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Commissioning Support
Fluticasone furoate/vilanterol
(Relvar Ellipta®▼)
For the treatment of chronic obstructive pulmonary disease
Commissioning guidance
When making a decision about the use of combination inhaler devices for the treatment of COPD, commissioners
may wish to consider the following:
 At current prices, Relvar Ellipta is one of the more cost-effective long-acting ß2-agonist/inhaled corticosteroid
(LABA/ICS) combination inhalers.
 When a combination inhaler is considered an appropriate option, NICE guidance recommends selection of the
least costly device.
 The availability of a once-daily dose may be beneficial in some patient groups.
Q4 rating: The evidence for efficacy of the Relvar Ellipta inhaler was
considered to be weak. Only three of six double-blind randomised controlled
trials (RCTs) identified, evaluated the licensed dose of Relvar Ellipta (92/22)
compared with placebo or a comparator licensed for use in the UK. In these
trials, the authors stated that where no statistically significant difference was
demonstrated for the primary endpoint, the statistical hierarchy used in the
analysis of results mean that no significance could be inferred for secondary
endpoints, which limited use of the reported data for the licensed dose in
one trial and data for patient oriented outcomes in two trials: St Georges
Respiratory Questionnaire and the Chronic Respiratory Questionnaire
dyspnoea domain.
Place in therapy in primary care
Prescribing guidance: Category A (Q4)
BNF: 3.2
Relvar Ellipta is suitable for prescribing in primary care for the treatment of COPD, within its licensed indications.
Q2
higher place
weaker evidence
Q1
higher place
stronger evidence
Q4
lower place
weaker evidence
Q3
lower place
stronger evidence
Strength of evidence for efficacy
The Q rating relates to the drug’s position on the effectiveness indicator grid.
The strength of the evidence is determined by the quality and quantity of studies that show significant efficacy of the drug
compared with placebo or alternative therapy. Its place in therapy in primary care takes into account safety and practical
aspects of using the drug in primary care, alternative options, relevant NICE guidance, and the need for secondary care input.
MTRAC considered the fluticasone furoate/vilanterol dry powder inhaler because it was a new treatment with potential for use in primary care.
Description of technology
Fluticasone furoate/vilanterol combination dry powder
inhaler (Relvar Ellipta®▼) is a once-daily inhaler
containing a LABA (vilanterol) and an ICS (fluticasone
furoate), both new medications for COPD. Two
strengths are provided: one containing 100 µg of
fluticasone furoate and 25 µg of vilanterol (delivered
doses 92 µg/22 µg), and one containing 200 µg of
fluticasone furoate and 25 µg of vilanterol (delivered
1
doses 184 µg/22 µg).
Only the lower 92/22 dose combination is licensed for
the symptomatic treatment of adults with COPD with a
FEV1<70% predicted normal (post-bronchodilator) with
an exacerbation history despite regular bronchodilator
1
therapy. The recommended dose is one inhalation per
day.
Background
COPD is an inflammatory disease characterised by
pulmonary airflow obstruction that is usually
progressive and not fully reversible. COPD is a
common cause of long-term disability and death that
presents a major burden to healthcare services. There
are estimated to be over 3 million people with COPD in
2
the UK.
January 2015
Quality and Outcomes Framework (QOF) data for
2012/13 show that the diagnosed prevalence of COPD
in the West Midlands is 1.8% (102,588 patients in
3
COPD disease registers). Between April 2012 and
March 2013, COPD was the primary diagnosis in
25,639 emergency hospital admissions in the West
4
Midlands.
2
The 2010 NICE clinical guideline on COPD stated that
in people with stable COPD who remain breathless or
have exacerbations despite using short-acting
bronchodilators as needed, the following should be
offered as maintenance therapy:
• if FEV1 ≥ 50% predicted: a LABA or a long acting
muscarinic antagonist (LAMA)
• if FEV1 < 50% predicted: a LABA plus ICS
combination inhaler, or a LAMA.
In people with stable COPD and an FEV1 ≥ 50%
predicted who remain breathless or have exacerbations
despite maintenance therapy with a LABA:
• consider a LABA plus ICS combination inhaler
• consider a LAMA in addition to a LABA where an ICS
is declined or not tolerated.
A LABA plus ICS combination inhaler in addition to a
LAMA should be considered in all people with stable
Page 1 of 2
COPD who remain breathless or have exacerbations
despite maintenance therapy with a LAMA, irrespective
2
of their FEV1.
Clinical evidence for efficacy and safety
Seven multicentre, double-blind RCTs were identified
that evaluated the Relvar Ellipta inhaler in patients with
COPD. Two trials were excluded from the review due to
5,6
short duration (28 days) and/or the use of an
6
unlicensed dose (368/22 µg). Five trials evaluated the
licensed dose of Relvar (92/22 µg) for the treatment of
7-10
Four of the trials also included comparisons
COPD.
with other dose combinations of Relvar (46/22, 184/22)
8-10
that will not be further described.
Various comparators were used in the trials assessing
8,9
Relvar, including placebo, single component
8,9
8fluticasone furoate and single component vilanterol,
10
neither of which is licensed as an individual treatment
for COPD. Relvar was also compared with twice daily
use of the licensed active comparator fluticasone
propionate (500 µg)/salmeterol (50 µg) via the
7
Accuhaler device (Seretide). For the purposes of this
summary, only comparisons with placebo and the
licensed active comparator are presented.
The trials ranged in duration from 12 to 24 weeks,
following a 2 to 4 week run-in period.
The active comparator trial evaluated the change in
lung function (FEV1: change in forced expiratory volume
in one second) from the pre-dose FEV1 at baseline
compared with the weighted mean 24-hour FEV1 after
7
12 weeks’ treatment (primary outcome). Two further
trials evaluated changes from baseline to the end of the
study in the weighted mean FEV1 at 0 to 4 hours postdose (peak), and at 23 to 24 hours post-dose
8,9
(trough). Secondary outcomes included measures of
dyspnoea (domain of the Chronic Respiratory
8,9
Questionnaire; CRQ-SAS) and change in health
7
status from baseline to trial end (St George’s
Respiratory Questionnaire score; SGRQ).
Results are reported for comparisons of the licensed
dose (92/22) of Relvar with a licensed active
comparator or placebo.
Compared with fluticasone propionate/salmeterol
7
500/50 in a 12-week trial (n=528), the change in FEV1
from baseline (pre-dose, day 1) to the end of the trial
(24-hour weighted mean FEV1 on day 84) was not
significantly different in patients using Relvar 92/22.
Mean ± SD changes in FEV1 for Relvar vs. Seretide
were 130 ± 222 mL vs. 108 ± 221 mL.
Due to the design of the trial, statistical significance
could not be inferred for the comparison of scores for
improvement of health status using the SGRQ.
According to the authors, the minimal clinically
important difference for improvement from baseline in
SGRQ was achieved in the Relvar group (mean ± SD
7
-4.3 ± 11.8) but not in the Seretide group (-3.0 ± 11.8).
9
Compared with placebo in a 24-week trial (n=1,030),
Relvar 92/22 was associated with significantly greater
increases in peak and trough FEV1 at the end of the
study than placebo; the differences between the groups
were +173 mL [95% CI 123 to 224] for peak FEV1 and
+115 mL [60 to 169] for trough FEV1 (p<0.001 for both
8
comparisons). In another 24 week trial (n=1,224), the
difference between Relvar 92/22 and placebo for peak
FEV1 was +214 mL [161 to 266] and for trough FEV1
the difference was +144 mL [91 to 197], but statistical
significance could not be inferred in this trial.
Dyspnoea scores were measured in both trials using
the CRQ-SAS. Both trials reported that there was no
clinically meaningful difference seen for Relvar vs.
8,9
placebo using this outcome measure.
Adverse events
For the comparison of Relvar with Seretide, the overall
incidence of adverse events (AEs) was similar, but
there were more AEs leading to withdrawal with Relvar
than Seretide (6 patients vs. 3) and more serious
7
adverse events (6 vs. 3). The most frequently reported
7
drug-related AE in the trial was oral candidiasis.
Exacerbations occurred in 2-3% of patients in the
7
comparative trial and 7-9% of Relvar-treated patients
8,9
in the placebo-controlled trials (10% with placebo).
Pneumonia was reported in one patient receiving
Relvar and in two patients receiving Seretide in the
7
comparative trial. There was one case of pneumonia
8
with Relvar treatment in one 24-week trial, and 5 cases
reported in the second 24-week trial vs. 3 cases in
9
placebo-treated patients.
Considerations for cost impact
 Based on QOF data for 2012/13, in the West
Midlands the average prevalence of diagnosed
COPD is 1.8% and there are 102,588 patients in
COPD disease registers.
 At current prices, the Relvar Ellipta inhaler (92/22,
one inhalation/day) costs £338 per patient per year.
[Price taken from MIMS, March 2015]
References
1. GlaxoSmithKline UK. Relvar Ellipta 92 micrograms/22
2.
3.
4.
5.
6.
7.
8.
9.
10.
micrograms inhalation powder. EMC 2014
http://www.medicines.org.uk/emc
CG101 Chronic obstructive pulmonary disease:
Management of chronic obstructive pulmonary disease in
adults in primary and secondary care (partial update).
NICE 2010 http://publications.nice.org.uk/chronicobstructive-pulmonary-disease-cg101/guidance
Quality and Outcomes Framework - 2012-13. HSIC
http://www.hscic.gov.uk/catalogue/PUB12262
Hospital Episode Statistics Data (HES). HSIC 2014
http://www.hscic.gov.uk/hes
Boscia JA et al. Clin Ther 2012; 34(8):1655-1666.
Lotvall J et al. BMJ Open 2012; 2(1):e000370.
Agusti A et al. Eur Respir J 2014; 43(3):763-772.
Martinez FJ et al. Respir Med 2013; 107(4):550-559.
Kerwin EM et al. Respir Med 2013; 107(4):560-569.
Dransfield MT et al. Lancet Respir Med 2013; 1(3):210223.
Launch date: January 2014
Manufacturer: GSK
WARNING: This sheet should be read in conjunction with the Summary of Product Characteristics
This guidance is based upon the published information available in English at the time the drug was considered. It remains open to review in the
event of significant new evidence emerging.
NICE TECHNOLOGY APPRAISAL GUIDANCE ON THE RELVAR ELLIPTA INHALER WAS NOT AVAILABLE AT TIME OF PUBLICATION OF THIS GUIDANCE
School of Pharmacy, Keele University, Keele, Staffordshire ST5 5BG
©Midlands Therapeutics Review & Advisory Committee
Tel: 01782 734131 Email: [email protected] Web: www.mtrac.co.uk
Date: January 2015