The diabetes drug pioglitazone (Actos) significantly improved psoriasis control when added to oral acitretin (Soriatane), data from a small clinical trial demonstrated. This could be an important finding due to the fact that many people with diabetes also have psoriasis.
Sunil Dogra, M.D., of the Postgraduate Institute of Medical Education and Research in Chandigarh, India, reported at the International Congress of Dermatology that, the combination led to a 64.2% reduction in psoriasis severity compared with 51.7% for acitretin alone.
Initial worsening of disease severity occurred less often with the combination, but the difference did not achieve statistical significance.
“From our study results it is apparent that the addition of pioglitazone to acitretin therapy can enhance antipsoriatic efficacy,” the investigators concluded.
“In comparison to other antipsoriatic drugs used in combination with acitretin, pioglitazone may offer a safer alternative, as it has been used in patients with diabetes mellitus for several years, and most placebo-controlled trials have shown the incidence of side effects due to pioglitazone to be approximately equal to that found with placebo.”
The rationale for using a thiazolidinedione drug to treat psoriasis came from evidence that activation of peroxisome-proliferator activated receptor-gamma (PPAR-?) may inhibit proliferation and promote cell differentiation.
Experience with troglitazone showed the drug reduced psoriasis disease activity and normalized histologic features of psoriatic skin, Dr. Dogra and colleagues noted. Moreover, studies of pioglitazone in psoriasis have shown response rates as high as 50%.
Given that acitretin and PPAR-? activators decrease proliferation, induce differentiation, and have anti-inflammatory activity, combining the drugs might lead to therapeutic synergy, the investigators theorized. Moreover, pioglitazone might counter acitretin-induced lipid abnormalities.
Dr. Dogra and colleagues compared the combination with acitretin alone in a randomized clinical trial involving 41 adult patients with plaque psoriasis requiring systemic therapy. Patients received acitretin 25 mg/d plus either pioglitazone 15 mg/d or placebo.
Patients had follow-up visits at two, four, eight, and 12 weeks. The primary efficacy endpoint was the change in Psoriasis Area and Severity Index from baseline to 12 weeks.
The baseline PASI score averaged 19.3 in the acitretin-placebo group and 17.5 in the acitretin-pioglitazone group. The mean PASI score had worsened at two weeks in 36.8% of the acitretin-pioglitazone group and 50% of the acitretin-placebo group.
At 12 weeks, the median PASI score in the pioglitazone group was 6.0, a reduction of 11.5 from baseline. That compared with a median score of 10.0 in the placebo group and a reduction of 9.7 from baseline. The difference translated into a statistically significant advantage in favor of acitretin-pioglitazone (P=0.045).
No unexpected adverse effects occurred in either treatment group, and no patients had any laboratory abnormalities during the study.
The investigators acknowledged the small size of the study, that they used the lowest available dose of pioglitazone, and that women of childbearing potential were excluded from the study.
“PPAR-? agonists are known to possess an array of beneficial effects, including decreased blood pressure, increased HDL, and improved fibrinolysis,” the investigators said.
“Moreover, the occurrence of diabetes, hypertension, and metabolic syndrome in patients with psoriasis is not uncommon. These conditions may coexist more often than predicted from the prevalence of either disorder alone. Pioglitazone may be particularly useful in these subsets of patients.”
The results warrant additional studies of the combination, including evaluations of the safety and efficacy of combining higher doses of pioglitazone with acitretin.
Dogra S, et al, “Efficacy and safety of combination of acitretin and pioglitazone in patients with moderate to severe chronic plaque type psoriasis: a randomized, double-blind, placebo-controlled clinical trial” ICD 2009; Abstract 343.