Insulin resistance impairs biologic agent response in moderate-to-severe plaque psoriasis: insights from a prospective cohort study in China.

ABSTRACT

BACKGROUND: Psoriasis and insulin resistance (IR) are closely related, but it remains unclear whether IR affects the treatment of patients with psoriasis. OBJECTIVE: To investigate whether IR impairs the treatment response to biologic agents in patients with moderate-to-severe plaque psoriasis. METHODS: This project was based on a prospective cohort study design. Data were collected from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH), which is a prospective cohort exploring treatment strategies for psoriasis in China. IR was assessed using triglyceride glucose-body mass index (TyG-BMI). Psoriasis severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Multiple logistic regression was used to explore the differences between patients with high and low levels of IR. Subgroup and sensitivity analyses were performed to examine the robustness of the study results. RESULTS: A total of 290 patients were included in the analysis. Based on median TyG-BMI, the patients were divided into two groups high and low IR. The high IR group exhibited a higher prevalence of diabetes, a higher BMI, and higher fasting blood glucose and triglyceride levels than the low IR group. Further analysis of treatment efficacy revealed that patients in the high IR group had lower PASI 75 [≥ 75% improvement in Psoriasis Area and Severity Index (PASI)], PASI 90 (≥ 90% improvement in PASI) and PGA 0/1 ('clear' or 'almost clear') response rates after 12 weeks of treatment. In the low IR group, 81.9% of patients achieved PASI 75, 58.3% achieved PASI 90 and 75.7% achieved PGA 0/1. However, the proportion of responses at each endpoint was significantly lower in the high IR group compared with the low IR group. The reduced PGA 0/1 response rate was more significant in the high IR group, indicated by lower odd ratios. Subsequent subgroup and sensitivity analyses produced consistent results. CONCLUSION: IR is associated with lower effectiveness of biologics in patients with psoriasis.

Psoriasis is a chronic and recurrent inflammatory skin disease mediated by T cells. Psoriasis not only impacts on the skin, but it also affects other body parts such as the joints. Historically, the treatment of psoriasis has been challenging. However, with advancements in research looking at how the immune system works and the development of biological agents (a type of drug), treatments for psoriasis have undergone profound changes. 'Biologics', as they are called, have shown remarkable improvements in psoriasis, including complete skin clearance. However, some people with psoriasis experience a poor or no response to treatment. Previous research has explored which factors may affect treatment response, including obesity and diabetes. In addition, insulin resistance plays a central role in the development of obesity and diabetes. We conducted the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH) study in China to investigate the effect of insulin resistance on the response to biologics in people with psoriasis. In our study, we used the 'TyG-BMI' (which stands for 'triglyceride glucose­body mass index') as a tool to assess insulin resistance and divided patients into 'high insulin resistance' and 'low insulin resistance' groups. Psoriasis severity was assessed using tools called the Psoriasis Area and Severity Index (PASI) and the Physician Global Assessment (PGA). Fewer people in the high insulin resistance group achieved a 75% or more improvement in PASI (PASI 75), a 90% or more improvement in PASI (PASI 90) and a PGA score of 'clear' or 'almost clear' (PGA 0/1) after 12 weeks of treatment. The reduced response to PGA 0/1 was more noticeable in the high insulin resistance group. We also carried out further analyses that supported these findings. Overall, our findings provide evidence that insulin resistance can hinder the effectiveness of biologics in some people with psoriasis.