Rituximab active in Sjogren's, advances to phase 3

Janis Kelly

October 28, 2004

Oct 28, 2004

San Antonio, TX - A pilot study of rituximab (Rituxan, MabThera; Genentech/IDEC) demonstrated reduced inflammatory activity and IgG-producing B cells in affected tissues of patients with primary Sjogren's syndrome, but combination with high-dose corticosteroids may be required to prevent serum sickness and other adverse reactions, Dr Justin Pijpe (University Hospital, Groningen, the Netherlands) reported at the American College of Rheumatology 2004 meeting [ 1 ]. Pijpe tells rheuma wire that a multicenter phase 3 study is expected to open within a year.

Reducing B-cell counts may reduce disease activity

Rituximab is a monoclonal antibody specific for the B-cell surface molecule CD20, and treatment with rituximab effectively depletes B cells. It is an attractive candidate for use in primary Sjogren's syndrome, in which high levels of B-cell autoreactivity are associated with increased levels of disease activity, systemic complications, and a 44-fold increased risk of B-cell lymphoma.

The purpose of this study was to investigate the safety and efficacy of rituximab in the treatment of patients with recently developed Sjogren's syndrome who still have substantial residual exocrine-gland function and might benefit from B-cell depletion. Pijpe pointed out that current treatments, including corticosteroids and hydroxychloroquine, do not effectively alleviate signs and symptoms and do not alter the disease course.

The phase 1/2 study included 15 patients with primary Sjogren's and B-cell hyperactivity (IgG >15 g/L), presence of autoantibodies, and disease duration of less than 4 years. None had prior use of immunosuppressive treatment.

Patients were treated with 4 infusions of rituximab (375 mg/m 2) given weekly. The preparatory regimen included prednisone 25 mg IV, clemastine 2 mg IV, and paracetamol 1 g PO.

Efficacy was evaluated by questionnaires (subjective complaints), sialometrical/chemical profile (parotid and submandibular/sublingual saliva), lacrimal function (Schirmer's test, Rose-Bengal test), and serological parameters (ESR, IgG, FACS analysis on B and T cells). Parotid glands were biopsied before and 3 months after treatment.

Pijpe reported that 8 patients have been treated, and 5 have completed the entire rituximab treatment sequence. Preliminary data on clinical efficacy showed improvement of subjective complaints (fatigue, sicca complaints, and health status) and an increase in salivary-gland function. Inflammatory activity in the saliva decreased following treatment. Treatment had little effect on lacrimal-gland function.

"Serological analysis showed overall a decrease of erythrocyte sedimentation rate and rheumatoid factor. Levels of IgG remained stable or decreased. Follow-up biopsies of the parotid gland showed an increase in IgA/IgG plasma cell ratio, suggesting a specific decrease of IgG-producing B cells in affected tissue," Pijpe reported.

Pijpe tells rheuma wire that B cells and rheumatoid factor began to reappear at 9 months after treatment.

Unexpected rate of adverse effects

Three patients developed a clinical picture resembling serum sickness after the second infusion, and treatment was stopped. These problems included fever, fatigue, arthralgia, purpura, and swollen lymph nodes.

"Adverse effects were worse than expected in patients with early primary Sjogren's without immunosuppressive therapy," Pijpe said. He suspects that the relatively low prednisone dose (25 mg) used with the rituximab infusion might account for the high level of side effects, although this dose had been enough to prevent adverse effects in lymphoma patients treated with rituximab.

"We expect that future studies will combine rituximab with high-dose corticosteroids," Pijpe said. "This open-label phase 1/2 study suggests rituximab as a promising therapy in the treatment of patients with early-onset primary Sjogren's syndrome. Serum sickness in 3 out of 8 patients warrants further analysis, since this side effect has been rarely observed."


  1. Pijpe J, Bootsma H, Van Imhoff G, et al. Rituximab (anti-CD20) for the treatment of primary Sjogren's Syndrome. American College of Rheumatology 2004 meeting; San Antonio, TX; October 16-21, 2004; Abstract 1510.


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