Minimal Disease Activity for Rheumatoid Arthritis: A Preliminary Definition

GEORGE A. WELLS, MAARTEN BOERS, BEVERLEY SHEA, PETER M. BROOKS, LEE S. SIMON, C. VIBEKE STRAND, DANIEL ALETAHA, JENNIFER J. ANDERSON, CLAIRE BOMBARDIER, MAXIME DOUGADOS, PAUL EMERY, DAVID T. FELSON, JAAP FRANSEN, DAN E. FURST, JOHANNA M.W. HAZES, KENT R. JOHNSON, JOHN R. KIRWAN, ROBERT B.M. LANDEWÉ, MARISSA N.D. LASSERE, KALEB MICHAUD, MARIA SUAREZ-ALMAZOR, ALAN J. SILMAN, JOSEF S. SMOLEN, DESIREE M.F.M. van der HEIJDE, PIET L.C.M. van RIEL, FRED WOLFE, and PETER S. TUGWELL

ABSTRACT.

Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met:

• The DAS28 definition places patients in MDA when DAS28 ≤ 2.85

• The core set definition places patients in MDA when they meet 5 of 7 criteria: (1) Pain (0–10) ≤ 2; (2) Swollen joint count (0–28) ≤ 1; (3) Tender joint count (0–28) ≤ 1; (4) Health Assessment Questionnaire (HAQ, 0–3) ≤ 0.5; (5) Physician global assessment of disease activity (0–10) ≤ 1.5; (6) Patient global assessment of disease activity (0–10) ≤ 2; (7) ESR ≤ 20. This set of 2 definitions gained approval of 73% of the attendees. These (and other) definitions will now be subject to further validation in other databases.(J Rheumatol 2005;32:2016-24)

Key Indexing Terms:

MINIMAL DISEASE ACTIVITY
RHEUMATOID ARTHRITIS
OUTCOME MEASURES
CLINICAL TRIALS
SURVEY

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From the Department of Epidemiology and Community Medicine, University of Ottawa; Institution of Population Health, Ottawa, Canada; Medical University Vienna, Vienna, Austria; Boston University School of Public Health, Boston, USA; Institution of Work and Health, University of Toronto, Toronto, Canada; University of Queensland, Royal Brisbane Hospital, Brisbane, Australia; Hopital Cochin, Rene Descartes University, Paris, France; University of Leeds, Leeds, UK; School of Medicine, Boston, USA; Department of Rheumatology, University Hospital Nijmegen; David Geffen School of Medicine, UCLA, Los Angeles, USA; Erasmus University Medical Center, Rotterdam, The Netherlands; Mater Hospital, University of Newcastle, Newcastle, Australia; University of Bristol, Bristol Royal Infirmary, Bristol, UK; University Hospital Maastricht, Maastricht, The Netherlands; Department of Rheumatology, St. George Hospital, Sydney, Australia; National Data Bank for Rheumatic Diseases, Wichita, USA; Baylor College of Medicine and Michael E. De Bakey VAMC, Houston, USA; University of Manchester, Manchester, UK; Harvard Medical School, Beth Israel Deaconess Medical Center, Boston; and Stanford University School of Medicine, Stanford, USA;

G.A. Wells, PhD, Department of Epidemiology and Community Medicine, University of Ottawa; M. Boers, MD, PhD, Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam; B. Shea, PhD Candidate, Institute of Population Health, University of Ottawa; D. Aletaha, MD, Medical University Vienna, Division of Rheumatology, Vienna General Hospital; J.J. Anderson, PhD, Boston University School of Public Health; C. Bombardier, MD, University of Toronto, Institute for Work and Health; P.M. Brooks, MD, University of Queensland, Royal Brisbane Hospital; M. Dougados, MD, Hopital Cochin, Rene Descartes University, Department of Rheumatology; P. Emery, MD, Rheumatology, University of Leeds; D.T. Felson, MD, School of Medicine, Boston University; J. Fransen, MD, Department of Rheumatology, University Hospital Nijmegen; D.E. Furst, MD, David Geffen School of Medicine, UCLA; J.M.W. Hazes, MD, Erasmus University Medical Center; K.R. Johnson, MD, Clinical Pharmacology, Mater Hospital, University of Newcastle; J.R. Kirwan, BSc, MD, Academic Rheumatology Unit, University of Bristol, Bristol Royal Infirmary; R.B.M. Landewé, MD, University Hospital Maastricht; M.N.D. Lassere, MB, PhD, Department of Rheumatology, St. George Hospital; K. Michaud, MSc, National Data Bank for Rheumatic Diseases; M. Suarez-Almazor, MD, PhD, Baylor College of Medicine, Michael E. De Bakey VAMC; A.J. Silman, MD, University of Manchester, ARC Epidemiology Unit; L. Simon, MD, Harvard Medical School, Beth Israel Deaconess Medical Center; J.S. Smolen, MD, Medical University Vienna, Division of Rheumatology, Vienna General Hospital; C.V. Strand, MD, Stanford University School of Medicine; D.M.F.M. van der Heijde, MD, PhD, University Hospital Maastrich; P.L.C.M. van Riel, MD, Department of Rheumatology, University Hospital Nijmegen; F. Wolfe, MD, National Data Bank for Rheumatic Diseases; P.S. Tugwell, MD, MSc, Institute of Population Health, University of Ottawa.

Address reprint requests to Dr. G. Wells, Department of Epidemiology and Community Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario KIH 8M5, Canada.

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