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.