PSO(riasis) Long, Inflammation: Can GLP-1 RAs Clear the Way?

Abstract

Background: Psoriasis is a common immune-mediated inflammatory skin condition affecting 2-3% of the world's population. It is characterized by erythematous, silver scaly plaques, and its pathogenesis involves genetic predisposition, environmental triggers, skin barrier disruption, and immune dysregulation, notably the IL-23/Th-17 pathway. Management ranges from topical treatments for mild disease to systemic therapies, including biologics, for moderate to severe cases. Psoriasis is associated with metabolic comorbidities such as obesity and insulin resistance, in which proinflammatory cytokines from adipose tissue can exacerbate psoriatic inflammation. Glucagon-like peptide-1 (GLP-1) receptor agonists, developed for type 2 diabetes mellitus, have shown anti-inflammatory properties and potential benefits in treating psoriasis.

Objective: To review and evaluate the available scientific data regarding the benefit or efficacy of GLP-1 receptor agonists in adult patients with plaque psoriasis.

Design: Systematic review.

Methods: A search was conducted on National Library of Medicine PubMed, Embase, Ovid MEDLINE, Cochrane Library, and Scopus using the terms “(GLP-1 agonist OR GLP-1 receptor agonist OR glucagon-like peptide-1 agonist OR GLP-1 RAs) AND (psoriasis). Various exclusion and inclusion criteria were applied; 1 randomized clinical trial and 2 case reports were selected to be analyzed, evaluated, and summarized for the purpose of this review.

Results: Study #1: Semaglutide treatment resulted in a statistically significant decrease in psoriasis severity (52.4%, p = 0.01), with a greater proportion of patients achieving Psoriasis Area Severity Index (PASI) 90 (46% vs. 7%) and 100 (8% vs. 0%) compared to controls. Quality of life also significantly improved in the treatment group, with median DLQI scores decreasing from 14 to 4 (p = 0.0002). In contrast, the control group did not show a statistically significant improvement in quality of life (p = 0.7). Level of evidence: 2c. Study #2: A patient treated with semaglutide experienced significant improvements over 10 months. PASI score improved from 12.0 at baseline to 0.2 (98.3% improvement) and Dermatology Life Quality Index (DLQI) score improved from 20 to 1 (95.0% improvement). Additionally, BMI decreased from 30.4 to 22.6 (25.7% improvement) and waist circumference decreased from 98 cm to 72 cm (26.5% improvement). Level of evidence: 4. Study #3: A patient treated with liraglutide for insulin resistance developed new psoriatic lesions. The lesions, which appeared after two weeks of therapy, persisted despite liraglutide discontinuation and topical treatment. Level of evidence: 4.

Conclusion: There are favorable yet mixed data from these studies that support the utility of glucagon-like peptide-1 receptor agonists in adult patients with psoriasis and obesity, type 2 diabetes mellitus, and/or insulin resistance. However, research is limited, and data is not powerful enough to definitively state the efficacy and generalizability at this time. Further research in this field is needed to confirm these findings, compare a glucagon-like peptide-1 receptor agonist directly with a standard first-line treatment, such as a biologic and with standardization of dosages, and elucidate the precise mechanisms of action and optimal patient selection for GLP-1 receptor agonist therapy in psoriasis management.