Jeffrey R Curtis1, Michael E Weinblatt2, Nancy A Shadick2, Cecilie H Brahe3,4, Mikkel Østergaard3,4, Merete Lund Hetland3,4, Saedis Saevarsdottir5,6, Megan Horton7, Brent Mabey7, Darl D Flake7, Rotem Ben-Shachar7, Eric H Sasso8, T W Huizinga9. 1. University of Alabama at Birmingham, 510 20th Street S, Birmingham, AL, USA. 2. Divison of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Boston, MA, USA. 3. Copenhagen Center for Arthritis Research and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Valdemar Hansens vej 17, Glostrup, Denmark. 4. Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen, Denmark. 5. Division of Rheumatology and Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, SE-171 77, Stockholm, Sweden. 6. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 7. Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT, USA. 8. Crescendo Bioscience, Inc., 180 Kimball Way, South San Francisco, CA, USA. esasso@myriad.com. 9. Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, Netherlands.
Abstract
BACKGROUND: The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors. METHODS: Four cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression. RESULTS: Univariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from < 2% in the low (1-29) adjusted MBDA category to 16% in the high (45-100) category. A modeled risk curve indicated that risk increased continuously, exceeding 40% for the highest adjusted MBDA scores. CONCLUSION: The adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI.
BACKGROUND: The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RApatients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors. METHODS: Four cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression. RESULTS: Univariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from < 2% in the low (1-29) adjusted MBDA category to 16% in the high (45-100) category. A modeled risk curve indicated that risk increased continuously, exceeding 40% for the highest adjusted MBDA scores. CONCLUSION: The adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI.
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