Date: Sunday, November 5, 2017
Session Title: Sjögren's Syndrome I: Clinical Assessment and Trial Outcomes
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: B lymphocytes are important in the pathogenesis of primary Sjögren’s syndrome (PSS), but two phase III trials (TEARS and TRACTISS) of the B cell depleting agent rituximab (RTX) failed to show an effect on their primary endpoints in PSS. It is possible that RTX may lack efficacy in a non-stratified PSS population, but other explanations for these negative results include the choice and timing of primary outcome. In a small single-site salivary gland ultrasound (SGUS) substudy in TEARS, more subjects in the RTX arm demonstrated improvement in parotid gland echostructure. Importantly, SGUS is an operator-dependent technique and we sought to compare the effects of RTX versus placebo on SGUS in PSS, in a multicentre, multiobserver randomised double-blind substudy of TRACTISS.
Methods: All subjects fulfilled 2002 American-European Consensus Group Criteria for PSS, were anti-Ro antibody positive, had symptomatic oral dryness and fatigue, some residual salivary flow, and evidence of systemic disease if disease duration was greater than 10 years. Subjects also consenting to SGUS were randomised to 1000mg RTX 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 size of hypoechoic foci. Baseline-adjusted values of TUS 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 RTX arm (defined as a 1 point improvement) as a function of the baseline score, age category, disease duration and time point.
Results: 66 patients (49.6% of the total study population) consented to SGUS, and 52 (39.1%; n=26 RTX and n=26 placebo) completed the baseline and at least one follow-up visit. Estimated baseline-adjusted TUS at week 16 was 6.2 (95% CI 5.4-7.0) for placebo and 5.0 (95% CI 4.4-5.6) for RTX, and at week 48, 6.1 (95% CI 5.5-6.6) and 4.8 (95% CI 4.2-5.4) respectively. Estimated between group differences (RTX-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 was the only domain to show statistically significant improvement with an OR of 6.8 (95% CI 1.1-43.0; p=0.043) at week 16 and 10.3 (95% CI 1.0-105.9; p=0.050) at week 48. Improvement of ≥1 point in TUS was associated with improvement in oral dryness VAS at week 16 (diff=15.9; CI 1.5 to 30.3; p=0.030) but not week 48.
Conclusion: TUS differed between study arms, favouring RTX. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker in PSS clinical trials.
To cite this abstract in AMA style:Fisher B, Everett C, Rout J, O'Dwyer J, Emery P, Pitzalis C, Ng WF, Carr A, Pease C, Price E, Sutcliffe N, Makdissi J, Tappuni A, Gendi N, Hall F, Ruddock S, Fernandez C, Hulme C, Davies K, Edwards CJ, Lanyon P, Moots RJ, Roussou E, Sharples L, Bombardieri M, Bowman S. Effect of Rituximab on a Salivary Gland Ultrasound Score in Primary Sjögren’s Syndrome: Results of Multicentre Double-Blind Randomised Controlled Trial Sub-Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/effect-of-rituximab-on-a-salivary-gland-ultrasound-score-in-primary-sjogrens-syndrome-results-of-multicentre-double-blind-randomised-controlled-trial-sub-study/. Accessed January 21, 2020.
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