Psoriasis affects about 3% of the general population, and 30% of these patients have moderate to severe disease. The more severely affected patients have significant physical and psychological impairments that affect all aspects of life, often leading to severe depression. Marked comorbidities have also been associated with moderate to severe psoriasis. 1 About a third of patients with psoriasis also have joint involvement, which ranges from morning stiffness to crippling psoriatic arthritis. 2 Until late into the 20th century, however, psoriasis was considered by many patients and physicians as purely a skin disease to be treated with various topical therapies, ultraviolet light, or both. Although these therapies benefited patients with mild to moderate psoriasis, they had limited efficacy and the potential for adverse effects (eg, atrophy of the skin and cutaneous oncogenesis, respectively). The most widely used systemic therapy, methotrexate, had efficacy in the treatment of psoriasis, but the cumulative dose was limited by hepatic toxicity. In general, acitretin was safer than methotrexate; however, both drugs are contraindicated during pregnancy. The third systemic drug approved for severe psoriasis in the 20th century was ciclosporin, which was very effective but the duration of therapy was limited by the potential for hypertension and pan-suppression of the immune system, potentially leading to increases in opportunistic infections and malignancies. 3 With the recognition of psoriasis as a chronic immune-mediated inflammatory disease of the skin, 4 the 21st century ushered in more specific therapies for psoriasis—ie, biological agents. The first of these agents, alefacept, affected T-cell trafficking, and like the other drug in this class, efalizumab, benefited the skin but not the joints. When tumour necrosis factor α was found to be a mediator of both psoriasis and psoriatic arthritis, inhibitors of this cytokine—etanercept, infliximab, and adalimumab—were approved for both disorders, thus providing concomitant benefits for the skin and the joints. 5

More recently, interleukins 12 and 23 have been found to have a major role in the pathophysiology of psoriasis. 6 In today’s Lancet, the findings by Craig Leonardi and Kim Papp and their respective colleagues in the PHOENIX 1 and 2 trials7, 8 confirm the importance of these cytokines. Their data show that subcutaneous