Outcomes and Findings of the International Rheumatoid Arthritis (RA) BIODAM Cohort for Validation of Soluble Biomarkers in RA

Walter P Maksymowych; Oliver FitzGerald; Mikkel Østergaard; Joanne Homik; Désirée van der Heijde; Robert G Lambert; Ori Elkayam; Sofia Ramiro; J Carter Thorne; Maggie J Larché; Gianfranco Ferraccioli; Marina Backhaus; Gerd R Burmester; Gilles Boire; Bernard Combe; Thierry Schaeverbeke; Alain Saraux; Maxime Dougados; Maurizio Rossini; Marcello Govoni; Luigi Sinigaglia; Alain Cantagrel; Cheryl Barnabe; Clifton O Bingham 3rd; Paul P Tak; Dirkjan van Schaardenburg; Hilde Berner Hammer; Joel Paschke; Rana Dadashova; Edna Hutchings; Alexandre Sepriano; Robert Landewé

doi:10.3899/jrheum.190302

Outcomes and Findings of the International Rheumatoid Arthritis (RA) BIODAM Cohort for Validation of Soluble Biomarkers in RA

J Rheumatol. 2020 Jun 1;47(6):796-808. doi: 10.3899/jrheum.190302. Epub 2019 Sep 1.

Authors

Walter P Maksymowych^{1

2

3}, Oliver FitzGerald^{4

5

6}, Mikkel Østergaard^{4

5

6}, Joanne Homik^{4

5

6}, Désirée van der Heijde^{4

5

6}, Robert G Lambert^{4

5

6}, Ori Elkayam^{4

5

6}, Sofia Ramiro^{4

5

6}, J Carter Thorne^{4

5

6}, Maggie J Larché^{4

5

6}, Gianfranco Ferraccioli^{4

5

6}, Marina Backhaus^{4

5

6}, Gerd R Burmester^{4

5

6}, Gilles Boire^{4

5

6}, Bernard Combe^{4

5

6}, Thierry Schaeverbeke^{4

5

6}, Alain Saraux^{4

5

6}, Maxime Dougados^{4

5

6}, Maurizio Rossini^{4

5

6}, Marcello Govoni^{4

5

6}, Luigi Sinigaglia^{4

5

6}, Alain Cantagrel^{4

5

6}, Cheryl Barnabe^{4

5

6}, Clifton O Bingham 3rd^{4

5

6}, Paul P Tak^{4

5

6}, Dirkjan van Schaardenburg^{4

5

6}, Hilde Berner Hammer^{4

5

6}, Joel Paschke^{4

5

6}, Rana Dadashova^{4

5

6}, Edna Hutchings^{4

5

6}, Alexandre Sepriano^{4

5

6}, Robert Landewé^{4

5

6}

Affiliations

¹ From the Departments of Medicine and Radiology, University of Alberta; CaRE Arthritis Ltd., Edmonton, Alberta; The Arthritis Program Research Group, Newmarket, Ontario; Divisions of Rheumatology and Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario; Departments of Medicine and Community Health Services, Cumming School of Medicine, University of Calgary, Calgary, Alberta; Rheumatology Department, CIUSSS de l'Estrie-CHUS, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland; Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen, Copenhagen, Denmark; Department of Rheumatology, Leiden University Medical Center, Leiden; Zuyderland Medical Center, Heerlen; Academic Medical Center/University of Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands; Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Divisions of Rheumatology and Internal Medicine, Catholic University of the Sacred Heart, Rome; Department of Rheumatology, Università di Verona, Verona; St. Anna Hospital, Ferrara (loc. Cona); Department of Rheumatology, Istituto Ortopedico Gaetano Pini, Milan, Italy; Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany; Departement de rhumatologie, Université de Montpellier, CHU Montpellier, Montpellier; Service de rhumatologie, CHU Brest, and Lymphocyte B et Autoimmunité (LBAI), U1227, Université de Brest, INSERM, F-29200 Brest; Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris; Centre de Rhumatologie, Hôpital Pierre Paul Riquet - Purpan, CHU de Toulouse, Toulouse; Service de Rhumatologie, CHU Bordeaux Pellegrin, Bordeaux, France; Divisions of Rheumatology and Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Maryland, USA; Amsterdam Rheumatology and Immunology Center, locations Reade and Amsterdam, University Medical Center, Amsterdam, the Netherlands; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. [email protected].
² W.P. Maksymowych is Chief Medical Officer of the International Project Management Group, CaRE Arthritis Ltd. [email protected].
³ W.P. Maksymowych, FRCP(C), Professor of Medicine, University of Alberta, and Chief Medical Officer, CaRE Arthritis Ltd.; O. FitzGerald, MD, Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital; M. Østergaard, DMSc, Professor of Rheumatology, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen; J. Homik, FRCP(C), Professor of Medicine, University of Alberta; D. van der Heijde, MD, Professor of Rheumatology, Department of Rheumatology, Leiden University Medical Center; R.G. Lambert, FRCP(C), Department of Radiology, University of Alberta; O. Elkayam, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center; S. Ramiro, MD, PhD, Department of Rheumatology, Leiden University Medical Center, and Zuyderland Medical Center; J.C. Thorne, FRCP(C), The Arthritis Program Research Group; M.J. Larché, MBChB, PhD, Divisions of Rheumatology and Clinical Immunology and Allergy, McMaster University; G. Ferraccioli, MD, Divisions of Rheumatology and Internal Medicine, Catholic University of the Sacred Heart; M. Backhaus, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital; G.R. Burmester, MD, Professor of Medicine, Department of Rheumatology and Clinical Immunology, Charité University Hospital; G. Boire, FRCP(C), Professor of Medicine, Rheumatology Department, CIUSSS de l'Estrie-CHUS, Université de Sherbrooke; B. Combe, MD, PhD, Professor of Rheumatology, Departement de rhumatologie, Université de Montpellier, CHU Montpellier; T. Schaeverbeke, MD, Service de Rhumatologie, CHU Bordeaux Pellegrin; A. Saraux, MD, Service de rhumatologie, CHU Brest, and LBAI, U1227, Université Brest, INSERM, F-29200 Brest; M. Dougados, MD, Professor of Medicine, Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité; M. Rossini, MD, Department of Rheumatology, Università di Verona; M. Govoni, MD, Associate Professor of Rheumatology, St. Anna Hospital; L. Sinigaglia, MD, Department of Rheumatology, Istituto Ortopedico Gaetano Pini; A. Cantagrel, MD, Centre de Rhumatologie, Hôpital Pierre Paul Riquet - Purpan, CHU de Toulouse; C. Barnabe, MD, Associate Professor, Departments of Medicine and Community Health Services, Cumming School of Medicine, University of Calgary; C.O. Bingham III, MD, Divisions of Rheumatology and Allergy and Clinical Immunology, Johns Hopkins University; P.P. Tak, MD, Professor of Medicine, Academic Medical Center, Amsterdam University Medical Center; D. van Schaardenburg, MD, Professor of Medicine, Amsterdam Rheumatology and Immunology Center, locations Reade and Amsterdam, University Medical Center; H. Berner Hammer, MD, Department of Rheumatology, Diakonhjemmet Hospital; J. Paschke, BSc, CaRE Arthritis Ltd.; R. Dadashova, MD, Project Manager, CaRE Arthritis Ltd.; E. Hutchings, RN, CaRE Arthritis Ltd.; A. Sepriano, MD, Department of Rheumatology, Leiden University Medical Center; R. Landewé, MD, Academic Medical Center, University of Amsterdam, and Zuyderland Medical Center. [email protected].
⁴ From the Departments of Medicine and Radiology, University of Alberta; CaRE Arthritis Ltd., Edmonton, Alberta; The Arthritis Program Research Group, Newmarket, Ontario; Divisions of Rheumatology and Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario; Departments of Medicine and Community Health Services, Cumming School of Medicine, University of Calgary, Calgary, Alberta; Rheumatology Department, CIUSSS de l'Estrie-CHUS, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland; Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen, Copenhagen, Denmark; Department of Rheumatology, Leiden University Medical Center, Leiden; Zuyderland Medical Center, Heerlen; Academic Medical Center/University of Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands; Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Divisions of Rheumatology and Internal Medicine, Catholic University of the Sacred Heart, Rome; Department of Rheumatology, Università di Verona, Verona; St. Anna Hospital, Ferrara (loc. Cona); Department of Rheumatology, Istituto Ortopedico Gaetano Pini, Milan, Italy; Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany; Departement de rhumatologie, Université de Montpellier, CHU Montpellier, Montpellier; Service de rhumatologie, CHU Brest, and Lymphocyte B et Autoimmunité (LBAI), U1227, Université de Brest, INSERM, F-29200 Brest; Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris; Centre de Rhumatologie, Hôpital Pierre Paul Riquet - Purpan, CHU de Toulouse, Toulouse; Service de Rhumatologie, CHU Bordeaux Pellegrin, Bordeaux, France; Divisions of Rheumatology and Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Maryland, USA; Amsterdam Rheumatology and Immunology Center, locations Reade and Amsterdam, University Medical Center, Amsterdam, the Netherlands; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
⁵ W.P. Maksymowych is Chief Medical Officer of the International Project Management Group, CaRE Arthritis Ltd.
⁶ W.P. Maksymowych, FRCP(C), Professor of Medicine, University of Alberta, and Chief Medical Officer, CaRE Arthritis Ltd.; O. FitzGerald, MD, Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital; M. Østergaard, DMSc, Professor of Rheumatology, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen; J. Homik, FRCP(C), Professor of Medicine, University of Alberta; D. van der Heijde, MD, Professor of Rheumatology, Department of Rheumatology, Leiden University Medical Center; R.G. Lambert, FRCP(C), Department of Radiology, University of Alberta; O. Elkayam, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center; S. Ramiro, MD, PhD, Department of Rheumatology, Leiden University Medical Center, and Zuyderland Medical Center; J.C. Thorne, FRCP(C), The Arthritis Program Research Group; M.J. Larché, MBChB, PhD, Divisions of Rheumatology and Clinical Immunology and Allergy, McMaster University; G. Ferraccioli, MD, Divisions of Rheumatology and Internal Medicine, Catholic University of the Sacred Heart; M. Backhaus, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital; G.R. Burmester, MD, Professor of Medicine, Department of Rheumatology and Clinical Immunology, Charité University Hospital; G. Boire, FRCP(C), Professor of Medicine, Rheumatology Department, CIUSSS de l'Estrie-CHUS, Université de Sherbrooke; B. Combe, MD, PhD, Professor of Rheumatology, Departement de rhumatologie, Université de Montpellier, CHU Montpellier; T. Schaeverbeke, MD, Service de Rhumatologie, CHU Bordeaux Pellegrin; A. Saraux, MD, Service de rhumatologie, CHU Brest, and LBAI, U1227, Université Brest, INSERM, F-29200 Brest; M. Dougados, MD, Professor of Medicine, Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité; M. Rossini, MD, Department of Rheumatology, Università di Verona; M. Govoni, MD, Associate Professor of Rheumatology, St. Anna Hospital; L. Sinigaglia, MD, Department of Rheumatology, Istituto Ortopedico Gaetano Pini; A. Cantagrel, MD, Centre de Rhumatologie, Hôpital Pierre Paul Riquet - Purpan, CHU de Toulouse; C. Barnabe, MD, Associate Professor, Departments of Medicine and Community Health Services, Cumming School of Medicine, University of Calgary; C.O. Bingham III, MD, Divisions of Rheumatology and Allergy and Clinical Immunology, Johns Hopkins University; P.P. Tak, MD, Professor of Medicine, Academic Medical Center, Amsterdam University Medical Center; D. van Schaardenburg, MD, Professor of Medicine, Amsterdam Rheumatology and Immunology Center, locations Reade and Amsterdam, University Medical Center; H. Berner Hammer, MD, Department of Rheumatology, Diakonhjemmet Hospital; J. Paschke, BSc, CaRE Arthritis Ltd.; R. Dadashova, MD, Project Manager, CaRE Arthritis Ltd.; E. Hutchings, RN, CaRE Arthritis Ltd.; A. Sepriano, MD, Department of Rheumatology, Leiden University Medical Center; R. Landewé, MD, Academic Medical Center, University of Amsterdam, and Zuyderland Medical Center.

PMID: 31474600
DOI: 10.3899/jrheum.190302

Abstract

Objective: The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings.

Methods: Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score.

Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor-positive or anticitrullinated protein antibody-positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively.

Conclusion: The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956).

Keywords: BIOMARKER; PROGNOSIS; RADIOGRAPHIC PROGRESSION; RISK ASSESSMENT.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Antirheumatic Agents* / therapeutic use
Arthritis, Rheumatoid* / diagnostic imaging
Arthritis, Rheumatoid* / drug therapy
Biomarkers
Disease Progression
Female
Humans
Middle Aged
Prospective Studies
Severity of Illness Index

Substances

Antirheumatic Agents
Biomarkers

Associated data

ClinicalTrials.gov/NCT01476956