SHANGHAI, China—Current strategies for treating systemic lupus erythematosus (SLE) have improved outcomes for many patients but are still far from adequate, according to speakers at the 8th International Congress on SLE.^1,2

"Lupus patients are surviving into the later stages of disease, but the price they pay is increased morbidity from a range of complications either from the disease itself or [from] the long-term consequences of therapeutic agents used to treat SLE," said Rosalind Ramsey-Goldman, MD, DrPH, professor of medicine at Northwestern University's Feinberg School of Medicine, in Chicago, Illinois.

Dr. Ramsey-Goldman blamed some of these unfavorable outcomes on medications that have a "generic" but not a "lupus-specific" anti-inflammatory or immunologic effect, as well as on treatment strategies that may not be effective, and on medications with significant short- and long-term toxicities. She said that as understanding of lupus pathogenesis improves, it will become possible to design new thearapies targeting specific pathways involved in lupus development or tissue damage.

But there are several hurdles. "Among the questions that must be answered is determining clearly defined and well-validated outcome measures that are sensitive to change in disease status…in terms of improvement in survival and quality of life, determining the optimal time to assess the appropriate outcomes, and accounting for not only disease damage but changing outcomes as our treatments evolve," Dr. Ramsey-Goldman pointed out.

Pierre Youinou, MD, with the laboratory of immunology at Brest University Medical School, in France, discussed the B-cell activating factor (BAFF) as one of those potential target treatments. He said that excess BAFF leads to B-cell accumulation and activation, as well as differentiation and autoantibody production. "Such effects, coupled with the striking similarity between the phenotype of BAFF transgenic mice and the presentation of patients with…SLE, support a role for this cytokine in the pathogenesis or maintenance of autoimmune settings. New evidence has indeed sparked a great deal of interest in the possibility that B-cells play a central role in the pathogenesis of SLE," he noted.

Because BAFF can produce a SLE-like disease in mice, Dr. Youinou said that a number of research groups are now examining the role of BAFF in human SLE and that early trials with recombinant high-affinity anti-BAFF monoclonal antibodies have met "the primary efficacy endpoint of reducing the symptoms, but need further evaluation."

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References

1. Ramsey-Goldman R. Pros and cons of current treatments for SLE: Do we need targeted therapies? Presented at: 8th International Congress on SLE; May 24, 2007; Shanghai, China.
2. Youinou P. BAFF, a potential therapeutic target in systemic lupus erythematosus. Presented at: 8th International Congress on SLE; May 24, 2007; Shanghai, China.