Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Five-Year Experience with Belimumab, a BLyS-Specific Inhibitor, in Patients with Systemic Lupus Erythematosus (SLE).
Merrill6, J. T., Wallace1, D. J., Furie4, R. A., Petri3, M. A., Stohl10, W., Chatham8, W. W., McCune9, J.
Cedars-Sinai/UCLA, Los Angeles, CA
USC Keck School of Medicine, Los Angeles, CA
Washington Hospital Center, Washington, DC
Human Genome Sciences, Inc, Rockville, Rockville, MD
Johns Hopkins University School of Medicine, Timonium, MD
North Shore LIJ Health System, Lake Success, NY
Oklahoma Center for Arthritis Therapy & Research, Tulsa, OK
Oklahoma Medical Research Foundation, Oklahoma City, OK
SUNY Downstate Medical Center, Brooklyn, NY
UAB Arthritis Clinical Intervention Program, Birmingham, AL
University of Michigan Health System, Ann Arbor, MI
To examine 5-year safety of belimumab in an open-label extension study of SLE patients and evaluate long-term efficacy in a subgroup similar to those in recent phase 3 trials.
449 SLE patients with SELENA-SLEDAI (SS) >=4 enrolled in a phase 2, 52-wk, randomized, double-blind study of belimumab 1, 4, or 10 mg/kg q28d vs placebo, plus background SLE therapy (NCT00071487). At wk 56, placebo patients received belimumab 10 mg/kg; prior belimumab patients received the same dose or 10 mg/kg. At wk 80, 296 patients (66%) entered an uncontrolled continuation study (belimumab 10 mg/kg; NCT00583362). The 5-y dataset was divided into ten 6-mo intervals for reporting efficacy and adverse events (AEs). Analyses of disease activity included the SS Flare Index (SFI) and SLE Responder Index (SRI): improvement in SS (>=4 pt), no new BILAG A or <2 new B flares, and no Physician's Global Assessment worsening (<0.3 pt) vs baseline. All efficacy assessments were limited to the seropositive (ANA titer >=1:80 and/or anti-dsDNA >=30 IU/mL) patient subgroup (n=321), who were similar to those patients enrolled in the phase 3 trials. Safety assessments were performed in all patients.
19% of patients dropped out during the placebo-controlled portion of the study, 296 enrolled in the open-label extension at wk 80, and the discontinuation rate has been 3%9%/y. Total belimumab exposure was 1415 patient-years (pty). Incidence rates (per 100 pty) of AEs remained stable or decreased over 5 y (table). In seropositive patients, SRI rate was 46% at wk 52 (vs 29% with placebo; p<0.05), increased to 55% by wk 76, and was maintained through wk 272 (59%). In this study, adjustments in background SLE therapy were permitted. The frequency of 1 new BILAG A or 2 new B flares decreased from 30% over the 1st 6 mo to 23% over the 2nd 6 mo (vs 33% and 25%, respectively, with placebo) and declined to 11% at the 4.55.0-y interval. The frequency of SFI flares decreased from 72% (severe 13%) over the 1st 6 mo to 62% (severe 8%) over the 2nd 6 mo (vs 76%[severe 9%] and 73%[severe 11%], respectively, with placebo) and further declined to 22% (severe 1%) at the 4.55.0-y interval. Autoantibody levels (anti-Sm, anti-dsDNA, anticardiolipin immunoglobulin-G) decreased over time with belimumab.
Belimumab added to standard-of-care therapy was well tolerated over 5 y. Seropositive patients treated with belimumab showed sustained improvement in disease activity, and a decline in BILAG and SFI flares over 5 y, without changing the background treatment rules.
To cite this abstract, please use the following information:
Merrill, J. T., Wallace, D. J., Furie, R. A., Petri, M. A., Stohl, W., Chatham, W. W., et al; Five-Year Experience with Belimumab, a BLyS-Specific Inhibitor, in Patients with Systemic Lupus Erythematosus (SLE). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1457