The status of biologic therapies in the treatment of moderate to severe psoriasis.

Psoriasis is a chronic inflammatory, immune-mediated, genetic disease predominantly affecting the skin and associated with significant patient morbidity. Conventional topical and systemic treatment options are numerous and generally effective, with varying degrees of success and rapidity of action. However, recurrence of disease is inevitable. Biologic agents that target pathogenic T cells have been shown to be effective in patients with moderate to severe psoriasis, with the remittive effects of alefacept encouraging in a small proportion of patients. Efalizumab recently was withdrawn from the US market after 5 years of use because of 3 cases of progressive multifocal leukoencephalopathy (PML), a serious life-threatening infection. The tumor necrosis factor alpha (TNF-alpha) inhibitors etanercept, infliximab, and adalimumab have demonstrated notable initial and maintenance efficacy in the treatment of moderate to severe psoriasis but require monitoring because of safety concerns, including risk for infections. A new class of biologic agents, anti-IL-12 and IL-23 antibodies (ustekinumab and ABT-874), shows significant promise for the treatment of moderate to severe psoriasis. However, as new agents in medicine, more evidence is required regarding long-term safety. Despite the efficacy of these biologic agents, which have revolutionized the therapy for moderate to severe psoriasis, complete clearances are not always obtained and relapses occur in a proportion of patients. To maintain better control of the disease, many physicians and patients are choosing combination or adjunctive therapies to augment the results seen with biologic agents. However, to date, there are no well-controlled studies demonstrating safety and/or efficacy of biologic agents in combination with other therapies. Prospective trials of this sort are therefore needed to better understand the potential risks and benefits of such approaches.