Cyclophosphamide is often used for induction of nephritis, but 30% of patients may still develop end-stage renal disease despite treatment, said Dr. Kahn. Mycophenolate mofetil has been shown to have equal efficacy to cyclophosphamide in induction of remission of nephritis, but sufficient pediatric data are lacking. Azathioprine is effective for maintenance therapy of nephritis after the induction phase.
Other options that are sometimes used include intravenous immunoglobulin, methotrexate, calcineurin inhibitors (such as tacrolimus), plasmapheresis, and autologous stem cell transplantation/immunoablative therapy.
More recently, the focus has been on target-specific therapy for SLE with potentially fewer side effects. Rituximab, which targets B cells that have the CD20 surface antigen, is sometimes used to treat resistant patients, but there is no strong clinical evidence to demonstrate its effectiveness in cSLE (Arthritis Rheum. 2009;61:482-7; Clin. J. Am. Soc. Nephrol. 2009;4:579-87).
Abatacept, which targets T cells by binding to B7 peripheral membrane protein, has shown some clinical benefit in a phase IIB randomized clinical trial, and is undergoing clinical testing as an add-on induction therapy with cyclophosphamide (Arthritis Rheum. 2010;62:3077-87). Belimumab, a monoclonal antibody that targets BLyS (B-lymphocyte stimulator)/BAFF (B-cell activating factor), is the first FDA-approved medication for SLE in more than 50 years, based on recent clinical trials that demonstrate increased efficacy and fewer flares of disease, compared with placebo (Arthritis Rheum 2009;61:1168-78; Lancet 2011;377:721-31).
Although recent data regarding belimumab provide some hope, it "may be naive to think that a target-specific therapy exists in this complex, polygenic, heterogeneous disease," commented Dr. Kahn.
In concluding his talk, Dr. Kahn spoke about some barriers to the effective treatment of cSLE. These include physicians’ failure to detect the subtle changes of early disease, a lack of awareness regarding the neuropsychiatric manifestations of the disease, and physicians’ fear of being overly aggressive with treatment. He also warned about overt or covert adolescent noncompliance, and the danger of adolescents’ dropping out of the health care system once they need to transition to adult care.