SAT0599 EXPLORING HETEROGENEITY IN RHEUMATOID ARTHRITIS: OUTCOMES UP TO 4 YEARS OF FOLLOW-UP IN PATIENT CLUSTERS IDENTIFIED BY DATA-DRIVEN ANALYSIS OF THE BRASS REGISTRY
Authors: Jeffrey R. Curtis, Michael E. Weinblatt, Kenneth Saag, Vivian Bykerk, Christina Charles-Schoeman, Stefano Fiore, Gregory St. John, Toshio Kimura, Shen Zheng, Clifton Bingham, Grace Wright, Martin Bergman, Kamala Nola, Daniel E. Furst, Nancy Shadick
Journal: Annals of the Rheumatic Diseases (2019)

Background:  Patients with rheumatoid arthritis (RA) may share characteristics that relate to their future outcomes.  Objectives:  To investigate clinical outcomes over a 4-year follow-up period in objectively identified RA patient clusters derived empirically via a data-driven approach using the BRASS registry.  Methods:  Patient clusters were identified by principal components (PC) and cluster analysis of demographic, socio-economic, health and disease characteristics of patients on entry (baseline) into the BRASS registry. Patients in BRASS are followed in the clinic at least annually and are sent questionnaires at 6-month intervals. Mean score was calculated at 12- and 24-months follow-up as observed for Clinical Disease Activity Index (CDAI), Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), BRASS self-administered Rheumatoid Arthritis Disease Activity Index (RADAI), swollen and tender joint count (SJC and TJC), Multidimensional Health Assessment Questionnaire (MDHAQ), and Functional Status Mental Health Index (FSMHI). Time to first infection and to first RA medication change over 4 years was analysed via Kaplan-Meier curves.  Results:  PC analysis of variables among 1443 patients recorded at entry into BRASS identified 41 PCs that capture the fundamental characteristics involved in RA. These PCs informed the identification of 5 novel patient clusters. Cluster 1 patients (“health low, RA uncontrolled, shorter RA duration”) exhibited the greatest reduction in TJC. Cluster 2 patients (“health high, RA controlled, shorter RA duration”) remained free of infection longer than other clusters. Cluster 3 patients (“health high, RA controlled, longer RA duration”) sustained the lowest mean SJC throughout follow-up. Cluster 4 patients (“health low–moderate, moderate RA”) exhibited the greatest improvement in mental health (FSMHI; Figure). Cluster 5 patients (“health low, RA uncontrolled, longer RA duration”) exhibited the highest CDAI scores (Figure) and maintained baseline line of therapy the longest.  Conclusion:  Five patient clusters identified by data-driven PC analysis of the BRASS registry exhibited distinct patterns of clinical outcome and management over a 4-year follow-up period. The clinical outcomes data suggest the clusters represent clinically meaningful categories of RA and illustrate the potential of data-driven patient profiling as a tool to support personalized medicine in RA. Validation in an independent dataset is ongoing.  Acknowledgement:  Study funding and medical writing support (Matt Lewis, Adelphi) provided by Sanofi and Regeneron Pharmaceuticals, Inc.  Disclosure of Interests:  Jeffrey R. Curtis Grant/research support from: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Consultant for: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, 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, Kenneth Saag Grant/research support from: Amgen, Ironwood/AstraZeneca, Horizon, SOBI, Takeda, Consultant for: Abbvie, Amgen, Ironwood/AstraZeneca, Bayer, Gilead, Horizon, Kowa, Radius, Roche/Genentech, SOBI, Takeda, Teijin, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Christina Charles-Schoeman Grant/research support from: Bristol-Myers Squibb, AbbVie, and Pfizer, Consultant for: Regeneron-Sanofi, Pfizer, and Gilead, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi, Gregory St. John Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Toshio Kimura Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Shen Zheng Consultant for: Sanofi, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Grace Wright Consultant for: Abbvie, Amgen, BMS, Exagen, LILLY, Myriad  Autoimmune, NOVARTIS, Pfizer, Sanofi Genzyme Regeneron, UCB, Speakers bureau: Abbvie, Amgen, BMS, Exagen, LILLY, Myriad Autoimmune, NOVARTIS, Sanofi Genzyme Regeneron, UCB, Martin Bergman Shareholder of: Johnson and Johnson (parent company of Janssen), Consultant for: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Kamala Nola Shareholder of: Gilead, Johnson & Johnson, Proctor & Gamble, Consultant for: Yes – Gilead, Sanofi Genzyme, Regeneron, Speakers bureau: Coherus, Daniel E. Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS Corbus, NIH, Novartis, Pfizer, Roche/Genentech, Consultant for: AbbVie, Actelion, Amgen, BMS, Cytori, Novartis, Pfizer, Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), Nancy Shadick Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron.