Kasia Owczarczyk, MD, University Hospital of Cologne, Germany, presented the results of a double-blind phase 2 trial which suggest that in patients with active rheumatoid arthritis (RA), despite methotrexate (MTX) treatment, a single course of two infusions of rituximab (alone or in combination with either cyclophosphamide or continued methotrexate) provided significant improvement in disease symptoms [Edwards JCW et al. N Engl J Med 2006]. Exact data depicting the degree of B-cell depletion, as well as the phenotype of residual B-cells in patients receiving rituximab monotherapy, in whom the use of standard DMARDs is precluded due to intolerance or inefficacy, is still lacking.

This study analyzed the kinetics of B-cell depletion and the phenotype of residual B-cells in 10 patients with active RA who were receiving rituximab monotherapy, as well as in 5 patients receiving a concomitant DMARD other than MTX (azathioprine, cyclosporine, leflunomide), and in 10 patients who received concurrent MTX therapy. All patients received 2g of rituximab (given as individual infusions) on days 1 and 15. CD19+ B-cell percentages were analyzed at baseline, on day 15, and at weeks 4, 8, 16, and 20. Absolute B-cell numbers were calculated based on WBC. Clinical response was analyzed using DAS28 and the EULAR response score.

This report presents preliminary data for 17 of the 25 patients who have completed a 4 month follow-up period after rituximab therapy.

Thirteen (13) patients achieved an effective B-cell deletion. Full depletion (<5 residual B-cell/ul) was achieved in 100% of patients in the rituximab monotherapy group; 2 of 3 patients receiving a DMARD other than MTX; and 6 of 8 patients receiving concomitant MTX therapy. The mean absolute CD19+ C-cell counts at the point of maximum deletion were similar in all groups.

When changes in the mean percentage of naïve (CD27-IgD+) and isotype-switched memory (CD27+ IgD-), double negative (CD27-IgD-), and plasma cells (CD20-CD19^lowCD38+) were further analyzed, all subtypes of B-cells were depleted including cells with plasma cell precursor phenotype (mean ±SD 52.99±16.88).

Patients receiving rituximab monotherapy achieved a mean reduction in DAS28 of 1.67 (±SD 0.76) vs 1.84 (± SD 1.44) in the MTX group and 0.7 (± SD 0.29) in the alternate DMARD group. Good to moderate EULAR clinical response was achieved by 76% of patients receiving concomitant MTX vs 55% of those receiving an alternate DMARD and 60% in those receiving rituximab monotherapy.

In this study, rituximab induced a profound depletion of the peripheral B-cell pool when administered in combination with MTX or alternative DMARDs as well as in monotherapy. The degree of B-cell depletion did not vary significantly between study groups. In all subjects residual B-cells expressed predominantly an isotype-switched memory cells' phenotype.

Patients receiving rituximab monotherapy achieved similar clinical responses compared with those receiving concomitant DMARD therapy. However, long-term follow-up data on the efficacy of rituximab monotherapy is still lacking and further analysis will show whether B-cell re-population occurs earlier in this setting.

These data suggest that rituximab monotherapy can be used effectively in patients, who – for a variety of reasons – are unable to receive adjuvant DMARD therapy.