A PILOT-STUDY OF 2-CHLORO-2'-DEOXYADENOSINE IN THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS-ASSOCIATED GLOMERULONEPHRITIS

Objective. To determine the safety and tolerability, as well as the cl inical and immunologic effects, of 2-chloro-2'-deoxyadenosine (2-CdA) in patients with systemic lupus erythematosus-associated glomeruloneph ritis. Methods. In a phase I study, 12 patients with proliferative lup us nephritis received 2-CdA either in weekly escalating intravenous tr eatments (0.15 mg/kg/week x 4, 0.1875 mg/kg/week x 4, 0.225 mg/kg/week x 4; n = 5) or in a continuous 7-day infusion (0.05 mg/kg/day; n = 7) . Safety, renal improvement, and immunologic effects were evaluated fo r 12 months. Results. Patients treated with 2-CdA showed peripheral ly mphocyte depletion without a significant reduction in neutrophil, mono cyte, or platelet numbers or hematocrit levels. Naive and memory T cel ls were decreased, as were lymphocytes with markers of early and late activation. Peripheral B cell depletion was not associated with signif icant decreases in serum immunoglobulin levels. Continuous infusion in duced better clinical responses than weekly infusions, as evidenced by 1) the percentage of patients showing complete response (43% versus 0 %), 2) the percentage with at least 50% reduction in proteinuria (43% versus 20%), 3) the percentage with at least a 50% reduction in urinar y dysmorphic red cells (57% versus 0%), and 4) the percentage in whom cellular casts disappeared (43% versus 0%), Several infections occurre d; these responded to standard antibiotic therapy. Conclusion. In this pilot study, 2-CdA was safely administered to 12 patients with lupus nephritis. It induced prolonged reductions in lymphocyte populations a nd may be efficacious in selected patients with lupus nephritis when a dministered as a continuous infusion.