This study is an evaluation of the effect of rituximab compared to placebo in combination with steroids on salivary flow and serological and clinical parameters in patients with primary SS.

Study design:

phase II trial

Study objective:

evaluation of the effect of rituximab compared to placebo in combination with steroids on salivary flow and serological and clinical parameters in patients with primary SS

Number of participating centres:

1

Duration:

follow-up 48 weeks

Study medication:

2 infusions on day 1 and day 15 rituximab infusions (1000 mg) or placebo infusions intravenous infusion of 100 mg of methylprednisolone before infusion of rituximab (or the placebo for rituximab), together with 60 mg per day of oral prednisone on days 2, 3, 16 and 17, 30 mg per day on days 4, 5, 18 and 19 and 15 mg per day on days 6 and 20

Primary objective/endpoint:

stimulated salivary gland function (stimulated submandibular/sublingual and parotid saliva)

Secondary objectives/endpoint:

Functional parameters Laboratory parameters Subjective parameters Histological/Molecular parameters

Number of subjects:

30 patients with primary SS (20 patients rituximab treatment, 10 patients placebo)

Inclusion Criteria:

• Stimulated whole saliva secretion ≥ 0,15 ml/min
• Male or female > 18 years
• Primary SS according to the revised European - U.S. criteria(22)
• Positive autoantibodies (IgM-Rf > 10 and SS-A and/or SS-B)
• Parotid gland biopsy (paraffine material and fresh frozen tissue) with characteristic features of SS performed at time of inclusion (no longer than 12 months ago)
• Use of reliable method of contraception during the study
• Written informed consent

Exclusion Criteria:

• The presence of any other connective tissue disease
• Preceding treatment with anti-TNF or other monoclonal antibodies
• Use of prednisone, hydroxychloroquine less than 1 month ago
• Use of MTX, cyclophosphamide, cyclosporin, azathioprine and other DMARDS less than 0,5 year ago
• Serum creatine > 2.8 mg/dl (250 micromol/l)
• ASAT or ALAT outside 1.5 x upper normal range of the laboratory
• Hb < 9 g/dl (5.6 mmol/l) for males and 8.5 g/dl (5.3 mmol/l) for females
• Neutrophil granulocytes less than 0.5 x 109/l
• Platelet count less then 50 x 109/l
• Positive pregnancy test or breast-feeding
• History of alcohol or drug abuse
• Serious infections
• Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which places the patient at an unacceptable risk for participation in the study
• History of any malignancy with the exception of completely resected basal cell carcinoma of the skin