Impact of Body Mass Index on Clinical and Structural Disease Severity in Rheumatoid Arthritis

Abstract

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive synovial inflammation and joint destruction. Emerging evidence highlights body mass index (BMI) as a modifier of disease severity, yet findings remain paradoxical, with obesity linked to greater systemic inflammation but attenuated structural progression. Understanding this duality has implications for prognosis, treatment optimization, and long-term outcomes in RA. Objective: This study aimed to investigate the impact of BMI on clinical disease activity, systemic inflammation, radiographic progression, treatment response, and remission in patients with RA treated with weight-dosed infliximab over 48 weeks. Methods: A longitudinal observational cohort of 187 RA patients (mean age 53 years, 74% female, mean disease duration 7.2 years) was analyzed. Patients were stratified by BMI categories (normal, overweight, obese). Outcomes included DAS28-ESR, CRP, ESR, Rau radiographic scores, remission rates by multiple criteria, treatment continuation, and mortality. Associations were examined using multivariable regression, hazard ratios, and odds ratios with 95% confidence intervals, adjusting for age, sex, and comorbidities. Results: Overweight and obese patients exhibited higher DAS28 scores (mean 4.32 and 4.43 vs. 4.20 in normal-weight; p < 0.05) and markedly increased odds of elevated CRP (OR = 6.1 and 13.4, respectively; p < 0.001). Radiographic progression was inversely related to BMI (–1.05 Rau units per BMI increase; p < 0.05). Obesity significantly reduced remission likelihood by SDAI (HR = 0.77; 95% CI: 0.62–0.97) and DAS28-CRP (HR = 0.78; 95% CI: 0.64–0.95). Treatment continuation declined with increasing BMI (93.8% in normal vs. 81.8% in obese; HR for discontinuation = 3.41; p = 0.029). Mortality analysis revealed excess respiratory mortality in underweight patients (sHR = 2.93; p = 0.011). Conclusion: Elevated BMI in RA is associated with heightened clinical disease activity, systemic inflammation, reduced treatment response, and lower remission rates, yet paradoxically protects against radiographic damage. These findings underscore the complex, multidimensional role of adiposity in RA and highlight the need for integrated strategies that address both metabolic dysfunction and disease phenotype.