PSORIASIS

What is psoriasis?

Psoriasis is a chronic inflammatory skin disorder characterised by red disc-like raised lesions with dry, silvery scaling, most frequently on the elbows, knees or scalp. There are periods when psoriasis flares up (a relapse) and quieter periods (remissions) The lesions build up because the rate of cell division of psoriasis skin is much higher than normal. Most cases are mild, but a few can be widespread and disfiguring. The cause of psoriasis is not known, but a genetic component and involvement of the immune system have been implicated. While not curable, treatment can bring periods of remission and improve both appearance and mood.

Who does psoriasis affect?

Psoriasis is thought to affect approximately two per cent of the population of the UK, but some people with mild psoriasis of limited extent may not seek medical help and hence go undetected. The disease usually occurs in young adults (15-40 years, with an average age of onset of 33), with men and women equally likely to be affected. About 5-10 per cent of people with psoriasis develop a form of arthritis. Psoriatic arthritis most often affects the joints of the fingers and toes and is somewhat more common in women than men.

Present treatments and shortcomings

Mild to moderate skin plaques are traditionally treated with formulations applied to the skin (known as topical preparations) containing either dithranol or coal tar and colloidal sulphur. Ointments containing the vitamin D derivatives calcipotriol (Dovonex, Leo), calcitriol (Silkis, Galderma), tacalcitol (Curatoderm, Crookes) or the vitamin A derivative tazarotene (Zorac, Allergan) are used to treat chronic plaques. Steroids applied to the skin are also frequent first-line treatments, but inflammation may recur when they are stopped. A combination of calcipotriol and the steroid betamethasone (Dovobet, Leo) is available for early use. Antibacterial and antifungal solutions may be useful in preventing infection of the inflamed skin.

Exposure to certain wavelengths of ultraviolet light while simultaneously taking psoralen, and the vitamin A derivative acetretin (Neotigason, Roche) can be beneficial in some cases. In severe psoriasis, the immunosuppressive medicines methotrexate and cyclosporin are effective, but cause general immunosuppression. Three biological treatments (medicines based on proteins) have also been authorised for use where other therapies have been ineffective - etanercept (Enbrel, Wyeth) and infliximab (Remicade, Schering-Plough), both of which are directed against Tumour Necrosis Factor alpha (TNF-α) which causes inflammation, and efalizumab (Raptiva, Serono).

None of the many treatments for psoriasis is entirely satisfactory. Many topical preparations are messy and slow-acting (4-6 weeks) and none eradicate the condition: relapse is inevitable. Acetretin persists in the body for a long time and can cause birth defects, so women of child-bearing age are warned not to become pregnant for two years after a course of treatment. Those using anti-TNF-α preparations must also be monitored carefully for serious infections, especially tuberculosis.

What's in the development pipeline?

Several more biological agents are in development. Nearest to becoming available is alefacept (Amevive, Astellas), a human fusion protein. Adalimumab (Humira, Abbott), a human anti-TNF-α monoclonal antibody that is already indicated for use in psoriatic arthritis, is also in late Phase 3 trial. In a study, nearly 80 per cent of patients treated with adalimumab achieved a reduction of 75 per cent or better in their psoriasis area and severity index (PASI) rating, compared with 35.5 per cent of those treated with methotrexate and 18.9 per cent of those given placebo. Other monoclonal antibodies in development include certolizumab pegol (UCB), an anti-TNF-α preparation, Centocor's CNTO-1275 (both at Phase 3) and ABT-874 (Abbott), which is at Phase 2.

Several new oral agents are in development:

• Isotechnika has ISA247 in Phase 3 trial. It appears to be better tolerated than other immunosuppressants, with little effect on kidney function or blood lipids. Patients with moderate to severe psoriasis experienced an average reduction in PASI score of 60 per cent over 24 weeks of treatment with this compound, and scores continued to improve over an additional 36 weeks.
• Biogen Idec's BG-12 is also in Phase 3 development. Patients taking this compound experienced a 68 per cent reduction in PASI after 16 weeks, as compared with a 10 per cent fall in those given placebo.
• Celgene has an anti-inflammatory compound (CC-10004) in Phase 2 trial in severe psoriasis
• Advitech has a growth factor-containing preparation (XP-828L) that has shown efficacy in mild-to-moderate psoriasis. It is derived from milk protein.

Other new Phase 2 compounds are being developed for topical administration:

• Cytochroma Inc has a new vitamin D analogue (CTA018)
• Leo has two compounds, 80185 (Phase 2 for body psoriasis and Phase 3 for scalp psoriasis) and 80190 (Phase 2 for facial psoriasis) that are also based on vitamin D
• Revotar Biopharma is investigating bimosiamose
• Vitae Pharmaceuticals has VTP-201227, which acts on two enzymes present in the skin that may be involved in healing of psoriatic lesions
• York Pharma is testing carbenoxolone
• Zelos Therapeutics is investigating topical use of Ostabolin-C.

The introduction of biological treatments has given a welcome stimulus to the development of new compounds for psoriasis. Although the causes and processes of the disease are still not well understood, these newer compounds focus on molecules that are known to be involved in its progress, and are more specific in their actions than older medicines such as steroids, vitamins and coal tar. There is, therefore, good hope of future treatments giving better control of symptoms with fewer troublesome side-effects and greater convenience in use.

FOR FURTHER INFORMATION CONTACT:

THE PSORIASIS ASSOCIATION
Milton House, 7 Milton Street
Northampton, NN2 7JG
Phone: 0845 676 0076 (Helpline)
Website: www.psoriasis-association.org.uk

PSORIATIC ARTHROPATHY ALLIANCE
P.O. Box 111
St Albans
Herts, AL2 3JQ
Phone: 0870 770 3212
Website: www.thepaa.org