New Therapies Step Up to the Plate for Gout

FORT LAUDERDALE, FLA. — The likely approval of febuxostat for treating gout means there soon will be an alternative for the underserved group of patients with severe disease who cannot tolerate allopurinol.

No new urate-lowering treatments for gout have been approved since 1964, but late last year the advisory panel of the Food and Drug Administration (FDA) voted 12–0, with 1 abstention, in favor of approval for this nonpurine selective xanthine oxidase inhibitor. The FDA usually follows the recommendations of its advisory panel.

Experience to date with febuxostat in more than 4,000 patients has shown that, unlike with allopurinol, there appears to be no need for dose adjustment in patients with mild to moderate renal dysfunction. Dosage concerns exist for patients with renal insufficiency taking allopurinol, because of the possible occurrence of toxic epidermal necrolysis, said Dr. Robert L. Wortmann, professor of medicine, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

There also have been no reports of hypersensitivity reactions, even in patients who previously had such reactions to allopurinol, most likely because of the two drugs' differences in structure, Dr. Wortmann said at a meeting sponsored by RHEUMATOLOGY NEWS and Skin Disease Education Foundation.

In a phase III clinical trial, 81% of patients receiving 80 mg febuxostat per day had serum urate levels below 6 mg/dL after 52 weeks of therapy, compared with 39% of patients receiving 300 mg allopurinol per day (N. Engl. J. Med. 2005;353:2450–61).

Although not all patients can tolerate allopurinol, that drug also is effective. However, it often is not prescribed in sufficiently high doses, according to Dr. Wortmann, who is a consultant to Takeda Pharmaceutical Co., the manufacturer of febuxostat. The drug is approved for doses up to 800 mg/day.

The goal of antihyperuricemic therapy is to lower the serum urate to 5–6 mg/dL. “If you lower the urate from 12 mg/dL to 7 or 7.5 mg/dL with allopurinol … all you are doing is retarding the rate at which the crystals will deposit,” he said.

Another agent being investigated for gout is uricase, which converts urease to the more soluble allantoin. A commercially available formulation, rasburicase, is used for the treatment of tumor lysis syndrome. Although that drug is very effective for lowering serum urate levels, it carries a black box warning regarding anaphylaxis, Dr. Wortmann said.

Accordingly, two companies have been working on developing pegylated formulations, based on the principle that the polyethylene glycol would make uricase less antigenic and increase the half-life. Dr. Wortmann disclosed that he is also a consultant to Savient Pharmaceuticals Inc., the manufacturer of one of these formulations, Puricase.

SDEF and this news organization are owned by Elsevier.

This proton density image shows a low to intermediate signal tophus. ©American College of Rheumatology Clinical Slide Collection 1972–2004

FORT LAUDERDALE, FLA. — The likely approval of febuxostat for treating gout means there soon will be an alternative for the underserved group of patients with severe disease who cannot tolerate allopurinol.

No new urate-lowering treatments for gout have been approved since 1964, but late last year the advisory panel of the Food and Drug Administration (FDA) voted 12–0, with 1 abstention, in favor of approval for this nonpurine selective xanthine oxidase inhibitor. The FDA usually follows the recommendations of its advisory panel.

Experience to date with febuxostat in more than 4,000 patients has shown that, unlike with allopurinol, there appears to be no need for dose adjustment in patients with mild to moderate renal dysfunction. Dosage concerns exist for patients with renal insufficiency taking allopurinol, because of the possible occurrence of toxic epidermal necrolysis, said Dr. Robert L. Wortmann, professor of medicine, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

There also have been no reports of hypersensitivity reactions, even in patients who previously had such reactions to allopurinol, most likely because of the two drugs' differences in structure, Dr. Wortmann said at a meeting sponsored by RHEUMATOLOGY NEWS and Skin Disease Education Foundation.

In a phase III clinical trial, 81% of patients receiving 80 mg febuxostat per day had serum urate levels below 6 mg/dL after 52 weeks of therapy, compared with 39% of patients receiving 300 mg allopurinol per day (N. Engl. J. Med. 2005;353:2450–61).

Although not all patients can tolerate allopurinol, that drug also is effective. However, it often is not prescribed in sufficiently high doses, according to Dr. Wortmann, who is a consultant to Takeda Pharmaceutical Co., the manufacturer of febuxostat. The drug is approved for doses up to 800 mg/day.

The goal of antihyperuricemic therapy is to lower the serum urate to 5–6 mg/dL. “If you lower the urate from 12 mg/dL to 7 or 7.5 mg/dL with allopurinol … all you are doing is retarding the rate at which the crystals will deposit,” he said.

Another agent being investigated for gout is uricase, which converts urease to the more soluble allantoin. A commercially available formulation, rasburicase, is used for the treatment of tumor lysis syndrome. Although that drug is very effective for lowering serum urate levels, it carries a black box warning regarding anaphylaxis, Dr. Wortmann said.

Accordingly, two companies have been working on developing pegylated formulations, based on the principle that the polyethylene glycol would make uricase less antigenic and increase the half-life. Dr. Wortmann disclosed that he is also a consultant to Savient Pharmaceuticals Inc., the manufacturer of one of these formulations, Puricase.

SDEF and this news organization are owned by Elsevier.

This proton density image shows a low to intermediate signal tophus. ©American College of Rheumatology Clinical Slide Collection 1972–2004

FORT LAUDERDALE, FLA. — The likely approval of febuxostat for treating gout means there soon will be an alternative for the underserved group of patients with severe disease who cannot tolerate allopurinol.

No new urate-lowering treatments for gout have been approved since 1964, but late last year the advisory panel of the Food and Drug Administration (FDA) voted 12–0, with 1 abstention, in favor of approval for this nonpurine selective xanthine oxidase inhibitor. The FDA usually follows the recommendations of its advisory panel.

Experience to date with febuxostat in more than 4,000 patients has shown that, unlike with allopurinol, there appears to be no need for dose adjustment in patients with mild to moderate renal dysfunction. Dosage concerns exist for patients with renal insufficiency taking allopurinol, because of the possible occurrence of toxic epidermal necrolysis, said Dr. Robert L. Wortmann, professor of medicine, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

There also have been no reports of hypersensitivity reactions, even in patients who previously had such reactions to allopurinol, most likely because of the two drugs' differences in structure, Dr. Wortmann said at a meeting sponsored by RHEUMATOLOGY NEWS and Skin Disease Education Foundation.

In a phase III clinical trial, 81% of patients receiving 80 mg febuxostat per day had serum urate levels below 6 mg/dL after 52 weeks of therapy, compared with 39% of patients receiving 300 mg allopurinol per day (N. Engl. J. Med. 2005;353:2450–61).

Although not all patients can tolerate allopurinol, that drug also is effective. However, it often is not prescribed in sufficiently high doses, according to Dr. Wortmann, who is a consultant to Takeda Pharmaceutical Co., the manufacturer of febuxostat. The drug is approved for doses up to 800 mg/day.

The goal of antihyperuricemic therapy is to lower the serum urate to 5–6 mg/dL. “If you lower the urate from 12 mg/dL to 7 or 7.5 mg/dL with allopurinol … all you are doing is retarding the rate at which the crystals will deposit,” he said.

Another agent being investigated for gout is uricase, which converts urease to the more soluble allantoin. A commercially available formulation, rasburicase, is used for the treatment of tumor lysis syndrome. Although that drug is very effective for lowering serum urate levels, it carries a black box warning regarding anaphylaxis, Dr. Wortmann said.

Accordingly, two companies have been working on developing pegylated formulations, based on the principle that the polyethylene glycol would make uricase less antigenic and increase the half-life. Dr. Wortmann disclosed that he is also a consultant to Savient Pharmaceuticals Inc., the manufacturer of one of these formulations, Puricase.

SDEF and this news organization are owned by Elsevier.

This proton density image shows a low to intermediate signal tophus. ©American College of Rheumatology Clinical Slide Collection 1972–2004