Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in March 2014. See summaries of product characteristics (SPCs), British national formulary (BNF), BNF for children (BNFc) or the MHRA or NICE websites for up-to-date information.

Summary

Relvar Ellipta is a combination inhaler containing 2 active ingredients not previously available for the treatment of asthma: fluticasone furoate (an inhaled corticosteroid [ICS]) and vilanterol (a long-acting beta‑2 agonist [LABA]). There are no published studies that compare fluticasone furoate/vilanterol with a currently available ICS/LABA combination inhaler or currently available ICS monotherapy for a patient-orientated primary outcome such as exacerbation rate.

Effectiveness

  • No statistically significant difference was found between fluticasone furoate/vilanterol 92/22 micrograms once daily and fluticasone propionate/salmeterol 250/50 micrograms twice daily for the 0–24 hour weighted mean forced expired volume in 1 second (FEV1) week‑24 change from baseline (1 randomised controlled trial [RCT]; n=806).

  • A statistically significant reduction (from 15.9% to 12.8%; p=0.036) was found in the adjusted probability of having a severe asthma exacerbation by 52 weeks with fluticasone furoate/vilanterol 92/22 micrograms once daily compared with fluticasone furoate 92 micrograms once daily (1 RCT; n=2020).

Safety

  • Systemic effects may occur with any ICS; particularly at high doses prescribed for long periods. Because fluticasone furoate is a new ICS more information about its effect on cortisol suppression relative to other inhaled corticosteroids is needed.

  • Cardiovascular events, particularly tachycardia, are known risks associated with LABAs. The summary of product characteristics states that fluticasone furoate/vilanterol should be used with caution in people with severe cardiovascular disease.

Patient factors

  • Administration is once-daily using a multi-dose dry powder inhalation device (the Ellipta device).

  • Two strengths are available for the treatment of asthma. The lower strength delivers fluticasone furoate 92 micrograms once daily (approximately equivalent to fluticasone propionate 250 micrograms twice daily). Because a lower strength is not available, the ability to step down treatment is limited.

  • In clinical trials the most commonly reported adverse reactions were headache and nasopharyngitis.

Resource implications

  • The cost of fluticasone furoate/vilanterol 92/22 micrograms is £27.80 for 30 days of treatment. The cost of fluticasone furoate/vilanterol 184/22 micrograms is £38.87 for 30 days of treatment.

  • The cost of other available ICS/LABA combination inhalers ranges from £29.26 to £76.00 for 30 days of treatment.

Key points

Relvar Ellipta is licensed for the regular treatment of asthma in adults and adolescents aged 12 years and older where use of a combination medicinal product (LABA and ICS) is appropriate, that is patients not adequately controlled with ICS and 'as needed' inhaled short-acting beta‑2 agonists. It is not licensed for use in patients who are already adequately controlled on both an ICS and a LABA, unlike the other 4 ICS/LABA combination inhalers that are licensed in the UK for the treatment of asthma (summaries of product characteristics: Seretide, Flutiform, Symbicort and Fostair).

For the treatment of asthma, 2 strengths of the Relvar Ellipta combination inhaler (with different doses of fluticasone furoate and the same dose of vilanterol) are available:

  • fluticasone furoate 92 micrograms plus vilanterol 22 micrograms (delivered dose leaving mouthpiece) and

  • fluticasone furoate 184 micrograms plus vilanterol 22 micrograms (delivered dose leaving mouthpiece).

In patients with asthma, fluticasone furoate 92 micrograms once a day is approximately equivalent to fluticasone propionate 250 micrograms twice a day and fluticasone furoate 184 micrograms once a day is approximately equivalent to fluticasone propionate 500 micrograms twice a day (summaries of product characteristics).

The British guideline on the management of asthma (SIGN guideline 101) published jointly by the Scottish Intercollegiate Guidelines Network and British Thoracic Society and accredited by NICE indicates that 250 micrograms fluticasone propionate twice a day is approximately equivalent to 1000 micrograms beclometasone dipropionate per day and 500 micrograms fluticasone propionate twice a day is approximately equivalent to 2000 micrograms beclometasone dipropionate per day.

For adults and young people aged over 12 years, the British guideline on the management of asthma recommends a trial of ICS plus LABA when asthma is uncontrolled by an ICS alone (step 3: initial add-on therapy). The guideline states that the first choice as add-on therapy to ICS is a LABA, which should be considered before going above a dose of 400 micrograms beclometasone dipropionate equivalents per day and certainly before going above 800 micrograms beclometasone dipropionate equivalents per day.

This evidence review is based on the 2 randomised controlled trials (RCTs) that provide the best published evidence for fluticasone furoate/vilanterol for treating asthma.

Woodcock et al. (2013) (n=806) found that there was no statistically significant difference between fluticasone furoate/vilanterol 92/22 micrograms once daily and fluticasone propionate/salmeterol 250/50 micrograms twice daily for the 0–24 hour weighted mean FEV1 week‑24 change from baseline. The study was designed to show superiority of fluticasone furoate/vilanterol and powered to detect a difference of 80 ml in the serial weighted mean FEV1 between the 2 groups. At entry to the study (prior to a 4‑week run-in period on ICS alone), 69% of participants were already using an ICS plus LABA (equivalent to step 3 or 4 of the British guideline on the management of asthma). Caution is needed in extrapolating the results of this study to people with less severe asthma.

Bateman et al. (2013) (n=2020) found that there was a statistically significant reduction from 15.9% to 12.8% in the risk of having a severe asthma exacerbation by 52 weeks with fluticasone furoate/vilanterol 92/22 micrograms once daily compared with fluticasone furoate 92 micrograms once daily. At entry to the study 60% of participants were already using an ICS plus LABA (equivalent to step 3 or 4 of the British guideline on the management of asthma).

There are limited published efficacy data available for the higher strength inhaler. O'Byrne et al. (2013) compared fluticasone furoate/vilanterol 184/22 micrograms once daily with fluticasone furoate 184 micrograms once daily and fluticasone propionate 500 micrograms twice daily. The co-primary outcome measures for this study were both disease orientated; the change from baseline in trough FEV1 and weighted mean 0–24 hour serial FEV1. The study found that fluticasone furoate/vilanterol statistically significantly improved both primary outcome measures compared with fluticasone furoate and fluticasone propionate.

In Woodcock et al. (2013) rates of serious adverse events and adverse events leading to withdrawal from the study were similar between fluticasone furoate/vilanterol 92/22 micrograms once daily and fluticasone propionate/salmeterol 250/50 micrograms twice daily, although no statistical analysis was provided. In a 52‑week safety study (Busse et al. 2013) oral/oropharyngeal candidiasis was more common with both strengths of fluticasone furoate/vilanterol once daily compared with fluticasone propionate 500 micrograms twice daily (6% and 7% compared with 3% respectively; no statistical analysis presented). Extrasystoles (bigeminy or trigeminy on Holter recording) were more common in the fluticasone furoate/vilanterol 184/22 micrograms group (7%) compared with the 92/22 microgram strength inhaler group (2%) or the fluticasone propionate group (3%).

According to the summaries of product characteristics during clinical trials, the most commonly reported (1/10 or more) adverse reactions were headache and nasopharyngitis. Other common adverse reactions reported (1/100 or more to less than 1/10) include candidiasis of the mouth and throat, upper respiratory tract infections, bronchitis, dysphonia, pyrexia, abdominal pain, arthralgia, back pain and oropharyngeal pain.

Local decision-makers will need to consider the available evidence on efficacy and safety, as well as the licensed indications, cost and individual patient factors, when making decisions about using Relvar Ellipta or another ICS/LABA combination inhaler.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.