Blood chemokine levels are markers of disease activity but not predictors of remission in early rheumatoid arthritis

Jonathan Aldridge, Anna-Carin Lundell, Kerstin Andersson, Linda Mark, Merete Lund Hetland, Mikkel Østergaard, Till Uhlig, Marte Schrumpf Heiberg, Espen A Haavardsholm, Michael Nurmohamed, Jon Lampa, Dan Nordström, Kim Hørslev-Petersen, Bjorn Gudbjornsson, Gerdur Gröndal, Ronald van Vollenhoven, Anna Rudin

Abstract

OBJECTIVES: In early rheumatoid arthritis (eRA) plasma levels of specific chemokines have been shown to correlate with disease activity. However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels in patients with untreated eRA.

METHODS: This study included 347 Swedish patients with untreated eRA from the larger NORD-STAR randomised treatment trial. Here, eRA patients were treated with methotrexate combined with either prednisolone, anti-TNF (certolizumab-pegol), CTLA-4Ig (abatacept) or anti-IL6 receptor (tocilizumab). The primary clinical outcome was remission by clinical disease activity index (CDAI) defined as CDAI ≤ 2.8. Disease activity was assessed by CDAI, DAS28-ESR, DAS28-CRP, swollen joint counts, tender joint counts, ESR and CRP. The plasma concentrations of 14 chemokines were measured at baseline and after 24 weeks of treatment by bead-based immunoassay or ELISA.

RESULTS: Baseline plasma concentrations of CXCL10, CXCL8, CXCL9, CXCL11, CXCL5 and CCL2 correlated with baseline disease activity measures. After 24 weeks of treatment, plasma levels of CXCL10, CXCL8, CXCL9, CXCL11 and CXCL13 decreased in all treatment groups except in patients treated with anti-IL6 receptor. In multivariate factor analysis, plasma chemokine levels at baseline could not differentiate patients who attained remission by week 24 from those who did not in any of the treatment groups.

CONCLUSIONS: In patients with untreated eRA, plasma levels of several chemokines correlate with disease activity at baseline but cannot predict remission after 24 weeks of treatment with methotrexate combined with prednisolone, anti‑TNF, CTLA‑4Ig or anti‑IL6R.

Original languageEnglish
JournalClinical and Experimental Rheumatology
Volume40
Issue number7
Pages (from-to)1393-1402
Number of pages10
ISSN0392-856X
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Antirheumatic Agents/therapeutic use
  • Arthritis, Rheumatoid/diagnosis
  • Biomarkers
  • Humans
  • Methotrexate/therapeutic use
  • Prednisolone/therapeutic use
  • Remission Induction
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors

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