Sjogrens Syndrome

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Eular 2006 Highlights

Sjogrens Syndrome


J. Pijpe, G. W. Van Imhoff, A. Vissink, C. G. M. Kallenberg, H. Bootsma

B cells have been implicated in the pathogenesis of Sjogrens syndrome. Since rituximab is an anti-CD20 monoclonal antibody that depletes B cells, Pijpe et al investigated its safety and efficacy in patients with Sjogrens.

In this phase II open label trial, 15 patients were treated with 4 infusions of 375 mg/kg rituximab plus 15 mg prednisone and clemastine. Eight of the patients had early primary Sjogrens Syndrome (pSS) defined by a short disease duration (< 4years), B cell hyperactivity (IgG > 15g/l), and the presence of autoantibodies (IgM-RF, anti-SSA/B). Seven of the patients had Sjogrens associated with mucosa associated lymphoid tissue lymphoma (MALT-lymphoma) localized in the parotid gland. Immunological, functional and subjective assessments were done at baseline and at 5 and 12 weeks post treatment initiation.

Results: Subjective complaints and salivary gland function improved significantly in 63% (5/8) of patients with pSS and in 29% (2/7) of MALT patients. Patients showed a rapid reduction in peripheral B cells with no effect on IgG levels. IgM-RF levels significantly decreased in the MALT/pSS patients.

Two MALT patients had exacerbations in disease following an early rise in IgM-RF levels. However, overall, 3 MALT patients achieved complete remission, 3 remained stable, and 1 showed disease progression.

In 4 of 15 patients, human anti-chimeric antibodies (HACAs) developed. Of the 3 pSS patients with a positive HACA, all had a clinical presentation of serum sickness.

Conclusion: Rituximab is may be an effective treatment in some patients with Sjogrens syndrome. Further studies with adjustments in the immunosuppressive therapy are warranted.

Editorial Comments: This was an open label study that combined patients with primary Sjogrens as well as patients with Sjogrens in association with associated MALT lymphoma of the parotid gland. The dosing regimen is different than is being pursued for the treatment of rheumatoid arthritis. While the study is dirty in terms of its design, combing patients with primary Sjogrens with patients with Sjogrens associated with a MALT Lymphoma of the parotid, there are several notable results from this study concerning both efficacy and safety. Symptomatic salivary improvement was greater in the patients with primary Sjogrens than in the patients with malignancy. Whether long term follow up will demonstrate continued improvement in symptoms remains to be seen.

As seen in other studies of autoimmune diseases, a decline in IgM rheumatoid factor was observed without an effect on overall IgG levels. Whether other IgG autoantibodies (e.g. ANA, anti-Ro) declined was not discussed. Of concern were serum sickness reactions in patients with pSS who developed HACAs. Whether this side effect will be seen in other autoimmune diseases is unclear, and whether the development of HACAs and HACA-associated serum sickness will be less when rituximab is administered with concomitant immunosuppressive agents will need to be monitored carefully in clinical trials and if the drug is used off-label for other conditions. Larger randomized studies of primary Sjogrens patients are needed to better understand the preliminary efficacy results demonstrated in this small study of rituximab for primary Sjogrens. The high frequency of HACA and associated serum sickness is a concern.