MIAMI BEACH — Rituximab treatment appears safe and efficacious for refractory systemic lupus erythematosus in children, Dr. Obioma Nwobi and colleagues reported in a poster at the annual Masters of Pediatrics conference sponsored by the University of Miami.
Average SLE Disease Activity Index scores improved from 43 at baseline to 28 at 6 months post treatment in 16 children. Rituximab was well tolerated in 15 patients, but one died 20 days after starting rituximab of acute bacterial endocarditis.
Rituximab (Rituxan) has come under scrutiny after two patients treated with rituximab for SLE developed progressive multifocal leukoencephalopathy (PML), a viral infection of the central nervous system.
SLE is not an approved indication for rituximab, which selectively depletes CD20+ B cells. It is approved only for the treatment of non-Hodgkin's lymphoma and refractory rheumatoid arthritis.
The death in the current study was likely “related to the severe immune suppression imposed by the use of Cytoxan prior to the rituximab,” senior author Dr. Carolyn Abitbol said in an interview.
“Although Cytoxan has long been considered the 'standard of care' in treating SLE nephritis because of its efficacy, the primary cause of death in lupus patients is infection,” she said.
The safety and efficacy of rituximab has been established in at least three adult SLE trials, numerous rheumatoid arthritis trials, and in more than 300,000 patients treated for lymphomas, said Dr. Abitbol, professor of pediatrics and clinical director of pediatric dialysis, University of Miami.
Dr. Abitbol agreed with a recent statement that the reported deaths were the results of extreme immunosuppression, and were not attributable to rituximab (the statement can be located online at www.hopkins-arthritis.som.jhmi.edu/news-archive/2007/genentech-PML.html
Rituximab infusions were administered weekly at an initial dose of 188 mg/m
Six months after treatment, significant decreases were observed from baseline in average urine albumin:creatinine ratio (3,756 mg/g vs. 361 mg/g), urine protein:creatinine ratio in patients not on dialysis (4.2 mg/dL vs. 0.7 mg/dL), and serum creatinine (1.2 mg/dL vs. 0.6 mg/dL).
Significant increases were seen in serum albumin levels (2.6 mg/dL vs. 3.5 mg/dL) and CD4 T cells (344 vs. 556). An insignificant increase in CD8 T cells also was observed (332 vs. 590). CD 20+ B cells decreased significantly at 6 months from baseline (243 vs. 74). B-cell depletion, measured serially over 6–18 months, lasted an average of 6–8 months.
The authors said collaborative controlled trials are needed in children to develop protocols for rituximab as a component of induction and/or maintenance therapy for SLE.