Background: Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by ocular and oral dryness or systemic manifestations.

Objective: To evaluate efficacy and harms of rituximab in adults with recent-onset or systemic pSS.

Design: Randomized, placebo-controlled, parallel-group trial conducted between March 2008 and January 2011. Study personnel (except pharmacists), investigators, and patients were blinded to treatment group. (ClinicalTrials.gov: NCT00740948).

Setting: 14 university hospitals in France.

Patients: 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analogue scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS.

Intervention: Randomization (1:1 ratio) to rituximab (1 g at weeks 0 and 2) or placebo.

Measurements: Primary end point was improvement of at least 30 mm in 2 of 4 VASs by week 24.

Results: No significant difference between groups in the primary end point was found (difference, 1.0% [95% CI, -16.7% to 18.7%]). The proportion of patients with at least 30-mm decreases in at least two of the four VAS scores was higher in the rituximab group at week 6 (22.4% vs. 9.1%; P = 0.036). An improvement of at least 30 mm in VAS fatigue score was more common with rituximab at weeks 6 (P < 0.001) and 16 (P = 0.012), and improvement in fatigue from baseline to week 24 was greater with rituximab. Adverse events were similar between groups except for a higher rate of infusion reactions with rituximab.

Limitation: Low disease activity at baseline and a primary outcome that may have been insensitive to detect clinically important changes.

Conclusion: Rituximab did not alleviate symptoms or disease activity in patients with pSS at week 24, although it alleviated some symptoms at earlier time points.