Gout
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《新英格兰医药杂志》
To the Editor: In discussing treatment options for gout (Oct. 23 issue),1 Terkeltaub omitted the emerging role of fenofibrate. This fibric-acid derivative is used to treat various forms of hyperlipidemia and has recently been shown to prevent the progression of coronary artery disease.2 Fenofibrate is unique among the fibrates because of its uricosuric properties and has been shown to lower serum urate levels by 19 percent in men with gout receiving established therapy with allopurinol.3 Remission of clinical episodes of gout over several years has also been reported.4
Furthermore, although this notion is controversial, high urate levels may be an independent risk factor for coronary artery disease.5 Fenofibrate might therefore have a particularly useful role in insulin-resistance syndromes, such as type 2 diabetes, because of its additional uricosuric effect.
Alastair L. Hepburn, M.R.C.P.
Imperial College
London W12 0NN, United Kingdom
a.hepburn@imperial.ac.uk
Michael D. Feher, M.D., F.R.C.P.
Chelsea and Westminster Hospital
London SW10 9NH, United Kingdom
Editor's note: Dr. Feher reports having received research support from Fournier Pharmaceuticals, which manufactures fenofibrate.
References
Terkeltaub RA. Gout. N Engl J Med 2003;349:1647-1655.
Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001;357:905-910.
Feher MD, Hepburn AL, Hogarth MB, Ball SG, Kaye SA. Fenofibrate enhances urate reduction in men treated with allopurinol for hyperuricaemia and gout. Rheumatology (Oxford) 2003;42:321-325.
Hepburn AL, Kaye SA, Feher MD. Long-term remission from gout associated with fenofibrate therapy. Clin Rheumatol 2003;22:73-76.
Fang J, Alderman MH. Serum uric acid and cardiovascular mortality: the NHANES 1 Epidemiologic Follow-up Study 1971-1992. JAMA 2000,283:2404-10.
Dr. Terkeltaub replies: I concur with Drs. Hepburn and Feher regarding the potential role of fenofibrate for treating both hyperlipidemia and hyperuricemia in persons with the metabolic syndrome. However, maximal lowering of serum urate levels by fenofibrate appears to be low, relative to that produced by conventional allopurinol, probenecid, or benzbromarone treatment regimens. Moreover, the adjunctive effects of two months of fenofibrate for serum urate lowering in men with gout and hypertriglyceridemia who were already receiving either allopurinol or benzbromarone averaged only 15 percent in a controlled trial.1
The role and efficacy of fenofibrate in the long-term management of hyperuricemia and in reducing tophus size and arthritis-attack frequency in gout remain to be established by adequately designed trials of sufficient duration, as opposed to limited case reports.2 It is not yet clear how renal insufficiency affects fenofibrate's urate-lowering capacity. Furthermore, precautions used when initiating primary treatment with uricosuric agents (e.g., probenecid) in order to lessen the risk of urolithiasis appear to be appropriate for instituting fenofibrate therapy in persons with hyperuricemia. Whether hyperuricemia is an independent factor in atherogenesis remains unclear. Therefore, it appears to be premature to advocate the use of fenofibrate for targeted management of asymptomatic hyperuricemia in patients with the metabolic syndrome.
Robert A. Terkeltaub, M.D.
Veterans Affairs Medical Center
San Diego, CA 92161
References
Takahashi S, Moriwaki Y, Yamamoto T, Tsutsumi Z, Ka T, Fukuchi M. Effects of combination treatment using anti-hyperuricemic agents with fenofibrate and/or losartan on uric acid metabolism. Ann Rheum Dis 2003;62:572-575.
Hepburn AL, Kaye SA, Feher MD. Long-term remission from gout associated with fenofibrate therapy. Clin Rheumatol 2003;22:73-76.
Furthermore, although this notion is controversial, high urate levels may be an independent risk factor for coronary artery disease.5 Fenofibrate might therefore have a particularly useful role in insulin-resistance syndromes, such as type 2 diabetes, because of its additional uricosuric effect.
Alastair L. Hepburn, M.R.C.P.
Imperial College
London W12 0NN, United Kingdom
a.hepburn@imperial.ac.uk
Michael D. Feher, M.D., F.R.C.P.
Chelsea and Westminster Hospital
London SW10 9NH, United Kingdom
Editor's note: Dr. Feher reports having received research support from Fournier Pharmaceuticals, which manufactures fenofibrate.
References
Terkeltaub RA. Gout. N Engl J Med 2003;349:1647-1655.
Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001;357:905-910.
Feher MD, Hepburn AL, Hogarth MB, Ball SG, Kaye SA. Fenofibrate enhances urate reduction in men treated with allopurinol for hyperuricaemia and gout. Rheumatology (Oxford) 2003;42:321-325.
Hepburn AL, Kaye SA, Feher MD. Long-term remission from gout associated with fenofibrate therapy. Clin Rheumatol 2003;22:73-76.
Fang J, Alderman MH. Serum uric acid and cardiovascular mortality: the NHANES 1 Epidemiologic Follow-up Study 1971-1992. JAMA 2000,283:2404-10.
Dr. Terkeltaub replies: I concur with Drs. Hepburn and Feher regarding the potential role of fenofibrate for treating both hyperlipidemia and hyperuricemia in persons with the metabolic syndrome. However, maximal lowering of serum urate levels by fenofibrate appears to be low, relative to that produced by conventional allopurinol, probenecid, or benzbromarone treatment regimens. Moreover, the adjunctive effects of two months of fenofibrate for serum urate lowering in men with gout and hypertriglyceridemia who were already receiving either allopurinol or benzbromarone averaged only 15 percent in a controlled trial.1
The role and efficacy of fenofibrate in the long-term management of hyperuricemia and in reducing tophus size and arthritis-attack frequency in gout remain to be established by adequately designed trials of sufficient duration, as opposed to limited case reports.2 It is not yet clear how renal insufficiency affects fenofibrate's urate-lowering capacity. Furthermore, precautions used when initiating primary treatment with uricosuric agents (e.g., probenecid) in order to lessen the risk of urolithiasis appear to be appropriate for instituting fenofibrate therapy in persons with hyperuricemia. Whether hyperuricemia is an independent factor in atherogenesis remains unclear. Therefore, it appears to be premature to advocate the use of fenofibrate for targeted management of asymptomatic hyperuricemia in patients with the metabolic syndrome.
Robert A. Terkeltaub, M.D.
Veterans Affairs Medical Center
San Diego, CA 92161
References
Takahashi S, Moriwaki Y, Yamamoto T, Tsutsumi Z, Ka T, Fukuchi M. Effects of combination treatment using anti-hyperuricemic agents with fenofibrate and/or losartan on uric acid metabolism. Ann Rheum Dis 2003;62:572-575.
Hepburn AL, Kaye SA, Feher MD. Long-term remission from gout associated with fenofibrate therapy. Clin Rheumatol 2003;22:73-76.