Defining pain trajectories in juvenile arthritis and associated patient characteristics.

Juvenile idiopathic arthritis (JIA) impacts up to 400 per 100,000 children, with a substantial number experiencing chronic pain. Despite its prevalence, research and treatment targeting chronic pain in JIA are limited. This study aims to model pain scores as latent pain trajectories (LPT) and explore the association between LPT and clinical and biological characteristics of patients. Data collected from the Electronic Health Records (EHR) included patient characteristics (e.g. age and biological sex), disease activity measures such as Active Joint Count (AJC) and Physician Global Assessment (PhGA), and patient reported outcomes (e.g. pain and well-being) of 233 patients. Blood plasma samples of 24 patients, acquired during routine care, were analyzed using Nulisa (120-plex Central Nervous System Disease Panel by Alamar) to quantify 127 protein concentrations. Follow-up was conducted in accordance with standard medical care, being every three months. The analysis included 233 patients, revealing a model with three distinct trajectories as most representative. Baseline disease activity, indicated by AJC and PhGA, did not significantly differ between trajectories (p = 0.4, p = 0.6, respectively). However, baseline Patient/Parent Global Assessment (PPGA) scores were significantly lower in the mild trajectory compared to moderate and chronic trajectories (p < 0.001). In an exploratory analysis of blood plasma samples of 24 patients 9 proteins (Aβ-40, GFAP, IGFBP7, IL-12p70, IL-2, IL-5, NPY, TREM2, UBB) differed between trajectories at baseline, while at follow-up 11 proteins differed (IL-4, pTau-217, IGF1R, IL-6, pTau-231, SNAP25, CXCL8, GOT1, CCL2, BACE1, CST3). No overlap between proteins at these different timepoints was as observed between the protein sets at baseline and follow-up. We identified three latent pain trajectories differentiating JIA patients' pain course as mild resolving, moderate slowly resolving, or moderate chronic. Older age was significantly associated with moderate and chronic trajectories. We observed trajectory‑related patterns in circulating protein concentrations in a small subset of patients, which should be confirmed in larger, prospectively designed cohorts.