Alice Goodman

June 02, 2011

June 2, 2011 (London, United Kingdom) — Six years of follow-up confirm the benefits of belimumab reported in phase 3 trials of systemic lupus erythematosus (SLE), according to the results of an open-label study announced here at the European League Against Rheumatism Congress 2011.

These benefits include durable sustained improvement in disease activity and decreases in severe flares. The drug was safe and generally well tolerated, which is promising because it is the first new drug for SLE in half a century, said lead investigator Michelle Petri, MD, from Johns Hopkins School of Medicine in Baltimore, Maryland.

"The initial message of phase 3 studies is reinforced with open-label follow-up, with a reduction in flares, reduction in the use of corticosteroids, and improvement in serologies," Dr. Petri announced, but warned that "the drug takes a while to act; serologies are improved at 1 month and clinical response is seen at 3 to 6 months."

Belimumab is a monoclonal antibody that inhibits soluble B-lymphocyte stimulator, which is a cytokine that is overexpressed in SLE and correlates with changes in disease activity.

Data presented were based on a 6-year follow-up of 449 patients with active autoantibody-positive SLE originally enrolled in a 1-year placebo-controlled, double-blind, randomized phase 2 trial. They were continued on 1 of 3 doses of belimumab for a total of 76 weeks in an open-label extension phase, and then put on belimumab 10 mg/kg for a long-term continuation open-label trial.

After 6 years of exposure to the drug, the response rate in SLE patients increased from 46% at week 52 (vs 29% with placebo) to 55% to 61%. The frequency of flares was 84% with belimumab (vs 85% with placebo) at 1 year, which declined to 42% at years. The frequency of flares was 17% with belimumab (vs 19% with placebo) at 1 year, which declined to 5% after 6 years of exposure to the drug.

Dr. Petri said that the complement level was normalized over time with belimumab and that the use of corticosteroids declined over time, with a mean reduction in corticosteroid use of 34% and an absolute reduction of 4.7 mg/day at 6 years, compared with baseline.

Adverse events decreased or stabilized over time, she added. Over the 6-year period, 5 deaths were reported: 2 from suicide, 1 from respiratory failure, 1 from coronary artery disease, and 1 from infection.

When asked how belimumab should be used, Dr. Petri advised: "Start belimumab when the standard of care is not working, especially in patients in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement."

"Belimumab should be considered a major advance," said Jane E. Salmon, MD, commenting on the long-term follow-up data. Dr. Salmon is director of the Lupus Center for Excellence and professor of medicine at the Hospital for Special Surgery and Weill-Cornell Medical Center in New York City.

"It is a new drug for SLE with a good safety record and evidence of moderate efficacy. We don't know yet if it will change the course of serious lupus, because patients with nephritis were not included in the studies," Dr. Salmon said.

Dr. Petri reports receiving research support and serving as a consultant for Human Genome Sciences/GlaxoSmithKline. Dr. Salmon has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2011: Abstract THU0409. Presented May 26, 2011.

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