The National Institute for Health and Care Excellence (NICE) has published final Technology Appraisal Guidance (TAG) for Entyvio (vedolizumab), the first gut-selective treatment for Crohn’s disease (CD). (1) NICE recommends vedolizumab as an option for use on the NHS for adults with moderately to severely active CD who have either failed,* or were intolerant or contraindicated to, an anti-TNF (tumour necrosis factor-alpha antagonist). NICE recognises vedolizumab as an innovative, cost-effective treatment that provides remission from symptoms. (1) The annual UK cost per CD patient in relapse is estimated to be £10,513. (4)
Vedolizumab is a 30 minute intravenous infusion given every eight weeks at a fixed dose of 300mg. (5) It works selectively in the gut to help block the entry of white blood cells, (5) reducing inflammation and associated symptoms, such as malnutrition, weight loss, urgent and frequent diarrhoea and rectal bleeding. (6)
These distressing symptoms can leave people housebound (7) and have a wide-ranging and devastating impact on mental health, relationships and employment. (1)
Crohn’s and Colitis UK, welcomes this recommendation and highlights that vedolizumab could make a fundamental difference in enabling some people with CD to get on with their lives. (3)
Dr Jeremy Sanderson, Consultant Gastroenterologist, commented “getting patients into remission and keeping them there long-term is the primary goal of treatment. For our patients, active disease has a huge negative impact across all aspects of daily life. Vedolizumab is an effective and much needed additional treatment option for patients with Crohn’s Disease.”
As part of its decision, NICE recognises that vedolizumab works differently to existing treatments for CD and considered this to be an innovation; (1) selectively targeting the immune system in the gut. (5) Importantly, clinical experts consulted by NICE felt that vedolizumab has a more favourable adverse event profile than existing biological treatments because of this ‘gut-specific’ effect and fewer systemic side effects. (1)
The key evidence to support vedolizumab use in the treatment of moderately to severely active CD comes from clinical data submitted from the GEMINI II and GEMINI III studies; (1) part of the Phase III clinical trial programme evaluating the efficacy and safety of vedolizumab in both CD and ulcerative colitis (UC) patients. (5)
Efficacy – the NICE guidance states that in the induction phase of the GEMINI II study, clinical remission was significantly higher in patients who received vedolizumab than placebo at week 6 (14.5% and 6.8% respectively, p=0.02). (1)† A sub-group analysis of the data showed that of those patients who had failed one or more anti-TNF therapy, 10.5% and 16.0% responded to vedolizumab at week 6 and 10 respectively, compared to placebo (4.3% and 8.6% respectively). (1)‡ In the maintenance phase, clinical remission at week 52 was significantly higher in patients who received vedolizumab compared to placebo (treatment difference: 17.4% in patients receiving vedolizumab every 8 weeks, p=0.0007). (1) A sub-group analysis of the data showed that of those patients who had failed one or more anti-TNF, 28.0% were in remission at week 52 compared to 12.8% on baseline therapies and placebo (treatment difference: 15.2%). (1)‡
A further study with a similar patient population (GEMINI III) highlighted that there was no statistically significant difference in clinical remission between patients treated with vedolizumab and placebo at week 6. (1) Analysis of the secondary outcomes of the study showed that, 26.6% of patients treated with vedolizumab were in remission at 10 weeks compared to 12.1% on baseline therapies and placebo (p=0.001). (8)‡§
Safety – the frequency of adverse events in the GEMINI II and GEMINI III studies with vedolizumab was similar to placebo (87% and 82% respectively), with the most common adverse event being exacerbation of CD (20.1% for vedolizumab and 21.6% for placebo). (1) Serious adverse events were more frequent in patients treated with vedolizumab than placebo (24.4% and 15.3% respectively). (1)
Adam Zaeske, Managing Director of Takeda UK and Ireland, commented “we are pleased to receive final NICE guidance for vedolizumab in CD as this brings patients a step closer to a much needed additional treatment option. Vedolizumab has been recommended by NICE and accepted by SMC for restricted use in CD, and across its full licenced indication in UC, within 18 months of EMA licence, which demonstrates both the treatment innovation of vedolizumab and our commitment to addressing unmet patient needs.”
Following the publication, clinical commissioning groups have an obligation to ensure that vedolizumab is made available to appropriate patients within 90 days and no later than 24 November 2015. (1) This guidance is contingent upon Takeda UK providing vedolizumab to the NHS within the terms of an agreed patient access scheme. (1)
The decision is the second positive NICE ruling for vedolizumab – on 5 June 2015, NICE published positive final guidance on vedolizumab for adults with moderately to severely active UC across its full licenced indication. (9)
*Failure is defined as the disease responding inadequately or as loss of response to treatment
† GEMINI II trial: CDAI-100 response at week 6, component of co-primary endpoint was not met. Secondary endpoints are considered exploratory
‡ Post-hoc analysis of clinical trial data; no statistical comparisons can be made
§ GEMINI III trial: primary endpoint was not met therefore secondary endpoints were considered exploratory
- www.nice.org.uk. Last accessed August 2015.
- NHS Choices. Crohn’s Disease – overview. http://www.nhs.uk/conditions/crohns-disease/pages/introduction.aspx. Last accessed August 2015.
- Crohn’s and Colitis UK Press Release: NICE recommends vedolizumab as a treatment option for Crohn’s Disease. http://www.crohnsandcolitis.org.uk/whats-new/nice-recommends-vedolizumab-as-a-treatment-option-for-crohns-disease. Last accessed August 2015.
- Ghosh N et al. A UK cost of care model for inflammatory bowel disease. Frontline Gastroenterology 2015;0:1–6. doi:10.1136/flgastro-2014-100514.
- Entyvio Summary of Product Characteristics. June 2014. http://www.medicines.org.uk/emc/medicine/28980. Last accessed July 2015.
- IBD Standards Group. Standards for the Healthcare of People who have Inflammatory Bowel Disease (IBD). http://www.ibdstandards.org.uk/uploaded_files/IBDstandards.pdf. Last accessed August 2015.
- Mason I. Continence care for patients with inflammatory bowel disease. Nursing Standard 2007;22(8):43–6.
- Sands BE 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):618–27.
- National Institute for Health and Care Excellence technology appraisal guidance [TA342] – Vedolizumab for treating moderately to severely active ulcerative colitis. June 2015. http://www.nice.org.uk/guidance/ta342. Last accessed August 2015.