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FRI0079 Response to mtx plus prednisone in camera ii using a multi-biomarker disease activity test (vectra™ da) and das28-esr
  1. M. S. Jurgens1,
  2. J. W. Bijlsma1,
  3. J. W. Jacobs1,
  4. M. F. Bakker1,
  5. F. P. Lafeber1,
  6. P. M. Welsing1,
  7. G. Cavet2,
  8. D. N. Chernoff2,
  9. E. H. Sasso2,
  10. W. Li2,
  11. D. J. Haney2
  1. 1Rheumatology & Clinical Immunology, UMC UTRECHT, Utrecht, Netherlands
  2. 2Crescendo Bioscience, Inc., South San Francisco, United States

Abstract

Background The CAMERA II study (Computer Assisted Management in Early RA) demonstrated that the addition of prednisone versus placebo to a MTX-based tight-control strategy increased effectiveness of therapy and reduced need for biological treatment.

Objectives The present study evaluated changes in biomarker levels over time with MTX+placebo and MTX+prednisone treatment, using the Multi-Biomarker Disease Activity (MBDA) blood test.

Methods Clinical and biomarker assessments were performed at monthly visits to 1 year for 92 patients who had MBDA test results available at baseline and ≥ 1 subsequent visit. Average number of visits with non-missing disease activity measures was 3.7 per patient. Concentrations of 12 serum biomarkers were combined to produce a score between 1 and 100 using the MBDA algorithm, which generates a validated measure of disease activity. Biomarker levels were also assessed individually but only to 5 months, to avoid subsequent protocol-mandated exposures to non-MTX DMARDs for insufficient responders. Correlation between DAS28-ESR change and MBDA change was assessed using Spearman’s correlation. Changes from baseline and comparisons of change in disease activity scores over time for MTX+placebo versus MTX+prednisone were analyzed by t-tests. Biomarker concentrations were analyzed as fractions relative to baseline using Mann Whitney U tests.

Results Changes from baseline to 1 year in DAS28-ESR and MBDA scores showed a significant correlation in the MTX+placebo arm (r = 0.57, p < 0.001, n = 31) and the MTX+prednisone arm (r = 0.57, p = 0.002, n = 28). Improvements in DAS28-ESR (p < 0.001) and MBDA (p= 0.01) scores were observed as early as 1 month post-BL in the MTX+prednisone arm. Significant improvement in the MTX+placebo arm was first observed at 2 months for DAS28-ESR (p = 0.02) and 4 months for MBDA (p = 0.03). DAS28-ESR and MBDA response profiles over time were similar, with mean changes at month 5 for MTX+placebo and MTX+prednisone being -2.2/-4.2 for DAS28-ESR, and -13/-21 for MBDA score. Individual biomarker response profiles differed: for some biomarkers, MTX+placebo had little/no effect but MTX+prednisone had significant effect (MMP-1, TNF-R1, VCAM-1, YKL4 and leptin); for others, MTX+placebo had a significant effect that was augmented ( CRP, IL-6, and VEGF) or not affected (SAA) by prednisone; and for some (EGF, MMP-3 and resistin) little or no effect occurred in either treatment arm.

Conclusions Responses assessed with the biomarker-based MBDA test and DAS28-ESR were greater and more rapid for therapy with MTX+prednisone than MTX+placebo, even though individual biomarkers differed in their response profiles. The MBDA test may be useful in combination with clinical assessment to evaluate early response to therapy with MTX or MTX+prednisone.

Disclosure of Interest M. Jurgens: None Declared, J. Bijlsma: None Declared, J. Jacobs: None Declared, M. Bakker: None Declared, F. Lafeber: None Declared, P. Welsing: None Declared, G. Cavet Consultant for: Crescendo Bioscience, Inc., D. Chernoff Employee of: Crescendo Bioscience, Inc., E. Sasso Employee of: Crescendo Bioscience, Inc., W. Li Employee of: Crescendo Bioscience, Inc., D. Haney Employee of: Crescendo Bioscience, Inc.

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