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AB0279 A Dynamic of the Multi-Biomarker Disease Activity Score in Methotrexate Incomplete Responders is Predictive for Clinical Response to Non-Biological or Biological Therapy in Early RA
  1. K. Hambardzumyan1,
  2. R.J. Bolce2,
  3. S. Saevarsdottir3,
  4. K. Forslind4,5,
  5. J.A. Karlsson6,
  6. E.H. Sasso2,
  7. D. Chernoff2,
  8. C.C. Hwang2,
  9. R.F. van Vollenhoven1,7
  1. 1Unit for Clinical Therapy Research, Inflammatory Diseases, Karolinska Institute, Stockholm, Sweden
  2. 2Crescendo Bioscience, South San Francisco, United States
  3. 3Rheumatology Unit, Department of Medicine, Karolinska Institute, Stockholm
  4. 4Department of Clinical Sciences, Section of Rheumatology, Lund University
  5. 5Section of Rheumatology, Department of Medicine, Helsingborg's Lasarett, Helsingborg
  6. 6Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Lund
  7. 7The Rheumatology Clinic, Karolinska University Hospital, Stockholm, Sweden


Background In our previous study (1) from the Swedish Farmacotherapy (SWEFOT) trial (2), we showed that a change of multi-biomarker disease activity (ΔMBDA) score (3) in methotrexate incomplete responders (MTX-IR) was predictive for subsequent response to non-biological triple therapy (TT; a combination of MTX with sulfasalazine and hydroxychloroquine) or to anti-tumour necrosis factor (anti-TNF) therapy.

Objectives To evaluate further how ΔMBDA score could be used to predict optimal choice of second-line treatment, by investigating different cut-offs and by comparing this to using the C-reactive protein (CRP) for prediction.

Methods 157 MTX-IR patients from the SWEFOT trial with complete data were grouped into those with and without big ΔMBDA (big decrease >22 and non-big decrease ≤22 respectively from baseline to Month 3) based on highest quartile. The change of CRP (ΔCRP) was studied in parallel using a cut-off based on the highest quartile (>28 & ≤28). Analysis was done by last observation carried forward. The proportion of clinical responders (DAS28 ≤3.2) across ΔMBDA groups between the two therapy arms was assessed by Breslow-Day test.

Results Among patients with ΔMBDA>22, 76% responded to TT and 47% to anti-TNF, while among the others more responded to anti-TNF (55% vs 38%; cross-comparison for all 4 groups p=0.016; figure 1). When based on ΔCRP responses were 50% and 39% versus 45% and 56% (p=0.226).

Conclusions In MTX-IR patients, an improvement in the MBDA scores by >22 predicts better response to subsequent Triple Therapy, and lack thereof predicts a better response to anti-TNF. The same analyses using CRP did not reveal similar results. Thus, monitoring patients during MTX treatment using the MBDA score may guide optimal therapy choice in MTX-IRs on the individual patient level.


  1. Hambardzumyan K, Bolce R, Saevarsdottir S, et al. FRI0005 In Early RA Patients with Non-Response to Methotrexate Monotherapy the Change in Multi-Biomarker Disease Activity Score is Differentially Associated with Subsequent Response to Non-Biological versus Biological Therapy. Annals of the rheumatic diseases. 2014 June 1, 2014;73(Suppl 2):382-3.

  2. van Vollenhoven RF, Geborek P, Forslind K, et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet. 2012 May 5;379(9827):1712-20. PubMed PMID: 22464340.

  3. Centola M, Cavet G, Shen Y, et al. Development of a multi-biomarker disease activity test for rheumatoid arthritis. PloS one. 2013;8(4):e60635. PubMed PMID: 23585841. Pubmed Central PMCID: 3621826.

Disclosure of Interest K. Hambardzumyan: None declared, R. Bolce Shareholder of: Myriad Genetics Inc., Employee of: Crescendo Bioscience, a wholly owned subsidiary of Myriad Genetics, Inc., S. Saevarsdottir: None declared, K. Forslind: None declared, J. Karlsson: None declared, E. Sasso Shareholder of: Myriad Genetics Inc., Employee of: Crescendo Bioscience, a wholly owned subsidiary of Myriad Genetics, Inc., D. Chernoff Consultant for: Crescendo Bioscience, a wholly owned subsidiary of Myriad Genetics, Inc., C. C. Hwang Shareholder of: Myriad Genetics Inc., Employee of: Crescendo Bioscience, a wholly owned subsidiary of Myriad Genetics, Inc., R. van Vollenhoven Grant/research support from: Abb Vie, BMS, GSK, Pfizer, Roch, UCB, Consultant for: Abb Vie, Biotest, BMS, Crescendo Bioscience, GSK, Janssen, Lilly, Merck, Pfizer, Roch, UCB, Vertex

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