Effectiveness and Safety of Different Doses of Pioglitazone in Psoriasis: A Meta-Analysis of Randomized Controlled Trials
Psoriasis is a chronic inflammatory skin disease affecting 2% to 4% of the global population. It is characterized by erythematous scales and is often associated with systemic comorbidities, significantly impacting patients’ quality of life. Traditional treatments such as methotrexate, acitretin, and cyclosporine are effective but carry risks of liver and kidney toxicity, carcinogenesis, and teratogenesis with long-term use. Thiazolidinediones (TZDs), a class of anti-diabetic drugs, have shown potential in treating psoriasis due to their anti-inflammatory and anti-proliferative effects. Pioglitazone, a TZD, has been studied for its efficacy and safety in psoriasis treatment, but its use remains limited. This meta-analysis aims to evaluate the effectiveness and safety of different doses of pioglitazone in treating psoriasis.
The study systematically searched PubMed, Ovid, Cochrane Library, Google Scholar, and Web of Science databases for randomized controlled trials (RCTs) published before February 2019. The inclusion criteria were RCTs comparing pioglitazone with placebo in psoriasis patients for at least 10 weeks, published in English. The primary outcomes were the proportion of patients achieving a 75% improvement in the Psoriasis Area and Severity Index (PASI-75) and the mean percent change in PASI score from baseline to the end of treatment. The quality of the included studies was assessed using the modified Jadad scale, and the evidence quality was evaluated using the GRADEpro Guideline Development Tool.
Six RCTs were included in the meta-analysis. The results showed that pioglitazone significantly reduced PASI scores compared to placebo at both 30 mg per day (P < 0.001, MD = -3.82, 95% CI = -5.70, -1.93) and 15 mg per day (P = 0.04, MD = -3.53, 95% CI = -6.86, -0.20). The PASI-75 response was also significantly higher in the pioglitazone group at 30 mg per day (P < 0.001, OR = 8.30, 95% CI = 3.99, 17.27) and 15 mg per day (P = 0.03, OR = 2.96, 95% CI = 1.08, 8.06). No statistically significant differences in total adverse events were observed between the pioglitazone and placebo groups. Common adverse reactions such as weight gain and elevated liver enzymes did not differ significantly between the two pioglitazone doses.
The therapeutic effect of the 30 mg dose was greater than that of the 15 mg dose, with no significant increase in adverse reactions. This suggests a dose-dependent improvement in psoriasis with pioglitazone. The drug’s safety profile was favorable, with no serious adverse events reported in the included studies. However, the meta-analysis had limitations, including significant heterogeneity in the pooled analysis of reduced PASI scores and the small sample sizes of some studies. The long-term efficacy and safety of pioglitazone in psoriasis treatment remain to be determined.
Pioglitazone acts through peroxisome proliferator-activated receptor gamma (PPAR-γ), which is expressed in skin keratinocytes. Activation of PPAR-γ inhibits keratinocyte proliferation, reduces inflammatory cell infiltration, and decreases the expression of inflammatory factors such as interleukin-2 and C-reactive protein. These mechanisms explain the beneficial effects of pioglitazone in psoriasis treatment. The drug’s safety in psoriasis patients is consistent with its established safety profile in diabetes treatment, where it does not increase the risk of cardiovascular events and may even reduce the risk of myocardial infarction and stroke.
The study’s findings provide valuable insights into the use of pioglitazone for psoriasis, particularly in patients with comorbid diabetes. The results suggest that pioglitazone is an effective and safe treatment option for psoriasis, with a dose-dependent therapeutic response. Further large-scale, long-term clinical trials are needed to confirm these findings and establish the role of pioglitazone in the management of psoriasis.
In conclusion, pioglitazone significantly improves psoriasis symptoms with a favorable safety profile. The 30 mg dose offers greater efficacy than the 15 mg dose, making it a promising treatment option for psoriasis patients, especially those with diabetes. Future research should focus on addressing the limitations of this meta-analysis and exploring the long-term benefits and risks of pioglitazone in psoriasis treatment.
doi.org/10.1097/CM9.0000000000000642
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