Physicians Often Missing Boat on Gout Therapy

SNOWMASS, COLO. – A disturbing proportion of gout cases are mismanaged by primary care physicians, and the blame falls squarely upon rheumatologists, according to one prominent gout expert.

"As rheumatologists, gout is our disease. The cause and pathophysiology are well understood, we can make the diagnosis with absolute certainty, and we’ve got great medicines. Yet today we all see people with tophi. That’s tragic. It shouldn’t exist. One of our biggest mistakes has been not being able to educate primary care physicians that having a tophus is bad, that it’s eroding cartilage and bone, and that it’s something we can prevent if we start urate-lowering therapy soon enough," Dr. Robert L. Wortmann said at the conference.

An estimated 8.3 million Americans have gout. Yet, the pharmaceutical industry says only 3.1 million of them are prescribed urate-lowering drugs. Five different studies show that a mere 40% of those on allopurinol are prescribed a dose sufficient to drive serum uric acid below 6 mg/dL, a key tenet of gout management, noted Dr. Wortmann, professor of medicine at Dartmouth Medical School in Hanover, N.H.

Moreover, poor treatment adherence is a huge problem in gout. A study of close to 4,200 gout patients started on urate-lowering drug therapy found that 56% of them were nonadherent (Arthritis Res. Ther. 2009;11(2):R46).

"I charge you all to go back from this meeting and try to communicate with all the primary care physicians you can about the principles of managing gout. People shouldn’t suffer from this," the rheumatologist declared.

He offered these major take home points:

Don’t prescribe urate-lowering drugs for asymptomatic hyperuricemia: This practice hasn’t been shown to prevent the future development of gout, yet it exposes patients to the risk of drug toxicities.

But don’t ignore asymptomatic hyperuricemia, either: Epidemiologic studies have linked asymptomatic hyperuricemia, defined by a serum urate in excess of 6.8 mg/dL, to increased risks of hypertension, cardiovascular disease, diabetes, chronic kidney disease, and all-cause mortality. The big unanswered question is whether using medications to lower serum urate in individuals with asymptomatic hyperuricemia reduces the risk of any of these conditions. That’s the subject of ongoing large clinical trials in high-risk patients. If those studies prove positive, clinical practice will change.

While awaiting the outcome of the prevention trials, it’s worth bearing in mind that Framingham Heart Study data indicate that individuals with a serum uric acid level above 9 mg/dL have a 22% chance of developing gout within the next 5 years. The major contributors to asymptomatic hyperuricemia include obesity, metabolic syndrome, and heavy consumption of fructose-containing beverages or alcohol. Those issues should be addressed.

Losartan is the only antihypertensive agent that’s uricosuric. Fenofibrate is the sole uricosuric drug indicated for dyslipidemia. Preferential consideration could be given to the use of these drugs in hypertensive and/or hyperlipidemic patients with asymptomatic hyperuricemia.

The important thing is not which oral agent you use for treatment of acute gout, it’s to initiate therapy as early as possible, at the first hint of an attack. Colchicine, maximum-dose NSAIDs, and oral prednisone dosed at 20 mg BID until symptoms have been gone for 1 week followed by another week at 20 mg/day – they’re all effective. And since they work by different mechanisms, they can beneficially be combined in refractory patients.

The old-school colchicine dosing regimen most physicians were taught has been cast aside of late. It had a high rate of diarrhea, an inhumane side effect in gout patients hobbled by a foot too sore to walk on. The former regimen has been replaced by 1.2 mg, given in a single dose, followed by 0.6 mg 1 hour later.

"This lower dose is just as effective as the old high-dose regimen of two 0.6-mg pills given at once and then one per hour for the next 5 hours. And the lower-dose program has the same side effect profile as placebo," Dr. Wortmann said.

Get the gout patient’s serum urate below 6 mg/dL using the lowest effective dose of the urate-lowering drug you’ve selected. Physicians have traditionally started gout patients on allopurinol at the standard dose of 300 mg/day. Recently, it has been demonstrated that the risk of developing allopurinol hypersensitivity syndrome is greatly reduced by starting off at 150 mg/day, checking the urate level 2 weeks later, then increasing to 300 mg/day if the serum urate isn’t below 6 mg/dL. After 2 weeks at 300 mg/day, check the urate again, and if it still isn’t below 6 mg/dL then bump the dose to 400 mg/day. Continue testing and titrating every 2 weeks until the serum urate is less than 6 mg/dL – and preferably less than 4 mg/dL if the patient has tophi – or until the maximum approved dose of 800 mg/day is reached.

The same start-low-and-titrate strategy applies to febuxostat, with a maximum approved dose of 80 mg/day.

"We have to educate primary care physicians to check the serum urate after starting therapy, and that, if it’s not below 6 mg/dL, they need to increase the dose. And if they don’t feel comfortable with that, they need to send the patient to us," the rheumatologist said.

Fortunately, patients who have a hypersensitivity reaction to allopurinol are very unlikely to experience one with febuxostat, and vice versa.

For patients who can’t reach the target serum urate with maximum-dose therapy, take heart: Second-line agents with impressive potency are well-along in the developmental pipeline.

Many labs now list the upper limit of normal for serum urate as 8 mg/dL or 8.5 mg/dL. Ignore that. This raised ceiling is simply the result of the changing demographics among the increasingly obese U.S. population in the last several decades. The definition of asymptomatic hyperuricemia remains unchanged: a serum urate greater than 6.8 mg/dL. And the target in patients with gout is still a serum urate less than 6 mg/dL. Merely dropping a gout patient’s urate from 10 to 8 or even 6.6 mg/dL isn’t doing any favors; the disease will continue to progress if the urate is above 6 mg/dL.

All gout is tophaceous. Even if tophi aren’t apparent on clinical examination, often they are radiographically. "This is a message that has to get out," Dr. Wortmann insisted.

Proposed American College of Rheumatology gout management guidelines call for starting urate-lowering drug therapy when a patient is experiencing three attacks per year. Dr. Wortmann takes issue with that.

"I would argue that once you’ve had a third attack of gout, period, you should be treated. Maybe even sooner. We need to prevent the erosion and bony destruction that occur with tophi," he said.

One audience member complained that his gout patients with comorbid renal insufficiency and/or cardiovascular disease often get caught in a revolving door. He titrates their allopurinol to an effective dose, but when they are later admitted to the hospital because of their comorbid condition the hospitalists, nephrologists, and/or cardiologists are shocked at the allopurinol dose and either reduce it or stop it altogether. The first that the rheumatologist learns of it is when patients reappear in his office with active gout. He then resumes their allopurinol at the previous dose, and they remain well controlled until the next hospitalization, when the same thing happens.

Dr. Wortmann responded that the solution requires convincing the nonrheumatologists in one-on-one conversation that urate-lowering therapy is not a one-size-fits-all matter. They need to understand that to get rid of gout, it’s necessary to drive the serum urate to the target of less than 6 mg/dL, and it helps to reassure them that that this will be accomplished using the lowest effective dose.

He reported serving as a consultant to Savient, Takeda, URL Pharmaceuticals, Novartis, and Ardea Biosciences.

SNOWMASS, COLO. – A disturbing proportion of gout cases are mismanaged by primary care physicians, and the blame falls squarely upon rheumatologists, according to one prominent gout expert.

"As rheumatologists, gout is our disease. The cause and pathophysiology are well understood, we can make the diagnosis with absolute certainty, and we’ve got great medicines. Yet today we all see people with tophi. That’s tragic. It shouldn’t exist. One of our biggest mistakes has been not being able to educate primary care physicians that having a tophus is bad, that it’s eroding cartilage and bone, and that it’s something we can prevent if we start urate-lowering therapy soon enough," Dr. Robert L. Wortmann said at the conference.

An estimated 8.3 million Americans have gout. Yet, the pharmaceutical industry says only 3.1 million of them are prescribed urate-lowering drugs. Five different studies show that a mere 40% of those on allopurinol are prescribed a dose sufficient to drive serum uric acid below 6 mg/dL, a key tenet of gout management, noted Dr. Wortmann, professor of medicine at Dartmouth Medical School in Hanover, N.H.

Moreover, poor treatment adherence is a huge problem in gout. A study of close to 4,200 gout patients started on urate-lowering drug therapy found that 56% of them were nonadherent (Arthritis Res. Ther. 2009;11(2):R46).

"I charge you all to go back from this meeting and try to communicate with all the primary care physicians you can about the principles of managing gout. People shouldn’t suffer from this," the rheumatologist declared.

He offered these major take home points:

Don’t prescribe urate-lowering drugs for asymptomatic hyperuricemia: This practice hasn’t been shown to prevent the future development of gout, yet it exposes patients to the risk of drug toxicities.

But don’t ignore asymptomatic hyperuricemia, either: Epidemiologic studies have linked asymptomatic hyperuricemia, defined by a serum urate in excess of 6.8 mg/dL, to increased risks of hypertension, cardiovascular disease, diabetes, chronic kidney disease, and all-cause mortality. The big unanswered question is whether using medications to lower serum urate in individuals with asymptomatic hyperuricemia reduces the risk of any of these conditions. That’s the subject of ongoing large clinical trials in high-risk patients. If those studies prove positive, clinical practice will change.

While awaiting the outcome of the prevention trials, it’s worth bearing in mind that Framingham Heart Study data indicate that individuals with a serum uric acid level above 9 mg/dL have a 22% chance of developing gout within the next 5 years. The major contributors to asymptomatic hyperuricemia include obesity, metabolic syndrome, and heavy consumption of fructose-containing beverages or alcohol. Those issues should be addressed.

Losartan is the only antihypertensive agent that’s uricosuric. Fenofibrate is the sole uricosuric drug indicated for dyslipidemia. Preferential consideration could be given to the use of these drugs in hypertensive and/or hyperlipidemic patients with asymptomatic hyperuricemia.

The important thing is not which oral agent you use for treatment of acute gout, it’s to initiate therapy as early as possible, at the first hint of an attack. Colchicine, maximum-dose NSAIDs, and oral prednisone dosed at 20 mg BID until symptoms have been gone for 1 week followed by another week at 20 mg/day – they’re all effective. And since they work by different mechanisms, they can beneficially be combined in refractory patients.

The old-school colchicine dosing regimen most physicians were taught has been cast aside of late. It had a high rate of diarrhea, an inhumane side effect in gout patients hobbled by a foot too sore to walk on. The former regimen has been replaced by 1.2 mg, given in a single dose, followed by 0.6 mg 1 hour later.

"This lower dose is just as effective as the old high-dose regimen of two 0.6-mg pills given at once and then one per hour for the next 5 hours. And the lower-dose program has the same side effect profile as placebo," Dr. Wortmann said.

Get the gout patient’s serum urate below 6 mg/dL using the lowest effective dose of the urate-lowering drug you’ve selected. Physicians have traditionally started gout patients on allopurinol at the standard dose of 300 mg/day. Recently, it has been demonstrated that the risk of developing allopurinol hypersensitivity syndrome is greatly reduced by starting off at 150 mg/day, checking the urate level 2 weeks later, then increasing to 300 mg/day if the serum urate isn’t below 6 mg/dL. After 2 weeks at 300 mg/day, check the urate again, and if it still isn’t below 6 mg/dL then bump the dose to 400 mg/day. Continue testing and titrating every 2 weeks until the serum urate is less than 6 mg/dL – and preferably less than 4 mg/dL if the patient has tophi – or until the maximum approved dose of 800 mg/day is reached.

The same start-low-and-titrate strategy applies to febuxostat, with a maximum approved dose of 80 mg/day.

"We have to educate primary care physicians to check the serum urate after starting therapy, and that, if it’s not below 6 mg/dL, they need to increase the dose. And if they don’t feel comfortable with that, they need to send the patient to us," the rheumatologist said.

Fortunately, patients who have a hypersensitivity reaction to allopurinol are very unlikely to experience one with febuxostat, and vice versa.

For patients who can’t reach the target serum urate with maximum-dose therapy, take heart: Second-line agents with impressive potency are well-along in the developmental pipeline.

Many labs now list the upper limit of normal for serum urate as 8 mg/dL or 8.5 mg/dL. Ignore that. This raised ceiling is simply the result of the changing demographics among the increasingly obese U.S. population in the last several decades. The definition of asymptomatic hyperuricemia remains unchanged: a serum urate greater than 6.8 mg/dL. And the target in patients with gout is still a serum urate less than 6 mg/dL. Merely dropping a gout patient’s urate from 10 to 8 or even 6.6 mg/dL isn’t doing any favors; the disease will continue to progress if the urate is above 6 mg/dL.

All gout is tophaceous. Even if tophi aren’t apparent on clinical examination, often they are radiographically. "This is a message that has to get out," Dr. Wortmann insisted.

Proposed American College of Rheumatology gout management guidelines call for starting urate-lowering drug therapy when a patient is experiencing three attacks per year. Dr. Wortmann takes issue with that.

"I would argue that once you’ve had a third attack of gout, period, you should be treated. Maybe even sooner. We need to prevent the erosion and bony destruction that occur with tophi," he said.

One audience member complained that his gout patients with comorbid renal insufficiency and/or cardiovascular disease often get caught in a revolving door. He titrates their allopurinol to an effective dose, but when they are later admitted to the hospital because of their comorbid condition the hospitalists, nephrologists, and/or cardiologists are shocked at the allopurinol dose and either reduce it or stop it altogether. The first that the rheumatologist learns of it is when patients reappear in his office with active gout. He then resumes their allopurinol at the previous dose, and they remain well controlled until the next hospitalization, when the same thing happens.

Dr. Wortmann responded that the solution requires convincing the nonrheumatologists in one-on-one conversation that urate-lowering therapy is not a one-size-fits-all matter. They need to understand that to get rid of gout, it’s necessary to drive the serum urate to the target of less than 6 mg/dL, and it helps to reassure them that that this will be accomplished using the lowest effective dose.

He reported serving as a consultant to Savient, Takeda, URL Pharmaceuticals, Novartis, and Ardea Biosciences.

SNOWMASS, COLO. – A disturbing proportion of gout cases are mismanaged by primary care physicians, and the blame falls squarely upon rheumatologists, according to one prominent gout expert.

"As rheumatologists, gout is our disease. The cause and pathophysiology are well understood, we can make the diagnosis with absolute certainty, and we’ve got great medicines. Yet today we all see people with tophi. That’s tragic. It shouldn’t exist. One of our biggest mistakes has been not being able to educate primary care physicians that having a tophus is bad, that it’s eroding cartilage and bone, and that it’s something we can prevent if we start urate-lowering therapy soon enough," Dr. Robert L. Wortmann said at the conference.

An estimated 8.3 million Americans have gout. Yet, the pharmaceutical industry says only 3.1 million of them are prescribed urate-lowering drugs. Five different studies show that a mere 40% of those on allopurinol are prescribed a dose sufficient to drive serum uric acid below 6 mg/dL, a key tenet of gout management, noted Dr. Wortmann, professor of medicine at Dartmouth Medical School in Hanover, N.H.

Moreover, poor treatment adherence is a huge problem in gout. A study of close to 4,200 gout patients started on urate-lowering drug therapy found that 56% of them were nonadherent (Arthritis Res. Ther. 2009;11(2):R46).

"I charge you all to go back from this meeting and try to communicate with all the primary care physicians you can about the principles of managing gout. People shouldn’t suffer from this," the rheumatologist declared.

He offered these major take home points:

Don’t prescribe urate-lowering drugs for asymptomatic hyperuricemia: This practice hasn’t been shown to prevent the future development of gout, yet it exposes patients to the risk of drug toxicities.

But don’t ignore asymptomatic hyperuricemia, either: Epidemiologic studies have linked asymptomatic hyperuricemia, defined by a serum urate in excess of 6.8 mg/dL, to increased risks of hypertension, cardiovascular disease, diabetes, chronic kidney disease, and all-cause mortality. The big unanswered question is whether using medications to lower serum urate in individuals with asymptomatic hyperuricemia reduces the risk of any of these conditions. That’s the subject of ongoing large clinical trials in high-risk patients. If those studies prove positive, clinical practice will change.

While awaiting the outcome of the prevention trials, it’s worth bearing in mind that Framingham Heart Study data indicate that individuals with a serum uric acid level above 9 mg/dL have a 22% chance of developing gout within the next 5 years. The major contributors to asymptomatic hyperuricemia include obesity, metabolic syndrome, and heavy consumption of fructose-containing beverages or alcohol. Those issues should be addressed.

Losartan is the only antihypertensive agent that’s uricosuric. Fenofibrate is the sole uricosuric drug indicated for dyslipidemia. Preferential consideration could be given to the use of these drugs in hypertensive and/or hyperlipidemic patients with asymptomatic hyperuricemia.

The important thing is not which oral agent you use for treatment of acute gout, it’s to initiate therapy as early as possible, at the first hint of an attack. Colchicine, maximum-dose NSAIDs, and oral prednisone dosed at 20 mg BID until symptoms have been gone for 1 week followed by another week at 20 mg/day – they’re all effective. And since they work by different mechanisms, they can beneficially be combined in refractory patients.

The old-school colchicine dosing regimen most physicians were taught has been cast aside of late. It had a high rate of diarrhea, an inhumane side effect in gout patients hobbled by a foot too sore to walk on. The former regimen has been replaced by 1.2 mg, given in a single dose, followed by 0.6 mg 1 hour later.

"This lower dose is just as effective as the old high-dose regimen of two 0.6-mg pills given at once and then one per hour for the next 5 hours. And the lower-dose program has the same side effect profile as placebo," Dr. Wortmann said.

Get the gout patient’s serum urate below 6 mg/dL using the lowest effective dose of the urate-lowering drug you’ve selected. Physicians have traditionally started gout patients on allopurinol at the standard dose of 300 mg/day. Recently, it has been demonstrated that the risk of developing allopurinol hypersensitivity syndrome is greatly reduced by starting off at 150 mg/day, checking the urate level 2 weeks later, then increasing to 300 mg/day if the serum urate isn’t below 6 mg/dL. After 2 weeks at 300 mg/day, check the urate again, and if it still isn’t below 6 mg/dL then bump the dose to 400 mg/day. Continue testing and titrating every 2 weeks until the serum urate is less than 6 mg/dL – and preferably less than 4 mg/dL if the patient has tophi – or until the maximum approved dose of 800 mg/day is reached.

The same start-low-and-titrate strategy applies to febuxostat, with a maximum approved dose of 80 mg/day.

"We have to educate primary care physicians to check the serum urate after starting therapy, and that, if it’s not below 6 mg/dL, they need to increase the dose. And if they don’t feel comfortable with that, they need to send the patient to us," the rheumatologist said.

Fortunately, patients who have a hypersensitivity reaction to allopurinol are very unlikely to experience one with febuxostat, and vice versa.

For patients who can’t reach the target serum urate with maximum-dose therapy, take heart: Second-line agents with impressive potency are well-along in the developmental pipeline.

Many labs now list the upper limit of normal for serum urate as 8 mg/dL or 8.5 mg/dL. Ignore that. This raised ceiling is simply the result of the changing demographics among the increasingly obese U.S. population in the last several decades. The definition of asymptomatic hyperuricemia remains unchanged: a serum urate greater than 6.8 mg/dL. And the target in patients with gout is still a serum urate less than 6 mg/dL. Merely dropping a gout patient’s urate from 10 to 8 or even 6.6 mg/dL isn’t doing any favors; the disease will continue to progress if the urate is above 6 mg/dL.

All gout is tophaceous. Even if tophi aren’t apparent on clinical examination, often they are radiographically. "This is a message that has to get out," Dr. Wortmann insisted.

Proposed American College of Rheumatology gout management guidelines call for starting urate-lowering drug therapy when a patient is experiencing three attacks per year. Dr. Wortmann takes issue with that.

"I would argue that once you’ve had a third attack of gout, period, you should be treated. Maybe even sooner. We need to prevent the erosion and bony destruction that occur with tophi," he said.

One audience member complained that his gout patients with comorbid renal insufficiency and/or cardiovascular disease often get caught in a revolving door. He titrates their allopurinol to an effective dose, but when they are later admitted to the hospital because of their comorbid condition the hospitalists, nephrologists, and/or cardiologists are shocked at the allopurinol dose and either reduce it or stop it altogether. The first that the rheumatologist learns of it is when patients reappear in his office with active gout. He then resumes their allopurinol at the previous dose, and they remain well controlled until the next hospitalization, when the same thing happens.

Dr. Wortmann responded that the solution requires convincing the nonrheumatologists in one-on-one conversation that urate-lowering therapy is not a one-size-fits-all matter. They need to understand that to get rid of gout, it’s necessary to drive the serum urate to the target of less than 6 mg/dL, and it helps to reassure them that that this will be accomplished using the lowest effective dose.

He reported serving as a consultant to Savient, Takeda, URL Pharmaceuticals, Novartis, and Ardea Biosciences.