Fulfilling an unmet need in psoriasis : do biologicals hold the key to improved tolerability?

Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Traditional systemic treatments, including methotrexate, ciclosporin, psoralen plus UVA (PUVA), oral retinoids and fumaric acid esters, are widely used for severe disease and are effective in the short term. Severe psoriasis is a chronic disease and patients and physicians have expressed concerns about possible harm from organ toxicity, such as skin cancer (PUVA), hyperlipidaemia (retinoids), renal (ciclosporin) or hepatotoxicity (methotrexate). Long-term monitoring is required and may not detect early organ damage. The pathophysiology of psoriasis remains to be clarified, but advances toward the understanding of the immunological basis of psoriasis have uncovered the involvement of immunological pathways; for example, the role of tumour necrosis factor (TNF)-alpha, T cell proliferation and T cell activation, and migration to the epidermis. This advancement in knowledge combined with developments in recombinant technologies has led to the development of target-specific therapies. Biological agents are defined as proteins that can be extracted from animal tissue or produced via recombinant DNA technologies and possess pharmacological activity. Adalimumab, alefacept, infliximab, efalizumab and etanercept are examples of biological agents currently used for the treatment of psoriasis. Some of these are also therapy for other autoimmune conditions, such as rheumatoid arthritis and Crohn's disease. These biological agents are effective in psoriasis but raise new safety concerns. Information on the safety of biological agents in conditions such as rheumatoid arthritis and Crohn's disease can not be directly extrapolated to psoriasis. An increased incidence of lymphomas has been postulated to be associated with etanercept, infliximab and adalimumab; serious infections, such as tuberculosis, have also been reported with these three biologicals, all of which target TNF-alpha. Demyelinating disorders, such as multiple sclerosis, have been reported with some biologicals as has congestive heart failure. Alefacept, because of its mechanism of action of lowering the number of active T cells, is associated with low T cell counts. Efalizumab has been associated with thrombocytopenia and haemolytic anaemia. Data on the safety of >2.5 years' continuous treatment with efalizumab are reassuring and a valuable beginning to understanding the role and risk of harm of long-term therapy for a chronic disease. Longer follow-up studies and safety databases, for each of the biologicals used in psoriasis, are needed to ensure both prolonged efficacy and minimal risk of harm.