Childhood-onset systemic lupus erythematosus (cSLE) is a rare but severe autoimmune disease with multisystem involvement, the incidence is 0.3/100000-0.9/100000 children-per year with a prevalence of 3.3/100000-8.8/100000 children. A higher frequency of cSLE is reported in Asians, African Americans, Hispanics, and native Americans. Median age of onset of cSLE is between 11 and 12 years (rare below 5 years), and 80% of patients are female. cSLE follows a more severe disease course than adult-onset SLE, with higher morbidity and lower survival rates.
Originally SLE nephritis was treated by steroids with a poor outcome which improved markedly with the introduction of cyclophosphamide. The first controlled trial reporting the short-term efficacy of cyclophosphamide for lupus nephritis in adults was published in 1971. Initially this combination was advocated for a prolonged period, but unfortunately the improved outcome was found to be associated with long-term side effects, which resulted in a further search for a less toxic, but equally effective regime. Most of the studies have been performed in adults and to a large extent the current recommendations are borrowed heavily from adult studies. The current therapeutic strategy for SLE nephritis distinguishes two distinct phases of treatment. The first phase is INDUCTION therapy which aims to control disease activity by inducing remission of disease flare (which may be the initial presentation or represent a new flare). It is at this point that potential organ-threatening and/or life-threatening disease needs to be aggressively treated. The second phase is MAINTENANCE, wherein the target is to avoid relapses and control the disease by limiting inflammation and damage.
Genentech, Inc. (NYSE: DNA) and Biogen Idec (Nasdaq: BIIB) announced that a Phase III study of Rituxan® (rituximab) plus mycophenolate mofetil (MMF) and corticosteroids in patients with lupus nephritis did not meet its primary endpoint of significantly reducing disease activity at 52 weeks. The primary endpoint evaluated improvements in kidney response as measured by standard laboratory tests used to assess kidney health. A preliminary analysis of the safety data did not reveal any new or unexpected safety signals in patients receiving Rituxan