TY - JOUR
T1 - Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome
AU - Simon, Anna
AU - Drewe, Elizabeth
AU - Van Der Meer, Jos W.M.
AU - Powell, Richard J.
AU - Kelley, Richard I.
AU - Stalenhoef, Anton F.H.
AU - Drenth, Joost P.H.
PY - 2004/5
Y1 - 2004/5
N2 - Hyperimmunoglobulinemia D (hyper-IgD) and periodic fever syndrome, a hereditary autoinflammatory syndrome, is characterized by lifelong recurrent episodes of fever and inflammation. No effective treatment is known. It is caused by a defect of mevalonate kinase, an enzyme that follows 3′-hydroxy-3′-methylglutaryl-coenzyme A (HMG-CoA) reductase in the isoprenoid pathway. We wanted to test the hypothesis that inhibition of HMG-CoA reductase would ameliorate the inflammatory attacks. Six patients with hyper-IgD syndrome and proven mevalonate kinase deficiency were followed up for 2 treatment periods with either simvastatin, 80 mg/d, or placebo for 24 weeks, separated by a 4-week washout period in a double-blind fashion. Simvastatin resulted in a drop in urinary mevalonic acid concentration in all patients and decreased the number of febrile days in 5 of 6 patients. No side effects were observed. These data offer preliminary evidence for the hypothesis that simvastatin may improve inflammatory attacks in the hyper-IgD syndrome. This highlights the anti-inflammatory properties of HMG-CoA reductase inhibition.
AB - Hyperimmunoglobulinemia D (hyper-IgD) and periodic fever syndrome, a hereditary autoinflammatory syndrome, is characterized by lifelong recurrent episodes of fever and inflammation. No effective treatment is known. It is caused by a defect of mevalonate kinase, an enzyme that follows 3′-hydroxy-3′-methylglutaryl-coenzyme A (HMG-CoA) reductase in the isoprenoid pathway. We wanted to test the hypothesis that inhibition of HMG-CoA reductase would ameliorate the inflammatory attacks. Six patients with hyper-IgD syndrome and proven mevalonate kinase deficiency were followed up for 2 treatment periods with either simvastatin, 80 mg/d, or placebo for 24 weeks, separated by a 4-week washout period in a double-blind fashion. Simvastatin resulted in a drop in urinary mevalonic acid concentration in all patients and decreased the number of febrile days in 5 of 6 patients. No side effects were observed. These data offer preliminary evidence for the hypothesis that simvastatin may improve inflammatory attacks in the hyper-IgD syndrome. This highlights the anti-inflammatory properties of HMG-CoA reductase inhibition.
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U2 - 10.1016/j.clpt.2004.01.012
DO - 10.1016/j.clpt.2004.01.012
M3 - Article
C2 - 15116060
AN - SCOPUS:2042501706
SN - 0009-9236
VL - 75
SP - 476
EP - 483
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 5
ER -