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Treatment with the targeted drug rituximab can significantly benefit some patients with severe lupus nephritis who do not respond to conventional therapy, according to results of a retrospective analysis reported in the March issue of the Clinical Journal of the American Society of Nephrology.
"Standard treatment for lupus nephritis, including corticosteroids and cyclophosphamide, is efficient but is still associated with refractory or relapsing disease, or severe deleterious effects," write Catherine Melander, MD, from the department of nephrology, Assistance Publique–Hôpitaux Paris, France, and colleagues. "Rituximab, a monoclonal chimeric anti-B cell antibody, is increasingly used in patients with lupus nephritis, but reported series were small and had a short follow-up."
The goal of this study was to assess long-term (>12 months) efficacy and safety of rituximab in 20 systemic lupus erythematosus patients with severe proliferative or membranous lupus nephritis.
The patients (19 women and 1 man) were identified from chart reviews from 8 French nephrology centers between October 2003 and December 2006. The patients had to have at least 12 months of follow-up data and have active class III, IV, or V lupus nephritis established by kidney biopsy less than 3 months before rituximab initiation. Kidney biopsy disclosed class IV lupus nephritis in 15 patients and class V lupus nephritis in 5 patients.
Rituximab was administered weekly for 4 weeks at a dose of 375 mg/m2 of body surface area, with the exception of 2 patients who received 3 injections. Twelve patients received rituximab for lupus nephritis refractory to standard treatment, 6 patients were treated for relapsing disease, and 2 patients received rituximab as first-line therapy. Three patients received cyclophosphamide concomitantly with rituximab. Ten patients received new injections of rituximab as maintenance therapy.
After a median follow-up of 22 months (range, 10 – 51 months), complete renal remission was obtained in 7 patients, and partial renal remission was obtained in 5 patients, for an overall renal response rate of 60%.
Among the 15 patients with class IV lupus nephritis, 66% responded to rituximab, including 5 complete renal remissions and 5 partial renal remissions. Two of the 5 patients treated with rituximab for class V lupus nephritis reached complete renal remission. There was no response to rituximab in patients with rapidly progressing glomerulonephritis.
The absence of renal remission was significantly associated with black ethnicity (P = .004) and with the absence of B cell depletion 1 month after rituximab initiation.
B cell depletion at 1 month occurred in all 11 responders compared with 1 of the 6 nonresponders (P < .001). In 2 patients, B cell depletion was not achieved until month 3. Neither patient responded to treatment, "suggesting the importance of early B cell depletion," the study authors write.
The rituximab injections were well-tolerated overall, the authors report. Two patients experienced headache, and 1 patient experienced nausea. Five patients had infections during follow-up, including septic shock and septic arthritis in 2 patients and viral infections, including oropharyngitis and cutaneous herpes zoster, in 3 patients. Moderate neutropenia was reported in 4 patients, and 2 patients experienced posterior reversible encephalopathy syndrome and were successfully treated with antihypertensive drugs. One of the patients who developed posterior reversible encephalopathy syndrome died from massive cerebral hemorrhage "in a context of incompletely controlled [systemic lupus erythematosus] and hypertension," according to the study authors.
They write that hyperreactive B cells seem to play a central role in the pathogenesis of systemic lupus erythematosus through the production of auto-antibodies, antigen processing and presentation, recruitment of auto-reactive T cells, interaction with antigen presenting cells, and secretion of cytokines. Because of this, targeting B cells could be a therapeutic option in systemic lupus erythematosus, especially lupus nephritis.
"Our study provides valuable information regarding rituximab efficacy in patients with severe [lupus nephritis]," the authors write. Although the study is not controlled, "it is highly unlikely that patients with severe lupus nephritis and renal insufficiency may be included in randomized controlled trials."
They conclude that rituximab could be an interesting option in refractory or relapsing lupus nephritis, excluding rapidly progressing glomerular nephritis, and they call for prospective studies to assess the efficiency of rituximab, with or without cyclophosphamide, in severe lupus nephritis.
The authors have disclosed no relevant financial relationships.
Clin J Am Soc Nephrol. 2009;4:579–587.
 
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