Treatment of active psoriatic arthritis with the PPARγ ligand pioglitazone:: an open-label pilot study

Objectives. Psoriatic arthritis (PsA) is an inflammatory joint disease, in which early neovascularization of affected skin and synovial tissue represents an important pathogenetic step in the disease process. Activation of the peroxisome proliferator activated receptor gamma (PPARgamma) showed anti-inflammatory effects in several in vitro and in vivo models (e.g. collagen-induced arthritis) by inhibition of angiogenesis and suppression of proinflammatory cytokines. Therefore, we studied the use of pioglitazone, a PPARgamma agonist originally developed for the treatment of diabetes, in patients with PsA. Methods. Ten patients with active PsA, seven males and three females, who showed at least two tender and two swollen joints despite stable treatment with an NSAID, were enrolled in this open-label study. All patients received a daily dose of 60 mg pioglitazone while continuing their current NSAID therapy. The primary endpoint was the PsARC (Psoriatic Arthritis Response Criterion); the secondary endpoints included the ACR20 response and improvement in the Psoriasis Area and Severity Index (PASI) in patients with more than 2% skin involvement. Patients were evaluated for endpoints at baseline and after 12 weeks. Results. After 12 weeks, six of 10 patients met the PsARC. The ACR20 response was achieved in five patients. The mean percentage reduction in PASI was 38%, with a clinically meaningful PASI 50 response in two of six patients. Median tender joint count (interquartile range) decreased from 12.0 (8.0-18.0) to 4.0 (2.0-10.0), and the median swollen joint count from 5.0 (4.0-8.0) to 2.0 (1.0-7.0) (P<0.05 for both). Median Health Assessment Questionnaire score changed from 1.0 (0.375-1.375) to 0.75 (0.375-1.0) (P<0.05). Three patients had to be withdrawn from the study due to inefficacy and side-effects. Major side-effects were oedema of the lower extremities and increase in weight. Conclusions. Treatment with a PPARgamma agonist appears to be a promising therapeutic principle in PsA, but the use of PPARgamma ligands might be limited by side-effects such as increase in weight and fluid retention.