Advice
Key points from the evidence
Key points from the evidence
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The content of this evidence summary was up-to-date in July 2014. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information. |
Summary
In 2 short‑term randomised controlled trials (RCTs: n=553) brimonidine tartrate gel was statistically significantly more effective than vehicle gel in reducing erythema in people with a clinical diagnosis of rosacea and moderate to severe erythema. However, 'success rates' (defined as a 2‑grade reduction in the severity of erythema as assessed by both patients and clinicians) were just 25% to 30% with brimonidine gel compared with about 10% for vehicle gel at day 29.
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Effectiveness In 2 RCTs (n=553), compared with vehicle gel:
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Safety
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Patient factors
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Resource implications
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Introduction and current guidance
Rosacea is a chronic relapsing disease of facial skin, characterised by recurrent episodes of facial flushing, persistent erythema, telangiectasia (fine, dilated blood vessels), papules and pustules. For the symptoms of flushing and erythema (without papules and pustules) there is historically no effective treatment in primary care, and management generally consists of lifestyle advice, including applying sunscreen and avoiding trigger factors when practical (Clinical Knowledge Summaries: rosacea).
Full text of Introduction and current guidance.
Product overview
Brimonidine tartrate gel (Mirvaso) is the first medicinal product to be approved for the symptomatic treatment of facial erythema of rosacea. Brimonidine tartrate is a highly selective alpha‑2 adrenergic receptor agonist, with potent vasoconstrictive and vasostabilising activity. Brimonidine tartrate gel is an aqueous gel that is applied to the face once daily (Brimonidine tartrate gel [Mirvaso] summary of product characteristics).
Full text of Product overview.
Evidence review
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This evidence summary is based on 2 short‑term, randomised, vehicle‑controlled phase III trials of identical design (trial A [n=260] and trial B [n=293]) of brimonidine tartrate gel in adults with a clinical diagnosis of rosacea and moderate to severe erythema (Fowler et al. 2013).
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In both RCTs, brimonidine tartrate gel was statistically significantly more effective than vehicle gel in reducing erythema.
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For the primary end point of 'success rate', defined as a 2‑grade improvement on both the 5‑point Clinician's Erythema Assessment (CEA) and the 5‑point Patient's Self‑Assessment (PSA) of erythema over 12 hours, the 'success rate' at day 29 (3 hours after application) was 31.5% with brimonidine gel and 10.9% with vehicle gel in trial A, and 25.4% with brimonidine gel and 9.2% with vehicle gel in trial B (both p<0.001 over 12 hours).
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The secondary end point of onset of efficacy (the '30‑minute effect'), defined as a 1‑grade improvement from baseline on both the CEA and PSA at 30 minutes on day 1, was seen in 27.9% of the brimonidine gel group and 6.9% of the vehicle gel group in trial A and 28.4% of the brimonidine gel group and 4.8% of the vehicle gel group in trial B (both p<0.001).
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At day 29 (3 hours after application), the 'responder rate' for a 1‑grade improvement on both the CEA and PSA was 70.9% with brimonidine gel and 32.8% with vehicle gel in trial A, and 71.1% with brimonidine gel and 40.1% with vehicle gel in trial B (both p<0.001 over 12 hours).
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At day 29, more people were 'satisfied' or 'very satisfied' with their appearance in the brimonidine gel groups than in the vehicle gel groups (no statistical analysis reported), and statistically significantly more people in the brimonidine gel groups reported overall improvement in erythema compared with those in the vehicle gel groups (p<0.001). However, a substantial number of people were not satisfied with their appearance. At day 29, 27.6% of people in the brimonidine gel group compared with 43.7% of people in the vehicle gel group were 'dissatisfied' or 'very dissatisfied' in trial A and 24.6% of people in the brimonidine gel group compared with 42.2% in the vehicle gel group were 'dissatisfied' or 'very dissatisfied' in trial B (no statistical analysis reported; European public assessment report for Mirvaso).
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The brimonidine tartrate gel summary of product characteristics states that the most commonly reported adverse reactions are erythema, pruritus, flushing and skin burning sensation, all occurring in between 1.2% and 3.3% of patients in clinical studies. They are typically mild to moderate in severity, and usually do not need treatment to be stopped.
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Both RCTs were short‑term (4‑week treatment phase and 4‑week follow‑up phase) and compared brimonidine tartrate gel with vehicle gel, not an active comparator. They were conducted in people with moderate to severe erythema (marked or fiery redness), and there is no evidence for the use of brimonidine tartrate gel in people with less severe erythema.
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Long‑term efficacy and safety data are limited to those available from an open‑label, non‑comparative study, which followed people for up to 12 months (Moore et al. 2014).
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Efficacy end points for erythema of rosacea are not clearly established. The CEA and PSA scales used in the brimonidine tartrate gel trials are novel scales based on subjective judgements, not objective measures, and defining what a clinically important change is on these scales is difficult.
Full text of Evidence review
Context
Management of facial erythema of rosacea generally consists of lifestyle advice. Off‑label propranolol or clonidine may be used to treat flushing (Primary Care Dermatology Society guidance on rosacea), but this use is not supported by evidence from RCTs. Mild or moderate papulopustular rosacea is usually treated with topical metronidazole or azelaic acid.
Full text of Context.
Estimated impact for the NHS
Brimonidine tartrate gel is the first medicinal product to be approved for the symptomatic treatment of facial erythema of rosacea. It may be an option for adults with a clinical diagnosis of rosacea and moderate to severe erythema (marked or fiery redness) because this was the population assessed in the clinical trials. However, specialists have advised that it is important to ensure that lifestyle recommendations, such as using high‑factor sunscreen and avoiding trigger factors, have been optimised before brimonidine is considered, and that these are continued throughout treatment with brimonidine.
Rosacea is a chronic condition and although brimonidine tartrate gel has a transient effect on erythema, it does not alter the course of the disease or have any effect on other features of rosacea, such as telangiectasia or inflammatory papules. It can be used up to once per day, but does not need to be used daily, and specialists have suggested that some people may only use brimonidine tartrate gel on days when they are particularly self‑conscious about their appearance. Before continuing longer‑term treatment with brimonidine tartrate gel, consideration will need to be given to how treatment efficacy can be assessed given the subjective nature of efficacy outcomes and the low response rates seen in the clinical trials.
Local decision makers will need to take into account the evidence for efficacy and safety, factors relating to individual people with rosacea and cost, when making decisions about using brimonidine tartrate gel.
The cost of brimonidine tartrate gel (Mirvaso) is £33.69 for a 30 g tube (excluding VAT; cost taken from MIMS, May 2014).
Full text of Estimated impact for the NHS.
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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. |