Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis

Joint Bone Spine. 2019 Mar;86(2):195-201. doi: 10.1016/j.jbspin.2018.05.006. Epub 2018 Jun 6.


Objectives: Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients.

Methods: Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi.

Results: A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, positive predictive values (PPV) of 72%, negative predictive values (NPV) of 82%, positive likelihood ratio (LR+) of 3.35 and negative likelihood ratio (LR-) of 0.28. Lower levels of prealbumin and S100A12 and higher level of platelet factor 4 than the determined cutoff at baseline in RA patients are good predictors for response to TNFi treatment globally as well as to Infliximab, Etanercept and Adalimumab individually.

Conclusion: A multivariate model combining 3 biomarkers (prealbumin, platelet factor 4 and S100A12) accurately predicted response of RA patients to TNFi and has potential in a daily practice personalized treatment.

Keywords: Adalimumab; Biomarkers; Etanercept; Infliximab; Platelet factor 4; Prealbumin; Prediction; Rheumatoid arthritis; S100A12; TNFα inhibitor.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Biological Products / therapeutic use
  • Biomarkers / blood
  • Cohort Studies
  • Female
  • France
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Platelet Factor 4 / blood*
  • Prealbumin / metabolism*
  • Predictive Value of Tests
  • Prospective Studies
  • S100A12 Protein / metabolism*
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / therapeutic use*


  • Antirheumatic Agents
  • Biological Products
  • Biomarkers
  • Prealbumin
  • S100A12 Protein
  • S100A12 protein, human
  • Tumor Necrosis Factor Inhibitors
  • Platelet Factor 4