Systemic therapies in psoriasis where started in the fifties with methotrexate. Later on, the synthetic retinoids, etretinate, and more recently acitretin were introduced. The third systemic drug that was approved for psoriasis in the 20th century was ciclosporin. In the last decade a group of more targeted therapies for psoriasis (collectively known as biological agents) have been introduced in its management. These new agents are targeting T-cell surface proteins (alefacept, and efalizumab), or tumour necrosis factor alpha (etanercept, infliximab, and adalimumab). As recent studies have suggested an important role for T helper 17 cells and the interleukins 12 and 23, several studies have investigated the role of targeting these molecules in psoriasis. In the May 17 issue of the Lancet, two articles describe the result of the PHOENIX 1 and 2 trials (that were phase III, double-blind, placebo-controlled studies). These studies evaluate the efficacy and safety in moderate to severe psoriasis of subcutaneous injections of ustekinumab, a human monoclonal antibody against the p40 protein (a subunit shared by both human interleukin 12 and 23). Patients received one dose of ustekinumab (45 mg or 90 mg) or placebo at weeks 0 and 4, and then every 12 weeks. Around 66 to 76% of the patients receiving ustekinumab achieved a PASI75 response, while this was only found in less than 5% of the patients receiving placebo. There were no differences in the proportion of side effects between patients receiving ustekinumab or placebo groups. The efficacy of ustekinumab was preserved with maintenance therapy (every 3 months) during 76 (PHOENIX 1 trial) or 52 weeks (PHOENIX 2 trial). When patients were withdrawn from ustekinumab, psoriasis lesions gradually recurred after 3 months. In addition, one of the trials identified a small proportion of partial responders, and the factors predicting this partial response were found to be a higher bodyweight, a history of inadequate response to one or more biological agent, a longer history of psoriasis, and a history of psoriatic arthritis. (more…)