Objective To study the safety and clinical efficacy of rituximab therapy for primary Sjögren’s syndrome, as well as investigate its mechanisms. Methods Patients with primary Sjögren’s syndrome were enrolled in an open-label trial and received rituximab (1 g) on days 1 and 15 and followed through week 52. The primary endpoint was safety, with secondary endpoints evaluating clinical and biologic efficacy. Blood was obtained for enumeration of lymphocyte subsets, measurement of serum autoantibodies and BAFF levels, and analysis of gene expression. Results Twelve female subjects with primary Sjögren’s syndrome were administered rituximab. They had a median (range) age of 51 (34–69) years and a median (range) disease duration of 8.0 (2–18) years. We observed no unexpected toxicities from rituximab therapy. Modest improvements were observed at week 26 in patient-reported symptoms of fatigue and oral dryness, with no significant improvement in the objective measures of lacrimal and salivary gland function. The recovery of blood B cells following the nadir from rituximab therapy was characterized by a predominance of transitional B cells and a lack of memory B cells. While blood B cell depletion was associated with an increase in serum BAFF levels, no significant changes were observed in the levels of serum anti-Ro/SSA, anti-La/SSB, and anti-muscarinic receptor 3 autoantibodies or in the blood IFN signature. Conclusion In primary Sjögren’s syndrome, a single treatment course of rituximab was not associated with any unexpected toxicities and led to only modest clinical benefits despite effective depletion of blood B cells.

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