical remission, were observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group.

VARSITY primary endpoint: Clinical remission at Week 52

Adapted from Sands BE et al. 2019.
Adapted from Sands BE et al. 2019.
Adapted from Sands BE et al. 2019.

Anti-TNFα, anti-tumour necrosis factor alpha; CI, confidence interval.
Adapted from Sands BE et al. 2019.

In VARSITY, significantly higher rates of clinical remission were achieved with vedolizumab compared with adalimumab in patients with moderately to severely active UC.

SAFETY5

Adverse events occurred in 62.7% of the patients (240 of 383) in the vedolizumab group and in 69.2% (267 of 386) in the adalimumab group. Serious adverse events occurred in 11.0% of the patients (42 of 383) in the vedolizumab group and in 13.7% (53 of 386) in the adalimumab group.
Exposure-adjusted incidence rates of infections and serious infections showed that both occurred less frequently with vedolizumab than with adalimumab (infections, 23.4 vs. 34.6 events per 100 patient-years; serious infections, 1.6 vs. 2.2 events per 100 patient-years). Herpes zoster infection was less frequent with vedolizumab than with adalimumab (0.5 vs. 4.2 per 100 patient-years), although Clostridium difficile infection was more frequent (1.1 vs. 0.6 per 100 patient-years).

Design4

A phase 3, randomised, placebo-controlled, double-blind, double-dummy study evaluating the efficacy and safety of subcutaneous vedolizumab as a maintenance therapy over 52 weeks in patients with moderately to severely active UC.

Treatment4

Open-label induction with intravenous vedolizumab 300 mg at Weeks 0 and 2. At Week 6, patients with clinical response were randomly assigned to maintenance treatment with subcutaneous vedolizumab 108 mg every 2 weeks, intravenous vedolizumab 300 mg every 8 weeks, or placebo.

Outcome measures4

Primary endpoint:

  • Clinical remission at Week 52 (complete Mayo score ≤2 and no individual sub score >1)

Secondary endpoints:

  • Mucosal healing at Week 52 (Mayo endoscopic subscore≤1)
  • Durable clinical response (clinical response at weeks 6 and 52)
    • Clinical response was defined as a reduction in total Mayo score of ≥3 points and ≥30% from baseline (week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1
  • Durable clinical remission (clinical remission at weeks 6 and 52)
  • Corticosteroid-free remission at Week 52 (among those with baseline corticosteroid use)

Results4

VISIBLE I primary endpoint: Proportion of Week 6 responders achieving clinical remission at Week 52

Adapted from Sandborn WJ et al. 2020.
CI, confidence interval; IV, intravenous; SC, subcutaneous.
Adapted from Sandborn WJ et al. 2020.

In VISIBLE I, significantly higher rates of clinical remission were achieved with vedolizumab SC compared with placebo and the rates of clinical
remission with subcutaneous vedolizumab and intravenous vedolizumab were similar in patients with moderately to severely active UC.

SAFETY4

Overall safety findings were similar between vedolizumab SC and IV. The most common AE was worsening of UC disease activity, with higher proportions of patients experiencing this AE in the placebo group (32.1%) than in either the vedolizumab SC (14.2%) or vedolizumab IV (11.1%) groups. Other common AEs were nasopharyngitis, anemia, and upper respiratory tract infection.
Injection-site reactions (ISRs; mainly rash, swelling, erythema, and pruritus) occurred in 11 patients (10.4%) receiving vedolizumab SC, 1 patient (1.9%) receiving vedolizumab IV (plus matching SC placebo), and 0 patients receiving placebo. Almost all ISRs were reported as mild in intensity and none were reported as a serious AE.

Design3

A phase 3, randomised, placebo-controlled, double-blind study evaluating the efficacy and safety of subcutaneous vedolizumab as a
maintenance therapy over 52 weeks in patients with moderately to severely active CD.

Treatment3

Open-label induction with intravenous vedolizumab 300 mg at Weeks 0 and 2. At Week 6, patients with clinical response (defined as patients with a ≥70-point decrease in CD Activity Index [CDAI] from baseline) were randomly
assigned to maintenance treatment with subcutaneous vedolizumab 108 mg every 2 weeks, or placebo.

Outcome measures3

Primary endpoint:

  • Clinical remission at Week 52 (CDAI score ≤150)

Secondary endpoints:

  • Enhanced clinical response at Week 52 (a drop of ≥100 in CDAI score)
  • Corticosteroid-free remission at Week 52 (among those with baseline corticosteroid use)
  • Clinical remission at Week 52 in anti-TNFα naïve patients

Results3

VISIBLE II primary endpoint: Proportion of Week 6 responders achieving clinical remission at Week 52

Adapted from Vermeire S et al. 2020.
CI, confidence interval; SC, subcutaneous.
Adapted from Vermeire S et al. 2020.

In VISIBLE II, significantly higher rates of clinical remission were achieved with subcutaneous
vedolizumab compared with placebo in patients with moderately to severely active CD.

SAFETY3

Injection-site reactions were reported for <3% of patients treated with vedolizumab SC. Serious infections, malignancy, and liver injury were ≤5% for both arms. The safety findings with vedolizumab SC remain in line with the known safety profile of vedolizumab IV in patients with CD.

Design7

A phase 3, multicentre, randomised, parallel-group, double-blinded, placebo controlled study to evaluate the efficacy, safety and tolerability of vedolizumab in patients with moderately to severely active UC. The study consisted of two separate induction and maintenance trials.

Treatment7

Induction with intravenous vedolizumab 300 mg or placebo at Weeks 0 and 2. At Week 6, patients with clinical response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 4 or 8 weeks until Week 52.

Outcome measures7

Primary endpoints:

Induction phase:

  • Proportion of patients with clinical response at Week 6 (≥3 point decrease in Mayo score, decreased ≥30% from baseline, and ≥1 point decrease in rectal bleeding subscore (RBS) or an absolute RBS of ≤1)

Maintenance phase:

  • Proportion of patients with clinical remission at Week 52 (complete Mayo score ≤2 and no individual subscore >1)

Secondary endpoints:

Induction phase:

  • Proportion of patients in clinical remission at Week 6 (complete Mayo score ≤2 and no individual subscore >1)
  • Mucosal healing at Week 6 (Mayo endoscopic subscore ≤1)

Maintenance phase:

  • Durable clinical response (response at both Weeks 6 and 52)
  • Durable clinical remission (remission at both Weeks 6 and 52)
  • Mucosal healing at Week 52 (Mayo endoscopic subscore ≤1)
  • Corticosteroid-free remission at Week 52 (among those with baseline corticosteroid use)
  • Health-related quality of life

Results7

All prespecified primary and secondary outcomes in the trials of induction and maintenance therapy were superior in
vedolizumab-treated patients vs. those who received placebo.

GEMINI I: Efficacy Results at Week 6
GEMINI I: Efficacy Results at Week 52

The placebo group includes those subjects who received vedolizumab at Week O and Week 2, and were randomised to receive placebo from Week 6 through Week 52.

* Clinical Response: Reduction to the Mayo Clinic score of at least 3 points and a decrease of at least 30% from the baseline score, with a decrease of at least 1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1.
† Clinical Remission: Mayo Clinic score of ≤2 points and no individual subscore >1 point.
‡Mucosal Healing: Mayo Clinic scale endoscopic subscore of ≤1 point.
§ Durable clinical response: Clinical response at Weeks 6 and 52.
¶ Durable clinical remission: Clinical remission at Weeks 6 and 52.
** Corticosteroid-free clinical remission was assessed in patients receiving oral glucocorticoids at baseline.
Adapted from Feagan BG et al. 2013.

In GEMINI I, vedolizumab was effective for inducing and maintaining a clinical response and remission in patients with moderately to
severely active UC.

SAFETY

In the combined studies of GEMINI I, II and III, the AEs that occurred in ≥5% were nausea, nasopharyngitis, upper respiratory tract infection, arthralgia, pyrexia, fatigue, headache and cough.7-9 In the 9-year GEMINI LTS study investigating the safety implications of long-term vedolizumab exposure, there were no new trends for infections, malignancies, infusion-related reactions, or hepatic events, as well as no cases of progressive multifocal leukoencephalopathy (PML). Vedolizumab had a safety profile suitable for the long-term treatment of moderately to severely active UC and CD.10


Design8

A phase 3, multicentre, randomised, parallel-group, double-blinded, placebo controlled study to evaluate the efficacy, safety and tolerability of vedolizumab in patients with moderately to severely active CD. The study consisted of two separate induction and maintenance trials.

Treatment8

Induction with intravenous vedolizumab 300 mg or placebo at Weeks 0 and 2. At Week 6, patients with clinical response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 4 or 8 weeks until Week 52.

Outcome measures8

Primary endpoints:

Induction phase:

  • Proportion of patients with clinical remission (CDAI score ≤150 points) at Week 6
  • Crohn’s Disease Activity Index (CDAI-100) response at Week 6

Maintenance phase:

  • Proportion of patients with clinical remission at Week 52

Secondary endpoints:

Induction phase:

  • Mean change in C-reactive protein levels from baseline to Week 6

Maintenance phase:

  • CDAI-100 response at Week 52
  • Corticosteroid-free remission at Week 52 (among those with baseline corticosteroid use)
  • Durable clinical remission (Clinical remission ≥ 80% of study visits including final visit)

Results8

  • Vedolizumab-treated patients were significantly more likely than patients receiving placebo to be in remission, but not a CDAI-100 response, at
    Week 6.
  • Patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at Week 52.
GEMINI II: Efficacy Results at Week 6
GEMINI II: Efficacy Results at Week 52

The placebo group includes those subjects who received vedolizumab at Week O and Week 2, and were randomised to receive placebo from Week 6 through Week 52.

CDAI, Crohn’s disease activity index.
* Clinical Remission: CDAI score of ≤150 points.
† Corticosteroid-free clinical remission was assessed in patients receiving oral glucocorticoids at baseline.
‡ Durable clinical remission: Clinical remission at ≥80% of study visits including final visit (Week 52).
Adapted from Sandborn WJ et al. 2013.

In GEMINI II, in patients who had a response to induction therapy with vedolizumab, the rates of clinical remission, CDAI-100 response, and corticosteroid-free remission at Week 52 were significantly higher among patients receiving vedolizumab compared to placebo.

SAFETY

In the combined studies of GEMINI I, II and III, the AEs that occurred in ≥5% were nausea, nasopharyngitis, upper respiratory tract infection, arthralgia, pyrexia, fatigue, headache and cough.7-9 In the 9-year GEMINI LTS study investigating the safety implications of long-term vedolizumab exposure, there were no new trends for infections, malignancies, infusion-related reactions, or hepatic events, as well as no cases of progressive multifocal leukoencephalopathy (PML). Vedolizumab had a safety profile suitable for the long-term treatment of moderately to severely active UC and CD.10


Design9

A phase 3, multicentre, randomised, double-blinded, placebo-controlled study to evaluate the efficacy, safety and tolerability of vedolizumab over 10 weeks in patients with moderately to severely active CD. A high proportion (~75%) of enrolled patients had previously failed anti-TNFα therapy.

Treatment9

Intravenous vedolizumab 300 mg or placebo at Weeks 0, 2, and 6.

Outcome measures9

Primary endpoint:

  • Proportion of the subpopulation patients who had previously failed anti-TNFα therapy in clinical remission (CDAI score ≤ 150) at Week 6

Secondary endpoints:

  • Proportion of patients in clinical remission at Week 6 in the overall study population (including an additional ~25% of anti-TNFα naive patients)
  • Proportion of patients in clinical remission at Week 10 in overall and anti-TNFα failure populations
  • Proportion of patients in clinical remission in overall and anti-TNFα failure populations at both Weeks 6 and 10
  • Proportion of patients with an enhanced clinical CDAI-100 response in the overall and anti-TNFα failure populations at Week 6

Results9

  • The clinical remission rate at Week 6 for the patients who had failed anti-TNFα was 15.2% for the vedolizumab-treated patients versus 12.1% for those who received placebo (p=0.433; relative risk, 1.2; 95% CI, 0.7-2.2)
  • While the primary endpoint of proportion of patients in clinical remission at Week 6 in the anti-TNFα failure subpopulation was not met,
    exploratory analyses show that clinically meaningful results were observed
  • The enhanced efficacy of vedolizumab at Week 10 vs. Week 6 in the GEMINI III study provides evidence of a later onset of efficacy of
    vedolizumab in patients with moderately to severely active CD, particularly in those who have previously failed anti-TNFα treatment

Anti-TNFα, anti-tumour necrosis factor alpha.
* Primary endpoint not met, p=0.433.
† Secondary endpoint to be viewed as exploratory by pre-specified statistically testing procedure.
‡ Sustained clinical remission: clinical remission at Week 6 and 10.
Adapted from Sands et al. 2014.

In GEMINI III, vedolizumab treatment provided clinically meaningful, but not statistically significant, improvements at Week 6 in anti-TNFα failure patients with moderately to severely active CD.

SAFETY

In the combined studies of GEMINI I, II and III, the AEs that occurred in ≥5% were nausea, nasopharyngitis, upper respiratory tract infection, arthralgia, pyrexia, fatigue, headache and cough.7-9 In the 9-year GEMINI LTS study investigating the safety implications of long-term vedolizumab exposure, there were no new trends for infections, malignancies, infusion-related reactions, or hepatic events, as well as no cases of progressive multifocal leukoencephalopathy (PML). Vedolizumab had a safety profile suitable for the long-term treatment of moderately to severely active UC and CD.10

Design10

A multinational, multicentre, open-label, phase 3 study investigating the long-term safety (LTS) and efficacy of vedolizumab in patients with
moderately to severely active CD or UC.

Treatment10

Open-label intravenous vedolizumab 300 mg every 4 weeks after completion or withdrawal from a phase 2 study, or one of the GEMINI phase 3 studies, or enrolment as a vedolizumab-naïve de novo patient.

Outcome measures10

Primary objective:

  • Evaluate long term safety profile of vedolizumab

Exploratory endpoint:

  • Health-related quality of life
  • Clinical outcomes
  • IBD-related procedures and hospitalisations

Results10

  • Enrolled patients (UC, n = 894; CD, n = 1349) median cumulative exposure was 42.4 months (range: 0.03-112.2) for UC and 31.5 months (range: 0.03-100.3) for CD
  • Over upto 9-years adverse events(AEs) occurred in 93% (UC) and 96% (CD) of patients, with UC (36%) and CD (35%) exacerbations most frequent
  • Serious adverse events (SAE) were reported in 31% of UC patients and 41% of CD patients
  • Disease exacerbation was the most frequent SAE in both UC and CD patients
  • Discontinuation due to AEs occurred in 15% of UC patients and 17% of CD patients
  • No new trends were observed for infections, malignancies, infusion-related reactions, or hepatic events
  • No cases of progressive multifocal leukoencephalopathy
  • Of the ten deaths (UC, n = 4; CD, n = 6), two were considered drug-related by local investigators (West Nile virus infection-related encephalitis and hepatocellular carcinoma)
GEMINI LTS: UC patients experiencing any AE
GEMINI LTS: UC patients experiencing AEs of specific interest

AE, adverse event; Q4W, dosed every 4 weeks; UC, ulcerative colitis.
Adapted from Loftus EV et a, 2020.

GEMINI LTS: CD patients experiencing any AE
GEMINI LTS: CD patients experiencing AEs of specific interest

AE, adverse event; CD, Crohn’s disease; Q4W, dosed every 4 weeks.
Adapted from Loftus EV et al. 2020.

GEMINI LTS provides evidence that vedolizumab has a favourable safety profile suitable for the long-term treatment of UC and CD.

SAFETY

In the combined studies of GEMINI I, II and III, the AEs that occurred in ≥5% were nausea, nasopharyngitis, upper respiratory tract infection, arthralgia, pyrexia, fatigue, headache and cough.7-9 In the 9-year GEMINI LTS study investigating the safety implications of long-term vedolizumab exposure, there were no new trends for infections, malignancies, infusion-related reactions, or hepatic events, as well as no cases of progressive multifocal leukoencephalopathy (PML). Vedolizumab had a safety profile suitable for the long-term treatment of moderately to severely active UC and CD.10

Design6

A retrospective, real-world, chart review study assessing the efficacy of second-line (2L) anti-TNFα treatment following first-line (1L) vedolizumab vs. first-line (1L) anti-TNFα treatment in biologic-naïve patients with moderately to severely active CD or UC.

Data presented at the United European Gastroenterology (UEG) Week 2019. Full trial data yet to be published within a peer reviewed journal.

Treatment6

Second line (2L) anti-TNFα after discontinuation of first line (1L) vedolizumab for any reason, or 1L anti-TNFα. Anti-TNFα therapies included were adalimumab, infliximab, golimumab and certolizumab pegol.

Outcome measures6

Endpoints included clinical response, clinical remission and treatment persistence.

Results6

EVOLVE: Outcomes for UC patients treated with 1L or 2L anti-TNFα treatments at 3 and 6 months

Adapted from Bressler B et al. 2019.

Anti-TNFα, anti-tumour necrosis factor alpha; UC, ulcerative colitis; 1L, first-line; 2L, second-line.

*Clinical response and clinical remission were assessed using pre-defined hierarchical algorithms of: Mayo Overall score > Mayo Partial score > medical record documentation of complete or partial response > physician global assessment.

† Treatment persistent was defined as patients who did not discontinue anti-TNFα treatments.

Adapted from Bressler B et al. 2019.

EVOLVE: Outcomes for CD patients treated with 1L or 2L anti-TNFα treatments at 3 and 6 months

Adapted from Bressler B et al. 2019.

Anti-TNFα, anti-tumour necrosis factor alpha, CD, Crohn’s disease; 1L, first-line; 2L, second-line.

*Clinical response and clinical remission were assessed using pre-defined hierarchical algorithms of: Crohn’s disease activity index > Harvey Bradshaw Index > Medical record documentation of complete or partial response > Physician global assessment.

† Treatment persistent was defined as patients who did not discontinue vedolizumab or anti-TNFα treatments.

Adapted from Bressler B et al. 2019.

In the real-world EVOLVE study, the cumulative rates of clinical response, clinical remission and persistence in CD and UC patients treated
second-line with anti-TNFα treatments (after 1L vedolizumab treatment) were similar to the rates in CD and UC patients treated with anti-TNFα treatments first-line.

SAFETY11

The EVOLVE study observed that in both UC and CD more patients experienced serious adverse events (SAEs) and serious infections (SIs) whilst on anti-TNFα treatment compared to treatment with vedolizumab.

In UC, SAEs were experienced by 8.2% of vedolizumab-treated patients (n=380) vs. 19.2% of anti-TNFα-treated patients (n=224). SIs were experienced by 2.9% of vedolizumab-treated patients vs. 4.5% of anti-TNFα-treated patients. The most commonly reported SAE and SI associated with vedolizumab was gastrointestinal infection (1.1%).

In CD, SAEs were experienced by 12.4% of vedolizumab-treated patients (n=218) vs. 19.1% of anti-TNFα treated patients (n=273). SIs were experienced by 2.8% of vedolizumab treated patients vs. 7.7% of anti-TNFα-treated patients. The most commonly reported SAE associated with vedolizumab treatment was small bowel obstruction (1.8%) and the most commonly reported SI was lower respiratory tract infection (1.4%).

All SAEs and SIs were reported irrespective of relationship to treatment, meaning that incidences may not reflect those directly related to treatments.

Adverse events should be reported. In the United Kingdom, reporting forms and information can be found at www.mhra.gov.uk/yellowcard.

Adverse events should also be reported to Takeda by e-mail at

AE.GBR-IRL@takeda.com