AMSTERDAM, The Netherlands – Within 15 years, the standard drug treatment of systemic lupus erythematosus (SLE) will have changed radically because lupus care is "moving from serendipity to sense" thanks to identification of key molecules in the disease process, David A. Isenberg, MD, told a plenary session at the EULAR 2006 meeting.1

"In the past 50 years the outlook for patients with SLE has improved considerably with mortality figures improving from 50% 5-year survival to around 80% 15-year survival," Dr. Isenberg, of the Centre for Rheumatology, University College London, UK, said. "This improvement has been brought about by the use of immunosuppressive drugs, renal dialysis, and renal transplantation. However, a significant number of patients continue to die of the disease and the morbidity for many others remains significant."

Nonspecific immunosuppression with drugs such as azathioprine and methotrexate is being replaced by blocking molecules known to be essential to the development of SLE. Dr. Isenberg discussed autologous bone-marrow transplant, abatacept (CTLA4Ig, OrenciaR, Bristol-Myers Squibb), B-cell tolerance induction, and B-cell depletion strategies.

"It is now evident that blocking B cells (using agents that bind CD20 and CD22) holds great promise. Likewise attempts to block ds DNA binding antibodies using a B-cell toleragen and peptides have also shown some encouraging results." Dr. Isenberg said. "A little more surprisingly (given their propensity to induce anti-ds–DNA antibodies when given to patients with rheumatoid arthritis) the use of TNF alpha blockade has been both attempted and shown to be successful in open label studies."

Although European studies of autologous transplant have produced some encouraging results, Dr. Isenberg said that transplant is best reserved for use "at the end of therapy, only when everything else has been tried." Abatacept, which is used in rheumatoid arthritis, was effective in a mouse model of lupus and is now in clinical trials. The synthetic toleragen abetimus (RiquentR, La Jolla Pharmaceuticals) continues in clinical development and has reduced renal flares in lupus patients, Dr. Isenberg said.

Under the category of "hot new things," Dr. Isenberg included B-cell depletion with rituximab (MabTheraR, RItuxanR). He discussed a trial of 40 lupus patients all of whom had failed other treatments when treated in a pilot study. Two infusions of rituximab reduced flares in most patients and was notable for producing benefits in a wide range of body systems, including the skin, central nervous system, musculoskeletal system, vasculitis, and kidney. "There were benefits right across the board," Dr. Isenberg. One patient in this group continues in long-standing B-cell depletion 5 years after receiving only 2 doses of rituximab.

Subsequent observations have shown that rituximab can also be repeated safely and effectively. "My clinical impression is that patients do better after the second and third treatments with rituximab than after the first course," Dr. Isenberg said. He also noted that kidney biopsies have shown "dramatic improvements in renal histology" after rituximab treatment in some patients. "The last year has been an 'annus mirabilis' for lupus research," Dr. Isenberg said. "The combination of new ideas about treatment complimented by the availablity of widely accepted activity, damage, and patient assessment tools and a willingness on behalf of the pharmaceutical industry to undertake several double control trials really is taking us into an new era of therapy for patients with SLE."

Reference