Risk of misclassification of rheumatoid arthritis activity in patients with depression: a prospective ultrasound study

Clin Rheumatol. 2026 Jul 21. doi: 10.1007/s10067-026-08299-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Depression is common in rheumatoid arthritis (RA) and may inflate patient-reported outcomes, leading to overestimation of disease activity and misclassification of treatment response. We evaluated the impact of depression severity on RA disease activity assessment at advanced therapy initiation and at follow-up, using musculoskeletal ultrasound (US), to distinguish objective synovial inflammation from symptom-driven disease burden.

METHODS: We prospectively evaluated disease activity measures across depression severity categories in RA patients initiating biologic or targeted synthetic DMARD (bDMARD/tsDMARD) therapy. Depression severity was assessed using the Patient Health Questionnaire (PHQ). Clinical examination and US assessment of 36 joints were performed at baseline, three and six months.

RESULTS: Among 164 RA patients, 110 (67.1%) had no or mild depressive symptoms, and 54 (32.9%) had moderate-to-severe depression. At baseline, patients with moderate-to-severe depression reported higher disease activity, including higher tender joint counts (13.5 vs 7; p = 0.003), higher pain VAS (7 vs 4; p < 0.001), and higher DAS28-ESR scores (5.71 vs 4.45; p = 0.005). In contrast, objective inflammatory measures were similar between groups, including swollen joint counts (6 vs 5; p = 0.742) and US synovitis scores (GLOESS: 22 vs 25; p = 0.371). At three and six months, objective disease activity improved similarly across depression groups. Subjective outcomes also improved over time, but residual tenderness and disability remained more prominent in the depression group.

CONCLUSION: Depression contributes to increased symptom burden independently of inflammatory disease activity in RA. Incorporating mental health assessment alongside objective measures such as US assessment is important to avoid overestimating disease severity and misjudging treatment response. Keypoints • Depression inflates patient-reported rheumatoid arthritis disease activity without a corresponding increase in objective inflammation. • Ultrasound-detected synovitis and swollen joint counts were similar across depression severity, despite higher DAS28 and pain scores in depressed patients. • Integrating ultrasound-based clinical assessment in patients with depression may reduce disease activity misclassification and prevent inappropriate treatment escalation. Key Indexing Terms: Rheumatoid Arthritis, Depression, Ultrasonography.

PMID:42479265 | DOI:10.1007/s10067-026-08299-1