78-WEEK SAFETY DATA FROM THE RANDOMIZED, DOUBLE-BLIND PHASE II/III EXPLORER STUDY OF PATIENTS WITH MODERATELY TO SEVERELY ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) TREATED WITH RITUXIMAB

Background: Multiple courses of rituximab (RTX) have been well tolerated in RA patients (pts). However, there has been no analysis of safety for 12 months after receipt of the 2nd course of RTX in SLE patients Objectives: We highlight safety from the EXPLORER trial through 78 wks. Methods: Pts on background immunosuppressants and corticosteroids were randomized to treatment with placebo (PLA) or RTX 1000 mg IV on days 1, 15, 168, and 182. Adverse events (AEs), serious AEs (SAEs), deaths, and antibodies to RTX (HACAs) were recorded from screening to wk78 or to termination visits for pts who prematurely discontinued. The safety-evaluable population included randomized pts who received any amount of RTX or PLA. HACA response was measured at baseline and every 3 months. Immunoglobulin (Ig) levels were measured at baseline and days 112, 168, 308, 364, 455, and 546. Results: 88 PLA and 169 RTX pts were included in the safety-evaluable populations. After the 2nd infusion of the 1st course (C1), 90.5% of RTX-treated pts depleted peripheral B cells. The % of pts with AEs and SAEs were comparable between groups. Infection/infestation SAEs were higher in PLA than RTX group (18.2% vs 11.2%). Infection rate over 78wks were 224 events/100 pt-years (pt-yr) for PLA and 227 events/100 pt-yr for RTX. Serious infections were 13.6 and 16.7 events/100 pt-yr for the PLA and RTX groups. Herpes virus infection-related AEs occurred in 8 (9.1%) pts in PLA compared with 26 (15.4%) in RTX; in RTX, 2 (1.2%) pts experienced SAEs (herpes zoster). The % of pts with infusion-related AEs during C1 was comparable between groups, but during C2, more RTX-treated pts had infusion-related AEs. HACAs were present in 48 (28.4%) and 3 (3.4%) pts in the RTX and PLA groups. At the 4th infusion, pts who were HACA+ experienced an infusion-related AE; 11 (23%) of the 48 HACA+ RTX treated pts developed infusion-related AEs (1 SAE) vs 14 (11%) of the HACA-RTX-treated pts. In the RTX group, 6 pts experienced neutropenia SAEs compared with none in PLA. Four cases of serum sickness (1 serious) were reported in the RTX group compared to none in the PLA group. At any time during the study, IgG levels were below the lower limit of normal (LLN) in 6.3% of RTX pts and 8.5% of PLA pts; IgM levels were below LLN in 28.7% of RTX pts and 9.7% of PLA pts. Mean IgG levels did not significantly fall in the RTX group over time. Low Ig levels did not correlate with serious infectious AEs. Conclusion: Pts who developed AEs and SAEs and overall infection rates were comparable between groups. However, infectious SAEs were higher in PLA pts. Pts with infusion reactions were similar in each group after the 1st and 2nd infusions; however, a greater number of RTX pts experienced infusion reactions after the 3rd and 4th infusions. Herpes viral infections, neutropenia, and serum sickness occurred more frequently in the RTX group. Disclosure of Interest: J.Merrill, Genentech, Consultant, Grant/Research Support K. Latinis, Genentech, Consultant, Research Support, Speakers Bureau T. Utset, Genentech, Consultant R. Furie, Genentech, Consultant, Grant/Research Support C. Neuwelt, Genentech, Roche, Biogen/Idec, Grant/Research Support, Speakers Bureau R. Looney, Genentech, Roche, Biogen/Idec, Consultant H. Hsieh, Genentech, Employee, Shareholder B. Wagner, Genentech, Employee P. Brunetta, Genentech, Employee, ShareholderCitation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 249Session: SLE, Sjgren's and APS Treatment (Poster Presentations )