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Incidence of hip and knee replacement in patients with rheumatoid arthritis following the introduction of biological DMARDs: an interrupted time-series analysis using nationwide Danish healthcare registers
  1. René Lindholm Cordtz1,2,
  2. Samuel Hawley3,
  3. Daniel Prieto-Alhambra3,4,
  4. Pil Højgaard1,2,
  5. Kristian Zobbe1,2,
  6. Søren Overgaard5,6,
  7. Anders Odgaard7,8,
  8. Lars Erik Kristensen2,
  9. Lene Dreyer1,2,8
  1. 1 Center for Rheumatology and Spine Diseases, Rigshospitalet-Gentofte, Copenhagen, Denmark
  2. 2 The Parker Institute, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark
  3. 3 Musculoeskeletal Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
  4. 4 GREMPAL Research Group, Idiap Jordi Gol and CIBERFes, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain
  5. 5 Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Odense, Denmark
  6. 6 Department of Clinical Research, University of Southern Denmark, Odense, Denmark
  7. 7 Department of Orthopaedic Surgery, Copenhagen University Hospital Herlev-Gentofte, Copenhagen, Denmark
  8. 8 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Dr René Lindholm Cordtz, Center for Rheumatology and Spine Diseases, Rigshospitalet-Gentofte, Kildegaardsvej 28, Copenhagen, DK-2900, Denmark; rene.lindholm.cordtz.03{at}


Objectives To study the impact of the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and associated rheumatoid arthritis (RA) management guidelines on the incidence of total hip (THR) and knee replacements (TKR) in Denmark.

Methods Nationwide register-based cohort and interrupted time-series analysis. Patients with incident RA between 1996 and 2011 were identified in the Danish National Patient Register. Patients with RA were matched on age, sex and municipality with up to 10 general population comparators (GPCs). Standardised 5-year incidence rates of THR and TKR per 1000 person-years were calculated for patients with RA and GPCs in 6-month periods. Levels and trends in the pre-bDMARD (1996–2001) were compared with the bDMARD era (2003–2016) using segmented linear regression interrupted by a 1-year lag period (2002).

Results We identified 30 404 patients with incident RA and 297 916 GPCs. In 1996, the incidence rate of THR and TKR was 8.72 and 5.87, respectively, among patients with RA, and 2.89 and 0.42 in GPCs. From 1996 to 2016, the incidence rate of THR decreased among patients with RA, but increased among GPCs. Among patients with RA, the incidence rate of TKR increased from 1996 to 2001, but started to decrease from 2003 and throughout the bDMARD era. The incidence of TKR increased among GPCs from 1996 to 2016.

Conclusion We report that the incidence rate of THR and TKR was 3-fold and 14-fold higher, respectively among patients with RA compared with GPCs in 1996. In patients with RA, introduction of bDMARDs was associated with a decreasing incidence rate of TKR, whereas the incidence of THR had started to decrease before bDMARD introduction.

  • rheumatoid arthritis
  • dmards (biologic)
  • epidemiology
  • orthopedic surgery
  • anti-tnf

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  • Handling editor Josef S Smolen

  • Contributors RLC and LD had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. RLC, DPA, LD, SH: study concept and design. RC and LD: acquisition of data. RC, SH, DPA: statistical analysis. All authors: interpretation of data; critical revision of the manuscript for important intellectual content. RLC: drafting of the manuscript. LD, AO, LEK, DPA and SO: study supervision.

  • Funding The study was funded by The Danish Rheumatism Association, The Bjarne Jensen Foundation, The Oak Foundation and The Danish Council for Independent Research. This work has been supported by the National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford. DPA is funded by a National Institute for Health Research Clinician Scientist award (CS-2013-13-012). This paper presents independent research funded by the NIHR. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests DPA’s research group has received research grants from Servier, UCB and Amgen; consultancy fees from UCB outside the present work. PH has received speaking fees from Celgene and UCB outside the present work. LEK has received fees for speaking and/or consultancy from Pfizer, AbbVie, Amgen, UCB, Celgene, BMS, Biogen, Sanofi, MSD, Novartis, Eli Lilly and Janssen Pharmaceuticals. LD has received speaking fees from MSD and UCB outside the present work.

  • Ethics approval Approval was given by the Danish Data Protection Agency (GEH-2014-043, I-Suite: 03166).

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