Objective. To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sjögren’s syndrome (SS) in a double-blind, randomized, placebo-controlled trial.

Methods. Patients with active primary SS, as determined by the revised American–European Consensus Group criteria, and a rate of stimulated whole saliva secretion of> 0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2: 1 (rituximab: placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables.

Results. Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean SD age of the patients receiving rituximab was 43 11 years and the disease duration was 63 50 months, while patients in the placebo group were age 43 17 years and had a disease duration of 67 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P 0.004) and several other variables (eg, B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness–like disease.

Conclusion. These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS.

Sjögren’s syndrome (SS) is a systemic autoimmune disease that is characterized by chronic inflammation of the salivary and lacrimal glands, resulting in xerostomia and keratoconjunctivitis sicca in 95% of patients (1). These symptoms are frequently accompanied by extraglandular manifestations such as Raynaud’s phenomenon, arthritis, arthralgia, and myalgia, and 85% of patients experience severe fatigue. Moreover, B cell hyperactivity, reflected by increased serum levels of IgG and IgM rheumatoid factor (RF) and the presence of anti-SSA and anti-SSB autoantibodies, is a common finding in SS. Furthermore, SS has a large impact on health-related quality of life, employment, and disability, as reflected by lower Short Form 36 (SF-36) health survey scores, reduced employment rates, and higher rates of disability in patients with SS compared with the general population (1).

ClinicalTrials. gov identifier: NCT00363350. Supported by Roche, Woerden, The Netherlands. JM Meijer, MD, DMD, PM Meiners, MD, A. Vissink, MD, DMD, PhD, FKL Spijkervet, DMD, PhD, W. Abdulahad, PhD, N. Kamminga, MD, E. Brouwer, MD, PhD, CGM Kallenberg, MD, PhD, H. Bootsma, MD, PhD: University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Address correspondence and reprint requests to A. Vissink, MD, DMD, PhD, Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. E-mail: a. vissink@ kchir …