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MRP8/14 serum levels as a strong predictor of response to biological treatments in patients with rheumatoid arthritis
  1. Ivy Y Choi1,
  2. Danielle M Gerlag1,
  3. Marieke J Herenius1,
  4. Rogier M Thurlings1,
  5. Carla A Wijbrandts1,
  6. Dirk Foell2,
  7. Thomas Vogl3,
  8. Johannes Roth3,
  9. Paul P Tak1,4,5,
  10. Dirk Holzinger2,3
  1. 1Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Paediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany
  3. 3Institute of Immunology, University Hospital Muenster, Muenster, Germany
  4. 4University of Cambridge, Cambridge, UK
  5. 5GlaxoSmithKline, Stevenage, UK
  1. Correspondence to Professor Paul P Tak, Department of Clinical Immunology and Rheumatology, Room F4-105, Academic Medical Center, University of Amsterdam, P.O. box 22700, Amsterdam 1100 DE, The Netherlands; p.p.tak{at}


Background One-third of rheumatoid arthritis (RA) patients treated with biological therapy show lack of response. The use of predictive biomarkers to identify responders to treatment may provide guidance in optimising treatment strategies and reduce unnecessary side effects and costs.

Objective To test the ability of myeloid-related proteins (MRP)8/14 protein complexes, an endogenous TLR-4 receptor agonist, to predict and monitor response to biologics in RA patients.

Methods 170 RA patients treated with adalimumab (n=86), infliximab (n=60) or rituximab (n=24) were categorised into clinical responders (n=123) and non-responders (n=47). MRP8/14 serum complexes were measured at baseline, and 4 and 16 weeks after initiation of treatment and related to response outcome.

Results Before initiation of treatment, responders showed significantly higher MRP8/14 protein complex levels compared with non-responders in each prospective cohort (p=0.010, p=0.001 and p<0.001, respectively). Logistic regression analysis showed that having high MRP8/14 baseline levels increased the odds of being a responder by 3.3 up to 55. In responders to adalimumab or infliximab treatment, MRP8/14 levels decreased after 4 weeks of treatment by 46% and 60% and after 16 weeks by 61% and 68%, respectively. In contrast, MRP8/14 levels were stable in non-responders. In patients treated with rituximab, MRP8/14 levels decreased by 59% after 16 weeks in responders and increased by 89% after 16 weeks in non-responders.

Conclusion Serum concentrations of MRP8/14 protein complex are a promising biomarker to predict response to biological therapy in active RA patients at baseline and could be used to monitor response to treatment across different mechanisms of action.

  • Anti-TNF
  • Rheumatoid Arthritis
  • Disease Activity

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