Background 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. Whilst RTX may lack efficacy in a non-stratified PSS population, other possible 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.
Objectives To compare the effects of RTX versus placebo on SGUS in PSS, in a multicentre, multiobserver substudy of TRACTISS.
Methods Subjects 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 in the RTX arm.
Conclusions TUS differed between study arms, favouring RTX. This encourages further research into SGUS as an imaging biomarker in PSS clinical trials.
Acknowledgements Funded by Arthritis Research UK. Roche provided RTX.
Disclosure of Interest B. Fisher Paid instructor for: Novartis, Roche, Virtualscopics, C. Everett: None declared, J. Rout: None declared, J. O'Dywer: None declared, P. Emery: None declared, C. Pitzalis: None declared, W.-F. Ng Consultant for: Pfizer, UCB, MedImmune, Takeda and Sanofi, A. Carr: None declared, C. Pease: None declared, E. Price: None declared, N. Sutcliffe: None declared, J. Makdissi: None declared, N. Gendi: None declared, F. Hall: None declared, S. Ruddock: None declared, C. Fernandez: None declared, C. Hulme: None declared, K. Davies: None declared, C. Edwards: None declared, P. Lanyon: None declared, R. Moots: None declared, E. Roussou: None declared, L. Sharples: None declared, M. Bombardieri Consultant for: GSK, Amgen/MedImmune and UCB, S. Bowman Consultant for: Cellgene, Glenmark, GSK, Eli Lilly, Novartis, Roche, Takeda, UCB