Defining pain trajectories in juvenile arthritis and associated patient characteristics

Product:

CNS Disease Panel 120

Topic:

Neurology

Disease Area:

Juvenile Idiopathic Arthritis (JIA) Pain

Sample Type:

Plasma

Topic/Product:

CNS Disease Panel 120

Disease Area:

Juvenile Idiopathic Arthritis (JIA) Pain

Sample Type:

Plasma

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Authors & Affiliations

Maarten O. Mensink, MD# ¹²³, Sytze de Roock, PhD# ¹³, Julia Drylewicz, PhD⁴, Kevin Jenniskens, PhD⁵, Nico Wulffraat, MD, PhD¹³, Joost F. Swart, MD, PhD$ ¹²³, and Niels Eijkelkamp, PhD$ ²³⁴

¹ Department of Pediatric Rheumatology/Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
² Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
³ Faculty of Medicine, Utrecht University, Utrecht, The Netherlands
⁴ Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
⁵ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.