Pilot trial: Pioglitazone versus placebo in patients with plaque psoriasis (the P6)

Background Disordered differentiation and hyperproliferation of keratinocytes with inflammation are the hallmarks of psoriasis. Ligand activation of peroxisome proliferator receptor-gamma (a class of nuclear receptors) by thiazolidinediones can normalize the histologic features of psoriasis. Method In a 10-week, double-blind, randomized, placebo-controlled, parallel-group study, 70 patients with moderate to severe psoriasis received one of the following treatments: pioglitazone 15 mg, pioglitazone 30 mg or placebo. Efficacy was evaluated by observing the change in the psoriasis area and severity index (PASI) after 10 weeks of treatment. Results There was a dose-dependent improvement in psoriasis. Median PASI scores at the end of 10 weeks were significantly reduced in the pioglitazone treatment groups as compared to the placebo-treated group. The psoriasis lesions cleared in more than 40% of patients treated with pioglitazone as compared to 12.5% of those with placebo. The percentage reduction in mean PASI scores was 21.6%,41.1% and 47.5% in the placebo, pioglitazone 15 mg, and 30 mg groups, respectively. No serious adverse events were detected. Conclusion This is the first report from a controlled trial demonstrating that pioglitazone could be considered as an efficacious and safe agent for the treatment of plaque psoriasis. The optimum dose and duration of pioglitazone therapy remain to be determined.