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Effect of rituximab on a salivary gland ultrasound score in primary Sjögren’s syndrome: results of the TRACTISS randomised double-blind multicentre substudy
  1. Benjamin A Fisher1,2,3,
  2. Colin C Everett4,
  3. John Rout5,
  4. John L O’Dwyer6,
  5. Paul Emery7,8,
  6. Costantino Pitzalis9,
  7. Wan-Fai Ng10,
  8. Andrew Carr11,
  9. Colin T Pease7,8,
  10. Elizabeth J Price12,
  11. Nurhan Sutcliffe13,
  12. Jimmy Makdissi14,
  13. Anwar R Tappuni14,
  14. Nagui S T Gendi15,
  15. Frances C Hall16,
  16. Sharon P Ruddock4,
  17. Catherine Fernandez4,
  18. Claire T Hulme6,
  19. Kevin A Davies17,
  20. Christopher John Edwards18,
  21. Peter C Lanyon19,
  22. Robert J Moots20,
  23. Euthalia Roussou21,
  24. Andrea Richards5,
  25. Linda D Sharples22,
  26. Michele Bombardieri9,
  27. Simon J Bowman1,2,3
  1. 1 National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre, Birmingham, UK
  2. 2 Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
  3. 3 Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  4. 4 Leeds Institute for Clinical Trials Research, University of Leeds, Leeds, UK
  5. 5 Birmingham Dental Hospital, Birmingham, UK
  6. 6 Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
  7. 7 Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  8. 8 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK
  9. 9 William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK
  10. 10 Institute of Cellular Medicine, University of Newcastle, Newcastle-upon-Tyne, UK
  11. 11 Newcastle Dental Hospital, Newcastle-upon-Tyne, UK
  12. 12 Great Western Hospital, Swindon, UK
  13. 13 Royal London Hospital, Barts Health NHS Trust, London, UK
  14. 14 Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  15. 15 Basildon and Thurrock University Hospital, Basildon, UK
  16. 16 Department of Clinical Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge, UK
  17. 17 Brighton and Sussex Medical School, University of Sussex, Brighton, UK
  18. 18 NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton, Southampton, UK
  19. 19 Nottingham University Hospitals NHS Trust, and Nottingham NHS Treatment Centre, Nottingham, UK
  20. 20 Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
  21. 21 Barking Havering and Redbridge University Hospitals NHS trust (BHRUT), King George Hospital, Goodmayes, UK
  22. 22 Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
  1. Correspondence to Dr Benjamin A Fisher, Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK; b.fisher{at}


Objectives To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren’s syndrome (PSS) in a multicentre, multiobserver phase III trial substudy.

Methods Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0–11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point.

Results 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were −1.2 (95% CI −2.1 to −0.3; P=0.0099) and −1.2 (95% CI −2.0 to −0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48.

Conclusions We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker.

Trial registration number 65360827, 2010-021430-64; Results.

  • sjøgren’s syndrome
  • ultrasonography
  • B cells

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  • Handling editor Tore K Kvien

  • Contributors BAF drafted the manuscript and CCE performed the statistical analyses. The content of this publication was determined by the authors. All authors contributed to the conception or design of the work, or the acquisition, analysis or interpretation of data. All authors reviewed and approved the manuscript.

  • Funding This study was funded by Arthritis Research UK (18810). Rituximab was provided free of charge by Hoffman La Roche.

  • Disclaimer The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

  • Competing interests BAF and SJB have received support from the NIHR Birmingham Biomedical Research Centre. BAF paid instructor/consultant for Novartis, Roche, BMS, Virtualscopics. W-FN is consultant for Pfizer, UCB, MedImmune, GSK, Takeda and Sanofi. MB is consultant for GSK, Amgen/MedImmune and UCB. SJB is consultant for Cellgene, Glenmark, GSK, Eli Lilly, Novartis, Roche, Takeda, UCB.

  • Ethics approval Leeds West Ethics Committee (ref. 10/H1307/99).

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

  • Correction notice This article has been corrected since it published Online First. The affiliation for Anwar Tappuni has been corrected.

  • Presented at An abstract of this work was previously presented at the 2017 American College of Rheumatology Annual Congress.

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