THU0065 VALIDATION OF THE ADJUSTED MULTI-BIOMARKER DISEASE ACTIVITY SCORE FOR PREDICTING RISK OF RADIOGRAPHIC PROGRESSION FOR PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Jeffrey R. Curtis, Michael E. Weinblatt, Nancy Shadick, Cecilie Heegaard Brahe, Mikkel Ǿstergaard, Merete L. Hetland, Saedis Saevarsdottir, Megan Horton, Brent Mabey, Darl Flake, Eric H. Sasso, Thomas Huizinga
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The multi-biomarker disease activity (MBDA) test has been adjusted to account for the effects of age, sex, and leptin (a surrogate for adiposity) in patients with rheumatoid arthritis (RA).<sup>1</sup> Using data from two cohorts (OPERA study and BRASS registry), this adjusted MBDA score was shown to be the best individual disease activity measure for predicting radiographic progression, and to provide significant additional information to DAS28-CRP in predicting radiographic progression. <h3>Objectives:</h3> To validate the association between the adjusted MBDA score and radiographic progression in two additional cohorts, and to evaluate the MBDA score for predicting risk of radiographic progression in four cohorts combined. <h3>Methods:</h3> Four cohorts with requisite data were identified: BRASS registry (N=424), OPERA study (N=164), SWEFOT study (N=235), and Leiden registry (N=163). For the SWEFOT and Leiden cohorts, association of disease activity measures and other factors with radiographic progression (change per year in total Sharp score [TSS]), was evaluated using linear regression. These variables included the adjusted MBDA score, seropositivity (RF and/or ACPA positive), DAS28-CRP, SDAI, CDAI, CRP, baseline total TSS, age, and sex, as available for each cohort. Estimates of risk for radiographic progression (change in TSS &gt;5) as a function of the adjusted MBDA score were calculated using logistic regression in separate and pooled analyses. <h3>Results:</h3> Among the tested measures of disease activity, the leptin-adjusted MBDA score was the most statistically significant univariate predicator of radiographic progression in the SWEFOT (P&lt;0.0001) and Leiden (P&lt;0.00001) cohorts, followed by CRP (p&lt;0.01, in each) (Table). No significant predictive ability was observed for DAS28-CRP, SDAI or CDAI in SWEFOT. DAS28-CRP was a weak predictor in the Leiden cohort (P&lt;0.05), (SDAI, CDAI unavailable). Among non-disease activity variables, baseline TSS and seropositivity were statistically significant predictors, to varying degrees. Neither age nor sex was significant (Table). When DAS28-CRP and the adjusted MBDA score were covariates in the same regression model in the Leiden cohort, DAS28-CRP was not a significant predictor, whereas the adjusted MBDA score remained significant (p=0.000054). When the SWEFOT, Leiden, OPERA and BRASS cohorts were combined (N=986), the adjusted MBDA score remained a significant predictor of radiographic progression, enabling the creation of a risk curve for radiographic progression relative to the continuous adjusted MBDA score. <h3>Conclusion:</h3> In two population-based observational cohorts, the adjusted MBDA score was validated and shown to be a more significant predictor of radiographic progression than conventional measures of RA disease activity. Four cohorts were combined to predict risk of radiographic progression using the continuous adjusted MBDA score for the first time. <h3>Reference:</h3> [1] Curtis JR,&nbsp;Flake IIDD,&nbsp;Weinblatt ME,&nbsp;et al.&nbsp;Adjustment of the multi-biomarker disease activity score to account for age, sex and adiposity in patients with rheumatoid arthritis.&nbsp;Rheumatology (Oxford).&nbsp;2018:key367-key367. <h3>Disclosure of Interests:</h3> Jeffrey R. Curtis Grant/research support from: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Consultant for: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Michael E. Weinblatt Shareholder of: Stock option: CanFite, Lycera, Scipher, Inmedix, Grant/research support from: Crescendo Bioscience, Bristol Myers Squibb, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, CanFite, Corrona, Crescendo, GlaxoSmithKline, Gilead, Horizon, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Scipher, Set Point, Nancy Shadick Grant/research support from: Bristol-Myers Squibb, Sanofi/Regeneron, Crescendo Biosciences, Mallinckrodt, Amgen, Consultant for: Consulting work for Bristol-Myers Squibb for under $10,000., Cecilie Heegaard Brahe Grant/research support from: Unrestricted grant: Novartis, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Saedis Saevarsdottir Employee of: Part-time employee at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project., Megan Horton Employee of: Myriad Genetics, Inc., Brent Mabey Employee of: Myriad Genetics, Inc., Darl Flake Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Eric H. Sasso Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience, Inc., Thomas Huizinga Consultant for: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience Inc., Nycomed, Boeringher, Takeda, Zydus, Epirus, Eli Lilly