A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis.
OBJECTIVE
CD40-CD40 ligand (CD40L) interactions play a significant role in the production of autoantibodies and tissue injury in lupus nephritis. We performed an open-label, multiple-dose study to evaluate the safety, efficacy, and pharmacokinetics of BG9588, a humanized anti-CD40L antibody, in patients with proliferative lupus nephritis. The primary outcome measure was 50% reduction in proteinuria without worsening of renal function.


METHODS
Twenty-eight patients with active proliferative lupus nephritis were scheduled to receive 20 mg/kg of BG9588 at biweekly intervals for the first 3 doses and at monthly intervals for 4 additional doses. Safety evaluations were performed on all patients. Eighteen patients receiving at least 3 doses were evaluated for efficacy.


RESULTS
The study was terminated prematurely because of thromboembolic events occurring in patients in this and other BG9588 protocols (2 myocardial infarctions in this study). Of the 18 patients for whom efficacy could be evaluated, 2 had a 50% reduction in proteinuria without worsening of renal function. Mean reductions of 38.9% (P < 0.005), 50.1% (P < 0.005), and 25.3% (P < 0.05) in anti-double-stranded DNA (anti-dsDNA) antibody titers were observed at 1, 2, and 3 months, respectively, after the last treatment. There was a significant increase in serum C3 concentrations at 1 month after the last dose (P < 0.005), and hematuria disappeared in all 5 patients with significant hematuria at baseline. There were no statistically significant reductions in lymphocyte count or serum immunoglobulin, anticardiolipin antibody, or rubella IgG antibody concentrations after therapy.


CONCLUSIONS
A short course of BG9588 treatment in patients with proliferative lupus nephritis reduces anti-dsDNA antibodies, increases C3 concentrations, and decreases hematuria, suggesting that the drug has immunomodulatory action. Additional studies will be needed to evaluate its long-term effects.
Boumpas
Dimitrios T
DT
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. boumpasd@med.uoc.gr
Furie
Richard
R
Manzi
Susan
S
Illei
Gabor G
GG
Wallace
Daniel J
DJ
Balow
James E
JE
Vaishnaw
Akshay
A
D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D019138:Antibodies, Blocking / Q000009:adverse effects / Q000627:therapeutic use*; D023201:CD40 Ligand / Q000276:immunology*; D003176:Complement C3 / Q000032:analysis; D005260:Female; D006417:Hematuria / Q000188:drug therapy*; D006801:Humans; D008181:Lupus Nephritis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D019138:Antibodies, Blocking; D003176:Complement C3; D023201:CD40 Ligand