1769 Syversen, et al: Biomarker validation for joint damage Personal non-commercial use only. The Journal of Rheumatology Copyright © 2009. All rights reserved. Testing of the OMERACT 8 Draft Validation Criteria for a Soluble Biomarker Reflecting Structural Damage in Rheumatoid Arthritis: A Systematic Literature Search on 5 Candidate Biomarkers SILJE W. SYVERSEN, ROBERT LANDEWE, DÉSIRÉE van der HEIJDE, JOAN M. BATHON, MAARTEN BOERS, VIVIAN P. BYKERK, OLIVER FITZGERALD, DAFNAD. GLADMAN, PATRICK GARNERO, PIET GEUSENS, HANI EL-GABALAWY, ROBERT D. INMAN, VIRGINIAKRAUS, TORE K. KVIEN, PHILIP J. MEASE, MIKKELØSTERGAARD, CHRISTOPHER J. RITCHLIN, PAUL-PETER TAK, WILLIAM J. TAYLOR, and WALTER P. MAKSYMOWYCH ABSTRACT. Objective. To test the OMERACT 8 draft validation criteria for soluble biomarkers by assessing the strength of literature evidence in support of 5 candidate biomarkers. Methods. A systematic literature search was conducted on the 5 soluble biomarkers RANKL, osteo- protegerin (OPG), matrix metalloprotease (MMP-3), urine C-telopeptide of types I and II collagen (U-CTX-I and U CTX-II), focusing on the 14 OMERACT 8 criteria. Two electronic voting exercis- es were conducted to address: (1) strength of evidence for each biomarker as reflecting structural damage according to each individual criterion and the importance of each individual criterion; (2) overall strength of evidence in support of each of the 5 candidate biomarkers as reflecting structur- al damage endpoints in rheumatoid arthritis (RA) and identification of omissions to the criteria set. Results. The search identified 111 articles. The strength of evidence in support of these biomarkers reflecting structural damage was low for all biomarkers and was rated highest for U-CTX-II [score of 6.5 (numerical rating scale 0–10)]. The lowest scores for retention of specific criteria in the draft set went to criteria that refer to the importance of animal studies, correlations with other biomarkers reflecting damage, and an understanding of the metabolism of the biomarker. Conclusion. Evidence in support of any of the 5 tested biomarkers (MMP-3, CTX-I, CTX-II, OPG, RANKL) was inadequate to allow their substitution for radiographic endpoints in RA. Three of the criteria in the draft criteria set might not be required, but few omissions were identified. (J Rheumatol 2009;36:1769–84; doi:10.3899/jrheum.090262) Key Indexing Terms: RHEUMATOIDARTHRITIS BIOMARKERS VALIDATION RADIOGRAPHY STRUCTURAL DAMAGE From the Department of Rheumatology, Diakonhjemmet Hospital/University of Oslo, Oslo, Norway; University Hospital Maastricht, Maastricht, The Netherlands; Leiden University Medical Center, Leiden, The Netherlands; Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands; University of Toronto, Rebecca MacDonald Center for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, University Health Network, Toronto, Canada; St. Vincents University Hospital, Dublin, Ireland; Toronto Western Research Institute, University Health Network, Toronto, Canada; INSERM Research Unit 664 and CCBR-SYNARC, Lyon, France; Internal Medicine/Rheumatology, Maastricht University Medical Centre, Maastricht, The Netherlands; Biomedical Research Centre, University Hasselt, Belgium; University of Manitoba, Winnipeg, Manitoba, Canada; University Health Network, University of Toronto, Toronto, Canada; Duke University Medical Center, Durham, North Carolina, USA; Swedish Medical Center, Seattle, Washington, USA; Departments of Rheumatology, Copenhagen University Hospitals at Herlev and Hvidovre, Copenhagen, Denmark; University of Rochester Medical Center, Rochester, New York, USA; Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Rehabilitation Teaching and Research Unit, University of Otago, Wellington, New Zealand; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. Walter P. Maksymowych is a Scientist of the Alberta Heritage Foundation for Medical Research. S.W. Syversen, MD, Department of Rheumatology, Diakonhjemmet Hospital/University of Oslo; R. Landewe, MD, PhD, Professor of Medicine, University Hospital Maastricht; D. van der Heijde, MD, PhD, Professor of Rheumatology, Leiden University Medical Center; J. Bathon, MD, Professor of Medicine, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine; M. Boers, MSc, MD, PhD, Professor of Clinical Epidemiology, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; V. Bykerk, MD, FRCPC, Assistant Professor of Medicine, University of Toronto, Rebecca MacDonald Center for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, University Health Network; O. FitzGerald, MD, FRCP(UK), Newman Clinical Research Professor, St. Vincents University Hospital; D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, Senior Scientist, Toronto Western Research Institute, University Health Network; P. Garnero, PhD, DSc, INSERM Research Unit 664 and www.jrheum.org Downloaded on October 31, 2021 from www.jrheum.org Downloaded on October 31, 2021 from www.jrheum.org Downloaded on October 31, 2021 from