Background/Purpose: Elevated circulating cytokines are present years before the onset of rheumatoid arthritis (RA). We conducted a prospective cohort study in an at-risk population of anti-cyclic citrullinated peptide (CCP) antibody positive individuals to determine if serum cytokines predict the development of incident inflammatory arthritis (IA).

Methods: Participants were recruited into the cohort if they were a first degree relative (FDR) of a RA proband or were screened at health fairs. For the present analysis we included n=137 CCP positive participants contributing 508 person-years of follow-up for the appearance of IA (CCP3.1 Inova). During follow-up 29 participants developed IA (defined as having at least 1 joint consistent with RA-like synovitis based on exam), and of those participants 22 were classified as RA by 2010 ACR/EULAR criteria. The concentrations of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α were quantified from stored serum at baseline and each follow-up visit for a total of n=525 visits. Each of these cytokines and chemokines have previously been implicated in RA pathogenesis. We conducted a survival (i.e. time-to-event) analysis using Cox proportional hazard models with log transformed cytokine concentrations as time-varying predictors and obtained hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Baseline characteristics by incident IA status are presented in Table 1. Participants who went on to develop IA were significantly more likely to test positive for the shared epitope compared to participants who did not develop IA (p-value = 0.02). We found a significant positive association of serum TNF-α with incident IA risk, adjusting for cohort (FDR or screened), shared epitope status and age at baseline (adjusted HR: 1.97; 95%CI: 1.08, 3.58). The association of IL-6 and IA risk trended in the same direction but did not reach statistical significance (adjusted HR: 1.27; 95%CI: 0.93, 1.74).

Conclusion: In a cohort of DMARD untreated CCP positive individuals, we demonstrated that circulating levels of TNF-α, a potential indicator of systemic inflammation, was positively associated with incident IA. This finding further supports the dysregulation or failure in the ability to resolve inflammation in preclinical RA patients.

Table 1

Table 2

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/associations-between-circulating-cytokines-and-incident-inflammatory-arthritis-in-an-anti-citrullinated-protein-antibody-positive-population/