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Evaluation of cytokine profiles in rheumatoid arthritis patients with clinically active disease and normal inflammatory indices

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Abstract

Objective

To assess the potential utility of a cytokine measurement in rheumatoid arthritis (RA) patients with active joint disease but normal acute phase reactants (APR).

Methods

RA patients in a longitudinal observational registry with available cytokine array data were included. Patients were categorized based on agreement/disagreement of physical examination and APR measurements: concordant high (CH) [high tender and/or swollen joint counts (TJC + SJC > 3) and APR (ESR ≥ 28 mm/h + CRP ≥ 1.5 mg/L)]; concordant low (CL) [TJC + SJC ≤ 3 and normal APR]. Discordant (D) [TJC + SJC > 3 and normal APR] patients were stratified into low, medium, and high-disease activity (DL, DM, DH). Weighted-average and log-transformed cytokine scores were calculated based on results of a cytokine array. Chi-square tests compared categorical variables by concordance status; t tests, Wilcoxon rank-sum tests, ANOVA models, and ordinary least squares (OLS) regressions were used to compare continuous measures.

Results

RA patients (n = 1467) were predominantly male (91%). Compared to CH patients (n = 174), D (n = 434) were younger, less frequently seropositive, with lower TJC, SJC, and DAS28-3v scores (p < 0.001). Cytokine scores for DL, DM, and DH groups were lower than CH patients (p < 0.001) and did not differ between DL, DM, and DH subgroups and were similar to CL (n = 356) patients. In multivariable analyses including CH and D patients, log-cytokine score was associated with higher DAS28-3v scores (p = 0.029). In multivariable analyses including CL patients, concordance status (p = 0.011) and ACPA (p = 0.013) were predictors of higher log cytokine score.

Conclusion

In this study, cytokine scores did not identify active joint disease in RA patients with normal APR.

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Funding

This work was supported by the following sources that fund the Veterans Affairs Rheumatoid Arthritis Registry (VARA): Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center; Veterans Affairs Health Services Research and Development Program of the Veterans Health Administration (HSR&D), Veterans Health Administration (Veterans Affairs Merit award); HSR&D Career Development Award, Grant Number: CDA 07-221.

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Authors and Affiliations

  1. Medstar Georgetown University Hospital, Washington, DC, USA

    Asha M. Alex & Gail S. Kerr

  2. Washington DC Veteran Affairs Medical Center, Washington, DC, USA

    Asha M. Alex & Gail S. Kerr

  3. University of Nebraska Medical Center & VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA

    Harlan Sayles & Ted R. Mikuls

  4. Howard University, Washington, DC, USA

    Gail S. Kerr

  5. Rheumatology Section, 151K, Veterans Affairs Medical Center, 50 Irving St, NW, Washington, DC, 20422, USA

    Gail S. Kerr

Authors
  1. Asha M. Alex
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  2. Harlan Sayles
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  3. Ted R. Mikuls
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  4. Gail S. Kerr
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Corresponding author

Correspondence to Gail S. Kerr.

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Key message

• RA patients with clinical evidence of inflammatory arthritis but normal APR are more often younger, seronegative, and had lower TJC, SJC counts, and DAS28-3v scores.

• A multiplex cytokine array, measured at a single time point, did not accurately identify active inflammation in patients with discordant RA disease activity measures

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Alex, A.M., Sayles, H., Mikuls, T.R. et al. Evaluation of cytokine profiles in rheumatoid arthritis patients with clinically active disease and normal inflammatory indices. Clin Rheumatol 38, 1075–1081 (2019). https://doi.org/10.1007/s10067-018-4379-5

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  • DOI: https://doi.org/10.1007/s10067-018-4379-5

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