Current Treatment Options for Psoriasis

Main Category: Eczema / Psoriasis
Article Date: 22 Nov 2004 - 0:00 PDT

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There is currently no cure for psoriasis and existing treatments are aimed at controlling the symptoms of the disease. The treatment of psoriasis ranges from topical therapies for mild psoriasis to phototherapy and/or systemic therapy for more severe cases of the disease. All of these are considered by patients to have drawbacks in terms of safety, convenience or effectiveness. However, the advent of new biological therapies may offer them new hope of safer, long-term treatment.

Biological therapies

Despite the many treatments available for psoriasis, the adverse events or inadequate efficacy of avai

lable therapies has created a need for safer and more effective long-term treatments.

Innovations in biotechnology have the potential to offer greater safety by building targeted drugs that interfere with specific targets in the pathogenesis of psoriasis. Several drugs are currently being developed to treat this disorder including efalizumab, which has received approval in the EU, US, Switzerland, Argentina, Brazil, Mexico and Australia. Other biological treatments being developed and in some cases on the market include alefacept, etanercept and infliximab.

Serono S.A. has 2 products in development for Psoriasis

Current therapies

Currently available psoriasis treatments include:

Topical therapy

Despite their shortcomings, topical therapies (i.e., creams) have remained the mainstay of treatment for many patients with mild psoriasis. They generally work relatively quickly at clearing the immediate lesions after application and are also generally well-tolerated. However, topical treatments have to be used repeatedly to be effective, as they are not good at maintaining remission of the disease.

Dithranol

-- Dithranol is a topical therapy that has been used to treat psoriasis for over a century. It is derived from Goa powder from the bark of the araroba tree.

-- Dithranol can be effective for mild to moderate psoriasis and is often used with ultraviolet B (UVB) treatments (see below) for more severe psoriasis.

-- A short application with high concentrations of dithranol has been shown to be as effective as an overnight or day-long application using lower concentrations.

-- There are, however, some key weaknesses that limit its use in psoriasis: it causes irritation and burning to the skin and it tends to stain anything it comes into contact with.

Corticosteroids

-- Topical corticosteroids - the most commonly prescribed treatments for psoriasis in many parts of the world - are synthetic drugs that resemble naturally-occurring hormones in the body. They are available in many strengths and formulations including creams, lotions, solutions, emollients, sprays, gels, ointments and medicated tapes.

-- Corticosteroids act by slowing down the growth of skin cells and decreasing the inflammation of lesions in patients with psoriasis. Although corticosteroids can quickly clear lesions, they typically do not produce long remissions, so the lesions associated with psoriasis often recur after a short time.

-- Side effects of prolonged corticosteroid use are numerous and include cutaneous atrophy, the formation of telangiectasia (elevated dark red blotches on the skin) and striae (stretch marks), the latter 'scars' are permanent.

Coal tars

-- Topical coal tars have helped treat psoriasis for centuries and can be used by themselves or combined with UVB1 (see below). By making the skin more sensitive to UV light, coal tar can cause a greater sensitivity to burning when combined with UV therapy. In fact, coal tars were once used as an essential component of the Goeckerman regimen2 (see below).

-- The use of tars slowed down when it was shown that other emollients (substances used to soothe the skin) were equally effective when used in conjunction with UVB light.1

-- The staining caused by tars has also greatly limited their use and attempts to make non-greasy tar preparations that do not stain the skin have not been successful.

-- Coal is also a designated carcinogen (COSHH - Committee of Substances Hazardous to Health).

Retinoids - topical

-- Retinoids (vitamin A derivatives) are the most recent developments for the topical treatment of psoriasis. Tazorotene is a retinoid used to treat mild to moderate plaque psoriasis, which can be used on most parts of the body, including the face, hairline and scalp.

-- Local irritation caused by retinoids has limited their use.2

Vitamin D analogues

The introduction of calcipotriol in the early 90s has provided an alternative to topical steroids, tars and dithranol. Calcitriol and tacalcitol have subsequently been introduced. Calcipotriol has shown equal or superior efficacy to other agents and is cosmetically more acceptable and generally well tolerated. However, local irritation does occur. These agents are not associated with th

e cutaneous atrophy of corticosteroids or the messiness of tars and dithranol.2 Salicylic acid

-- Salicylic acid is a chemical that helps remove scale on lesions. This then allows topical medications to better penetrate the skin.

Overall topical agents are time consuming to apply and have moderate efficacy.

Phototherapy

Patients with psoriasis that does not respond to or is too widespread for topical treatments are candidates for phototherapy. This involves exposing the skin to wavelengths of UV light, which has a therapeutic benefit in psoriasis. Phototherapy is a standard treatment for patients with moderate to severe psoriasis who have not responded to topical therapies.

Climatotherapy

-- Sunlight can have a beneficial effect on psoriasis. Climatotherapy has been used in the Dead Sea, Israel, for many years.2 Because of its position at the lowest point on earth and the haze of minerals in the atmosphere over the Dead Sea, burning rays of short wavelength UVB light are filtered out, allowing more exposure to longer wavelength therapeutic UVB rays.

Broadband and narrowband UVB

-- This form of phototherapy involves exposing the skin to a particular wavelength of UV light called UVB that is effective for treating psoriasis. UVB is present in natural sunlight.

-- Broadband UVB phototherapy has been used to treat psoriasis since the 1920s.

-- Studies have shown that the optimum wavelength of UVB for the treatment of psoriasis is close to 311 nm and this has lead to the development of bulbs that emit UVB radiation in a 'narrowband' at this optimum wavelength.

-- Narrowband UVB is significantly more effective than broadband UVB2 and thus far seems to be substantially safer than PUVA (see below).

PUVA (psoralen plus UVA)

-- PUVA, also called photochemotherapy, was developed in the 1970s and involves the combination of a light-sensitising medication (psoralen) followed by irradiation with UVA (like UVB, UVA is found in natural sunlight).2 Psoralen makes the skin more sensitive and responsive to this type of UV light.

-- Bath PVA is also practiced where the psoralen is put in a bath: the patient soaks before entering the UVA cabinet.

-- Long-term PUVA therapy can lead to premature ageing of the skin and also increases significantly a person's risk of skin cancer (basal cell carcinoma and superficial cell carcinoma).2 Consequently, the maximum recommended exposure should not be exceeded.

The Goeckerman regimen

-- Patients with severe or disabling psoriasis may go to hospital or psoriasis treatment centres for concentrated treatment with UVB and topical coal tar. This is known as the Goeckerman regimen and usually takes at least three or four weeks of daily treatment.

Systemic treatments

In patients who do not respond to phototherapy or who cannot comply with the frequent phototherapy visits needed to achieve clearing, several systemic drugs are available. Systemic drugs affect the whole body.

Methotrexate

-- Methotrexate was initially developed as a treatment for cancer. It has also been used for many years in the treatment of psoriasis. It works by binding to an enzyme involved in the growth of cells and therefore slows down skin-cell growth in psoriasis. Because of its mechanism of action, methotrexate also affects normal cells, including foetal cells, bone marrow and sperm cells.

-- One of the big disadvantages of methotrexate is that its long-term use has been associated with liver damage and in many countries guidelines call for routine liver biopsies in patients taking long-term methotrexate.2

-- In a recent study , it was shown that 48% of patients were not able to stay on treatment after one year.

Cyclosporin

-- Cyclosporin appears to slow down the rate of skin growth by inhibiting the immune system (the immune system plays a critical role in the development of psoriasis).

-- Cyclosporin has been used for the treatment of psoriasis for more than a decade. However, its long-term use is associated with nephrotoxicity (kidney damage)2 and the American Academy of Dermatology (AAD) guidelines stipulate a maximum use of one year.

Oral retinoids

-- Oral retinoids are related to vitamin A. They affect how cells regulate their behaviour, including how quickly they grow and shed from the skin's surface. Retinoids are only moderately effective as monotherapy and are associated with numerous side effects such as hair loss and thinning of the nails.

-- When used in combination with UVB phototherapy or PUVA, low doses of the retinoid acitretin are very effective, allowing substantial clearing with fewer phototherapy visits and fewer side effects.2

-- Retinoids have been associated with birth defects, so they cannot be given to women who could potentially become pregnant. Retinoids treatment has to have been stopped for three year before a woman can become pregnant

References

1 van de Kerkhof PC. Therapeutic strategies: rotational therapy and combinations. Clin Exp Dermatol 2001; 26:356 -361.

2 Lebwohl M. Psoriasis. Lancet 2003;361:1197-1204.

3 Larko O. Treatment of psoriasis with a new UVB-lamp. Acta Dermatol Venereol 1989;69:357-359.

4 Heyendael V.M.R, et al. Methotrexate versus Cyclosporine in Moderate-to-Severe Chronic Plaque Psoriasis. New England Journal of Medicine 2003;349:658-65.

Serono S.A. has 2 products in development for Psoriasis