(RE)TREATMENT WITH RITUXIMAB IN PATIENTS WITH ACTIVE PRIMARY SJÖGREN'S SYNDROME

Background: No adequate treatment for Sjögren's syndrome is available yet. Rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, is a promising agent for the treatment of various autoimmune disorders. Recently, Pijpe et al. reported rituximab to be effective in patients with active and early primary SS over a 3 month period. In this study the retreatment and long term follow up of these patients will be discussed.Objectives: To investigate the efficacy and safety of (re)treatment with B cell depletion therapy (rituximab) in patients with early primary Sjögren's syndrome (pSS) and in patients with pSS and a mucosa-associated lymphoid tissue (MALT)-type lymphoma.Methods: This follow-up study included 15 patients (8 early pSS, 7 MALT/pSS) who participated in an open phase II pilot study since june 2003.(1) Patients were treated with 4 infusions of rituximab (375 mg/m per infusion) given weekly after pre-treatment with prednisone (25 mg) and clemastine. The effect of rituximab was evaluated, assessing salivary/lacrimal function, clinical response and adverse effects. Six of 15 patients (40%) were retreated with a second course of 4 infusions of rituximab.Results: Fourteen patients (7 early pSS, 7 MALT/pSS) were available for follow up with a mean follow up of 48 weeks (12-72 weeks).In patients with early pSS stimulated salivary flow rate significantly increased and subjective symptoms significantly improved. There was a rapid decrease of peripheral B cells. These parameters all returned to baseline after 6-9 months. Five patients received a second course of rituximab (after 9-11 months) due to disease relapse. Retreatment resulted again in a significant improvement of the salivary flow rate and subjective symptoms, together with a decrease in B cells.Six of the 7 MALT/pSS patients were effectively treated with rituximab. One of these 6 patients had a recurrence of the MALT lymphoma after 9 months and was successfully retreated with rituximab. The remaining MALT/pSS patient had progressive MALT disease and severe extraglandular Sjögren disease within three months after the start of rituximab treatment and, therefore, treatment with cyclophosphamide was added.Three of the 14 patients (21%) developed serum sickness; all 3 were early pSS patients. Two patients developed serum sickness after the second infusion of the first course, and one patient developed serum sickness after the second infusion of the second course. Treatment was stopped after development of serum sickness. These three patients all developed HACA's after the first infusion of the first course.Conclusion: Rituximab is effective for 6-9 months, especially in early pSS patients with active disease. Retreatment resulted in similar good clinical response. The development of serum sickness in 21% of the patients suggests that a higher dose of corticosteroids is required during rituximab treatment.References: 1. Pijpe J et al. Arthritis Rheum 2005;52:2740-50.Citation: Ann Rheum Dis, volume 65, supplement II, year 2006, page 476Session: SLE, Sjogren and APS: etiology, pathogenesis and animal models