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

Jeffrey Curtis¹, Michael Weinblatt ², Kenneth Saag ¹, Vivian Bykerk ³, Christina Charles-Schoeman ⁴, Stefano Fiore ⁵, Gregory St John ⁶, Toshio Kimura ⁷, Shen Zheng ⁵, Clifton Bingham ⁸, Grace Wright ⁹, Martin Bergman ¹⁰, Kamala Nola ¹¹, Daniel Furst ⁴ and Nancy Shadick ², ¹University of Alabama at Birmingham, Birmingham, AL, ²Brigham and Women's Hospital, Boston, MA, ³Hospital for Special Surgery, New York City, NY, ⁴University of California, Los Angeles, CA, ⁵Sanofi Genzyme, Bridgewater, NJ, ⁶Regeneron Pharmaceuticals, Inc., Tarrytown, NY, ⁷Regeneron Pharmaceuticals, Inc, Tarrytown, NY, ⁸Johns Hopkins University, Baltimore, MD, ⁹Private Practice, New York City, NY, ¹⁰Drexel University College of Medicine, Stockholm, Sweden, ¹¹Lipscomb University College of Pharmacy & Health Sciences, Nashville, TN

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: outcomes and patient outcomes, phenotypes, registry, Rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 12, 2019

Title: 5T114: RA – Diagnosis, Manifestations, & Outcomes IV: Outcomes (2846–2851)

Session Type: ACR Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Patients with rheumatoid arthritis (RA) may share characteristics that relate to their future outcomes. We investigated 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 using patient data collected at 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 of clinical measures were observed at 12- and 24-months of follow-up including 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 were 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, moderate RA duration”) 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 the highest persistence of therapies at baseline without change.

Conclusion: Five patient clusters identified by data-driven PC analysis of the BRASS registry exhibited distinct patterns of clinical outcomes and management over 4 years. The clinical outcomes data suggest the clusters represent clinically meaningful profiles 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.

Disclosure: J. Curtis, AbbVie, 2, 5, Abbvie, 2, 5, AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB, 2, 5, Amgen, 2, 5, Amgen Inc., 2, 5, BMS, 2, 5, Bristol-Myers Squibb, 2, 5, Corrona, 2, 5, Crescendo, 2, 5, Eli Lilly, 2, 5, Eli Lilly and Company, 2, 5, Genentech, 2, 5, Janseen, 5, Janssen, 2, 5, Janssen Research & Development, LLC, 2, Lilly, 2, 5, Myriad, 2, 5, Patient Centered Outcomes Research Insitute (PCORI), 2, Pfizer, 2, 5, Radius Health, Inc., 9, Regeneron, 2, 5, Roche, 2, 3, 5, Roche/Genentech, 5, UCB, 2, 5; M. Weinblatt, Abbvie, 5, AbbVie, 5, Amgen, 5, BMS, 2, 5, Bristol Myers Squibb, 2, 5, Bristol-Myers Squibb, 2, 5, Canfite, 1, 4, Corrona, 5, Crescendo Bioscience, 2, 5, Eli Lilly and Company, 5, Gilead, 5, Glaxo-Smith Kline, 5, GlaxoSmithKline, 5, GSK, 5, Horizon, 5, Lilly, 5, Lily, 5, Lycera, 1, 4, 5, Merck, 5, Novartis, 5, Pfizer, 5, Roche, 5, Samsung, 5, Samsung Bioepis Co., Ltd., 5, Sanofi Regeneron, 2, Sanofi/Regeneron, 2, Sanofi-Regeneron, 2, Scipher, 1, 4, 5, Set Point, 5, SetPoint, 5, Squibb, 5, Vorso, 1; K. Saag, Abbvie, 5, AbbVie, 5, Amgen, 2, 5, Ampel, 2, Bayer, 5, Gilead, 5, Horizon, 2, 5, Ironwood/AstraZeneca, 2, 5, Kowa, 5, kowa, 5, Mereo, 2, Radius, 5, Radius Health, 2, 5, Roche/Genentech, 5, SOBI, 2, 5, Sobi, 2, 5, Takeda, 2, 5, Teijin, 5, Tejin, 5; V. Bykerk, AbbVie, 5, Amgen, 1, 2, 3, 5, 8, Brainstorm Therapeutics, 1, 2, 3, 5, 8, Bristol-Myers Squibb, 5, Genentech, 5, Gilead, 5, NIH, 2, Pfizer, 1, 2, 3, 5, 8, Regeneron, 5, Regeneron Pharmaceuticals, Inc, 5, Sanofi, 5, Sanofi/Genzyme-Regeneron, 5, Sanofi-Genzyme/Regeneron, 1, 2, 3, 5, 8, Scipher, 1, 2, 3, 5, 8, The Cedar Hill Foundation, 9, UCB, 1, 2, 3, 5, 8, UCB Pharma, 5; C. Charles-Schoeman, Abbvie, 2, AbbVie, 2, Amgen, 5, BMS, 2, Bristol Myers Squibb, 2, Gilead, 5, Octapharma, 2, 5, Pfizer, 2, 5, Regeneron, 5, Regeneron/Sanofi, 5, Sanofi, 5; S. Fiore, Sanofi, 1, 3; G. St John, Regeneron, 1, 3, 4, Regeneron Pharmaceuticals, Inc, 1, 3; T. Kimura, Regeneron, 1, 3, Regeneron Pharmaceuticals, Inc, 1, 3; S. Zheng, Sanofi, 3, 5; C. Bingham, Abbvie, 5, AbbVie, 5, BMS, 2, 5, Bristol Meyer Squibb, 2, 5, Bristol Myers-Squibb, 2, 5, Bristol-Myers Squibb, 2, 5, Eli Lilly, 5, Eli/Lilly, 5, Genentech/Roche, 5, Janssen, 5, Janssen Research & Development, LLC, 2, Pfizer Inc, 5, Regeneron/Sanofi, 5, Sanofi/Regeneron, 5; G. Wright, AbbVie, 5, 8, Abbvie, 5, 8, Amgen, 5, 8, Autoimmune, 5, 8, BMS, 5, 8, Exagen, 5, 8, Lilly, 5, 8, Myriad, 5, 8, Myriad Autoimmune, 5, 8, Novartis, 5, 8, Pfizer, 5, 8, Regeneron, 5, 8, Sanofi Genzyme, 5, 8, UCB, 5, 8; M. Bergman, Abbvie, 5, 8, AbbVie, 5, 8, AbbVie, BMS, Celgene Corporation, Genentech, Janssen, Merck, Novartis, Pfizer, Sanofi, 5, AbbVie, Celgene Corporation, Novartis, Pfizer, Sanofi, 8, Amgen, 5, 8, BMS, 5, 8, Celgene, 5, 8, Genentech, 5, Genentech/Roche, 5, 8, Genentech-Roche, 5, Gilead, 5, GlaxoSmithKline, 8, GSK, 8, Horizon, 5, Janssen, 5, 8, JNJ (parent of Janssen), 1, JNJ stock, 1, Johnson & Johnson, 1, 4, Johnson and Johnson, 1, Merck, 5, 8, Novartis, 5, 8, Pfizer, 5, 8, Sandoz, 5, Sanofi, 5, 8, Sanofi/Regeneron, 5, 8, Sanofi-Regeneron, 5, 8; K. Nola, Coherus, 8, Gilead, 1, 5, Johnson & Johnson, 1, Proctor & Gamble, 1, Regeneron, 5, Sanofi Genzyme, 5; D. Furst, Actelion, 2, 5, Actelion Pharmaceuticals, 2, 5, Amgen, 2, 5, BMS, 2, 5, CME, 5, 8, Corbus, 2, 5, Galapagos, 2, 5, Galapogos Novartis, 5, GlaxoSmithKline, 2, GSK, 2, 5, NIH, 2, Novartis, 2, 5, Pfizer, 2, 5, Roche/Genentech, 2, 5, Sanofi, 2, 5; N. Shadick, BMS, 2, Crescendo Biosciences, 2, Mallinckrodt, 2, Sanofi Regeneron, 2, Sanofi/Regeneron, 2.

To cite this abstract in AMA style:

Curtis J, Weinblatt M, Saag K, Bykerk V, Charles-Schoeman C, Fiore S, St John G, Kimura T, Zheng S, Bingham C, Wright G, Bergman M, Nola K, Furst D, Shadick N. 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 [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/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/. Accessed .

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