Multi-biomarker disease activity score as a predictor of disease relapse in patients with rheumatoid arthritis stopping TNF inhibitor treatment

PLoS One. 2018 May 23;13(5):e0192425. doi: 10.1371/journal.pone.0192425. eCollection 2018.


Objective: Successfully stopping or reducing treatment for patients with rheumatoid arthritis (RA) in low disease activity (LDA) may improve cost-effectiveness of care. We evaluated the multi-biomarker disease activity (MBDA) score as a predictor of disease relapse after discontinuation of TNF inhibitor (TNFi) treatment.

Methods: 439 RA patients who were randomized to stop TNFi treatment in the POET study were analyzed post-hoc. Three indicators of disease relapse were assessed over 12 months: 1) restarting TNFi treatment, 2) escalation of any DMARD therapy and 3) physician-reported flare. MBDA score was assessed at baseline. Associations between MBDA score and disease relapse were examined using univariate analysis and multivariate logistic regression.

Results: At baseline, 50.1%, 35.3% and 14.6% of patients had low (<30), moderate (30-44) or high (>44) MBDA scores. Within 12 months, 49.9% of patients had restarted TNFi medication, 59.0% had escalation of any DMARD and 57.2% had ≥1 physician-reported flare. MBDA score was associated with each indicator of relapse. At least one indicator of relapse was observed in 59.5%, 68.4% and 81.3% of patients with low, moderate or high MBDA scores, respectively (P = 0.004). Adjusted for baseline DAS28-ESR, disease duration, BMI and erosions, high MBDA scores were associated with increased risk for restarting TNFi treatment (OR = 1.85, 95% CI 1.00-3.40), DMARD escalation (OR = 1.99, 95% CI 1.01-3.94) and physician-reported flare (OR = 2.00, 95% 1.06-3.77).

Conclusion: For RA patients with stable LDA who stopped TNFi, a high baseline MBDA score was independently predictive of disease relapse within 12 months. The MBDA score may be useful for identifying patients at risk of relapse after TNFi discontinuation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Biomarkers / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Recurrence
  • Risk Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Withholding Treatment*


  • Biomarkers
  • Tumor Necrosis Factor-alpha

Grants and funding

ZonMw/VWS had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Crescendo Bioscience funded the shipping of serum samples to its laboratory and the generation of biomarker data, and provided support in the form of salary for one author [EHS] and consulting fee for another [DC], but did not have any additional role in the study design, data collection or decision to publish the manuscript. Authors EHS and DC participated in designing analyses and preparing the manuscript for this study. The specific roles of these authors are articulated in the ‘author contributions’ section.