NICE technology appraisal lists those patients who will be eligible for new drug therapies, as Dr Alison Roberts explains
In July 2006, NICE published guidance on the use of two recently marketed drugs for the treatment of psoriasis.1
Psoriasis is a relatively common chronic skin disease affecting approximately 2% of the population,1 and can present significant challenges in terms of management.
The irritation, soreness, mild pruritus, constant desquamation, and embarrassment over the skin's appearance causes a burden to sufferers that is often not recognized. Treatment involves control and reducing the severity of the disease; there is currently no cure for psoriasis. Most available treatments have limitations in terms of their effectiveness: topical treatments are time-consuming and messy to apply; systemic treatments have potentially serious side-effects and can be poorly tolerated.
People with psoriasis are known to experience considerable psychological and social morbidity – hospital admissions may mean time off work and loss of earnings; and attending hospital appointments requires employers, friends and/or family to be understanding and supportive.
In addition, the stigma of having skin that looks and feels abnormal is immense,and often results in patients avoiding situations where their skin may be exposed. This can have adverse effects on their general enjoyment of life.
NICE has acknowledged all of these points in their technology appraisal,1 having consulted with a wide range of organizations, including professional medical and nursing groups from both primary and secondary care. Patient support groups have also been consulted.
New drugs for psoriasis
The two drugs under consideration are etanercept (a recombinant human tumour necrosis factor inhibitor) and efalizumab (a T-cell modulator). Both drugs are licensed for the treatment of adults with plaque psoriasis.
Many GPs will have been asked about these new types of drug by patients who have read articles in the press that suggest dramatic results. This guidance is, therefore, extremely welcome as it provides clear factual information about eligibility (Box 1), administration, possible sideeffects and monitoring.
The eligibility criteria listed in Box 1 will allow the selection of those patients with severe psoriasis for whom NICE currently feels these treatments should be reserved.1
|Box 1: In order to be eligible for either of these drugs the patient must have:|
I am in agreement with this means of assessing patients; although I expect there may be a few patients who do not meet these criteria, but where a case could be made for a trial of these drugs. Calculating the DLQI and PASI scores will require an extended consultation before commencing treatment, and again after 12 weeks. The hidden staffing costs involved here may not have been fully considered by NICE and will inevitably add to the cost of prescribing these drugs.
Initial treatment should be with etanercept. The starting dose is 25 mg twice a week by subcutaneous injection.1
The most frequent adverse events are:
- injection site reactions
- allergic reactions.
Less common but more serious adverse reactions are mentioned in the summary of product characteristics.2
The NICE committee looked at the evidence for efficacy and found a number of clinical trials of good quality. A statistically significant improvement in psoriasis was found to occur in patients treated with etanercept compared with placebo, with no statistically significant difference in the incidence of side-effects. No haematological monitoring is required for etanercept.1
NICE has recommended that therapy is continued for 12 weeks, after which time response to treatment should be assessed. An adequate response is defined as either:
- a 75% reduction in the PASI score from when the treatment started (i.e. PASI 75) or
- a 50% reduction in the PASI score (PASI 50) and a 5 point reduction in the DLQI from when treatment started.
These standards ensure a fairly consistent approach to assessing patients, and may remove some of the subjectivity that inevitably occurs when re-assessing patients.
NICE was guided by expert clinicians about how long the drugs should be used for before the likelihood of a response could be reasonably accurately assessed.The experts indicated that in their clinical experience, 12 weeks was a sufficient period of time during which it would become clear whether a patient was likely to respond to treatment with etanercept or efalizumab.1
Efalizumab can be used if patients have failed to respond to, or are intolerant of etanercept. The selection criteria are the same for both drugs, although the manufacturers state that efalizumab should not be used in guttate, erythrodermic or pustular psoriasis.
Efalizumab is given by weekly subcutaneous injection – an initial single dose of 0.7 mg/kg body weight followed by weekly subcutaneous injections of 1.0 mg/kg body weight (maximum single dose should not exceed a total of 200 mg).
The most common side-effects are:
- mild to moderate dose-related flu-like symptoms
Unlike etanercept, some monitoring is required – there is a risk of thrombocytopenia, and so monthly platelet counts are recommended for the first 3 months, and 3-monthly for long-term treatment. Monitoring response to treatment is the same as for etanercept, i.e. using PASI scores and the DLQI.
Concerns and precautions
NICE has commented on a possible increased risk of skin cancer, particularly in patients who have had significant exposure to ultraviolet light therapy in the past.
GPs who care for the patients that receive these treatments need to be aware of this risk. They are in a good position to look out for long-term complications, some of which may not become apparent for several years.
NICE has recommended that a database containing details of all patients treated with these drugs should be established. It is to be called the British Association of Dermatologists Biological Interventions Register (BADBIR), and seems to be a wise precaution, which will enable the long-term consequences of all 'biological' tharapies to be more fully quantified.
There is no real experience of using these drugs alongside current systemic treatments. NICE suggests that further trials comparing etanercept with efalizumab would be welcome, along with trials comparing their use in combination with, for example, methotrexate or ciclosporin.
I was surprised to read that, having conducted a formal evidence synthesis, NICE concluded that both drugs are less effective than either infliximab, methotrexate and ciclosporin in the treatment of psoriasis; and efalizumab is less effective than etanercept.1
The guidance does not mention that both etanercept and efalizumab are contraindicated in pregnancy and breastfeeding, and certain other conditions.3
Cost of treatment
Both drugs are relatively expensive: etanercept costs £89.38/25 mg vial (approximately £180 per week); efalizumab costs £169.20 for 125 mg – the dose is 1 mg/kg after the first dose (which is 0.7 mg/kg), and the maximum dose per injection is 200 mg.1 It is given once a week, and the approximate cost per week of efalizumab will depend on the weight of the patient.
NICE has looked at cost-effectiveness and attempted to calculate the cost per quality of life year gained. The analysis was hampered by a lack of accurate data on prescribing and hospital admissions in both primary and secondary care.
Unfortunately, a lot of prescribed treatments, particularly topical agents, are less than effective, and because of difficulties with using them, concordance can be a real issue. Cost calculations may assume that treatments used have been beneficial, which is not always the case, and may lead to inaccuracies.
So how useful is this guidance for healthcare professionals working in primary care? As a GPwSI in dermatology, I feel it provides very welcome background information and sensible recommendations regarding the place of these products within the current therapeutic range.
The Psoriasis Association has also given a warm welcome to the guidance.4
New treatments for psoriasis are extremely welcome as they offer hope to many sufferers who are unresponsive to, or unable to take, currently available therapies. The technology appraisal is to be reviewed in 2008, by which time the place of etanercept and efalizumab in the treatment of psoriasis will have become clearer, and adjustments to eligibility criteria could be considered.
Having seen the guidance I now feel better placed to answer patients' questions, provide more detailed information, and recommend sources of further information.
- National Institute for Health and Care Excellence. Etanercept and efalizumab for the treatment of adults with psoriasis. NICE Technology Appraisal Guidance 103. London: NICE, 2006.
- www.emea.eu.int/humandocs/Humans/EPAR/ enbrel/enbrel.htm
- British National Formulary, 51st edition. London: British Medical Association and the Royal Pharmaceutical Society of Great Britain, 2006.