Serum level of reactive oxygen metabolites (ROM) at 12 weeks of treatment with biologic agents for rheumatoid arthritis is a novel predictor for 52-week remission

Clin Rheumatol. 2017 Feb;36(2):309-315. doi: 10.1007/s10067-016-3479-3. Epub 2016 Nov 17.


We have shown that serum levels of reactive oxygen metabolites (ROM) were associated with C-reactive protein (CRP) and disease activity score based on the examination of 28 joints (DAS28) in patients with rheumatoid arthritis (RA); however, their clinical significance as biomarkers has not been elucidated. Forty-eight biologic agent (BA)-naïve RA patients were included in this study. Associations between serum levels of ROM, CRP, matrix metalloproteinase-3 (MMP-3), DAS28-erythrocyte sedimentation rate (ESR), and Health Assessment Questionnaire (HAQ) at 12 weeks of treatment and DAS28 (ESR) remission at 52 weeks (52-week remission) were investigated. The ROM serum level at baseline in the remission group (n = 34) was 527 ± 132 Carratelli units (U.Carr) (normal range <300), decreased to 335 ± 79.1 at 4 weeks, and remained low thereafter. In the non-remission group (n = 14), the ROM serum level at baseline was 592 ± 113 U.Carr, decreased to 450 ± 152 at 4 weeks, but gradually increased thereafter. Among significantly different factors at 12 weeks between the remission and non-remission groups, ROM and DAS28 (ESR) were identified as predictors of 52-week remission (p = 0.045, odds ratio 0.985, 95% confidence interval 0.97-1.000 for ROM). The cutoff value of ROM was determined to be 381.5 U.Carr (sensitivity 0.833, specificity 0.871). These results show that serum ROM levels can predict remission with high accuracy and could be a useful biomarker for achieving remission in the current treat-to-target strategy for RA.

Keywords: Biologic agents; Predictor; Reactive oxygen metabolites (ROM); Remission; Rheumatoid arthritis.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Area Under Curve
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Biological Products / therapeutic use*
  • Biomarkers / metabolism
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Humans
  • Matrix Metalloproteinase 3 / metabolism
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Reactive Oxygen Species / blood*
  • Remission Induction
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Antirheumatic Agents
  • Biological Products
  • Biomarkers
  • Reactive Oxygen Species
  • C-Reactive Protein
  • MMP3 protein, human
  • Matrix Metalloproteinase 3