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14-06-2012 | Immunology | Article

Researchers call for bortezomib trials in SLE


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MedWire News: The myeloma drug bortezomib could represent a novel treatment option for patients with systemic lupus erythematosus (SLE), reported researchers at The European League Against Rheumatism's Annual Congress of Rheumatology, held in Berlin, Germany.

Treatment with up to four cycles of the proteasome inhibitor resulted in significant decreases in SLE disease activity and antidouble-stranded-(ds)-DNA antibodies in a small case series of patients with the condition.

Lead researcher Reinhard Voll (University Medical Center Freiburg, Germany) said the data indicate that "clinical trials should be initiated to explore the use of bortezomib as induction therapy in patients with refractory SLE."

Voll explained that long-lived plasma cells secreting pathogenic autoantibodies may contribute to refractory disease courses of SLE, because such cells are resistant to conventional therapies. Eliminating these cells by inhibiting their proteasomes with drugs such as bortezomib could benefit patients with SLE.

Following positive trials in mice, the researchers treated 13 SLE patients, who had not sufficiently responded to or did not tolerate conventional drugs, with intravenous bortezomib 1.3 mg/m2 of body surface area on days 1, 4, and 8, plus day 11 in seven of the patients. Treatment cycles were repeated up to four times with 10 to 14 days between cycles.

All patients gave informed consent to the off-label treatment, and most also received dexamethasone 20 mg.

As well as significant reductions in anti-dsDNA antibodies, to almost undetectable levels is some cases, there were reductions of up to 50% in levels of extractable nuclear antibodies.

SLE disease activity index scores decreased by at least 4 points in 12 of the 13 patients, with the greatest decreases observed in three patients who had initial scores of 20 or higher. These patients experienced declines of more than 10 points with bortezomib treatment.

Furthermore, proteinuria declined within 6 weeks of treatment in all patients with active lupus nephritis, and one patient reached normal protein excretion within 4 months.

Three patients had to stop treatment because of adverse events, two for polyneuropathy and one for fever. Other adverse events included herpes zoster infection, urinary tract infection, headache, nausea, rhinitis, and allergic skin reaction, each occurring in one or two patients.

Voll also noted that protective vaccine antibody titers to hepatitis B surface antigen and tetanus toxoid, which can be affected by bortezomib treatment, decreased, but remained within the protective range.

He concluded: "The proteasome inhibitor bortezomib may provide an effective new therapy for refractory SLE."

By Laura Cowen

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