B Cells and Lupus

New and emerging therapies target autoimmune antibody-producing B Cells

Following the success of biologic drugs in treating rheumatoid arthritis (RA), researchers are now examining their potential for lupus. Unlike other immunosuppressants, which work by suppressing the entire immune system, biologics selectively target certain cells implicated in the development of the disease. A number of biologics, including Benlysta (a new drug for lupus approved by the FDA in March of 2011), target B cells -- immune system cells that make antibodies to viruses and other invading pathogens. 

Scientists believe that in individuals who have lupus, the B-cell antibody production process goes awry, generating autoimmune antibodies (antibodies that attack and destroy the body's own healthy tissues) and secreting cytokines (proteins produced by certain immune system cells) that induce inflammation. 

B-cell depletion therapy for lupus. One approach to tackling this aberrant antibody production is a process known as B-cell depletion therapy. Although early studies showed that the RA drug rituximab (Rituxan) effectively depleted B cells and reduced disease activity, two important phase III randomized, controlled trials failed to show any difference between Rituxan and placebo. Although the results were disappointing, scientists have not abandoned this strategy altogether. Preliminary evidence from additional studies suggests that Rituxan may help ameliorate some of the complications that can occur in people with lupus, such as antiphospholipid antibody syndrome. 

B-cell receptor inhibition for lupus. Another approach, called B-cell receptor inhibition, is also under investigation. B-cell receptor inhibitors work by reducing the enhanced activation of B cells that occurs in people with lupus. Results from a small 12-week phase II randomized, controlled trial of the B-cell receptor inhibitor epratuzumab showed that it significantly reduced disease activity in patients with moderate to severe active lupus. 

B-cell survivor-factor inhibition for lupus. A third strategy, and the one upon which Benlysta is based, is known as B-cell survivor-factor inhibition. Drugs in this class reduce the actions of a protein (B lymphocyte stimulator, or BLyS) that increases the life span and inflammatory potential of B cells. 

In a study presented at the annual meeting of the American College of Rheumatology, researchers reported that in a 52-week phase III trial of 865 lupus patients, those who took 1 mg/kg or 10 mg/kg of the drug along with standard therapy (prednisone and immunosuppressants) had significant reductions in disease activity, flare rates, use of prednisone and time to first flare compared with placebo users. Data from an extension of that study to 76 weeks show that the results were sustained. 

Source:

Johns Hopkins Health Alerts