Obesity and risk of immune-mediated inflammatory diseases: a real-world propensity score-matched cohort study using electronic health records

Obesity is a growing global health concern and a chronic inflammatory state that may influence immune tolerance and autoimmunity. While previous studies have examined links between obesity and selected immune-mediated inflammatory diseases (IMIDs), the broader impact of obesity across a wide spectrum of IMIDs remains unclear. We conducted a large-scale cohort study using the TriNetX global electronic health record database. Adults aged ≥ 18 years with a body mass index (BMI) ≥ 18.5 kg/m 2 recorded between 2015 and 2019 were included. Participants were classified as obese (BMI ≥ 30) or non-obese (BMI 18.5–29.9), with a confirmatory BMI recorded within 60 days. Individuals with pregnancy-related diagnoses or pre-existing IMIDs were excluded. Fifteen IMIDs were assessed as primary outcomes. Propensity score matching was performed, and Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses, dose–response analyses, and control outcomes were used to evaluate robustness and specificity. A total of 698,624 matched pairs were analyzed. Obesity was significantly associated with increased risks of several IMIDs, particularly psoriatic arthritis (HR 1.74, 95% CI 1.59–1.89), type 1 diabetes mellitus (HR 1.41, 95% CI 1.36–1.47), and rheumatoid arthritis (HR 1.20, 95% CI 1.16–1.25). Inverse associations were observed for Sjögren’s syndrome (HR 0.86, 95% CI 0.81–0.90) and systemic sclerosis (HR 0.75, 95% CI 0.65–0.87). Findings were robust across multiple sensitivity analyses. A dose–response gradient was observed for several IMIDs, with significant linear trends for rheumatoid arthritis and psoriasis (P for trend < 0.05). Obesity is associated with increased risks for several, but not all, IMIDs, with dose–response patterns in select conditions. These findings highlight the immunological impact of excess adiposity and support further research to evaluate obesity as a potentially modifiable risk factor for certain autoimmune diseases.