Effect of rituximab on a salivary gland ultrasound score in primary Sjögren's syndrome: results of the TRACTISS randomised double-blind multicentre substudy.

Autor:	Fisher BA; National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre, Birmingham, UK.; Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.; Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK., Everett CC; Leeds Institute for Clinical Trials Research, University of Leeds, Leeds, UK., Rout J; Birmingham Dental Hospital, Birmingham, UK., O'Dwyer JL; Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK., Emery P; Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK., Pitzalis C; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK., Ng WF; Institute of Cellular Medicine, University of Newcastle, Newcastle-upon-Tyne, UK., Carr A; Newcastle Dental Hospital, Newcastle-upon-Tyne, UK., Pease CT; Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK., Price EJ; Great Western Hospital, Swindon, UK., Sutcliffe N; Royal London Hospital, Barts Health NHS Trust, London, UK., Makdissi J; Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Tappuni AR; Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Gendi NST; Basildon and Thurrock University Hospital, Basildon, UK., Hall FC; Department of Clinical Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge, UK., Ruddock SP; Leeds Institute for Clinical Trials Research, University of Leeds, Leeds, UK., Fernandez C; Leeds Institute for Clinical Trials Research, University of Leeds, Leeds, UK., Hulme CT; Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK., Davies KA; Brighton and Sussex Medical School, University of Sussex, Brighton, UK., Edwards CJ; NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton, Southampton, UK., Lanyon PC; Nottingham University Hospitals NHS Trust, and Nottingham NHS Treatment Centre, Nottingham, UK., Moots RJ; Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK., Roussou E; Barking Havering and Redbridge University Hospitals NHS trust (BHRUT), King George Hospital, Goodmayes, UK., Richards A; Birmingham Dental Hospital, Birmingham, UK., Sharples LD; Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK., Bombardieri M; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK., Bowman SJ; National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre, Birmingham, UK.; Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.; Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2018 Mar; Vol. 77 (3), pp. 412-416. Date of Electronic Publication: 2017 Dec 23.
DOI:	10.1136/annrheumdis-2017-212268
Abstrakt:	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. Competing Interests: 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. (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
Databáze:	MEDLINE
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