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Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a cohort of patients treated in daily practice (RA BIODAM)
  1. Sofia Ramiro1,2,
  2. Robert BM Landewé2,3,
  3. Désirée van der Heijde1,
  4. Alexandre Sepriano1,4,
  5. Oliver FitzGerald5,
  6. Mikkel Ostergaard6,
  7. Joanne Homik7,
  8. Ori Elkayam8,
  9. J Carter Thorne9,
  10. Margaret Larche10,
  11. Gianfranco Ferraciolli11,
  12. Marina Backhaus12,
  13. Gilles Boire13,
  14. Bernard Combe14,
  15. Thierry Schaeverbeke15,
  16. Alain Saraux16,
  17. Maxime Dougados17,
  18. Maurizio Rossini18,
  19. Marcello Govoni19,
  20. Luigi Sinigaglia20,
  21. Alain G Cantagrel21,
  22. Cornelia F Allaart1,
  23. Cheryl Barnabe22,
  24. Clifton O Bingham23,
  25. Paul P Tak3,24,25,
  26. Dirkjan van Schaardenburg3,
  27. Hilde Berner Hammer26,
  28. Rana Dadashova27,
  29. Edna Hutchings27,
  30. Joel Paschke28,
  31. Walter P Maksymowych28
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands
  3. 3Department of Rheumatology, Amsterdam Rheumatology Center, Amsterdam, The Netherlands
  4. 4NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
  5. 5St Vincent’s University Hospital and Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland
  6. 6Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  7. 7Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
  8. 8Tel Aviv Sourasky Medical Center and the ”Sackler” Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  9. 9Southlake Regional Health Centre, University of Toronto, Toronto, Ontario, Canada
  10. 10Departments of Medicine and Pediatrics, Divisions of Rheumatology, Clinical Immunolgoy and Allergy, McMaster University, Hamilton, Ontario, Canada
  11. 11Catholic University of the Sacred Heart, Roma, Italy
  12. 12Park-Klinik Weissensee, Academic Hospital of the Charité, Berlin, Germany
  13. 13Department of Medicine/Division of Rheumatology, Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSS de l’Estrie-CHUS), Universite de Sherbrooke, Sherbrooke, Quebec, Canada
  14. 14CHU Montpellier and Montpellier University, Montpellier, France
  15. 15Department of Rheumatology, FHU ACRONIM, University Hospital of Bordeaux, University of Bordeaux, Bordeaux, France
  16. 16Rheumatology, CHU Brest, Brest, France
  17. 17Rheumatology Department, Paris Descartes University, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France
  18. 18Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy
  19. 19Rheumatology Unit, S. Anna Hospital and University of Ferrara, Ferrara, Italy
  20. 20Department of Rheumatology, Gaetano Pini Institute, Milan, Italy
  21. 21Department of Rheumatology, Paul Sabatier University, Toulouse, France
  22. 22Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
  23. 23Johns Hopkins University, Baltimore, Maryland, USA
  24. 24Department of Rheumatology, Ghent University, Ghent, Belgium
  25. 25Department of Medicine, Cambridge University, Cambridge, United Kingdom
  26. 26Diakonhjemmet Hospital, Oslo, Norway
  27. 27CaRE Arthritis LTD, Edmonton, Alberta, Canada
  28. 28CaRE Arthritis LTD, University of Alberta, Edmonton, Alberta, Canada
  1. Correspondence to Dr Sofia Ramiro, Rheumatology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands; sofiaramiro{at}gmail.com

Abstract

Objectives To investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.

Methods RA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definitions. The association between T2T and remission was tested in generalised estimating equations models.

Results In total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52).

Conclusion In daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.

  • rheumatoid arthritis
  • treat-to-target
  • remission

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors All authors made contributions to conception and/or implementation of the study, were involved in reviewing and revising the manuscript and gave final approval to the version to be published.

  • Funding BIODAM was financially supported by an unrestricted grant from AbbVie. AS is supported by a doctoral grant from 'Fundação para a Ciência e Tecnologia' (SFRH/BD/108246/2015).

  • Competing interests SR: Received research grants and/or consultancy fees from AbbVie, Eli Lilly, MSD, Novartis and Sanofi. RL: Received consulting fees from AbbVie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Roche, UCB and is Director of Rheumatology Consultancy BV. DvdH: Received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma and is Director of Imaging Rheumatology BV. AS: Received speaking fees from Novartis. OFG: Received research grants and/or consultancy fees from AbbVie, Eli Lilly, Celgene, Novartis, UCB, Pfizer, Amgen and Janssen. MØ: Received research support, consultancy fees and/or speaker fees form Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. OE: Received grants and personal fees from Pfizer, Abbvie, Roche, Janssen, Novartis and Lilly. JCT: Received research grants and/or consulting fees from AbbVie, Amgen, Celgene, Centocor, Lilly, Medexux/Medac, Merck, Novartis, Pfizer, Sandoz and Sanofi. ML: Received advisory board honoraria from AbbVie, Actelion, Boehringer Ingelheim, BMS, Janssen, Novartis, Pfizer, Sanofi, Roche and an unrestricted educational grant from AbbVie. GF: Received research grants and/or consultancy fees from Novartis, Roche, BMS, Pfizer, AbbVie, Lilly, Janssen, MSD, Boehringer-Ingelheim and UCB. MB: Received research grants from AbbVie Co.KG, Roche, Novartis and Pfizer; received speaking fees from Actelion, AbbVie Co.KG, BMS, Celgene, Gilead, Janssen, Lilly, MSD, Novartis, Sanofi Genzyme, Roche, Pfizer and UCB. GB: Received consulting fees from Eli Lilly, Janssen, Novartis and Pfizer; received speaker fees from BMS, Merck and Pfizer. Industry support for investigator-initiated research initiatives from Abbvie, Amgen, BMS, Celgene, Eli Lilly, Jannsen, Merck, Pfizer, Roche and UCB. BC: Received consulting fees from AbbVie, BMS, Eli-Lilly, Gilead, Janssen, Merck, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. TS: Received consulting fees from Lilly, Novartis, Pfizer and Sanofi; received research financial support from Pfizer and Lilly. AS: Received research grants and/or consultancy fees from AbbVie, BMS, Chugai, Eli Lilly, MSD, Nordic pharma, Novartis, Pfizer, Sanofi and UCB. MD: Received research grants and/or honorarium fees for his participation at advisory boards and/or symposium organised by Pfizer, AbbVie, Lilly, Novartis, BMS, Roche, UCB and Merck. MR: Received advisory board honoraria, consultancy fees and/or speaker fees from Abiogen, Amgen, Abbvie, BMS, Celgene, Eli-Lilly, MSD, Novartis, Pfizer, Sanofi, Sandoz and UCB. MG: Received advisory board honoraria, consultancy fees and/or speaker fees from Abbvie, Alfa-Sigma, BMS, Celgene, MSD, Novartis, Pfizer, Roche and Sanofi. LS: Received speaker fees from Amgen,Eli Lilly, Abbvie, Roche and BMS. AGC: Received consultancy fees from BMS, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, AbbVie, Celgene and Nordic Pharma; received research grants from Pfizer, UCB, AbbVie and Celgene. CB: Received advisory board honoraria from Gilead, Pfizer, Novartis, Eli Lily, Roche and Amgen; speaking fees from UCB, BMS and Abbvie. COB III: Consultant to Abbvie, BMS, Gilead, Lilly, Pfizer, Genentech/Roche and Sanofi/Regeneron. Grant support from BMS and Janssen. PPT: Currently an employee of Kintai Therapeutics, Cambridge MA. Kintai Therapeutics has not been involved in this work. HBH: Received fees for speaking and/or consulting from AbbVie, BMS, Pfizer, UCB, Roche, MSD and Novartis. WPM: Received consulting fees from AbbVie, Boehringer Ingelheim, Celgene, Eli-Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma and is Chief Medical Officer of CARE Arthritis Limited.

  • Patient consent for publication Not required.

  • Ethics approval The study received ethical approval from the local ethics committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available.

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