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Patient-reported outcomes and safety in patients undergoing synovial biopsy: comparison of ultrasound-guided needle biopsy, ultrasound-guided portal and forceps and arthroscopic-guided synovial biopsy techniques in five centres across Europe
  1. Søren Andreas Just1,
  2. Frances Humby2,
  3. Hanne Lindegaard1,
  4. Laurent Meric de Bellefon3,4,
  5. Patrick Durez4,
  6. Elsa Vieira-Sousa5,6,
  7. Rui Teixeira5,6,
  8. Maria Stoenoiu4,
  9. Jens Werlinrud7,
  10. Sofie Rosmark1,
  11. Pia Veldt Larsen8,
  12. Arthur Pratt9,10,
  13. Ernest Choy11,
  14. Nagui Gendi12,
  15. Maya H Buch13,14,
  16. Christopher J Edwards15,
  17. Peter C Taylor16,
  18. Iain B McInnes17,
  19. João Eurico Fonseca5,6,
  20. Costantino Pitzalis2 and
  21. Andrew Filer18
  1. 1 Department of Rheumatology, Odense University Hospital, Odense, Denmark
  2. 2 Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London, London, UK
  3. 3 Department of Rheumatology, Saint-Pierre University Hospital, Brussels, Belgium
  4. 4 Rhumatologie, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique (IREC), Bruxelles, Belgium
  5. 5 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
  6. 6 Rheumatology Department, Hospital de Santa Maria, CHLN, Lisbon Academic Medical Centre, Lisbon, Portugal
  7. 7 Department of Orthopedics, Odense University Hospital, Odense, Denmark
  8. 8 Epidemiology and Biostatistics, Department of Public Health, University of Southern Denmark, Odense, Denmark
  9. 9 Institute of Cellular Medicine, Newcastle University, Newcastle, UK
  10. 10 Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle, UK
  11. 11 CREATE Centre, Section of Rheumatology, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
  12. 12 Basildon University Hospital, Basildon, UK
  13. 13 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
  14. 14 NIHR Leeds Musculoskeletal Biomedical Research Centre, Leeds, UK
  15. 15 Southampton MSK Research Unit, NIHR Clinical Research Facility, University Hospital Southampton, Southampton, UK
  16. 16 Botnar Research Centre, NDORMS, Oxford University, Oxford, UK
  17. 17 Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
  18. 18 Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, UK
  1. Correspondence to Søren Andreas Just; soeren.andreas.just{at}


Background We present a European multicenter study, comparing safety data and patient-reported outcomes (PRO) from patients undergoing synovial biopsy using ultrasound-guided needle biopsy (US-NB), ultrasound-guided portal and forceps (US-P&F) or arthroscopic-guided (AG) procedures.

Objectives To describe safety and PRO data on joint indices of pain, stiffness and swelling before and after biopsy, procedural discomfort, joint status compared with before biopsy and willingness to undergo a second biopsy for each technique and compare the three techniques. To evaluate the impact on PRO and safety data of corticosteroid therapy as part of the biopsy procedure and sequential biopsy procedures.

Methods Data were collected on the day of biopsy and 7–14 days postprocedure. Joint pain, swelling and stiffness indices were recorded as 0–100  mm Visual Analogue Scale; qualitative outcome variables on five-point Likert scales. Groups were compared with linear regression, adjusting for disease activity, corticosteroid therapy and prebiopsy PRO value and accounting for repeated measurements.

Results A total of 524 synovial biopsy procedures were documented (402 US-NB, 65 US-P&F and 57 AGSB). There were eight adverse events (1.5%) with no difference between biopsy methods (p=0.55). All PROs were improved 2  weeks postprocedure, and there were no differences in postbiopsy change in PROs between biopsy methods. Corticosteroid administration, whether intramuscular (n=62) or intra-articular (n=38), did not result in more adverse events (p=0.81) and was associated with reduction in postbiopsy swelling (p<0.01). Sequential biopsy procedures (n=103 patients) did not result in more adverse events (p=0.61) or worsening in PRO data.

Conclusion Overall, our results do not suggest a significant difference in safety or patient tolerability between US-NB, US-P&F and AGSB sampling. Further, corticosteroid therapy as part of the biopsy procedure and sequential biopsies is safe and well tolerated in patients.

  • patient perspective
  • arthritis
  • rheumatoid arthritis
  • early rheumatoid arthritis
  • ultrasonography

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  • CP and AF are joint last authors.

  • SAJ and FH contributed equally.

  • Contributors All authors have contributed substantially in the process of completing this study. AF was involved in the development of the Biopsy PRO domains. SAJ was involved in the conception of the study. SAJ, HLI, FH, CP and AF contributed to the designing of the study. SAJ, HL, LB, PD, ES, RT, MS, JW, SR AP, EC, NG, MB, CE, PT, IM, CP, FH and AF were responsible for the

    aggregation of data. SAJ and PVL contributed to the statistics. All authors contributed to the interpretation of data, drafting and revising, final approval and agreed to be accountable.

  • Funding SAJ is supported by grants from The Danish Rheumatism Association and Odense University Hospital PhD Fund and Fund for clinical research. AF was supported by Arthritis Research UK Fellowship (grant 18547) and the Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (grant 20298) and the European Community’s Collaborative project FP7-HEALTH-F2-2012-305549 ‘Euro-TEAM’. This is a summary of independent research funded by the National Institute for Health Research’s (NIHR) Birmingham Biomedical Research Centre programme, supported by the National Institute for Health Research/Wellcome Trust Clinical Research Facility at University Hospitals Birmingham NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The STRAP trial is jointly funded through project grants from AR-UK and MRC and the R4RA trial funded by NIHR.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval UK, London: R4RA (12/WA/0307) and STRAP (14/WA/1209). UK, Birmingham: West Midlands Black Country Research Ethics Committee, references 12/WM/0258 and 07/H1203/57. Denmark, Odense: the SynRA study is approved by the regional ethics review board (S-20140062) and the Danish data protection agency (2008-58-0035). Belgium, Brussels: Cliniques Universitaires Saint Luc, Comité d’éthique, references CEHF-FORM-023 / REV 001. Portugal, Lisbon: Biobank of Instituto de Medicina Molecular (ethics approval from 17/09-2008 and National Data Protection Committee approval number 74/35 from 2011).

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

  • Data sharing statement Data in this study is property of the respective centres involved. Sharing of the data can therefore be accepted if a specific request is received, and all centers hereafter accept.

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