OP0008 PRIMARY ANALYSIS OF A DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING TRIAL OF RITUXIMAB, AN ANTI-CD20 MONOCLONAL ANTIBODY, IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING METHOTREXATE (DANCER TRIAL)
P. Emery, A. Filipowicz-Sosnowska, L. Szczepanski, A. Racewicz, J. Schechtman, R. M. Fleischmann, R. Van Vollenhoven, N. F. Li, S. Agarwal, E. Hessey, T. M. Shaw

The DANCER trial is a large Phase IIa safetly and efficacy study of rituximab (RTX) in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment. In this abstract, week 24 data are reported.

There were nine treatment arms in this study in a 3x3 configuration: RTX on days 1 and 15 (placebo, 500 mg or 100 mg) with glucocorticoid (placebo, 100 mg methylprednisolone iv or 100 mg iv + 60 mg/d prednisone po on days 2-7 + 30 mg/d prednisone po on days 8-14). Patients were included if, 1) SJC and TJC > 8, 2) CRP or ESR were elevated, 3) on MTX 10-25 mg/week, and 4) previously failed on 1-5 DMARDs/biologics other than MTX.

Results: The data presented here are from week 24 analysis in 367 rheumatoid factor positive patients only. The drop-out rate by week 24 was greatest in the placebo group compared to that in the RTX 500mg and RTX 1000mg group, 35%, 9%, and 14% respectively. The incidence of serious adverse events was 2.7%, 7.3% and 6.8% in placebo, 500 mg and 1000 mg RTX groups, respectively. The table below represents the efficacy data at week 24 for the 367 RF+ ITT patients.

Conclusion: RTX is significantly more efficacious than MTX alone in patients with active RA. The addition of glucocorticoids to the treatment regime did not produce any increased efficacy to the combination of RTX and MTX. No significant dosing effects were observed with the two dose of RTX.

Editorial Comments: This was a somewhat complex 9-arm study that addressed several questions regarding the administration of Rituximab in patients with RA. This study demonstrated that two x 500 mg doses Rituximab were similar in terms of most efficacy outcomes compared to the previously reported higher dose of two x 1000 mg infusions. The prespecified analysis presented only those patients who were rheumatoid factor positive (79% of the total randomized).

This study demonstrated that the efficacy of Rituximab at 500 mg x 2 was similar to the efficacy demonstrated for 1000 mg x 2, with numerical but not statistical significance in most outcomes between the two regimens. Whether this subset is more responsive that RF negative patients was not reported. The oral presentation included additional information concerning the details of this study that were also covered in more detail in two posters, SAT 072 and SAT 077, in particular the effect of different steroid regimens. In prior Rituximab studies, study mandated higher doses of oral corticosteroids were given through the periinfusional period. This study evaluated the efficacy and safety differences without steroids, with only 100 mg methyprednisolone with each infusion, or with the 100 mg methyprednoisolone with a tapering dose of oral corticosteroids (total prednisone equivalent including IV was 810 mg over 2 weeks). There was no additional efficacy demonstrated for the addition of either IV or po steroids. However, 100 mg methyprednisolone IV premedication reduced the rate of first infusion reactions. The addition of the oral prednisone taper neither added to efficacy nor further reduced the infusion related events.

Infusion related events were common occurring in 39 and 46% of patients receiving 500 mg or 1000 mg Rituximab without corticosteroids, but reduced with corticosteroids to 26-27% for 500 mg Rituximab, and 32-35% in the 1000 mg Rituximab group. It was notable that infusion reactions were reported at a high frequency (17-25%) even in patients who received only placebo. Serious adverse events were also increased in groups receiving Rituximab compared to placebo. While these data add to the currently available information for Rituximab in RA, it is hoped that additional data to better define both safety and efficacy of different dosing regimens of Rituximab, and the minimal requirements for corticosteroids will be forthcoming at future meetings.

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