Disheartening News for Lupus Patients

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.