Effects of biologics and small-molecule inhibitors on lipid profiles in patients with psoriasis or psoriatic arthritis: An analysis of current evidence.
Available evidence reveals markedly divergent metabolic signatures across biologics and small-molecule inhibitors, highlighting the need for further investigations. To address this knowledge gap, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies in patients with psoriasis or psoriatic arthritis (PsA) to quantify the short- and long-term effects of targeted therapies on lipid profiles. PubMed, Embase, and Cochrane databases were searched for RCTs and observational studies published through July 25, 2025. Eligible randomized RCTs were evaluated using the Cochrane Risk of Bias tool, while nonrandomized studies were assessed using the Methodological Index for Non-Randomized Studies. All lipid effect estimates were derived from within-group pre-to-post changes in patients with psoriasis or PsA. Thirty-six articles involving 21,477 patients with psoriasis and 3098 patients with PsA (total 24,575) across seven targets were analyzed. The long-term use of Janus kinase inhibitors (JAKi) significantly increases total cholesterol (TC; weighted mean difference [WMD] = 7.03; 95% confidence interval [CI] = 1.22, 12.84), triglyceride (TG; WMD = 19.98; 95% CI = 13.82, 26.14), high-density lipoprotein cholesterol (HDL-c; WMD = 6.87; 95% CI = 4.38, 9.36), and low-density lipoprotein cholesterol (LDL-c; WMD = 12.37; 95% CI = 7.24, 17.50) levels. Long-term tumor necrosis factor alpha inhibitors (TNFi) significantly lowers TC (WMD = -8.40; 95% CI = -15.21, -1.60), TG (WMD = -15.22; 95% CI = -21.92, -8.51), and LDL-c (WMD = -10.61; 95% CI = -16.77, -4.45) levels while raising HDL-c (WMD = 4.13; 95% CI = 1.23; 7.03) levels. Long-term interleukin-17 A inhibitors significantly increases TG (WMD = 7.31; 95% CI = 3.17, 11.46) levels, whereas IL-23p19 inhibitors yield the opposite effect (WMD = -32.08; 95% CI = -51.87, -12.30). Our data underscore the need for routine lipid monitoring during TNF-α- and JAK-targeted therapy in patients with psoriasis or PsA. Due to the limitations of our analysis, well-designed prospective trials with extended follow-up periods are warranted to validate and refine these observations.
