In Depth | Entyvio: gut-selective immunosuppressant for inflammatory bowel disease

Takeda has launched Entyvio (vedolizumab) for the treatment of moderate to severe Crohn's disease and ulcerative colitis when conventional therapy or a tumour necrosis factor (TNF) inhibitor is inappropriate.

Entyvio is given as 300mg by iv inf over 30 mins at 0, 2 and 6 weeks then every 8 weeks thereafter
Entyvio is given as 300mg by iv inf over 30 mins at 0, 2 and 6 weeks then every 8 weeks thereafter

PHARMACOLOGY

Vedolizumab is a humanised IgG1 monoclonal antibody that binds to α4β7 integrin, which is preferentially expressed on certain lymphocytes in the gut. The binding prevents adhesion of these lymphocytes to mucosal endothelial cells, reducing the gastrointestinal inflammation characteristically seen in Crohn's disease and ulcerative colitis.1

CLINICAL STUDIES

The safety and efficacy of vedolizumab as induction and maintenance therapy for ulcerative colitis were evaluated in two integrated randomised controlled trials involving 895 patients with active disease (Mayo Clinic score 6-12, sigmoidoscopy subscore ≥2 and disease extending ≥15cm from the anal verge).2

Induction therapy in ulcerative colitis

Patients in the induction trial were randomised to receive intravenous vedolizumab (300mg, n=225) or placebo (n=149) (cohort 1) at week 0 and 2. An additional 521 patients received open-label vedolizumab (cohort 2).2

Clinical response

The primary endpoint for induction therapy was clinical response, defined as a reduction in the Mayo Clinic score of ≥3 and a decrease of ≥30% from the baseline score, plus a decrease of ≥1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1.2 

At week 6, a significantly greater proportion of patients in the vedolizumab group achieved a clinical response than in the placebo group (47.1% versus 25.5%, p <0.001). Similar results were observed in cohort 2, with 44.3% of patients achieving a clinical response.2

Maintenance therapy in ulcerative colitis

Patients from either cohort with a response to vedolizumab at week 6 were included in the maintenance trial and randomised to receive vedolizumab every 8 weeks (n=122) or every 4 weeks (n=125), or placebo (n=126).2

At week 52, patients assigned to continued vedolizumab therapy were more likely to have clinical remission (Mayo Clinic score ≤2 and no subscore >1) than those switched to placebo (41.8% and 44.8% for vedolizumab every 8 weeks or 4 weeks, respectively, versus 15.9% for placebo [p<0.001 for both]).2

Efficacy in Crohn’s disease

Efficacy and safety of vedolizumab were also evaluated in a parallel-group, randomised controlled trial involving 1,115 patients with Crohn’s disease for at least three months and a score of 220 to 450 on the Crohn’s Disease Activity Index (CDAI).3

Patients in the induction study were randomised to receive vedolizumab (300mg, n=220) or placebo (n=148) at weeks 0 and 2 (cohort 1). A further 747 patients received open-label vedolizumab (cohort 2).3

Clinical remission

At week 6, the proportion of patients achieving clinical remission (CDAI score ≤150) was significantly greater in the vedolizumab group than in the placebo group (14.5% versus 6.8%, p=0.02). However, rates of CDAI-100 response (≥100-point decrease) did not differ significantly between the two groups (31.4% for vedolizumab versus 25.7% for placebo, p=0.23). In cohort 2, 17.7% of patients achieved clinical remission and 34.4% had a CDAI-100 response.3

Maintenance therapy in Crohn’s disease

Patients from either cohort with a clinical response to vedolizumab (≥70-point decrease in CDAI score) at week 6 were included in the maintenance trial (n=461).3 

At week 52, 39% of patients in the vedolizumab 8-weekly dosing group and 36.4% of those in the 4-weekly dosing group were in clinical remission compared with 21.6% of those in the placebo group (p<0.001 and p=0.004, respectively).3

Safety


The frequency of adverse effects observed in the ulcerative colitis trial was similar in the treatment and placebo groups.In the Crohn’s disease study adverse events were more common in the vedolizumab group, with a greater incidence of nasopharyngitis, infections and serious infections than in the placebo group.3

References

  1. Entyvio Summary of Product Characteristics, May 2014.
  2. Feagan BG et al. N Engl J Med 2013;369:699-710.
  3. Sandborn WJ et al. N Engl J Med 2013;369:711-21.

 

View Entyvio drug record

Further information: Takeda

Follow MIMS on Twitter

Sign up to MIMS bulletins


Read these next

NICE approves vedolizumab for Crohn's disease

NICE approves vedolizumab for Crohn's disease

The integrin inhibitor vedolizumab (Entyvio) has been...

Ulcerative colitis treatment recommended by NICE

Ulcerative colitis treatment recommended by NICE

Vedolizumab (Entyvio) has been accepted by NICE for...

Metoject pens replace prefilled syringes

Metoject pens replace prefilled syringes

Medac has launched Metoject PEN (methotrexate) a single-use...

Humira licensed for paediatric Crohn's

Humira licensed for paediatric Crohn's

The licensed indications for Humira (adalimumab) have...

Humira approved for use in moderate Crohn's disease

Humira approved for use in moderate Crohn's disease

The licensed indications for Humira (adalimumab) have...

Gut-selective antibody shows promise for inflammatory bowel disease

Gut-selective antibody shows promise for inflammatory bowel disease

A new type of biologic drug is effective in treating...


MIMS Clinics

Prescribing news and resources for key therapeutic areas, collated by the MIMS editors.

Register or Subscribe to MIMS

GPs can get MIMS print & online and GPonline for free when they register online – take 2 minutes, and make sure you get your free MIMS access! If you're not a GP, you can subscribe to MIMS for full access.

Register or subscribe

MIMS bulletins

News and updates straight to your inbox.

Prescribing Update: Fortnightly news bulletin
Alert:
Urgent prescribing updates
Spotlight: Disease-themed monthly round-up

Sign me up

MIMS Dermatology

Read the latest issue online exclusively on MIMS Learning.

Read MIMS Dermatology

Mobile apps

MIMS: access the full drug database and quick-reference tables on the go

MIMS Diagnosis and Management: concise information on signs and symptoms, investigations and diseases

Promo Image

Clinical calculators

Handy calculators and conversions for primary care.