ABSTRACT

As has been discussed in other chapters, we have systemic therapies for psoriasis that are quite effective. However all existing systemic therapies have safety and tolerability concerns. Cyclosporine causes hypertension and renal toxicity, which generally limits its use to <1 year (1). Psoralen/ultraviolet A (PUVA) increases the risk of skin cancer with long-term use and is generally not the treatment of choice in patients with type I or II skin who have had more than 200 treatments (1). The most widely used agent, methotrexate, commonly causes asthenia and evidence of hepatotoxicity and, less commonly, bone marrow toxicity and pneumonitis. Chronically it can cause cirrhosis and portal fibrosis in significant numbers of patients (1). Curiously we can find no published reports in which psoriasis area severity index (PASI) endpoints were used to assess the efficacy of psoriasis treated with methotrexate. In a recent study to assess further its mechanism of action we assessed the efficacy, via PASI, of methotrexate in 25 consecutive patients requiring systemic therapy for psoriasis (K. Callis, 2002 Society of Investigative Dermatology, poster #220). In this study, 23 of 25 patients completed the aggressive treatment program starting at 15 mg/week and moving to as much as 30 mg/week over 6 months. A surprise was that although 65% had az50% reduction in PASI, only 26% had az75% reduction and only 3 (13%) achieved z95% reduction. We conclude from this study that methotrexate is less effective than is commonly believed (>70% who tolerate the drug achieving >75% improvement (2)) when assessed in a prospective

fashion using PASI, the current standard of assessment of improvement. Thus, despite having several effective systemic agents for psoriasis there is an unmet need for psoriasis therapies that have long-lasting efficacy and few side effects.