4 YEAR EXPERIENCE OF BELIMUMAB, A FULLY HUMAN MONOCLONAL ANTIBODY, IN THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

J.T. Merrill, R. Furie, D.J. Wallace, J. McKay, E.M. Ginzler, F. Wellborne, C. Aranow, M. Burnette, N. Mishra, L. Pineda, J. Zhong, D. Hough, W. Freimuth, LBSL02/99 Study GroupOMRF, OK City, OK NSLIJHS, Lake Success, NY Cedars-Sinai UCLA, Los Angeles, CA OK Ctr for Arth Ther & Res, Tulsa, OK SUNY Downstate, Brooklyn, NY Houston Inst for Clin Res, Houston, TX Feinstein Inst for Med Res, Manhasset, NY Tampa Med Grp, Tampa, FL Wake Forest U, Winston-Salem, NC HGS, Rockville, MD Clin Res, HGS, Rockville, United States US/CanadaObjectives: To provide 4 yr results of belimumab in SLE patients. Methods: 449 SLE pts enrolled in a phase 2, placebo (plc)-controlled, 52-wk trial of belimumab (1, 4, 10 mg/kg, monthly) plus standard background SLE therapy. In the 24-wk extension, plc pts switched to belimumab 10 mg/kg, and belimumab pts remained on the same dose could be increased to 10 mg/kg at discretion of the investigator. After 76 wks, all remaining pts (n=296) received belimumab 10 mg/kg. Safety was monitored monthly. The 4-yr safety dataset was divided into eight 6-month intervals for reporting adverse event (AE) rates. Interval 1 represents the initial belimumab treatment which for plc pts began in the extension period. Disease activity assessments using SELENA SLEDAI (SS) and Physician's Global Assessment (PGA) were conducted every 4 to 8 wks. Post-hoc analyses identified a subgrp of serologically active pts for which belimumab was efficacious. Results: By 4 yrs, overall belimumab exposure was 1,143 pt yrs. The incidence rates (per 100 pt yrs) of all AE categories including serious AEs, and overall and serious infections decreased over 4 yrs (Table 1). At wk 52, serologically active pts on belimumab had significantly greater improvements in mean SS scores (29% vs 14% plc, p=0.0435) and in PGA (33% vs 11% plc, p=0.0011) from baseline. After 4 yrs, SS and PGA both improved 44% from baseline. In plc to belimumab pts, SS and PGA improved 40% and 31%, respectively from baseline. Table 1. AE incidence rate (per 100 patient-years) 6-month intervalsAll belimumab-treated patients 12345678 (0-0.5yr)(0.5-1yr)(1-1.5yr)(1.5-2yr)(2-2.5yr)(2.5-3yr)(3-3.5yr)(3.5-4yr) Number of patients (patient-yrs)424 (206)400 (184)353 (166)314 (147)284 (136)261 (122)218 (100)182 (82) Overall AEs194183183184179163163158 Serious AEs211817171916127 Overall infections119107103111105957678 Serious infections6.85.43.65.42.93.31.03.7 Malignant neoplasm0.50.51.21.400.81.01.2 Discontinued due to any AE5.48.13.62.01.52.43.01.2 Conclusion: Belimumab was generally well tolerated with background SLE therapy during long-term exposure. In serologically active pts, belimumab treatment resulted in sustained improvement in SLE disease activity over 4 yrs. Disclosure of Interest: JT Merrill, HGS, investigator and consultant R Furie, HGS, investigator and consultant DJ Wallace, HGS, investigator and consultant J McKay, HGS, investigator EM Ginzler, HGS, grant/research - support F Wellborne, HGS, grant/research - support C Aranow, HGS, grant/research - support M Burnette, HGS, investigator N Mishra, HGS, investigator L Pineda, HGS, Employee J Zhong, HGS, Employee D Hough, HGS, Employee W Freimuth, HGS, EmployeeCitation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 254Session: SLE, Sjgren's and APS Treatment (Poster Presentations )