Differential Impact of Body Mass Index on Minimal Disease Activity Across Therapies in Psoriatic Arthritis

Abstract

Objectives Overweight and obesity are associated with reduced odds of achieving minimal disease activity (MDA). Whether this effect is mediated by direct inflammation or psychosocial factors remains unclear. This study aimed to assess a) the influence of body mass index (BMI) on MDA and its components, b) study this association across drug classes. Methods Patients with available body mass index (BMI) values were selected from a large longitudinally assessed PsA cohort followed from 1978. These patients are followed every 6 months with comprehensive documentation of demographic data, clinical and patient-reported outcomes, and treatment details. Generalized estimating equations (GEE) were used to assess the association of BMI with MDA and its subcomponents, adjusting for age, sex, anxiety, depression, fibromyalgia, smoking, radiographic damage (modified Steinbrocker score), osteoarthritis, use of TNFi and PDE4i. We also evaluated the association between BMI at drug initiation and longitudinally assessed BMI (to incorporate effects of drugs on BMI) with MDA across 6 drug classes (TNFi, IL-17i, IL-23i, IL-12/23i, JAKi, PDE4i) using univariable and multivariable GEE. The multivariable model was adjusted for age, sex, anxiety, depression, fibromyalgia, smoking, radiographic damage (modified Steinbrocker score), osteoarthritis, and line of treatment. Results Of 1291 patients included, the mean age was 44.7 (SD 13) years, and 44% were males. The mean BMI was 28.8 (SD 6.36) kg/m2. 582 patients received b- and/or tsDMARDs (80 patients - infliximab, 353 - other TNFis, 166 - IL17i, 64 - IL12/23i, 71 - IL23i, 32 - JAKi, and 57 - PDE4i). Higher BMI was significantly associated with lower odds of MDA [OR 0.97; 95% CI 0.94-0.99], and worse outcomes across multiple MDA subcomponents, including enthesitis, tender joint count, PASI, patient pain, global assessments, and HAQ, but not swollen joint count in the multivariable model (Figure 1A). In multivariable models for drug stratified analyses, both BMI at drug initiation [0.95 (0.93-0.98)] and longitudinally assessed BMI [0.95 (0.92-0.97)] were significantly associated with reduced MDA in the TNFi group. BMI did not impact the response across infliximab and other drug groups (Figure 1B and 1C). Conclusion BMI is independently associated with reduced odds of being in MDA, largely driven by subjective and skin domains. The impact appears most pronounced among patients treated with TNFis, but not infliximab or other drug classes. This highlights the need for tailored therapeutic strategies in obese PsA patients and the potential importance of addressing psychosocial factors and weight management in clinical care.