ASSESSMENT OF FLARES IN LUPUS (SLE) PATIENTS IN A PLACEBO-CONTROLLED RANDOMIZED PHASE II/III STUDY OF RITUXIMAB (EXPLORER)

Background: SLE patients (pts) with moderate to severe disease activity (>1 BILAG A or >2 BILAG B domain scores) despite background immunosuppressives and corticosteroids were randomized to receive rituximab (RTX) or placebo. Although statistically significant differences in the primary and secondary outcome measures were not observed, an exploratory analysis was performed to evaluate the impact of RTX on the intensity and frequency of disease flares. Objectives: To assess in those pts who achieved response whether RTX affected: 1) times to moderate or severe flares, 2) annualized flare rates, and 3) prednisone usage during flares. Methods: The BILAG index was scored every 4 wks for 52 wks after the first study drug treatment. Only pts who achieved response (BILAG C, D, or E domain scores for all domains before wk 52) were included in this analysis. A severe flare was defined as > 1 BILAG A or > 3 BILAG B domain scores in a pt who previously met criteria for response; a moderate flare was defined as 2 BILAG B domain scores following response; an A flare was defined as > 1 new BILAG A domain scores Kaplan-Meier estimates were used to assess times to flare, and the p-values were based on log-rank tests. Annualized flare rates were calculated using the number of flares a patient experienced during the study; the p-value was based on Poisson regression model. Only flares that occurred after the protocol-mandated prednisone taper at 12 weeks were incorporated into the analysis of prednisone usage during flares. Results: 58 of 88 placebo-treated and 127 of 169 RTX-treated pts achieved response during the study and therefore qualified for this subset analysis. Whereas the times to first moderate or severe flares were no different in the two treatment groups, there was a trend towards a prolonged time to first A flare in the RTX group (Hazard Ratio=0.612; p=0.052). Annualized severe and moderate flare rates were similar in both groups, but the mean annualized A flare rate in the RTX group was significantly lower than in the placebo group (0.86 vs 1.41; p=0.038). Although prednisone was increased in 23 of 138 (16.7%) severe flares, the frequencies with which prednisone was increased were not significantly different between the RTX and placebo groups (19.5% vs.12.5%; p=0.2778). Conclusion: There was no difference between RTX and placebo in preventing moderate or severe flares after remission was achieved. However, RTX treatment was associated with a lower annualized A flare rate, and a trend towards prolonging the time to A flare was observed. Disclosure of Interest: Joan Merrill, Genentech, consultant; Jill Buyon, Genentech, consultant; Richard Furie, Genentech, grant support; Kevin Latinis, Genentech, consultant; Caroline Gordon, Roche, consultant; Hsin-Ju Hsieh, Genentech, employee/shareholder; Paul Brunetta, Genentech, employee/shareholder.Citation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 71Session: Abstract Session: SLE treatment (Oral Presentations )