Adherence to Treat-to-target Management in Rheumatoid Arthritis and Associated Factors: Data from the International RA BIODAM Cohort

Alexandre Sepriano; Sofia Ramiro; Oliver FitzGerald; Mikkel Østergaard; Joanne Homik; Désirée van der Heijde; Ori Elkayam; 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; Robert Landewé; Walter P Maksymowych

doi:10.3899/jrheum.190303

Adherence to Treat-to-target Management in Rheumatoid Arthritis and Associated Factors: Data from the International RA BIODAM Cohort

J Rheumatol. 2020 Jun 1;47(6):809-819. doi: 10.3899/jrheum.190303. Epub 2019 Sep 15.

Authors

Alexandre Sepriano^{1

2

3}, Sofia Ramiro^{1

2

3}, Oliver FitzGerald^{1

2

3}, Mikkel Østergaard^{1

2

3}, Joanne Homik^{1

2

3}, Désirée van der Heijde^{1

2

3}, Ori Elkayam^{1

2

3}, J Carter Thorne^{1

2

3}, Maggie J Larché^{1

2

3}, Gianfranco Ferraccioli^{1

2

3}, Marina Backhaus^{1

2

3}, Gerd R Burmester^{1

2

3}, Gilles Boire^{1

2

3}, Bernard Combe^{1

2

3}, Thierry Schaeverbeke^{1

2

3}, Alain Saraux^{1

2

3}, Maxime Dougados^{1

2

3}, Maurizio Rossini^{1

2

3}, Marcello Govoni^{1

2

3}, Luigi Sinigaglia^{1

2

3}, Alain Cantagrel^{1

2

3}, Cheryl Barnabe^{1

2

3}, Clifton O Bingham 3rd^{1

2

3}, Paul P Tak^{1

2

3}, Dirkjan van Schaardenburg^{1

2

3}, Hilde Berner Hammer^{1

2

3}, Joel Paschke^{1

2

3}, Rana Dadashova^{1

2

3}, Edna Hutchings^{1

2

3}, Robert Landewé^{1

2

3}, Walter P Maksymowych^{4

5

6}

Affiliations

¹ From the Department of Rheumatology, Leiden University Medical Center, Leiden; Zuyderland Medical Center, Heerlen; Academic Medical Center/University of Amsterdam, Amsterdam University Medical Center, Amsterdam; Amsterdam Rheumatology and Immunology Center, locations Reade and Amsterdam, University Medical Center, Amsterdam, the Netherlands; Newman Clinical Research, 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; University of Alberta, Edmonton, Alberta; The Arthritis Program Research Group, Newmarket, Ontario; Divisions of Rheumatology and Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario; Rheumatology Department, Centre Intégré Universitaire en Santé et Services Sociaux (CIUSSS) de l'Estrie-Centre Hospitalier Universitaire de Sherbrooke (CHUS), Université de Sherbrooke, Sherbrooke, Quebec; Departments of Medicine and Community Health Services, Cumming School of Medicine, University of Calgary, Calgary, Alberta; CaRE Arthritis Ltd., Edmonton, Alberta, Canada; 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, Centre Hospitalier Universitaire (CHU) Montpellier, Montpellier; Service de rhumatologie, Centre National de Référence des Maladies Autoimmunes Rares de l'Adulte CERAINO, and UMR1227, Lymphocytes B et Autoimmunité (LBAI), Université de Brest, INSERM, LabEx Immunothérapies Grand Ouest (IGO), 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; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
² W.P. Maksymowych is Chief Medical Officer of the International Project Management Group, CaRE Arthritis, Ltd.
³ A. Sepriano, MD, PhD applicant, Department of Rheumatology, Leiden University Medical Center; S. Ramiro, MD, PhD, Department of Rheumatology, Leiden University Medical Center, and Zuyderland Medical Center; O. FitzGerald, MD, Newman Clinical Research, 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; O. Elkayam, MD, Department of Rheumatology, Tel Aviv Sourasky 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, Professor, 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, Professor, Service de Rhumatologie, CHU Bordeaux Pellegrin; A. Saraux, MD, Professor, Service de rhumatologie, Centre National de Référence des Maladies Autoimmunes Rares de l'Adulte CERAINO, and UMR1227, LBAI, Université de Brest, INSERM, LabEx IGO; 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, Ferrara (loc. Cona); L. Sinigaglia, MD, Department of Rheumatology, Istituto Ortopedico Gaetano Pini; A. Cantagrel, MD, Professor, 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, Professor, 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, CaRE Arthritis Ltd.; E. Hutchings, RN, CaRE Arthritis Ltd.; R. Landewé, MD, Academic Medical Center/University of Amsterdam, and Zuyderland Medical Center; W.P. Maksymowych, FRCP(C), Professor of Medicine, University of Alberta, and Chief Medical Officer, CaRE Arthritis Ltd.
⁴ From the Department of Rheumatology, Leiden University Medical Center, Leiden; Zuyderland Medical Center, Heerlen; Academic Medical Center/University of Amsterdam, Amsterdam University Medical Center, Amsterdam; Amsterdam Rheumatology and Immunology Center, locations Reade and Amsterdam, University Medical Center, Amsterdam, the Netherlands; Newman Clinical Research, 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; University of Alberta, Edmonton, Alberta; The Arthritis Program Research Group, Newmarket, Ontario; Divisions of Rheumatology and Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario; Rheumatology Department, Centre Intégré Universitaire en Santé et Services Sociaux (CIUSSS) de l'Estrie-Centre Hospitalier Universitaire de Sherbrooke (CHUS), Université de Sherbrooke, Sherbrooke, Quebec; Departments of Medicine and Community Health Services, Cumming School of Medicine, University of Calgary, Calgary, Alberta; CaRE Arthritis Ltd., Edmonton, Alberta, Canada; 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, Centre Hospitalier Universitaire (CHU) Montpellier, Montpellier; Service de rhumatologie, Centre National de Référence des Maladies Autoimmunes Rares de l'Adulte CERAINO, and UMR1227, Lymphocytes B et Autoimmunité (LBAI), Université de Brest, INSERM, LabEx Immunothérapies Grand Ouest (IGO), 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; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. walter.maksymowych@carearthritis.com.
⁵ W.P. Maksymowych is Chief Medical Officer of the International Project Management Group, CaRE Arthritis, Ltd. walter.maksymowych@carearthritis.com.
⁶ A. Sepriano, MD, PhD applicant, Department of Rheumatology, Leiden University Medical Center; S. Ramiro, MD, PhD, Department of Rheumatology, Leiden University Medical Center, and Zuyderland Medical Center; O. FitzGerald, MD, Newman Clinical Research, 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; O. Elkayam, MD, Department of Rheumatology, Tel Aviv Sourasky 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, Professor, 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, Professor, Service de Rhumatologie, CHU Bordeaux Pellegrin; A. Saraux, MD, Professor, Service de rhumatologie, Centre National de Référence des Maladies Autoimmunes Rares de l'Adulte CERAINO, and UMR1227, LBAI, Université de Brest, INSERM, LabEx IGO; 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, Ferrara (loc. Cona); L. Sinigaglia, MD, Department of Rheumatology, Istituto Ortopedico Gaetano Pini; A. Cantagrel, MD, Professor, 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, Professor, 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, CaRE Arthritis Ltd.; E. Hutchings, RN, CaRE Arthritis Ltd.; R. Landewé, MD, Academic Medical Center/University of Amsterdam, and Zuyderland Medical Center; W.P. Maksymowych, FRCP(C), Professor of Medicine, University of Alberta, and Chief Medical Officer, CaRE Arthritis Ltd. walter.maksymowych@carearthritis.com.

PMID: 31523049
DOI: 10.3899/jrheum.190303

Abstract

Objective: Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.

Methods: Patients with RA from 10 countries who were 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 per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).

Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. Failure of adherence to T2T-LDA was noted in 1765 visits (40.5%). In the baseline multivariable model, a high number of comorbidities (OR 1.10, 95% CI 1.02-1.19), smoking (OR 1.32, 95% CI 1.08-1.63) and high number of tender joints (OR 1.03, 95% CI 1.02-1.04) were independently associated with failure to implement T2T, while anticitrullinated protein antibody/rheumatoid factor positivity (OR 0.63, 95% CI 0.50-0.80) was a significant facilitator of T2T. Results were similar in the longitudinal model.

Conclusion: Lack of adherence to T2T in the RA BIODAM cohort was evident in a substantial proportion despite being a protocol requirement, and this could be predicted by clinical features. [Rheumatoid Arthritis (RA) BIODAM cohort; ClinicalTrials.gov: NCT01476956].

Keywords: BEST TREATMENT PRACTICES; RHEUMATOID ARTHRITIS; TREAT-TO-TARGET.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antirheumatic Agents* / therapeutic use
Arthritis, Rheumatoid* / drug therapy
Humans
Remission Induction
Rheumatoid Factor
Severity of Illness Index
Treatment Outcome
Tumor Necrosis Factor Inhibitors

Substances

Antirheumatic Agents
Tumor Necrosis Factor Inhibitors
Rheumatoid Factor

Associated data

ClinicalTrials.gov/NCT01476956