AB1243 TRAINING AND VALIDATION OF A MULTIVARIATE PREDICTOR OF RISK OF RADIOGRAPHIC PROGRESSION FOR PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: T. Huizinga, M. E. Weinblatt, N. Shadick, C. Heegaard Brahe, M. Ǿstergaard, M. L. Hetland, S. Saevarsdottir, M. Horton, B. Mabey, D. Flake, R. Ben-Shachar, E. Sasso, A. Gutin, E. Hitraya, J. Lanchbury, J. Curtis
Journal: Annals of the Rheumatic Diseases (2020)

Background: The multi-biomarker disease activity (MBDA) score, adjusted for age, sex and adiposity (MBDA adj ), has been shown to be better than several conventional disease activity measures for predicting risk for radiographic progression (RP) in patients with rheumatoid arthritis (RA). 1 Serologic status and other non-disease activity measures are also predictive of RP risk. Combining them with the MBDA adj should result in a stronger prognostic test for RP than any one measure alone. Objectives: Develop a multivariate model for predicting risk for RP that includes the adjusted MBDA score and other known predictors of RP. Methods: Four RA cohorts were used, two for training (OPERA and BRASS, n=555) and two for validation (SWEFOT and Leiden, n=397). Each pair of cohorts was heterogeneous in disease duration and treatment history. BMI data were not available for one validation cohort, so a BMI surrogate was modeled using forward selection with the two training cohorts and 3 others (CERTAIN, InFoRM, RACER) (N=1411). An RP risk score was then trained using forward selection in a linear mixed-effects regression, considering disease-related and demographic variables as predictors of change in modified total Sharp score over one year (ΔmTSS), with a random effect on cohort. The RP risk score was validated as a predictor of RP with two cutoffs (ΔmTSS &gt;3 and &gt;5) using logistic mixed-effects regression. Odds ratios (OR) and 95% profile likelihood-based confidence intervals (CI) were calculated from the models and significance was assessed by likelihood ratio tests. Risk curves were generated to show probability of RP as a function of the RP risk score. Results: The BMI surrogate included leptin, sex, age and age 2 and correlated well with BMI (ρ = 0.76). In training, the most significant independent predictors of RP were MBDA adj (p = 0.00020), seropositivity (p = 9.3 x 10 -5 ), BMI surrogate score (p = 0.013) and use of targeted therapy (p = 0.0026). The final model was: RP risk score = 0.024 x MBDA adj + 0.093 if seropositive – 0.063 x BMI surrogate score – 0.61 if using a targeted therapy. In validation, the OR (95% CI) of the RP risk score for predicting ΔTSS &gt;3 or &gt;5 were 2.2 (1.6, 3.2) (p = 2.6 × 10 -6 ) and 3.1 (2.0, 5.0) (p = 5.7 × 10 -8 ), respectively (Figure 1). The odds of a patient having RP increases by 50% for each 21-unit or 15-unit increase in MBDA adj , for RP defined as ΔTSS &gt;3 or &gt;5, respectively. Figure 1. Conclusion: A multivariate model containing adjusted MBDA score, seropositivity, a BMI surrogate and use of targeted therapy has been trained and validated as a prognostic test for radiographic progression in RA. References: [1]Curtis, et al. Rheumatology [Oxford]. 2018;58:874 Disclosure of Interests: Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Michael E. Weinblatt Grant/research support from: BMS, Amgen, Lilly, Crescendo and Sonofi-Regeneron, Consultant of: Horizon Therapeutics, Bristol-Myers Squibb, Amgen, Abbvie, Crescendo, Lilly, Pfizer, Roche, Gilead, Nancy Shadick Grant/research support from: Mallinckrodt, BMS, Lilly, Amgen, Crescendo Biosciences, and Sanofi-Regeneron, Consultant of: BMS, Cecilie Heegaard Brahe: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Saedis Saevarsdottir Employee of: Part-time at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project, Megan Horton Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Brent Mabey Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Darl Flake Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Rotem Ben-Shachar Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Eric Sasso Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Alexander Gutin Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Elena Hitraya Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Jerry Lanchbury Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB