B CELL DEPLETION THERAPY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): LONG TERM FOLLOW UP AND PREDICTORS OF RESPONSE

Background: Open uncontrolled studies have suggested that B cell depletion therapy (BCDT) will be a promising therapy for the treatment of patients with refractory SLE. However, the factors which predict outcome and the long term safety of this treatment are unknown.Objectives: We describe the clinical outcome and safety profile of BCDT in patients with SLE during long term follow up. Autoantibody profile was also examined as a possible predictor of flare of disease.Methods: Since 2000, 41 patients with refractory SLE have been treated with BCDT (based on rituximab) using a combination protocol with cyclophosphamide and steroid cover, of whom 35 have had a minimum of 6 months follow up. Patients were assessed clinically with the BILAG activity index at 1 to 3 monthly intervals. Baseline autoantibody profiles were measured by ELISA (Sheild Diagnostics, Dundee) at the time of diagnosis. Adverse events and duration of B cell depletion (CD19 < 0.005 x 109/L) were noted. Flare was defined as a new BILAG A or two new subsequent Bs in any organ system.Results: The mean duration of follow up was 37 months (range 6 -79) and 28 patients had follow up for more than a year. Two patients were lost to follow up and were excluded from the analysis. Of the 33 patients (minimum follow up duration 6 months), 12 patients have remained well. The mean time to flare (TTF) was 10 months post-BCDT. Of the 20 patients who flared, 11 flared between 6 to 12 months post-BCDT. The median duration of B cell depletion was 4 months (range 2 -15). Two patients remain depleted at the time of analysis (73 and 8 months). One patient did not deplete at all. Patients with anti-ENA antibodies (20/32) were more likely to flare at any time after BCDT with an odds ratio (OR) of 6 (p = 0.03). Patients with anti-Sm (9/32) or anti-La (5/32) were more likely to flare (OR 9, p = 0.0497 and OR 10, p = 0.04 respectively). Patients with low serum C3 at baseline (27/32) had a shorter time to flare post-BCDT (median TTF 12 months). The median TTF for normal C3 patients has not been reached (p = 0.0001). B cell depletion was beneficial clinically with a decrease of median global BILAG scores from 13 to 5 at 5 to 8 months (p < 0.0001). There was improvement of serological parameters with median dsDNA titres decreasing from 203 to 74 IU/mL at 6 months (p = 0.002) and increase of median C3 from 0.73 to 0.9 gm/L at 6 months (p = 0.0013). Thirteen patients have been retreated with at least another cycle of rituximab. Serious adverse events observed were pneumococcal sepsis, severe serum sickness reaction and seizure related to hyponatriaemia. Two patients have died. One developed varicella pneumonitis shortly after the second cycle of rituximab and the other had pancarditis related to active lupus after B cell repopulation.Conclusion: One third of patients remain well after BCDT without needing further standard immunosuppressive agents. Most flares occurred between 6 to 12 months post-BCDT. Autoantibody profiling may help identify which patients will have a more sustained response. Patients with low baseline serum C3 or the presence of anti-ENA antibodies were more likely to flare at any time post-BCDT. Although the long term safety profile of B cell depletion therapy is so far favourable, ongoing vigilance is recommended.Citation: Ann Rheum Dis, volume 66, supplement II, year 2007, page 56Session: Abstract Session: SLE clinical