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Cyclosporin is one of the most effective therapies for patients with psoriasis; however, its chronic use is associated with a high risk for renal toxicity. ISA247 is an oral calcineurin inhibitor developed to remove the nephrotoxicity of cyclosporin while preserving its efficacy. Investigators performed a multicenter, double-blinded trial of three doses of ISA247 versus placebo in 439 patients with chronic, stable plaque psoriasis. The analysis was intent-to-treat, and the groups were well matched.
At 12 weeks, only 4% of placebo recipients showed improvement of 75% or better in the posttreatment PASI score, compared with 16%, 25%, and 47% of the ISA247 patients treated, respectively, with 0.2, 0.3, and 0.4 mg/kg twice daily. This efficacy level was maintained at 24 weeks. Few side effects occurred, but one patient in the middle-dose group and seven patients in the high-dose group had decreases in their glomerular filtration rates.
Papp K et al. Efficacy of ISA247 in plaque psoriasis: A randomised, multicentre, double-blind, placebo-controlled phase III study. Lancet 2008 Apr 19; 371:1337.
Naldi L. The search for effective and safe disease control in psoriasis. Lancet 2008 Apr 19; 371:1311.
Comment
ISA247 is efficacious, but not at the usual cyclosporin level. The response is similar to that observed with etanercept after 12 to 24 weeks and with efalizumab after 24 to 48 weeks. However, these comparisons may not be reasonable because study designs often differ, and the agents were not compared directly. The observed toxicity was minimal, but the study was short-term and the patients were relatively healthy and were not taking other commonly prescribed agents that can enhance nephrotoxicity. An editorialist laments FDA licensing requirements that curb our ability to do head-to-head comparisons between approved drugs and this new agent.