Impact of Extra-Articular Manifestations of Rheumatoid Arthritis on Health-Related Quality of Life, Disease Activity, Functional Status, Pain Severity, and Psychosocial Outcomes

Abstract

Background: Rheumatoid arthritis (RA) is a systemic immune-mediated disease in which extra-articular manifestations (EAMs) may contribute substantially to overall disease burden beyond synovitis, yet their integrated impact on health-related quality of life (HRQoL) remains incompletely quantified. Objective: To evaluate the association between EAM presence and burden with HRQoL, disease activity, functional disability, pain severity, and psychosocial outcomes in a contemporary RA cohort. Methods: This study was conducted from oct 2024 to march 2025 In this multicenter prospective observational study, 330 adults with RA (ACR/EULAR 2010 criteria) were assessed at baseline and 12 months. Clinician-confirmed EAMs were recorded. Outcomes included SF-36, EQ-5D-5L, DAS28, HAQ-DI, pain visual analogue scale (VAS), and Hospital Anxiety and Depression Scale (HADS). Multivariable linear regression and mixed-effects models adjusted for demographic and clinical confounders. Results: EAMs were present in 23.3% (77/330). Compared with patients without EAMs, those with EAMs had significantly lower SF-36 Physical Component Summary (21.61 ± 5.62 vs 31.30 ± 5.28; adjusted β −9.55, 95% CI −11.00 to −8.10; p < 0.001) and EQ-5D index (0.42 ± 0.08 vs 0.61 ± 0.09; adjusted β −0.19, 95% CI −0.21 to −0.16; p < 0.001), alongside higher DAS28, HAQ-DI, pain VAS, and HADS scores (all p < 0.001). A graded dose–response relationship was observed with increasing EAM count (p for trend < 0.001). Despite clinical improvement at 12 months, HRQoL differences persisted. Conclusion: EAMs are independently and cumulatively associated with clinically meaningful impairment across physical, mental, and social domains in RA, underscoring the need for systematic screening and multidisciplinary management targeting both inflammatory and patient-reported outcomes.