Etanercept and efalizumab for the treatment of adults with psoriasis

2 Clinical need and practice

2.1 Psoriasis is an inflammatory skin disease that is characterised by an accelerated rate of turnover of the top layer of the skin (epidermis). Although it is a chronic progressive condition, its course may be erratic, with flare-ups and remissions.

2.2 The cause of psoriasis is not fully understood but evidence suggests that there is a strong genetic component and that it is mediated by abnormal T lymphocytes. Environmental factors also play a role, and it has been established that in some cases factors such as emotional stress or infection may trigger the first episode of psoriasis and may also cause exacerbations. Some medications may also cause exacerbations.

2.3 The most common form (80%) of psoriasis is chronic plaque psoriasis (psoriasis vulgaris), which is characterised by well-demarcated, often symmetrically distributed, thickened, red, scaly plaques. There is considerable variation in both the size and the number of the plaques, which can range from one or two small plaques to 100% body coverage. Although the plaques can affect any part of the skin, they are typically found on the extensor surfaces of the knees and elbows, and on the scalp. It is estimated that 5–7% of all people with psoriasis, and approximately 40% of those with extensive skin disease, develop joint inflammation, which is known as psoriatic arthritis (PsA).

2.4 There are few data on the prevalence and incidence of psoriasis in the UK but estimates suggest that it affects approximately 2% of the population. Males and females are affected equally by the condition and there is a higher incidence in white people than in members of other ethnic groups.

2.5 A UK study of people with severe psoriasis found that 60% had taken time off work in the previous year as a direct result of their condition. People with severe disease may require a number of hospitalisations each year; the average length of a hospital stay is around 20 days.

2.6 Psoriasis is generally graded as mild, moderate or severe. Several different scales for measuring the severity of psoriasis are also used, which are variably based on the following criteria: the proportion of body surface area affected; the disease activity (degree of plaque redness, thickness and scaling); the response to previous therapies; and the impact of the disease on the person.

2.7 The Psoriasis Area Severity Index (PASI) is the most widely used measurement tool for psoriasis in clinical trials. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). A PASI score of more than ten has been shown to correlate with a number of indicators commonly associated with severe disease such as the need for hospital admission. Trial outcomes are generally reported in terms of the number of people reaching a specified percentage reduction in PASI from their baseline score (for example, PASI 75 is a 75% reduction from baseline score). The European Medicines Agency (EMEA) recognises the achievement of a PASI 75 as an indicator in clinical trials that severe psoriasis has responded to treatment.

2.8 Psoriasis has been shown to affect health-related quality of life (HRQoL) to an extent similar to the effects of other chronic diseases such as depression, myocardial infarction, hypertension, congestive heart failure or type 2 diabetes. In general, increased severity of psoriasis is associated with decreased HRQoL. However, the degree of this effect on quality of life is also dependent on the area of the body affected by psoriasis. Thus, even mild psoriasis in the flexures or exposed areas such as the face can be very distressing. The Dermatology Life Quality Index (DLQI) is a validated HRQoL measure that consists of ten questions covering symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Scores range from 0 (best HRQoL) to 30 (worst possible HRQoL). A score of greater than 10 is considered to correlate with a substantial effect on a person's HRQoL.

2.9 There is no cure for psoriasis but there is a wide range of topical and systemic treatments that can potentially manage the condition. Most treatments, however, only reduce the severity rather than stop the episodes, and the psoriasis therefore has to be treated continually and on a long-term basis. The choice of treatment depends on a number of factors including the severity of the condition and the extent of body surface area affected. In general, the evidence base for many of these therapies is not well developed.

2.10 Mild to moderate psoriasis, particularly when a limited area of skin is involved, can be managed with topical treatments, including emollients and occlusive dressings, keratolytics (salicylic acid), coal tar, dithranol, corticosteroids, retinoids and vitamin D analogues. The burden for the person with psoriasis can be considerable as many of the preparations have a strong smell, are messy and require application two or three times a day.

2.11 More severe, resistant and/or extensive psoriasis can be treated with photo(chemo)therapy, acitretin (an oral retinoid) and oral drugs that act on the immune system, such as ciclosporin, methotrexate and hydroxycarbamide. Oral treatments can be given alone or in conjunction with topical therapies. All the oral therapies have the potential to cause severe long-term side effects, and monitoring is required. The toxic effects are cumulative and therefore many people with psoriasis require 'rotational therapy' in order to minimise the cumulative toxicity of any one treatment.

2.12 There is very little information on current practice in treating psoriasis in the NHS and it is likely that there are widespread variations in service. There are also few data on the current service costs; nearly 1 million prescriptions for psoriasis therapies were dispensed in 2003 at a cost of £27.8 million. This does not include treatments that are also used for other conditions (for example, corticosteroids or methotrexate) or costs associated with treatment in secondary or tertiary care. Excluding drug costs, mean costs for inpatient care have been estimated at £5215 per patient.