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 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 ϳ95% 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.

This study determined disease activity levels, PASS and MCII of ESSDAI and ESSPRI. These results will help designing future clinical trials in SS. For evaluating systemic complications, the proposal is to include patients with moderate activity (ESSDAI≥5) and define response to treatment as an improvement of ESSDAI at least three points. For addressing patient-reported outcomes, inclusion of patients with unsatisfactory symptom state (ESSPRI≥5) and defining response as an improvement of ESSPRI at least one point or 15% seems reasonable.

The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS.

SS has a large impact on HR-QOL, employment and disability.