Eprodisate for the treatment of renal disease in AA amyloidosis.
BACKGROUND
Amyloid A (AA) amyloidosis is a complication of chronic inflammatory conditions that develops when proteolytic fragments of serum amyloid A protein (SAA) are deposited in tissues as amyloid fibrils. Amyloid deposition in the kidney causes progressive deterioration in renal function. Eprodisate is a member of a new class of compounds designed to interfere with interactions between amyloidogenic proteins and glycosaminoglycans and thereby inhibit polymerization of amyloid fibrils and deposition of the fibrils in tissues.


METHODS
We performed a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of eprodisate in patients with AA amyloidosis and kidney involvement. We randomly assigned 183 patients from 27 centers to receive eprodisate or placebo for 24 months. The primary composite end point was an assessment of renal function or death. Disease was classified as worsened if any one of the following occurred: doubling of the serum creatinine level, reduction in creatinine clearance by 50% or more, progression to end-stage renal disease, or death.


RESULTS
At 24 months, disease was worsened in 24 of 89 patients who received eprodisate (27%) and 38 of 94 patients given placebo (40%, P=0.06); the hazard ratio for worsening disease with eprodisate treatment was 0.58 (95% confidence interval, 0.37 to 0.93; P=0.02). The mean rates of decline in creatinine clearance were 10.9 and 15.6 ml per minute per 1.73 m(2) of body-surface area per year in the eprodisate and the placebo groups, respectively (P=0.02). The drug had no significant effect on progression to end-stage renal disease (hazard ratio, 0.54; P=0.20) or risk of death (hazard ratio, 0.95; P=0.94). The incidence of adverse events was similar in the two groups.


CONCLUSIONS
Eprodisate slows the decline of renal function in AA amyloidosis. (ClinicalTrials.gov number, NCT00035334.)
Dember
Laura M
LM
Boston University School of Medicine, Boston, MA 02118, USA. ldember@bu.edu
Hawkins
Philip N
PN
Hazenberg
Bouke P C
BP
Gorevic
Peter D
PD
Merlini
Giampaolo
G
Butrimiene
Irena
I
Livneh
Avi
A
Lesnyak
Olga
O
Puéchal
Xavier
X
Lachmann
Helen J
HJ
Obici
Laura
L
Balshaw
Robert
R
Garceau
Denis
D
Hauck
Wendy
W
Skinner
Martha
M
D000686:Amyloidosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D001172:Arthritis, Rheumatoid / Q000150:complications; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D010505:Familial Mediterranean Fever / Q000150:complications; D005260:Female; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011407:Propane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011507:Proteinuria; D000685:Serum Amyloid A Protein / Q000187:drug effects; D013451:Sulfonic Acids / Q000009:adverse effects / Q000627:therapeutic use*
D006025:Glycosaminoglycans; D000685:Serum Amyloid A Protein; D013451:Sulfonic Acids; C520274:eprodisate; D003404:Creatinine; D011407:Propane