Dr Alison Roberts welcomes the guidance from NICE and a new treatment for patients with the severe form of the disease
It has been almost 2 years since NICE published technology appraisal guidance (TA103)1 on the use of Etanercept and efalizumab for the treatment of adults with psoriasis. The new NICE technology appraisal on Infliximab for the treatment of adults with psoriasis has just been released,2 which considers where infliximab should lie within the current spectrum of treatments. Infliximab is another ‘biological’ treatment that adds a further useful option for those patients in whom disease is severe and extensive, and which is not responding to existing therapies.
Psoriasis is a common chronic inflammatory disease of the skin affecting approximately 2% of Caucasians. Psoriasis has a worldwide distribution with prevalence varying according to race and geographic location.3 Many patients cope well with mild psoriasis, which often runs a variable course, but for those who unfortunately have more extensive disease, any new additions to the therapeutic armamentarium will be welcomed.
Recognition and treatment
Psoriasis can be recognised from the scaly plaques that can occur on all visible areas of the skin. It can also affect the flexures, scalp, and nails. The physical effects are soreness, pruritus, and constant desquamation of dry skin. Psoriasis also causes considerable psychological and social morbidity—hospital admissions may mean time off work and loss of earnings, and being able to attend hospital appointments requires a level of understanding and support from employers, friends, or family. 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, such as when swimming or attending a gym. Holidays can cause a lot of worry.
Treatment is generally about controlling and reducing the severity of the disease and not about curing it. Currently available treatments have limitations in terms of effectiveness—topical treatments are time consuming and messy to apply. Ultraviolet light therapy is a valuable treatment for plaque psoriasis, and can be repeated at intervals if the disease recurs, up to a lifetime limit of exposure. However, it is not helpful for psoriasis affecting the scalp, nails, and flexures. Systemic treatments have potentially serious side-effects and can be poorly tolerated but they are effective for some patients.
Effectiveness of infliximab
Evidence for the effectiveness of infliximab, based on a number of randomised controlled trials comparing the agent with placebo, was considered by the NICE guideline development group. They also heard the views of clinical specialists and patient experts, who said that in clinical practice, infliximab is associated with a higher response rate and a more rapid and longer-lasting response than other therapies with a comparable adverse-effect profile, particularly in patients with severe disease.2
Infliximab is a cytokine inhibitor, which acts by inhibiting the activity of tumour necrosis factor.4 As with etanercept and efalizumab, NICE has advised use of the psoriasis area severity index (PASI) and the dermatology life quality index (DLQI)5 as tools for establishing which patients will be entitled to receive infliximab.
The PASI is a means of measuring the area of skin affected and the severity of the psoriasis. Erythema, thickness, and amount of scale are assessed on a rating of 0–4 and an ‘area score’ is also made—the scores for each body area are then combined using a formula that generates a final score.6 This is a well respected tool for measuring degrees of psoriasis and is an acceptable method to use. It takes roughly 15–20 minutes to do and there will probably be variation between different PASI scorers, however, on balance, it gives a fairly reproducible measure of severity. The DLQI comprises 10 questions scored from 0–3 (maximum score of 30). It covers aspects of daily life that might be affected by having psoriasis and is an excellent assessment tool.
The guideline recommends certain criteria for treatment with infliximab to be considered. These are if:2
- disease is very severe, as defined by a total PASI of ?20 and a DLQI of >18
- the psoriasis has failed to respond to standard systemic therapies such as ciclosporin, methotrexate, or psoralen and long-wave ultraviolet radiation (PUVA), or the person is intolerant to or has a contraindication to these treatments.
Overall, NICE concluded that infliximab should be reserved for patients with very severe psoriasis who may need a treatment that has a rapid onset of action. Treatment with infliximab should be continued beyond 10 weeks only in people whose psoriasis has shown an adequate response to treatment within this time frame.2 An adequate response is defined as either:2
- a 75% reduction in the PASI score from when treatment started (PASI 75) or
- a 50% reduction in the PASI score (PASI 50) and a five-point reduction in the DLQI from when treatment started.
When using the DLQI, healthcare professionals should be careful to ensure that they take account of a patient’s disabilities (such as physical impairments) or linguistic or other communication difficulties, when reaching conclusions on the severity of plaque psoriasis.1 This is a very welcome recommendation, which hopefully will reduce the risk of patients who are less able to argue for their place on the treatment programme, for whatever reason, missing out on a possibly effective treatment option.
Some patients will be unable to start treatment with infliximab because of contraindications, including moderate or severe heart failure and active infections.1 Adverse sequelae, which may lead some to discontinue treatment, include infusion-related reactions, infections, and delayed hypersensitivity reactions.
Before treatment with infliximab is initiated, patients must be screened for both active and inactive tuberculosis, and given that the drug can cause haematological side-effects and reactivate hepatitis,7 baseline full blood count and liver/renal function tests are advisable prior to commencing treatment.
As with other biological agents, time needs to be spent counselling patients in detail about infliximab, as this drug is powerful both in terms of potential benefits and possible unwanted effects.
The patient needs to be in hospital to receive the infusion and should be monitored closely for 1–2 hours afterwards, with resuscitation equipment available for immediate use.4
Infliximab is expensive, £419.62 per 100 mg vial,4 and it is given as a 5 mg/kg intravenous infusion over a 2-hour period followed by additional 5 mg/kg infusions at 2 and 6 weeks then every 8 weeks thereafter.2 If the more severely affected patients only are selected for treatment, infliximab is as cost effective as etanercept given continuously for this group.2
The guideline development group heard evidence from clinical specialists and patient experts that, in clinical practice, infliximab is associated with a higher response rate and a more rapid and longer-lasting response than other therapies with a comparable adverse effect profile, particularly in patients with severe disease.2
The approval of infliximab by NICE makes a welcome addition to the existing biological agents that have previously been approved for use in psoriasis. However it should be borne in mind that the long-term effects of biological agents are not fully known as they are relatively newly developed drugs. The British Association of Dermatologists is establishing a register of patients receiving such drugs.8 This will mean that the longer-term effects of these treatments can be analysed across a larger population.
- Although expensive, infliximab is an effective treatment for severe psoriasis that is resistant to conventional therapies
- Before infliximab is used, the patient should be carefully pre-assessed by a dermatologist
- It needs to be given in hospital as a 2-hour infusion every 2 months after an initial series of three infusions in 2 months
- Estimated annual costs per patient=£11,750a
- For PBC this treatment is best negotiated as a package at PCT level or higher under an agreed tariff
- National Institute for Health and Care Excellence. Etanercept and efalizumab for the treatment of adults with psoriasis. Technology Appraisal 103. London: NICE, 2006.
- National Institute for Health and Care Excellence. Infliximab for the treatment of adults with psoriasis. Technology Appraisal 134. London: NICE, 2008.
- Campalini E, Barker J. The clinical genetics of psoriasis. Current Genomics 2005; 6: 51–60.
- British National Formulary. BNF 55. London: Royal Pharmaceutical Society, 2008.
- Finlay A, Khan G. Dermatology Life Quality Index (DLQI)—a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19 (3): 210–216.
- Feldman S, Krueger G. Psoriasis assessment tools in clinical trials. Ann Rheum Dis 2005; 64 (Suppl 2): ii65–68; discussion ii69–73.