Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Effect of Rituximab Treatment on BAFF Levels in Patients with Primary Sjgren's Syndrome: A Placebo-Controlled Clinical Trial.

Pollard2,  Rodney, Abdulahad2,  Wayel, Meijer2,  Jiska, Kroese2,  Frans, Spijkervet2,  Fred, Kallenberg1,  Cees, Vissink2,  Arjan

Univer Med Center Groningen, Groningen, The Netherlands
Univer Med Center Groningen

Objective:

To assess the effect of rituximab (anti-CD20) treatment on B-cell activating factor (BAFF) levels in patients with primary Sjögren's syndrome (pSS).

Background:

pSS is a systemic autoimmune disease characterized by mononuclear infiltrates of B-and T-cells in exocrine glands eventually leading to destruction of these glands. B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF)-ligand family, is essential for the control of B-cell maturation and survival.

Methods:

In a randomised double-blinded placebo-controlled trial patients were treated on days 1 and 15 with either rituximab (n= 20) or placebo (n= 10). To minimise side effects (infusion reactions, serum sickness), all patients were pre-medicated with methylprednisolone and oral prednisone. Fresh blood samples were collected at various time points (before, 5, 12, 36 and 48 weeks following treatment). In addition, age- and sex-matched blood samples were collected from healthy controls (n=10). BAFF levels were assessed by Enzyme-Linked Immunosorbent Assay (R&D Systems). In addition, percentages and numbers of B-cell subsets were examined by four-color cytometry.

Results:

Depletion of B-cells was observed in the rituximab treated group after infusion, while B-cell levels remained unchanged after placebo treatment. B-cells reappeared in the rituximab treated group within 24 to 48 weeks after treatment. Repopulation of the B-cell compartment started with reappearance of transitional B-cells, followed by naïve B-cells, and a relative late recovery of memory B-cells. At baseline, BAFF levels were significantly increased in all pSS-patients in comparison to healthy controls.

Placebo-treated patients showed a slight (0.5 fold, p<0.05), but significant, increase in BAFF levels only at week 5, likely due to methylprednisolone administration.

Strikingly, long-term elevated levels of BAFF (3.0–4.0 fold, p<0.05) were observed during 36 weeks following rituximab-treatment. By week 48, BAFF levels had reached baseline values in rituximab treated group.

Conclusion:

These preliminary data show a sharp increase in BAFF levels after rituximab therapy. These levels appear to correlate negatively with the presence of B-cells in the peripheral blood. BAFF could be involved in the pathogenesis of SS, possibly by triggering the activation of self-antigen-driven autoimmune B-cells. Since BAFF levels are much higher after rituximab treatment, this may also have implications for manifestations of the disease, related to therapy. This observation might be important for treatment strategies with biologicals like anti-BAFF and /or B-cell depletion. Extended data are in progress and can be presented at the ACR meeting.

To cite this abstract, please use the following information:
Pollard, Rodney, Abdulahad, Wayel, Meijer, Jiska, Kroese, Frans, Spijkervet, Fred, Kallenberg, Cees, et al; Effect of Rituximab Treatment on BAFF Levels in Patients with Primary Sjgren's Syndrome: A Placebo-Controlled Clinical Trial. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1892
DOI: 10.1002/art.29657

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