BARCELONA, Spain—Treatment with belimumab (LymphoStat-B), a human monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS®), produces a sustained improvement in systemic lupus erythematosus (SLE) symptoms in 46% of patients by 52 weeks, compared with 29% of patients who received placebo, reports Ellen Ginzler, MD, at EULAR 2007 in Barcelona, Spain.1 Dr. Ginzler is professor of medicine and chief of rheumatology at the State University of New York-Downstate Medical Center, in Brooklyn, New York.

"While the results demonstrated that treatment with belimumab resulted in a sustained improvement in SLE symptoms in patients with serologically active disease, we also confirmed that combining multiple disease activity measures is a successful method of assessing overall disease activity and appears to be associated with the presence of biomarkers and quality of life improvements in responders," Dr. Ginzler said.

Novel combined endpoint improves assessment of SLE symptoms

The 449 patients enrolled in this 52-week study received belimumab in doses of 1 mg/kg, 4 mg/kg, 10 mg/kg, or placebo plus SLE standard therapy. Overall, about 70% of patients were taking prednisone and/or antimalarials and 50% of these patients were also taking an immunosuppressant. At baseline, 71.5% of the patients had serological SLE activity.

A combined response was seen in 46% of serologically active patients taking belimumab at week 52 versus 29% of those given placebo (P = .006). This response increased to 56% for the belimumab-treated group at week 76. Patients treated with belimumab also showed improvements in physician global assessment (PGA) and SF-36 physical component score. Responders had a greater reduction in activated B-cells, the study showed. There was also a 50% reduction in levels of anti-dsDNA titre among belimumab responders.

Historically, it has been difficult to adequately measure the therapeutic responses to drug
intervention in lupus patients owing to the heterogeneous presentation of the disease. The new study used a novel endpoint that takes into account three commonly used measures of disease progression—SELENA SLEDAI (SS), PGA, and the British Isles Lupus Assessment Group (BILAG) index for classified flares (new 1A or 2B). The combined endpoint incorporated a response parameter of an improvement in SS score of >e;4 points with no new BILAG 1A or 2B flares and no worsening in PGA (<0.3 point increase) as well as controls against worsening in other organ systems.

As a result of these positive findings, two global phase III studies of belimumab are now under way, Dr. Ginzler said.

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Reference

1. Ginzler E, Furie R, Wallace D, et al. Novel combined response endpoint shows that belimumab (fully human monoclonal antibody to B-lymphocyte stimulator [BLYS]) improves or stabilizes SLE disease activity in a phase 2 trial. Presented at: EULAR 2007 Meeting; June 13-16, 2007; Barcelona, Spain. Abstract OP0018.