Rheumatology: April 2008 Archives

The monoclonal antibody Rituxan (rituximab) is not clinically effective in patients with systemic lupus erythematosus (SLE) who do not have lupus nephritis, according to data from a 52-week phase 2/3 study. The results were announced today by the drug's US comarketers, Genentech and Biogen Idec. A phase 3 study of Rituxan in lupus nephritis, which affects approximately one third of SLE patients, is currently recruiting subjects.

In today's reported study, 257 patients with moderate-to-severe SLE received 2 infusions (15 days apart) of randomized Rituxan or placebo in a double-blind fashion, in addition to background prednisone therapy. Patients were retreated at 6 months and evaluated every 4 weeks. At 1 year, the proportions of patients who reached the primary endpoint—a major or partial clinical response per the BILAG index score—were not statistically different between the 2 treatment groups. (Percentages were not provided in the companies' press release.) The assessment of 6 secondary endpoints also failed to show statistical treatment differences.

Current long-time therapies for SLE, which may affect more than 1.5 million Americans according to the Lupus Foundation of America, include corticosteroids; the corticosteroid-sparing agents methotrexate, cyclophosphamide, and azathioprine; and the anti-organ-rejection agent mycophenolate mofetil (CellCept; Roche). Given the potential roles of B cells in the pathogenesis of SLE, including antigen presentation and the production of autoantibodies, the investigation of anti-B-cell therapies like Rituxan in SLE is mechanistically founded. Another B-cell targeted therapy, which is entering phase 3 development in SLE, is belimumab (LymphoStat B)—a fully human monoclonal antibody that inhibits the cytokine B-lymphocyte stimulator (BLyS).

BILAG = British Isles Lupus Assessment Group.