P04 Insulin resistance is associated with multiple comorbidities of psoriasis and significantly reduces the efficacy of biologics in patients with psoriasis: an analysis from SPEECH in China

Abstract Introduction Psoriasis is known to be associated with multiple comorbidities; however, the specific mechanisms underlying these comorbidities remain unknown, and there is a lack of related biomarkers. Patients with psoriasis have been shown to have a significant association with insulin resistance (IR), a pathophysiological state that can predispose individuals to a range of diseases. Therefore, we conducted a study to investigate the association between IR and psoriatic comorbidities. Methods Based on the Shanghai Psoriasis Effectiveness Evaluation Cohort (SPEECH), we conducted a large cross-sectional study and a prospective cohort study. SPEECH is a significant cohort study conducted in Shanghai. Comorbidities we evaluated mainly included circulatory disorders, metabolic diseases, and psycho-psychological disorders. Evaluation of comorbidities was primarily based on electronic medical records. The evaluation of IR is based on the triglyceride glucose (TyG), and TyG-body mass index (TyG-BMI), which have demonstrated excellent agreement with IR. Results A total of 732 patients were included in the study, comprising 15.0% patients with cardiovascular diseases (CVD), 25.0% with hypertension, 12.2% with diabetes, 42.1% with non-alcoholic fatty liver disease (NAFLD), and 16.1% with obesity. Additionally, 29.9% of patients had anxiety and 14.2% of patients had depression. Subsequent logistic regression analysis revealed that nearly all comorbidities were linked to insulin resistance, with TyG-BMI showing a more significant association with comorbidities due to a larger odds ratio (OR) [OR (95% confidence interval): CVD = 1.615 (1.405–1.925), hypertension = 1.527 (1.045–1.964), diabetes = 3.335 (1.167–5.636), NAFLD = 2.584 (1.708–3.944), obesity = 2.228 (1.698–4.028), anxiety = 1.063 (0.993–1.124), depression = 1.936 (1.003–2.129)]. Trend analysis indicated a dose-dependent relationship between IR and comorbidities. Subgroup analysis results indicated a significant association between IR and comorbidities across different subgroups, suggesting the robustness of the main analysis. Several sensitivity analyses were subsequently conducted. Initially, patients treated with acitretin, methotrexate, and cyclosporine were excluded from the analysis, yielding results consistent with the main analysis. Similarly, when analysing only those with mild-to-moderate psoriasis, a similar conclusion was reached. Then we conducted a prospective study in a cohort of 345 patients with moderate-to-severe psoriasis to investigate the impact of IR on the efficacy of biologics. After 12 weeks of treatment, 85.32% of patients with low levels of IR achieved psoriasis area and severity index (PASI) 75, 60.11% achieved PASI 90, and 77.69% achieved PGA 0/1, while patients with higher levels of IR showed lower response rates. Conclusion IR may serve as a crucial factor linking psoriasis to these comorbidities. Furthermore, IR has been shown to impair the efficacy of biologics in psoriasis. In light of these findings, we recommend that the detection of IR be incorporated as a routine component of clinical diagnosis and treatment for psoriasis.