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

Objectives T o compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjogren's syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. Methods S ubjects 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.