ARTHRITIS & RHEUMATOLOGY Vol. 66, No. 4, April 2014, pp 794–802 DOI 10.1002/art.38304 © 2014, American College of Rheumatology Development and Validation of Modified Disease Activity Scores in Rheumatoid Arthritis Superior Correlation With Magnetic Resonance Imaging–Detected Synovitis and Radiographic Progression Joshua F. Baker, 1 Philip G. Conaghan, 2 Josef S. Smolen, 3 Daniel Aletaha, 3 Justine Shults, 4 Paul Emery, 5 Daniel G. Baker, 6 and Mikkel Østergaard 7 Objective. To develop and validate composite dis- ease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imag- ing (MRI) and radiographic progression, in comparison with conventional measures, in patients with rheuma- toid arthritis (RA). Methods. This study was conducted as a second- ary study of 2 RA clinical trials, GO-BEFORE (de- velopment cohort) and GO-FORWARD (validation co- hort). Generalized estimating equations were used to evaluate independent cross-sectional associations of component variables (from all time points) with con- current MRI measures of synovitis and bone edema in the development cohort. Based on regression coeffi- cients, modified versions of the Disease Activity Score in 28 joints (M-DAS28), Simplified Disease Activity Index (M-SDAI), and Clinical Disease Activity Index (M-CDAI) were generated for each subject in the vali- dation cohort. The M-DAS28, M-SDAI, and M-CDAI scores were compared to conventional scores of disease activity with regard to associations with MRI measures of synovitis and radiographic progression, assessed using Pearson’s and Spearman’s correlations, linear/ logistic regression, and receiver operating characteristic analysis. Results. Four variables were independently asso- ciated with MRI-detected synovitis and bone edema in the development cohort: C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), swollen joint count in 28 joints (SJC28), and evaluator’s global assessment of disease activity using a visual analog scale (EvGA score). Modified disease activity scores were generated using the regression coefficients ob- tained in the synovitis models for all subjects in the validation cohort; modified scores were calculated as M-DAS28  0.49  ln(CRP)  0.15  SJC28  0.22  This study is a secondary analysis of the GO-BEFORE (ClinicalTrials.gov identifier NCT00361335) and GO-FORWARD (NCT00264550) randomized clinical trials. Funding for the original trials was provided by Janssen Biotech, Inc. There was no additional funding for the secondary study. 1 Joshua F. Baker, MD, MSCE: University of Pennsylvania and Philadelphia VA Medical Center, Philadelphia; 2 Philip G. Conaghan, MBBS, PhD, FRACP, FRCP: University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, and Leeds Teaching Hos- pitals NHS Trust, Leeds, UK; 3 Josef S. Smolen, MD, Daniel Aletaha, MD: Medical University of Vienna, Vienna, Austria; 4 Justine Shults, PhD: University of Pennsylvania, Philadelphia; 5 Paul Emery, MA, MD, FRCP: University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Rheumatic and Mus- culoskeletal Medicine, Leeds Teaching Hospitals NHS Trust, and Chapel Allerton Hospital, Leeds, UK; 6 Daniel G. Baker, MD: Janssen Research and Development, LLC, Spring House, Pennsylvania; 7 Mik- kel Østergaard, MD, PhD, DMSc: Glostrup Hospital and University of Copenhagen, Copenhagen, Denmark. Dr. Conaghan has received speaking fees and/or honoraria from Bristol-Myers Squibb, Janssen, Merck, Pfizer, Novartis, and Roche. Dr. Smolen has received consulting fees, speaking fees, and/or honoraria from Janssen (less than $10,000). Dr. Emery has received consulting fees, speaking fees, and/or honoraria from Pfizer, Merck, Abbvie, UCB, Roche, Bristol-Myers Squibb, Lilly, and Novartis (less than $10,000 each). Dr. D. G. Baker owns stock or stock options in Janssen Research and Development. Dr. Østergaard has received consulting fees and/or honoraria from Abbott/Abbvie, Bristol-Myers Squibb, Centocor, Janssen, GlaxoSmithKline, Merck, Mundipharma, Novo Nordisk, Pfizer, Schering-Plough, Roche, UCB, and Wyeth (less than $10,000 each) and research support from Abbott/Abbvie, Cento- cor, Merck, and Pfizer. Address correspondence to Joshua F. Baker, MD, MSCE, Division of Rheumatology, Department of Medicine, University of Pennsylvania, 8 Penn Tower Building, 34th Street and Civic Center Boulevard, Hospital of the University of Pennsylvania, Philadelphia, PA 19104. E-mail: bakerjo@uphs.upenn.edu. Submitted for publication June 10, 2013; accepted in revised form November 26, 2013. 794