Gout

Screen for diabetes and aggressively manage risk factors in patients with gout, especially women, investigators concluded from a retrospective, matched cohort study published Oct. 2 in Annals of the Rheumatic Diseases.

They found that women have a 71% greater risk of developing diabetes if they have gout (hazard ratio, 1.71; 95% confidence interval, 1.51-1.93; P less than .001), and men with gout have a 22% greater risk (HR, 1.22; 95% CI, 1.13-1.31; P less than .001), compared with the general population.

The study “suggests that gout may be independently associated with an increased risk of diabetes. These findings were independent of BMI [body mass index], lifestyle factors, and other known risk factors. The magnitude of excess diabetes risk in gout was significantly larger among women than men, both in risk difference and relative risk, and these findings persisted across all age categories. These findings support aggressive management of risk factors of diabetes in patients with gout,” concluded senior investigator Dr. Hyon K. Choi and his colleagues at Boston University (Ann. Rheum. Dis. 2014 Oct. 2 [doi: 10.1136/annrheumdis-2014-205827]).

Using 15 years’ worth of data from the U.K. Health Improvement Network, which contains the records of about 7.3 million patients, the investigators matched 35,339 patients with newly diagnosed gout with up to 5 control subjects for age, sex, and BMI; they then looked to see who subsequently developed diabetes.

Among patients with gout, there were 10.1 cases of new-onset diabetes in women and 9.5 cases in men per 1,000 person-years. Among the 137,056 controls without gout, there were 5.6 cases of new-onset diabetes in women and 7.2 cases in men per 1,000 person-years.

After adjustment for smoking, alcohol consumption, physician visits, comorbidities, medication use, and BMI as a continuous variable, gout increased the risk of diabetes by 48% in women (HR, 1.48; 95% CI, 1.29-1.68; P less than .001) and by 15% in men (HR, 1.15; 95% CI, 1.06-1.24; P less than .001). The sex difference persisted across age groups.

Gout patients consumed more alcohol, visited their doctor more often, had more health problems, and took steroids and diuretics more frequently than did those who did not have gout. Overall, 72.4% of the gout cases were in men with a mean age of 62.7 years; the rest were in women, but women with gout tended to be a bit older, with a mean age of 67.9 years.

Perhaps, “low-grade inflammation among patients with gout promote[s] the diabetogenic process,” the investigators wrote. “Alternatively, the link may stem from the shared metabolic factors of the two conditions, such as the correlates of the metabolic syndrome or shared genes. Furthermore, the link between hyperuricemia and the risk of type 2 diabetes may originate at the renal level, as insulin resistance and higher insulin levels are known to reduce renal excretion of urate,” they noted.

It’s unclear why women seem to be more affected. “SUA [serum uric acid] levels in men are about 1 mg/dL higher than in women during adulthood, although levels in women increase around natural menopause. Thus, the physiological impact of uric acid levels, which are high enough to cause gout, could be stronger among women than men. Furthermore, female gout patients may have higher SUA levels on average than male gout patients, which could also contribute to a larger association with the risk of diabetes among women,” they suggested.

Dr. Choi previously linked gout to the development of diabetes, but only in men with high cardiovascular risk profiles (Rheumatology 2008;47:1567-70).

The investigators had no disclosures. The work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

[email protected]

Screen for diabetes and aggressively manage risk factors in patients with gout, especially women, investigators concluded from a retrospective, matched cohort study published Oct. 2 in Annals of the Rheumatic Diseases.

They found that women have a 71% greater risk of developing diabetes if they have gout (hazard ratio, 1.71; 95% confidence interval, 1.51-1.93; P less than .001), and men with gout have a 22% greater risk (HR, 1.22; 95% CI, 1.13-1.31; P less than .001), compared with the general population.

The study “suggests that gout may be independently associated with an increased risk of diabetes. These findings were independent of BMI [body mass index], lifestyle factors, and other known risk factors. The magnitude of excess diabetes risk in gout was significantly larger among women than men, both in risk difference and relative risk, and these findings persisted across all age categories. These findings support aggressive management of risk factors of diabetes in patients with gout,” concluded senior investigator Dr. Hyon K. Choi and his colleagues at Boston University (Ann. Rheum. Dis. 2014 Oct. 2 [doi: 10.1136/annrheumdis-2014-205827]).

Using 15 years’ worth of data from the U.K. Health Improvement Network, which contains the records of about 7.3 million patients, the investigators matched 35,339 patients with newly diagnosed gout with up to 5 control subjects for age, sex, and BMI; they then looked to see who subsequently developed diabetes.

Among patients with gout, there were 10.1 cases of new-onset diabetes in women and 9.5 cases in men per 1,000 person-years. Among the 137,056 controls without gout, there were 5.6 cases of new-onset diabetes in women and 7.2 cases in men per 1,000 person-years.

After adjustment for smoking, alcohol consumption, physician visits, comorbidities, medication use, and BMI as a continuous variable, gout increased the risk of diabetes by 48% in women (HR, 1.48; 95% CI, 1.29-1.68; P less than .001) and by 15% in men (HR, 1.15; 95% CI, 1.06-1.24; P less than .001). The sex difference persisted across age groups.

Gout patients consumed more alcohol, visited their doctor more often, had more health problems, and took steroids and diuretics more frequently than did those who did not have gout. Overall, 72.4% of the gout cases were in men with a mean age of 62.7 years; the rest were in women, but women with gout tended to be a bit older, with a mean age of 67.9 years.

Perhaps, “low-grade inflammation among patients with gout promote[s] the diabetogenic process,” the investigators wrote. “Alternatively, the link may stem from the shared metabolic factors of the two conditions, such as the correlates of the metabolic syndrome or shared genes. Furthermore, the link between hyperuricemia and the risk of type 2 diabetes may originate at the renal level, as insulin resistance and higher insulin levels are known to reduce renal excretion of urate,” they noted.

It’s unclear why women seem to be more affected. “SUA [serum uric acid] levels in men are about 1 mg/dL higher than in women during adulthood, although levels in women increase around natural menopause. Thus, the physiological impact of uric acid levels, which are high enough to cause gout, could be stronger among women than men. Furthermore, female gout patients may have higher SUA levels on average than male gout patients, which could also contribute to a larger association with the risk of diabetes among women,” they suggested.

Dr. Choi previously linked gout to the development of diabetes, but only in men with high cardiovascular risk profiles (Rheumatology 2008;47:1567-70).

The investigators had no disclosures. The work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

[email protected]

Screen for diabetes and aggressively manage risk factors in patients with gout, especially women, investigators concluded from a retrospective, matched cohort study published Oct. 2 in Annals of the Rheumatic Diseases.

They found that women have a 71% greater risk of developing diabetes if they have gout (hazard ratio, 1.71; 95% confidence interval, 1.51-1.93; P less than .001), and men with gout have a 22% greater risk (HR, 1.22; 95% CI, 1.13-1.31; P less than .001), compared with the general population.

The study “suggests that gout may be independently associated with an increased risk of diabetes. These findings were independent of BMI [body mass index], lifestyle factors, and other known risk factors. The magnitude of excess diabetes risk in gout was significantly larger among women than men, both in risk difference and relative risk, and these findings persisted across all age categories. These findings support aggressive management of risk factors of diabetes in patients with gout,” concluded senior investigator Dr. Hyon K. Choi and his colleagues at Boston University (Ann. Rheum. Dis. 2014 Oct. 2 [doi: 10.1136/annrheumdis-2014-205827]).

Using 15 years’ worth of data from the U.K. Health Improvement Network, which contains the records of about 7.3 million patients, the investigators matched 35,339 patients with newly diagnosed gout with up to 5 control subjects for age, sex, and BMI; they then looked to see who subsequently developed diabetes.

Among patients with gout, there were 10.1 cases of new-onset diabetes in women and 9.5 cases in men per 1,000 person-years. Among the 137,056 controls without gout, there were 5.6 cases of new-onset diabetes in women and 7.2 cases in men per 1,000 person-years.

After adjustment for smoking, alcohol consumption, physician visits, comorbidities, medication use, and BMI as a continuous variable, gout increased the risk of diabetes by 48% in women (HR, 1.48; 95% CI, 1.29-1.68; P less than .001) and by 15% in men (HR, 1.15; 95% CI, 1.06-1.24; P less than .001). The sex difference persisted across age groups.

Gout patients consumed more alcohol, visited their doctor more often, had more health problems, and took steroids and diuretics more frequently than did those who did not have gout. Overall, 72.4% of the gout cases were in men with a mean age of 62.7 years; the rest were in women, but women with gout tended to be a bit older, with a mean age of 67.9 years.

Perhaps, “low-grade inflammation among patients with gout promote[s] the diabetogenic process,” the investigators wrote. “Alternatively, the link may stem from the shared metabolic factors of the two conditions, such as the correlates of the metabolic syndrome or shared genes. Furthermore, the link between hyperuricemia and the risk of type 2 diabetes may originate at the renal level, as insulin resistance and higher insulin levels are known to reduce renal excretion of urate,” they noted.

It’s unclear why women seem to be more affected. “SUA [serum uric acid] levels in men are about 1 mg/dL higher than in women during adulthood, although levels in women increase around natural menopause. Thus, the physiological impact of uric acid levels, which are high enough to cause gout, could be stronger among women than men. Furthermore, female gout patients may have higher SUA levels on average than male gout patients, which could also contribute to a larger association with the risk of diabetes among women,” they suggested.

Dr. Choi previously linked gout to the development of diabetes, but only in men with high cardiovascular risk profiles (Rheumatology 2008;47:1567-70).

The investigators had no disclosures. The work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

[email protected]

Patients undergoing cardiac surgery who took colchicine had significantly less postpericardiotomy syndrome than did those on placebo, but this protective effect did not extend to postoperative atrial fibrillation and pericardial or pleural effusions in the double-blind COPPS-2 trial.

The failure of colchicine to prevent postoperative atrial fibrillation (AF) was probably due to more frequent adverse events (36 vs. 21 with placebo), especially gastrointestinal intolerance (26 vs. 12), and drug discontinuation (39 vs. 32), since a prespecified on-treatment analysis showed a significant reduction in AF in patients tolerating the drug, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.

"The high rate of adverse effects is a reason for concern and suggests that colchicine should be considered only in well-selected patients," Dr. Imazio and his associates wrote in an article on COPPS-2 simultaneously published online (JAMA 2014 [doi:10.1001/jama.2014.11026]).

Colchicine has been a promising strategy for postpericardiotomy syndrome prevention, besting methylprednisolone and aspirin in a large meta-analysis (Am. J. Cardiol. 2011;108:575-9).

In the largest trial, COPPS (Colchicine for the Prevention of the Postpericardiotomy Syndrome), Dr. Imazio reported that colchicine significantly reduced the incidence of postpericardiotomy syndrome (8.9% vs. 21.1%), postoperative pericardial effusions (relative risk reduction, 43.9%), and pleural effusions (RRR, 52.3%) at 12 months, compared with placebo (Am. Heart J. 2011;162:527-32 and Eur. Heart J. 2010;31:2749-54). Colchicine was given for 1 month, beginning on the third postoperative day with a 1-mg twice-daily loading dose.

In COPPS-2, the 360 consecutive candidates for cardiac surgery also were given colchicine or placebo for 1 month, but treatment was started 48-72 hours before surgery to pretreat patients and improve colchicine’s ability to prevent postoperative systemic inflammation and its complications.

Colchicine also was administered using weight-based dosing (0.5 mg twice daily in patients weighing at least 70 kg or 0.5 mg once daily in those under 70 kg), and they avoided the loading dose in an effort to improve adherence.

"However, we observed a 2-fold increase of adverse effects and study drug discontinuations compared with those reported in the COPPS trial, likely due to significant vulnerability of patients in the perioperative phase, when the use of antibiotics and proton pump inhibitors is common and also increases the risk of gastrointestinal effects (e.g., diarrhea)," explained Dr. Imazio of Maria Vittoria Hospital and the University of Torino (Italy).

Still, colchicine provided significant protection in the COPPS-2 primary outcome of postpericardiotomy syndrome, compared with placebo (19.4% vs. 29.4%; 95% confidence interval, 1.1%-18.7%). The number needed to treat was 10.

The outcome did not differ significantly among predetermined subgroups based on age, sex, and presence or absence of pericardial effusion, although colchicine was especially efficacious in the setting of systemic inflammation with elevated C-reactive protein, the authors noted.

The intention-to-treat analysis revealed no significant differences between the colchicine and placebo groups for postoperative AF (33.9% vs. 41.7%; 95% CI, –2.2%-17.6%) or postoperative pericardial/pleural effusion (57.2% vs. 58.9%; 95% CI, –8.5%-11.7%).

The prespecified on-treatment analysis, however, showed a 14.2% absolute difference in postoperative AF, favoring colchicine over placebo (27% vs. 41.2%; 95% CI, 3.3%-24.7%).

"While the efficacy of colchicine for postpericardiotomy syndrome prevention is confirmed, the extent of efficacy for postoperative AF needs to be further investigated in future trials," Dr. Imazio stated.

Ongoing studies also will better clarify the potential of colchicine using lower doses that may be better tolerated.

The 360 patients were evenly randomized from 11 centers in Italy between March 2012 and March 2014. Their mean age was 67.5 years, 69% were men, and 36% had planned valvular surgery. Key exclusion criteria were absence of sinus rhythm at enrollment, urgent cardiac surgery, cardiac transplantation, and contraindications to colchicine.

COPPS-2 was supported by the Italian National Health Service and FARGIM. Acarpia provided the study drug. Dr. Imazio reported no conflicts of interest. A coauthor reported consultancy for Servier, serving on an advisory board for Boehringer Ingelheim, and lecturer fees from Abbott, AstraZeneca, Merck, Serono, Richter Gedeon, and Teva.

Patients undergoing cardiac surgery who took colchicine had significantly less postpericardiotomy syndrome than did those on placebo, but this protective effect did not extend to postoperative atrial fibrillation and pericardial or pleural effusions in the double-blind COPPS-2 trial.

The failure of colchicine to prevent postoperative atrial fibrillation (AF) was probably due to more frequent adverse events (36 vs. 21 with placebo), especially gastrointestinal intolerance (26 vs. 12), and drug discontinuation (39 vs. 32), since a prespecified on-treatment analysis showed a significant reduction in AF in patients tolerating the drug, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.

"The high rate of adverse effects is a reason for concern and suggests that colchicine should be considered only in well-selected patients," Dr. Imazio and his associates wrote in an article on COPPS-2 simultaneously published online (JAMA 2014 [doi:10.1001/jama.2014.11026]).

Colchicine has been a promising strategy for postpericardiotomy syndrome prevention, besting methylprednisolone and aspirin in a large meta-analysis (Am. J. Cardiol. 2011;108:575-9).

In the largest trial, COPPS (Colchicine for the Prevention of the Postpericardiotomy Syndrome), Dr. Imazio reported that colchicine significantly reduced the incidence of postpericardiotomy syndrome (8.9% vs. 21.1%), postoperative pericardial effusions (relative risk reduction, 43.9%), and pleural effusions (RRR, 52.3%) at 12 months, compared with placebo (Am. Heart J. 2011;162:527-32 and Eur. Heart J. 2010;31:2749-54). Colchicine was given for 1 month, beginning on the third postoperative day with a 1-mg twice-daily loading dose.

In COPPS-2, the 360 consecutive candidates for cardiac surgery also were given colchicine or placebo for 1 month, but treatment was started 48-72 hours before surgery to pretreat patients and improve colchicine’s ability to prevent postoperative systemic inflammation and its complications.

Colchicine also was administered using weight-based dosing (0.5 mg twice daily in patients weighing at least 70 kg or 0.5 mg once daily in those under 70 kg), and they avoided the loading dose in an effort to improve adherence.

"However, we observed a 2-fold increase of adverse effects and study drug discontinuations compared with those reported in the COPPS trial, likely due to significant vulnerability of patients in the perioperative phase, when the use of antibiotics and proton pump inhibitors is common and also increases the risk of gastrointestinal effects (e.g., diarrhea)," explained Dr. Imazio of Maria Vittoria Hospital and the University of Torino (Italy).

Still, colchicine provided significant protection in the COPPS-2 primary outcome of postpericardiotomy syndrome, compared with placebo (19.4% vs. 29.4%; 95% confidence interval, 1.1%-18.7%). The number needed to treat was 10.

The outcome did not differ significantly among predetermined subgroups based on age, sex, and presence or absence of pericardial effusion, although colchicine was especially efficacious in the setting of systemic inflammation with elevated C-reactive protein, the authors noted.

The intention-to-treat analysis revealed no significant differences between the colchicine and placebo groups for postoperative AF (33.9% vs. 41.7%; 95% CI, –2.2%-17.6%) or postoperative pericardial/pleural effusion (57.2% vs. 58.9%; 95% CI, –8.5%-11.7%).

The prespecified on-treatment analysis, however, showed a 14.2% absolute difference in postoperative AF, favoring colchicine over placebo (27% vs. 41.2%; 95% CI, 3.3%-24.7%).

"While the efficacy of colchicine for postpericardiotomy syndrome prevention is confirmed, the extent of efficacy for postoperative AF needs to be further investigated in future trials," Dr. Imazio stated.

Ongoing studies also will better clarify the potential of colchicine using lower doses that may be better tolerated.

The 360 patients were evenly randomized from 11 centers in Italy between March 2012 and March 2014. Their mean age was 67.5 years, 69% were men, and 36% had planned valvular surgery. Key exclusion criteria were absence of sinus rhythm at enrollment, urgent cardiac surgery, cardiac transplantation, and contraindications to colchicine.

COPPS-2 was supported by the Italian National Health Service and FARGIM. Acarpia provided the study drug. Dr. Imazio reported no conflicts of interest. A coauthor reported consultancy for Servier, serving on an advisory board for Boehringer Ingelheim, and lecturer fees from Abbott, AstraZeneca, Merck, Serono, Richter Gedeon, and Teva.

Patients undergoing cardiac surgery who took colchicine had significantly less postpericardiotomy syndrome than did those on placebo, but this protective effect did not extend to postoperative atrial fibrillation and pericardial or pleural effusions in the double-blind COPPS-2 trial.

The failure of colchicine to prevent postoperative atrial fibrillation (AF) was probably due to more frequent adverse events (36 vs. 21 with placebo), especially gastrointestinal intolerance (26 vs. 12), and drug discontinuation (39 vs. 32), since a prespecified on-treatment analysis showed a significant reduction in AF in patients tolerating the drug, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.

"The high rate of adverse effects is a reason for concern and suggests that colchicine should be considered only in well-selected patients," Dr. Imazio and his associates wrote in an article on COPPS-2 simultaneously published online (JAMA 2014 [doi:10.1001/jama.2014.11026]).

Colchicine has been a promising strategy for postpericardiotomy syndrome prevention, besting methylprednisolone and aspirin in a large meta-analysis (Am. J. Cardiol. 2011;108:575-9).

In the largest trial, COPPS (Colchicine for the Prevention of the Postpericardiotomy Syndrome), Dr. Imazio reported that colchicine significantly reduced the incidence of postpericardiotomy syndrome (8.9% vs. 21.1%), postoperative pericardial effusions (relative risk reduction, 43.9%), and pleural effusions (RRR, 52.3%) at 12 months, compared with placebo (Am. Heart J. 2011;162:527-32 and Eur. Heart J. 2010;31:2749-54). Colchicine was given for 1 month, beginning on the third postoperative day with a 1-mg twice-daily loading dose.

In COPPS-2, the 360 consecutive candidates for cardiac surgery also were given colchicine or placebo for 1 month, but treatment was started 48-72 hours before surgery to pretreat patients and improve colchicine’s ability to prevent postoperative systemic inflammation and its complications.

Colchicine also was administered using weight-based dosing (0.5 mg twice daily in patients weighing at least 70 kg or 0.5 mg once daily in those under 70 kg), and they avoided the loading dose in an effort to improve adherence.

"However, we observed a 2-fold increase of adverse effects and study drug discontinuations compared with those reported in the COPPS trial, likely due to significant vulnerability of patients in the perioperative phase, when the use of antibiotics and proton pump inhibitors is common and also increases the risk of gastrointestinal effects (e.g., diarrhea)," explained Dr. Imazio of Maria Vittoria Hospital and the University of Torino (Italy).

Still, colchicine provided significant protection in the COPPS-2 primary outcome of postpericardiotomy syndrome, compared with placebo (19.4% vs. 29.4%; 95% confidence interval, 1.1%-18.7%). The number needed to treat was 10.

The outcome did not differ significantly among predetermined subgroups based on age, sex, and presence or absence of pericardial effusion, although colchicine was especially efficacious in the setting of systemic inflammation with elevated C-reactive protein, the authors noted.

The intention-to-treat analysis revealed no significant differences between the colchicine and placebo groups for postoperative AF (33.9% vs. 41.7%; 95% CI, –2.2%-17.6%) or postoperative pericardial/pleural effusion (57.2% vs. 58.9%; 95% CI, –8.5%-11.7%).

The prespecified on-treatment analysis, however, showed a 14.2% absolute difference in postoperative AF, favoring colchicine over placebo (27% vs. 41.2%; 95% CI, 3.3%-24.7%).

"While the efficacy of colchicine for postpericardiotomy syndrome prevention is confirmed, the extent of efficacy for postoperative AF needs to be further investigated in future trials," Dr. Imazio stated.

Ongoing studies also will better clarify the potential of colchicine using lower doses that may be better tolerated.

The 360 patients were evenly randomized from 11 centers in Italy between March 2012 and March 2014. Their mean age was 67.5 years, 69% were men, and 36% had planned valvular surgery. Key exclusion criteria were absence of sinus rhythm at enrollment, urgent cardiac surgery, cardiac transplantation, and contraindications to colchicine.

COPPS-2 was supported by the Italian National Health Service and FARGIM. Acarpia provided the study drug. Dr. Imazio reported no conflicts of interest. A coauthor reported consultancy for Servier, serving on an advisory board for Boehringer Ingelheim, and lecturer fees from Abbott, AstraZeneca, Merck, Serono, Richter Gedeon, and Teva.

PARIS – Women have different predisposing risk factors for gout than do men, who more often fit the stereotypical profile of patients with gout who consume foods that increase the risk of the disease.

In the study based on data collected from participants in the Consortium of Rheumatology Researchers of North America (CORRONA) gout registry, women with gout were more likely to have taken predisposing medications and to have more gout-associated comorbidities, whereas men were more likely to consume foods linked to the disorder, such as alcohol and red meat, according to Dr. Leslie Harrold, scientific director of the CORRONA gout registry.

"We live in an era of personalized medicine," she said in an interview. "These findings speak to the need to tailor our evaluations and treatments based on the patient. There cannot be a one-size-fits-all approach. We need to approach women with gout differently than men with gout."

Patients in the gout study were enrolled in 2012-2013. Data gathered from patients and their rheumatologists at study enrollment included demographics, predisposing factors (comorbid conditions, medications, diet), gout disease characteristics, current treatments, and physical exam findings.

The 54 participating rheumatologists enrolled 1,167 gout patients (239 women). Women were significantly older than men (71 years vs. 61 years) and had higher body mass index (34 kg/m² vs. 23 kg/m²). They also were significantly more likely to have hypertension (77% vs. 57%), diabetes (28% vs. 17%), and renal disease (25% vs. 14%).

Women also had a shorter duration of gout when enrolled (6 years vs. 11 years) and were less likely to have a crystal-proven diagnosis (26% vs. 35%).

Medication risk factors for gout, such as diuretics, were more common in women (49% vs. 22%), while dietary risk factors were more frequent in men, who consumed significantly more beer, hard liquor, beef, and pork, Dr. Harrold reported at the annual European Congress of Rheumatology.

Although the clinical features of gout were similar between the genders at the time of initial diagnosis, women reported more frequent disability. Women were more likely to have contraindications to treatment with NSAIDs or colchicine, but women with tophi or active disease – defined as two or more flares per year – used urate-lowering therapy at a rate that was not statistically different from men (78% vs. 84%).

"I think what is most interesting is that the profile of men and women with gout differs," said Dr. Harrold of the division of rheumatology at the University of Massachusetts, Worcester. "Doctors usually have a single concept of the typical patient. But instead, here we have to realize that the typical woman with gout is different than the typical man with gout. That should frame our evaluation of suspected cases."

A number of pharmaceutical companies have financially supported the CORRONA registry. In the last 5 years, Dr. Harrold has received research funding from Takeda and has a pending grant with AstraZeneca.

[email protected]

PARIS – Women have different predisposing risk factors for gout than do men, who more often fit the stereotypical profile of patients with gout who consume foods that increase the risk of the disease.

In the study based on data collected from participants in the Consortium of Rheumatology Researchers of North America (CORRONA) gout registry, women with gout were more likely to have taken predisposing medications and to have more gout-associated comorbidities, whereas men were more likely to consume foods linked to the disorder, such as alcohol and red meat, according to Dr. Leslie Harrold, scientific director of the CORRONA gout registry.

"We live in an era of personalized medicine," she said in an interview. "These findings speak to the need to tailor our evaluations and treatments based on the patient. There cannot be a one-size-fits-all approach. We need to approach women with gout differently than men with gout."

Patients in the gout study were enrolled in 2012-2013. Data gathered from patients and their rheumatologists at study enrollment included demographics, predisposing factors (comorbid conditions, medications, diet), gout disease characteristics, current treatments, and physical exam findings.

The 54 participating rheumatologists enrolled 1,167 gout patients (239 women). Women were significantly older than men (71 years vs. 61 years) and had higher body mass index (34 kg/m² vs. 23 kg/m²). They also were significantly more likely to have hypertension (77% vs. 57%), diabetes (28% vs. 17%), and renal disease (25% vs. 14%).

Women also had a shorter duration of gout when enrolled (6 years vs. 11 years) and were less likely to have a crystal-proven diagnosis (26% vs. 35%).

Medication risk factors for gout, such as diuretics, were more common in women (49% vs. 22%), while dietary risk factors were more frequent in men, who consumed significantly more beer, hard liquor, beef, and pork, Dr. Harrold reported at the annual European Congress of Rheumatology.

Although the clinical features of gout were similar between the genders at the time of initial diagnosis, women reported more frequent disability. Women were more likely to have contraindications to treatment with NSAIDs or colchicine, but women with tophi or active disease – defined as two or more flares per year – used urate-lowering therapy at a rate that was not statistically different from men (78% vs. 84%).

"I think what is most interesting is that the profile of men and women with gout differs," said Dr. Harrold of the division of rheumatology at the University of Massachusetts, Worcester. "Doctors usually have a single concept of the typical patient. But instead, here we have to realize that the typical woman with gout is different than the typical man with gout. That should frame our evaluation of suspected cases."

A number of pharmaceutical companies have financially supported the CORRONA registry. In the last 5 years, Dr. Harrold has received research funding from Takeda and has a pending grant with AstraZeneca.

[email protected]

PARIS – Women have different predisposing risk factors for gout than do men, who more often fit the stereotypical profile of patients with gout who consume foods that increase the risk of the disease.

In the study based on data collected from participants in the Consortium of Rheumatology Researchers of North America (CORRONA) gout registry, women with gout were more likely to have taken predisposing medications and to have more gout-associated comorbidities, whereas men were more likely to consume foods linked to the disorder, such as alcohol and red meat, according to Dr. Leslie Harrold, scientific director of the CORRONA gout registry.

"We live in an era of personalized medicine," she said in an interview. "These findings speak to the need to tailor our evaluations and treatments based on the patient. There cannot be a one-size-fits-all approach. We need to approach women with gout differently than men with gout."

Patients in the gout study were enrolled in 2012-2013. Data gathered from patients and their rheumatologists at study enrollment included demographics, predisposing factors (comorbid conditions, medications, diet), gout disease characteristics, current treatments, and physical exam findings.

The 54 participating rheumatologists enrolled 1,167 gout patients (239 women). Women were significantly older than men (71 years vs. 61 years) and had higher body mass index (34 kg/m² vs. 23 kg/m²). They also were significantly more likely to have hypertension (77% vs. 57%), diabetes (28% vs. 17%), and renal disease (25% vs. 14%).

Women also had a shorter duration of gout when enrolled (6 years vs. 11 years) and were less likely to have a crystal-proven diagnosis (26% vs. 35%).

Medication risk factors for gout, such as diuretics, were more common in women (49% vs. 22%), while dietary risk factors were more frequent in men, who consumed significantly more beer, hard liquor, beef, and pork, Dr. Harrold reported at the annual European Congress of Rheumatology.

Although the clinical features of gout were similar between the genders at the time of initial diagnosis, women reported more frequent disability. Women were more likely to have contraindications to treatment with NSAIDs or colchicine, but women with tophi or active disease – defined as two or more flares per year – used urate-lowering therapy at a rate that was not statistically different from men (78% vs. 84%).

"I think what is most interesting is that the profile of men and women with gout differs," said Dr. Harrold of the division of rheumatology at the University of Massachusetts, Worcester. "Doctors usually have a single concept of the typical patient. But instead, here we have to realize that the typical woman with gout is different than the typical man with gout. That should frame our evaluation of suspected cases."

A number of pharmaceutical companies have financially supported the CORRONA registry. In the last 5 years, Dr. Harrold has received research funding from Takeda and has a pending grant with AstraZeneca.

[email protected]

PARIS – Men with gout are significantly more likely to experience erectile dysfunction than are those without the disorder, Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

In a survey of 201 men, erectile dysfunction (ED) occurred in 76% of 83 with gout and 52% of those without gout – a significant difference. In addition, 43% of those with gout and ED had severe erection difficulty – significantly more than those who had ED alone (30%).

Dr. Schlesinger, chief of rheumatology and connective tissue research at the Robert Wood Johnson Medical School, New Brunswick, N.J., said that ED can be a symptom of underlying cardiovascular disease. The small penile blood vessels can become atherosclerotic before the larger coronary vessels. The association between gout and ED remained significant even when she controlled for several cardiovascular risk factors: diabetes, hypertension, smoking, fasting glucose, and glomerular filtration rate.

Because of ED’s prevalence in this population – and because of its apparent association with cardiovascular disease – she advised that all men with gout be screened for sexual health.

"It’s not something physicians normally think to do" because of mutual embarrassment, she added.

[email protected]

On Twitter @alz_gal

PARIS – Men with gout are significantly more likely to experience erectile dysfunction than are those without the disorder, Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

In a survey of 201 men, erectile dysfunction (ED) occurred in 76% of 83 with gout and 52% of those without gout – a significant difference. In addition, 43% of those with gout and ED had severe erection difficulty – significantly more than those who had ED alone (30%).

Dr. Schlesinger, chief of rheumatology and connective tissue research at the Robert Wood Johnson Medical School, New Brunswick, N.J., said that ED can be a symptom of underlying cardiovascular disease. The small penile blood vessels can become atherosclerotic before the larger coronary vessels. The association between gout and ED remained significant even when she controlled for several cardiovascular risk factors: diabetes, hypertension, smoking, fasting glucose, and glomerular filtration rate.

Because of ED’s prevalence in this population – and because of its apparent association with cardiovascular disease – she advised that all men with gout be screened for sexual health.

"It’s not something physicians normally think to do" because of mutual embarrassment, she added.

[email protected]

On Twitter @alz_gal

PARIS – Men with gout are significantly more likely to experience erectile dysfunction than are those without the disorder, Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

In a survey of 201 men, erectile dysfunction (ED) occurred in 76% of 83 with gout and 52% of those without gout – a significant difference. In addition, 43% of those with gout and ED had severe erection difficulty – significantly more than those who had ED alone (30%).

Dr. Schlesinger, chief of rheumatology and connective tissue research at the Robert Wood Johnson Medical School, New Brunswick, N.J., said that ED can be a symptom of underlying cardiovascular disease. The small penile blood vessels can become atherosclerotic before the larger coronary vessels. The association between gout and ED remained significant even when she controlled for several cardiovascular risk factors: diabetes, hypertension, smoking, fasting glucose, and glomerular filtration rate.

Because of ED’s prevalence in this population – and because of its apparent association with cardiovascular disease – she advised that all men with gout be screened for sexual health.

"It’s not something physicians normally think to do" because of mutual embarrassment, she added.

[email protected]

On Twitter @alz_gal

SNOWMASS, COLO. – Evidence from three observational studies suggests colchicine has a strong protective effect against cardiovascular events in gout patients.

These data add to mounting evidence that the venerable 2,400-year-old medication also reduces the incidence of cardiac events in patients at elevated risk who don’t have gout, Dr. Michael H. Pillinger said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

He was a coinvestigator in the three observational studies, two of which are ongoing with only interim results available.

The first of these observational studies was a retrospective, cross-sectional pilot study of 1,288 gout patients in the New York Harbor Healthcare System Veterans Affairs database. The demographics, baseline comorbidities, and cardiovascular risk factors in the 576 colchicine users and 712 nonusers were closely similar. The key finding in this snapshot study: the prevalence of a history of acute MI was 1.2% in the colchicine users, compared with 2.6% in the non-users with gout, for a significant 54% relative risk reduction (J. Rheumatol. 2012;39:1458-64).

"That degree of risk reduction seems too good to be believed, and it probably is," according to Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.

But the next observational study showed a similar-size benefit. This was a retrospective cohort study of New York VA gout patients. It included only gout patients who met American College of Rheumatology diagnostic criteria as confirmed by manual chart review. There were 410 colchicine users with a collective 1,184 years of active use and another 682 years of lapse time, along with 234 colchicine nonusers with 1,041 years of follow-up time. Again, baseline demographics and comorbidities were remarkably similar for the two groups.

In an interim analysis, the incidence of acute MI was 0.7% among active users of colchicine, 2.0% in lapsed former users, and 3.1% in the nonuser controls. This translated to an incidence rate of 0.003 MIs per person-year in the colchicine users, 0.007 per person-year in the controls, and 0.009 MIs per person-year during a combined 1,723 person-years in the combined control group plus lapsed former users, for relative risk reductions of 57% and 67%, respectively. Still, the final results aren’t in yet, and this study is limited by a small number of events to date, its retrospective design, and the potential for confounding by indication, Dr. Pillinger noted.

Gout patients on colchicine in these two VA studies were on 0.6-1.2 mg/day rather than the now-standard 0.5 mg.

The latest observational study is a retrospective cohort study being conducted in collaboration with Dr. Peter Berger, chair of cardiology at the Geisinger Health System in Danville, Pa. To date, it includes 3,064 gout patients. The MI incidence thus far is 6.3/100 person-years in the colchicine users and 11.2/100 person-years among lapsed users. After controlling for potential confounders such as age, hypertension, and diabetes in a logistic regression analysis, however, the trend for reduced MI risk in the colchicine users hasn’t yet reached significance. Stay tuned, Dr. Pillinger said.

The mechanistic rationale by which colchicine might reduce cardiovascular events in gout patients lies in the fact that it is an anti-inflammatory drug and atherosclerosis is a powerfully inflammatory process. Colchicine is known to suppress production of TNF-alpha, interleukin-1beta, and other inflammatory cytokines by neutrophils, macrophages, and endothelial cells. These cell types are present in atherosclerotic plaque, the rheumatologist explained.

By the same rationale, colchicine might well be cardioprotective in individuals without gout. One strong piece of supporting evidence comes from a 3-year, randomized, observer-blinded clinical trial in which 532 Australian patients with stable coronary artery disease on background statin and antiplatelet therapy received 0.5 mg/day of colchicine or not. The composite primary endpoint comprised acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke occurred in 5.3% of the colchicine group, compared with 16.0% of controls. That’s a 67% relative risk reduction, with a highly favorable number-needed-to-treat of 11 (J. Am. Coll. Cardiol. 2013;61:404-10).

Dr. Pillinger reported being the recipient of research grants from Takeda, which markets colchicine (Colcrys), and Savient, which markets the gout drug pegloticase (Krystexxa).

[email protected]

SNOWMASS, COLO. – Evidence from three observational studies suggests colchicine has a strong protective effect against cardiovascular events in gout patients.

These data add to mounting evidence that the venerable 2,400-year-old medication also reduces the incidence of cardiac events in patients at elevated risk who don’t have gout, Dr. Michael H. Pillinger said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

He was a coinvestigator in the three observational studies, two of which are ongoing with only interim results available.

The first of these observational studies was a retrospective, cross-sectional pilot study of 1,288 gout patients in the New York Harbor Healthcare System Veterans Affairs database. The demographics, baseline comorbidities, and cardiovascular risk factors in the 576 colchicine users and 712 nonusers were closely similar. The key finding in this snapshot study: the prevalence of a history of acute MI was 1.2% in the colchicine users, compared with 2.6% in the non-users with gout, for a significant 54% relative risk reduction (J. Rheumatol. 2012;39:1458-64).

"That degree of risk reduction seems too good to be believed, and it probably is," according to Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.

But the next observational study showed a similar-size benefit. This was a retrospective cohort study of New York VA gout patients. It included only gout patients who met American College of Rheumatology diagnostic criteria as confirmed by manual chart review. There were 410 colchicine users with a collective 1,184 years of active use and another 682 years of lapse time, along with 234 colchicine nonusers with 1,041 years of follow-up time. Again, baseline demographics and comorbidities were remarkably similar for the two groups.

In an interim analysis, the incidence of acute MI was 0.7% among active users of colchicine, 2.0% in lapsed former users, and 3.1% in the nonuser controls. This translated to an incidence rate of 0.003 MIs per person-year in the colchicine users, 0.007 per person-year in the controls, and 0.009 MIs per person-year during a combined 1,723 person-years in the combined control group plus lapsed former users, for relative risk reductions of 57% and 67%, respectively. Still, the final results aren’t in yet, and this study is limited by a small number of events to date, its retrospective design, and the potential for confounding by indication, Dr. Pillinger noted.

Gout patients on colchicine in these two VA studies were on 0.6-1.2 mg/day rather than the now-standard 0.5 mg.

The latest observational study is a retrospective cohort study being conducted in collaboration with Dr. Peter Berger, chair of cardiology at the Geisinger Health System in Danville, Pa. To date, it includes 3,064 gout patients. The MI incidence thus far is 6.3/100 person-years in the colchicine users and 11.2/100 person-years among lapsed users. After controlling for potential confounders such as age, hypertension, and diabetes in a logistic regression analysis, however, the trend for reduced MI risk in the colchicine users hasn’t yet reached significance. Stay tuned, Dr. Pillinger said.

The mechanistic rationale by which colchicine might reduce cardiovascular events in gout patients lies in the fact that it is an anti-inflammatory drug and atherosclerosis is a powerfully inflammatory process. Colchicine is known to suppress production of TNF-alpha, interleukin-1beta, and other inflammatory cytokines by neutrophils, macrophages, and endothelial cells. These cell types are present in atherosclerotic plaque, the rheumatologist explained.

By the same rationale, colchicine might well be cardioprotective in individuals without gout. One strong piece of supporting evidence comes from a 3-year, randomized, observer-blinded clinical trial in which 532 Australian patients with stable coronary artery disease on background statin and antiplatelet therapy received 0.5 mg/day of colchicine or not. The composite primary endpoint comprised acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke occurred in 5.3% of the colchicine group, compared with 16.0% of controls. That’s a 67% relative risk reduction, with a highly favorable number-needed-to-treat of 11 (J. Am. Coll. Cardiol. 2013;61:404-10).

Dr. Pillinger reported being the recipient of research grants from Takeda, which markets colchicine (Colcrys), and Savient, which markets the gout drug pegloticase (Krystexxa).

[email protected]

SNOWMASS, COLO. – Evidence from three observational studies suggests colchicine has a strong protective effect against cardiovascular events in gout patients.

These data add to mounting evidence that the venerable 2,400-year-old medication also reduces the incidence of cardiac events in patients at elevated risk who don’t have gout, Dr. Michael H. Pillinger said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

He was a coinvestigator in the three observational studies, two of which are ongoing with only interim results available.

The first of these observational studies was a retrospective, cross-sectional pilot study of 1,288 gout patients in the New York Harbor Healthcare System Veterans Affairs database. The demographics, baseline comorbidities, and cardiovascular risk factors in the 576 colchicine users and 712 nonusers were closely similar. The key finding in this snapshot study: the prevalence of a history of acute MI was 1.2% in the colchicine users, compared with 2.6% in the non-users with gout, for a significant 54% relative risk reduction (J. Rheumatol. 2012;39:1458-64).

"That degree of risk reduction seems too good to be believed, and it probably is," according to Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.

But the next observational study showed a similar-size benefit. This was a retrospective cohort study of New York VA gout patients. It included only gout patients who met American College of Rheumatology diagnostic criteria as confirmed by manual chart review. There were 410 colchicine users with a collective 1,184 years of active use and another 682 years of lapse time, along with 234 colchicine nonusers with 1,041 years of follow-up time. Again, baseline demographics and comorbidities were remarkably similar for the two groups.

In an interim analysis, the incidence of acute MI was 0.7% among active users of colchicine, 2.0% in lapsed former users, and 3.1% in the nonuser controls. This translated to an incidence rate of 0.003 MIs per person-year in the colchicine users, 0.007 per person-year in the controls, and 0.009 MIs per person-year during a combined 1,723 person-years in the combined control group plus lapsed former users, for relative risk reductions of 57% and 67%, respectively. Still, the final results aren’t in yet, and this study is limited by a small number of events to date, its retrospective design, and the potential for confounding by indication, Dr. Pillinger noted.

Gout patients on colchicine in these two VA studies were on 0.6-1.2 mg/day rather than the now-standard 0.5 mg.

The latest observational study is a retrospective cohort study being conducted in collaboration with Dr. Peter Berger, chair of cardiology at the Geisinger Health System in Danville, Pa. To date, it includes 3,064 gout patients. The MI incidence thus far is 6.3/100 person-years in the colchicine users and 11.2/100 person-years among lapsed users. After controlling for potential confounders such as age, hypertension, and diabetes in a logistic regression analysis, however, the trend for reduced MI risk in the colchicine users hasn’t yet reached significance. Stay tuned, Dr. Pillinger said.

The mechanistic rationale by which colchicine might reduce cardiovascular events in gout patients lies in the fact that it is an anti-inflammatory drug and atherosclerosis is a powerfully inflammatory process. Colchicine is known to suppress production of TNF-alpha, interleukin-1beta, and other inflammatory cytokines by neutrophils, macrophages, and endothelial cells. These cell types are present in atherosclerotic plaque, the rheumatologist explained.

By the same rationale, colchicine might well be cardioprotective in individuals without gout. One strong piece of supporting evidence comes from a 3-year, randomized, observer-blinded clinical trial in which 532 Australian patients with stable coronary artery disease on background statin and antiplatelet therapy received 0.5 mg/day of colchicine or not. The composite primary endpoint comprised acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke occurred in 5.3% of the colchicine group, compared with 16.0% of controls. That’s a 67% relative risk reduction, with a highly favorable number-needed-to-treat of 11 (J. Am. Coll. Cardiol. 2013;61:404-10).

Dr. Pillinger reported being the recipient of research grants from Takeda, which markets colchicine (Colcrys), and Savient, which markets the gout drug pegloticase (Krystexxa).

[email protected]

SNOWMASS, COLO. – The current American College of Rheumatology gout guidelines contain a number of recommendations that may come as a surprise to rheumatologists and primary care physicians alike.

The guidelines state, for example, that urate-lowering therapy should be undertaken routinely in any patient with an established diagnosis of gout who has comorbid chronic kidney disease (CKD) that is stage 2 or worse, meaning an estimated glomerular filtration rate of 89 mL/minute per 1.73 m² or less.

The rationale is that it’s particularly important to try to prevent acute gout attacks in such patients because their renal dysfunction makes it problematic to use colchicine and NSAIDs to quell attacks. Intriguing studies suggest that lowering serum urate may actually slow progression of CKD, Dr. Michael H. Pillinger said at the Winter Rheumatology symposium sponsored by the American College of Rheumatology.

The guidelines name the other indications for urate lowering in gout patients as the presence of a tophus on clinical examination or an imaging study, a history of two or more gout attacks per year, or a history of kidney stones.

Traditionally, urate-lowering therapy has been initiated during quiescent periods, but the ACR guidelines state that it also can be started during an acute attack if effective anti-inflammatory management has been instituted.

"This goes against what I was taught," observed Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.

The guidelines (Arthritis Care Res. 2012;64:1431-46 and 1447-61) emphasize the importance of a treat-to-target approach.

"The primary care physicians I talk to still don’t know this. The ACR recommends a minimum serum urate target of less than 6.0 mg/dL, but the guidelines are very clear that if 6 isn’t good enough, you keep going. You go below 5. When I see patients with tophaceous gout, my target is never 6. My target is 5 or 4. That’s what I teach my fellows," explained Dr. Pillinger, who served on an expert panel that advised the guideline-writing task force.

The ACR urate-lowering algorithm begins with either allopurinol or febuxostat (Uloric) as first-line therapy. The guideline committee, which expressly excluded cost as a consideration, offered no guidance as to which xanthine oxidase inhibitor is preferred. Dr. Pillinger noted that febuxostat is a more specific xanthine oxidase inhibitor, is simpler to dose, and is far less likely to cause hypersensitivity reactions than is allopurinol. It is also more effective, although not dramatically more so. And it is considerably more expensive.

Febuxostat is approved by the Food and Drug Administration specifically for use in patients with mild to moderate CKD. Allopurinol is not. However, the gout guidelines endorse the use of allopurinol in that setting.

When allopurinol is the initial drug, the guidelines recommend dosing it in a manner that is different from how most physicians have been using it, the rheumatologist said. The recommended starting dose is lower than has been customary: 100 mg/day, and 50 mg/day in patients with stage 4 or 5 CKD. The drug is to be titrated upward every 2-5 weeks as needed to achieve the target urate level. The maximum dose is 800 mg/day, even in patients with comorbid CKD. Although the guidelines don’t provide guidance as to the size of the stepwise dosing increases, Dr. Pillinger usually boosts the allopurinol dose by 100 mg at a time, or 50 mg in patients with CKD.

"Most patients don’t get to target at 300 mg/day. You’ve got to go higher," he said.

An important innovation in the current guidelines is the recommendation for testing for the HLA-B*5801 allele in patients of Korean, Thai, or Han Chinese ancestry who are being considered for allopurinol therapy. The presence of this allele confers a several hundred–fold increased risk of allopurinol hypersensitivity.

Probenecid is endorsed as the alternative first-line urate-lowering agent, but only if at least one xanthine oxidase inhibitor is contraindicated or not tolerated. No other agents get the nod as first-line therapy.

The guidelines state that if a patient’s serum urate is not at target despite maximum-dose therapy with a first-line xanthine oxidase inhibitor, it is not appropriate to switch to the other xanthine oxidase inhibitor. Instead, it is time to add a uricosuric agent: probenecid, losartan, or fenofibrate. If the urate level still is not at target and the patient is generally well, with few gout attacks, then that’s an acceptable result. However, if the patient has moderate tophaceous gout or chronic gouty arthropathy, it’s appropriate to place the patient on pegloticase (Krystexxa) while discontinuing all other urate-lowering agents.

The ACR guidelines stress that it is vital to always try to prevent gout attacks during initiation of urate-lowering therapy. The recommended first-line agents for prophylaxis are low-dose colchicine or a low-dose NSAID, with prednisone at a dose not to exceed 10 mg/day reserved as second-line therapy in the event the first-line agents are not tolerated or are ineffective.

Prophylaxis is supposed to continue as long as a patient has any evidence of disease activity. And once all symptoms and tophi have resolved, all measures needed to keep the serum urate below 6.0 mg/dL are to be continued indefinitely.

"For most patients," Dr. Pillinger concluded, "gout treatment is almost always forever."

He reported having received research grants from Takeda, which markets febuxostat in the United States, and Savient, which markets pegloticase.

[email protected]

SNOWMASS, COLO. – The current American College of Rheumatology gout guidelines contain a number of recommendations that may come as a surprise to rheumatologists and primary care physicians alike.

The guidelines state, for example, that urate-lowering therapy should be undertaken routinely in any patient with an established diagnosis of gout who has comorbid chronic kidney disease (CKD) that is stage 2 or worse, meaning an estimated glomerular filtration rate of 89 mL/minute per 1.73 m² or less.

The rationale is that it’s particularly important to try to prevent acute gout attacks in such patients because their renal dysfunction makes it problematic to use colchicine and NSAIDs to quell attacks. Intriguing studies suggest that lowering serum urate may actually slow progression of CKD, Dr. Michael H. Pillinger said at the Winter Rheumatology symposium sponsored by the American College of Rheumatology.

The guidelines name the other indications for urate lowering in gout patients as the presence of a tophus on clinical examination or an imaging study, a history of two or more gout attacks per year, or a history of kidney stones.

Traditionally, urate-lowering therapy has been initiated during quiescent periods, but the ACR guidelines state that it also can be started during an acute attack if effective anti-inflammatory management has been instituted.

"This goes against what I was taught," observed Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.

The guidelines (Arthritis Care Res. 2012;64:1431-46 and 1447-61) emphasize the importance of a treat-to-target approach.

"The primary care physicians I talk to still don’t know this. The ACR recommends a minimum serum urate target of less than 6.0 mg/dL, but the guidelines are very clear that if 6 isn’t good enough, you keep going. You go below 5. When I see patients with tophaceous gout, my target is never 6. My target is 5 or 4. That’s what I teach my fellows," explained Dr. Pillinger, who served on an expert panel that advised the guideline-writing task force.

The ACR urate-lowering algorithm begins with either allopurinol or febuxostat (Uloric) as first-line therapy. The guideline committee, which expressly excluded cost as a consideration, offered no guidance as to which xanthine oxidase inhibitor is preferred. Dr. Pillinger noted that febuxostat is a more specific xanthine oxidase inhibitor, is simpler to dose, and is far less likely to cause hypersensitivity reactions than is allopurinol. It is also more effective, although not dramatically more so. And it is considerably more expensive.

Febuxostat is approved by the Food and Drug Administration specifically for use in patients with mild to moderate CKD. Allopurinol is not. However, the gout guidelines endorse the use of allopurinol in that setting.

When allopurinol is the initial drug, the guidelines recommend dosing it in a manner that is different from how most physicians have been using it, the rheumatologist said. The recommended starting dose is lower than has been customary: 100 mg/day, and 50 mg/day in patients with stage 4 or 5 CKD. The drug is to be titrated upward every 2-5 weeks as needed to achieve the target urate level. The maximum dose is 800 mg/day, even in patients with comorbid CKD. Although the guidelines don’t provide guidance as to the size of the stepwise dosing increases, Dr. Pillinger usually boosts the allopurinol dose by 100 mg at a time, or 50 mg in patients with CKD.

"Most patients don’t get to target at 300 mg/day. You’ve got to go higher," he said.

An important innovation in the current guidelines is the recommendation for testing for the HLA-B*5801 allele in patients of Korean, Thai, or Han Chinese ancestry who are being considered for allopurinol therapy. The presence of this allele confers a several hundred–fold increased risk of allopurinol hypersensitivity.

Probenecid is endorsed as the alternative first-line urate-lowering agent, but only if at least one xanthine oxidase inhibitor is contraindicated or not tolerated. No other agents get the nod as first-line therapy.

The guidelines state that if a patient’s serum urate is not at target despite maximum-dose therapy with a first-line xanthine oxidase inhibitor, it is not appropriate to switch to the other xanthine oxidase inhibitor. Instead, it is time to add a uricosuric agent: probenecid, losartan, or fenofibrate. If the urate level still is not at target and the patient is generally well, with few gout attacks, then that’s an acceptable result. However, if the patient has moderate tophaceous gout or chronic gouty arthropathy, it’s appropriate to place the patient on pegloticase (Krystexxa) while discontinuing all other urate-lowering agents.

The ACR guidelines stress that it is vital to always try to prevent gout attacks during initiation of urate-lowering therapy. The recommended first-line agents for prophylaxis are low-dose colchicine or a low-dose NSAID, with prednisone at a dose not to exceed 10 mg/day reserved as second-line therapy in the event the first-line agents are not tolerated or are ineffective.

Prophylaxis is supposed to continue as long as a patient has any evidence of disease activity. And once all symptoms and tophi have resolved, all measures needed to keep the serum urate below 6.0 mg/dL are to be continued indefinitely.

"For most patients," Dr. Pillinger concluded, "gout treatment is almost always forever."

He reported having received research grants from Takeda, which markets febuxostat in the United States, and Savient, which markets pegloticase.

[email protected]

SNOWMASS, COLO. – The current American College of Rheumatology gout guidelines contain a number of recommendations that may come as a surprise to rheumatologists and primary care physicians alike.

The guidelines state, for example, that urate-lowering therapy should be undertaken routinely in any patient with an established diagnosis of gout who has comorbid chronic kidney disease (CKD) that is stage 2 or worse, meaning an estimated glomerular filtration rate of 89 mL/minute per 1.73 m² or less.

The rationale is that it’s particularly important to try to prevent acute gout attacks in such patients because their renal dysfunction makes it problematic to use colchicine and NSAIDs to quell attacks. Intriguing studies suggest that lowering serum urate may actually slow progression of CKD, Dr. Michael H. Pillinger said at the Winter Rheumatology symposium sponsored by the American College of Rheumatology.

The guidelines name the other indications for urate lowering in gout patients as the presence of a tophus on clinical examination or an imaging study, a history of two or more gout attacks per year, or a history of kidney stones.

Traditionally, urate-lowering therapy has been initiated during quiescent periods, but the ACR guidelines state that it also can be started during an acute attack if effective anti-inflammatory management has been instituted.

"This goes against what I was taught," observed Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.

The guidelines (Arthritis Care Res. 2012;64:1431-46 and 1447-61) emphasize the importance of a treat-to-target approach.

"The primary care physicians I talk to still don’t know this. The ACR recommends a minimum serum urate target of less than 6.0 mg/dL, but the guidelines are very clear that if 6 isn’t good enough, you keep going. You go below 5. When I see patients with tophaceous gout, my target is never 6. My target is 5 or 4. That’s what I teach my fellows," explained Dr. Pillinger, who served on an expert panel that advised the guideline-writing task force.

The ACR urate-lowering algorithm begins with either allopurinol or febuxostat (Uloric) as first-line therapy. The guideline committee, which expressly excluded cost as a consideration, offered no guidance as to which xanthine oxidase inhibitor is preferred. Dr. Pillinger noted that febuxostat is a more specific xanthine oxidase inhibitor, is simpler to dose, and is far less likely to cause hypersensitivity reactions than is allopurinol. It is also more effective, although not dramatically more so. And it is considerably more expensive.

Febuxostat is approved by the Food and Drug Administration specifically for use in patients with mild to moderate CKD. Allopurinol is not. However, the gout guidelines endorse the use of allopurinol in that setting.

When allopurinol is the initial drug, the guidelines recommend dosing it in a manner that is different from how most physicians have been using it, the rheumatologist said. The recommended starting dose is lower than has been customary: 100 mg/day, and 50 mg/day in patients with stage 4 or 5 CKD. The drug is to be titrated upward every 2-5 weeks as needed to achieve the target urate level. The maximum dose is 800 mg/day, even in patients with comorbid CKD. Although the guidelines don’t provide guidance as to the size of the stepwise dosing increases, Dr. Pillinger usually boosts the allopurinol dose by 100 mg at a time, or 50 mg in patients with CKD.

"Most patients don’t get to target at 300 mg/day. You’ve got to go higher," he said.

An important innovation in the current guidelines is the recommendation for testing for the HLA-B*5801 allele in patients of Korean, Thai, or Han Chinese ancestry who are being considered for allopurinol therapy. The presence of this allele confers a several hundred–fold increased risk of allopurinol hypersensitivity.

Probenecid is endorsed as the alternative first-line urate-lowering agent, but only if at least one xanthine oxidase inhibitor is contraindicated or not tolerated. No other agents get the nod as first-line therapy.

The guidelines state that if a patient’s serum urate is not at target despite maximum-dose therapy with a first-line xanthine oxidase inhibitor, it is not appropriate to switch to the other xanthine oxidase inhibitor. Instead, it is time to add a uricosuric agent: probenecid, losartan, or fenofibrate. If the urate level still is not at target and the patient is generally well, with few gout attacks, then that’s an acceptable result. However, if the patient has moderate tophaceous gout or chronic gouty arthropathy, it’s appropriate to place the patient on pegloticase (Krystexxa) while discontinuing all other urate-lowering agents.

The ACR guidelines stress that it is vital to always try to prevent gout attacks during initiation of urate-lowering therapy. The recommended first-line agents for prophylaxis are low-dose colchicine or a low-dose NSAID, with prednisone at a dose not to exceed 10 mg/day reserved as second-line therapy in the event the first-line agents are not tolerated or are ineffective.

Prophylaxis is supposed to continue as long as a patient has any evidence of disease activity. And once all symptoms and tophi have resolved, all measures needed to keep the serum urate below 6.0 mg/dL are to be continued indefinitely.

"For most patients," Dr. Pillinger concluded, "gout treatment is almost always forever."

He reported having received research grants from Takeda, which markets febuxostat in the United States, and Savient, which markets pegloticase.

[email protected]

SNOWMASS, COLO. – Pegloticase (Krystexxa) is a gout drug that’s expensive, inconveniently administered by intravenous infusion every 2 weeks, and saddled with a substantial rate of immunogenicity, with infusion reactions that can include anaphylaxis.

So why does gout authority Dr. Michael H. Pillinger call pegloticase "a greatly underestimated and underutilized drug"? And why do the current American College of Rheumatology gout guidelines recommend pegloticase for refractory gout?

"Nothing else we have will get rid of tophi the way this drug gets rid of tophi," Dr. Pillinger explained at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

"Why do we care about that? Because tophi are erosive, they’re damaging, and also because they’re much more extensive than we think they are," said Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.

Besides, the safety concern regarding this powerhouse urate-lowering drug has been resolved. The infusion reactions are readily avoidable. Pegloticase is not a drug rheumatologists should be scared of, he emphasized.

Dr. Pillinger cited an eye-opening study that demonstrated just how much larger gout patients’ total body urate burden actually is compared with what’s apparent clinically. Investigators at the University of British Columbia, Vancouver, used dual-energy CT to assess urate deposits in 20 consecutive patients with tophaceous gout and 10 controls with other arthritic conditions. Physical evaluation of the gout patients turned up 111 areas of urate deposition; dual-energy CT revealed 440 such areas. The mean total urate volume was a hefty 40.2 cm³ (Ann. Rheum. Dis. 2009;68:1609-12).

"There’s a lot more tophi under the surface," Dr. Pillinger commented.

Pegloticase is a recombinant porcine uricase that’s modified with a baboon N-terminus. It’s pegylated to reduce immunogenicity to the uricase and increase stability and half-life. Paradoxically, the drug is still quite immunogenic because many patients develop antibodies to the polyethylene glycol used in pegylation.

The drug’s urate-lowering effect is unmatched. Within 12-24 hours of the first dose, the plasma uric acid level plummets to almost nothing.

"What happens is that very, very quickly these patients are going to split into two groups. For one group this is the greatest drug in the world; their uric acid remains almost undetectable – and that’s in our sickest refractory patients. And then there’s another group that starts to fail. It’s in the neighborhood of 30%-40% of patients, so it’s a real problem. We know they’re failing because their uric acid level starts rising. They’re making antibodies and inactivating the drug every time it’s given. And they’re the ones who get bad infusion reactions," the rheumatologist explained.

The solution to using pegloticase safely is to routinely measure serum urate 1-2 days before each infusion. If the serum urate climbs to 6 mg/dL on one or two occasions, it’s time to discontinue the drug.

"For everybody else, they’re going to do really, really well," Dr. Pillinger said.

A key point emphasized in the 2012 ACR gout guidelines (Arthritis Care Res. 2012;64:1431-46; 1447-61) is that when patients go on pegloticase, all other urate-lowering therapies must be stopped as a matter of safety. Otherwise, it’s impossible to use the pre-infusion plasma urate measurement to determine if pegloticase has stopped working.

The ACR guidelines recommend pegloticase as third-line urate-lowering therapy in patients who are not at target despite maximum-dose therapy with a xanthine oxidase inhibitor plus second-line therapy with probenecid, losartan, or fenofibrate.

Dr. Pillinger reported having received research grants from Savient, which markets pegloticase, and Takeda.

[email protected]

SNOWMASS, COLO. – Pegloticase (Krystexxa) is a gout drug that’s expensive, inconveniently administered by intravenous infusion every 2 weeks, and saddled with a substantial rate of immunogenicity, with infusion reactions that can include anaphylaxis.

So why does gout authority Dr. Michael H. Pillinger call pegloticase "a greatly underestimated and underutilized drug"? And why do the current American College of Rheumatology gout guidelines recommend pegloticase for refractory gout?

"Nothing else we have will get rid of tophi the way this drug gets rid of tophi," Dr. Pillinger explained at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

"Why do we care about that? Because tophi are erosive, they’re damaging, and also because they’re much more extensive than we think they are," said Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.

Besides, the safety concern regarding this powerhouse urate-lowering drug has been resolved. The infusion reactions are readily avoidable. Pegloticase is not a drug rheumatologists should be scared of, he emphasized.

Dr. Pillinger cited an eye-opening study that demonstrated just how much larger gout patients’ total body urate burden actually is compared with what’s apparent clinically. Investigators at the University of British Columbia, Vancouver, used dual-energy CT to assess urate deposits in 20 consecutive patients with tophaceous gout and 10 controls with other arthritic conditions. Physical evaluation of the gout patients turned up 111 areas of urate deposition; dual-energy CT revealed 440 such areas. The mean total urate volume was a hefty 40.2 cm³ (Ann. Rheum. Dis. 2009;68:1609-12).

"There’s a lot more tophi under the surface," Dr. Pillinger commented.

Pegloticase is a recombinant porcine uricase that’s modified with a baboon N-terminus. It’s pegylated to reduce immunogenicity to the uricase and increase stability and half-life. Paradoxically, the drug is still quite immunogenic because many patients develop antibodies to the polyethylene glycol used in pegylation.

The drug’s urate-lowering effect is unmatched. Within 12-24 hours of the first dose, the plasma uric acid level plummets to almost nothing.

"What happens is that very, very quickly these patients are going to split into two groups. For one group this is the greatest drug in the world; their uric acid remains almost undetectable – and that’s in our sickest refractory patients. And then there’s another group that starts to fail. It’s in the neighborhood of 30%-40% of patients, so it’s a real problem. We know they’re failing because their uric acid level starts rising. They’re making antibodies and inactivating the drug every time it’s given. And they’re the ones who get bad infusion reactions," the rheumatologist explained.

The solution to using pegloticase safely is to routinely measure serum urate 1-2 days before each infusion. If the serum urate climbs to 6 mg/dL on one or two occasions, it’s time to discontinue the drug.

"For everybody else, they’re going to do really, really well," Dr. Pillinger said.

A key point emphasized in the 2012 ACR gout guidelines (Arthritis Care Res. 2012;64:1431-46; 1447-61) is that when patients go on pegloticase, all other urate-lowering therapies must be stopped as a matter of safety. Otherwise, it’s impossible to use the pre-infusion plasma urate measurement to determine if pegloticase has stopped working.

The ACR guidelines recommend pegloticase as third-line urate-lowering therapy in patients who are not at target despite maximum-dose therapy with a xanthine oxidase inhibitor plus second-line therapy with probenecid, losartan, or fenofibrate.

Dr. Pillinger reported having received research grants from Savient, which markets pegloticase, and Takeda.

[email protected]

SNOWMASS, COLO. – Pegloticase (Krystexxa) is a gout drug that’s expensive, inconveniently administered by intravenous infusion every 2 weeks, and saddled with a substantial rate of immunogenicity, with infusion reactions that can include anaphylaxis.

So why does gout authority Dr. Michael H. Pillinger call pegloticase "a greatly underestimated and underutilized drug"? And why do the current American College of Rheumatology gout guidelines recommend pegloticase for refractory gout?

"Nothing else we have will get rid of tophi the way this drug gets rid of tophi," Dr. Pillinger explained at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

"Why do we care about that? Because tophi are erosive, they’re damaging, and also because they’re much more extensive than we think they are," said Dr. Pillinger, a rheumatologist and director of the crystal diseases study group at New York University.

Besides, the safety concern regarding this powerhouse urate-lowering drug has been resolved. The infusion reactions are readily avoidable. Pegloticase is not a drug rheumatologists should be scared of, he emphasized.

Dr. Pillinger cited an eye-opening study that demonstrated just how much larger gout patients’ total body urate burden actually is compared with what’s apparent clinically. Investigators at the University of British Columbia, Vancouver, used dual-energy CT to assess urate deposits in 20 consecutive patients with tophaceous gout and 10 controls with other arthritic conditions. Physical evaluation of the gout patients turned up 111 areas of urate deposition; dual-energy CT revealed 440 such areas. The mean total urate volume was a hefty 40.2 cm³ (Ann. Rheum. Dis. 2009;68:1609-12).

"There’s a lot more tophi under the surface," Dr. Pillinger commented.

Pegloticase is a recombinant porcine uricase that’s modified with a baboon N-terminus. It’s pegylated to reduce immunogenicity to the uricase and increase stability and half-life. Paradoxically, the drug is still quite immunogenic because many patients develop antibodies to the polyethylene glycol used in pegylation.

The drug’s urate-lowering effect is unmatched. Within 12-24 hours of the first dose, the plasma uric acid level plummets to almost nothing.

"What happens is that very, very quickly these patients are going to split into two groups. For one group this is the greatest drug in the world; their uric acid remains almost undetectable – and that’s in our sickest refractory patients. And then there’s another group that starts to fail. It’s in the neighborhood of 30%-40% of patients, so it’s a real problem. We know they’re failing because their uric acid level starts rising. They’re making antibodies and inactivating the drug every time it’s given. And they’re the ones who get bad infusion reactions," the rheumatologist explained.

The solution to using pegloticase safely is to routinely measure serum urate 1-2 days before each infusion. If the serum urate climbs to 6 mg/dL on one or two occasions, it’s time to discontinue the drug.

"For everybody else, they’re going to do really, really well," Dr. Pillinger said.

A key point emphasized in the 2012 ACR gout guidelines (Arthritis Care Res. 2012;64:1431-46; 1447-61) is that when patients go on pegloticase, all other urate-lowering therapies must be stopped as a matter of safety. Otherwise, it’s impossible to use the pre-infusion plasma urate measurement to determine if pegloticase has stopped working.

The ACR guidelines recommend pegloticase as third-line urate-lowering therapy in patients who are not at target despite maximum-dose therapy with a xanthine oxidase inhibitor plus second-line therapy with probenecid, losartan, or fenofibrate.

Dr. Pillinger reported having received research grants from Savient, which markets pegloticase, and Takeda.

[email protected]

SAN DIEGO – The number of Americans with gout has climbed sevenfold during the last 50 years, according to Dr. Eswar Krishnan.

The population burden of illness imposed by gout has risen both in men and women across all age groups, but most strikingly so in men older than 65 years, said Dr. Krishnan, director of clinical epidemiology in the division of immunology and rheumatology at Stanford (Calif.) University.

He turned to National Health and Nutrition Examination Survey (NHANES) data to gain a more precise picture of U.S. trends in gout prevalence over time than has previously been available. He accomplished this by comparing age- and sex-specific rates from the 1959-1962 and the 2009-2010 editions of the long-running Centers for Disease Control and Prevention–sponsored surveys.

The unadjusted population-based prevalence of self-reported gout jumped from 6 cases per 1,000 during 1959-1962 to 26 per 1,000 in 2009-2010. The estimated number of gout cases climbed from 1.1 million in 1960 to 8.1 million in 2010. Yet the proportion of gout patients who were women remained steady at 31% over time.

The mean age of Americans with gout rose over the half-century from 54 to 61 years among men and from 55 to 65 years among women, he reported at the annual meeting of the American College of Rheumatology.

Statistical analysis indicated that the increase in gout cases among women during the last 50 years could be accounted for entirely by the much-discussed societal growth in abdominal obesity. In contrast, the explanation for the increased prevalence of gout in men was multifactorial. The bulk of the increase was associated with an increased life span and the graying of America, coupled with higher rates of hypertension, diabetes, and abdominal obesity.

However, an immeasurable portion of the increase in gout during the past half-century is probably due to increased awareness of the disease among the U.S. population, Dr. Krishnan added.

NHANES is sponsored by the Centers for Disease Control and Prevention. Dr. Krishnan reported having received research grants from Takeda, which markets gout medication.

[email protected]

SAN DIEGO – The number of Americans with gout has climbed sevenfold during the last 50 years, according to Dr. Eswar Krishnan.

The population burden of illness imposed by gout has risen both in men and women across all age groups, but most strikingly so in men older than 65 years, said Dr. Krishnan, director of clinical epidemiology in the division of immunology and rheumatology at Stanford (Calif.) University.

He turned to National Health and Nutrition Examination Survey (NHANES) data to gain a more precise picture of U.S. trends in gout prevalence over time than has previously been available. He accomplished this by comparing age- and sex-specific rates from the 1959-1962 and the 2009-2010 editions of the long-running Centers for Disease Control and Prevention–sponsored surveys.

The unadjusted population-based prevalence of self-reported gout jumped from 6 cases per 1,000 during 1959-1962 to 26 per 1,000 in 2009-2010. The estimated number of gout cases climbed from 1.1 million in 1960 to 8.1 million in 2010. Yet the proportion of gout patients who were women remained steady at 31% over time.

The mean age of Americans with gout rose over the half-century from 54 to 61 years among men and from 55 to 65 years among women, he reported at the annual meeting of the American College of Rheumatology.

Statistical analysis indicated that the increase in gout cases among women during the last 50 years could be accounted for entirely by the much-discussed societal growth in abdominal obesity. In contrast, the explanation for the increased prevalence of gout in men was multifactorial. The bulk of the increase was associated with an increased life span and the graying of America, coupled with higher rates of hypertension, diabetes, and abdominal obesity.

However, an immeasurable portion of the increase in gout during the past half-century is probably due to increased awareness of the disease among the U.S. population, Dr. Krishnan added.

NHANES is sponsored by the Centers for Disease Control and Prevention. Dr. Krishnan reported having received research grants from Takeda, which markets gout medication.

[email protected]

SAN DIEGO – The number of Americans with gout has climbed sevenfold during the last 50 years, according to Dr. Eswar Krishnan.

The population burden of illness imposed by gout has risen both in men and women across all age groups, but most strikingly so in men older than 65 years, said Dr. Krishnan, director of clinical epidemiology in the division of immunology and rheumatology at Stanford (Calif.) University.

He turned to National Health and Nutrition Examination Survey (NHANES) data to gain a more precise picture of U.S. trends in gout prevalence over time than has previously been available. He accomplished this by comparing age- and sex-specific rates from the 1959-1962 and the 2009-2010 editions of the long-running Centers for Disease Control and Prevention–sponsored surveys.

The unadjusted population-based prevalence of self-reported gout jumped from 6 cases per 1,000 during 1959-1962 to 26 per 1,000 in 2009-2010. The estimated number of gout cases climbed from 1.1 million in 1960 to 8.1 million in 2010. Yet the proportion of gout patients who were women remained steady at 31% over time.

The mean age of Americans with gout rose over the half-century from 54 to 61 years among men and from 55 to 65 years among women, he reported at the annual meeting of the American College of Rheumatology.

Statistical analysis indicated that the increase in gout cases among women during the last 50 years could be accounted for entirely by the much-discussed societal growth in abdominal obesity. In contrast, the explanation for the increased prevalence of gout in men was multifactorial. The bulk of the increase was associated with an increased life span and the graying of America, coupled with higher rates of hypertension, diabetes, and abdominal obesity.

However, an immeasurable portion of the increase in gout during the past half-century is probably due to increased awareness of the disease among the U.S. population, Dr. Krishnan added.

NHANES is sponsored by the Centers for Disease Control and Prevention. Dr. Krishnan reported having received research grants from Takeda, which markets gout medication.

[email protected]

SAN DIEGO – Patients who achieve a serum uric acid level of less than 6 mg/dL based on current gout management guidelines demonstrated a 37% reduction in progression of renal disease, a large retrospective study showed.

"There are numerous studies showing that people with renal disease can develop hyperuricemia," Dr. Gerald D. Levy said during a press briefing at the annual meeting of the American College of Rheumatology. "Some of them will also develop gout. There are a few small studies showing that in humans, you can reverse hyperuricemia with urate lowering therapy and make an impact in renal disease. We wanted to see if this is true."

Dr. Levy of the division of rheumatology in the department of internal medicine at Kaiser Permanente Medical Group, Downey, Calif., was the lead investigators in a study of 111,992 Kaiser Permanente Southern California patients with a serum uric acid (SUA) level of 7 mg/dL or greater from Jan. 1, 2002, to Dec. 31, 2010. Patients with at least 12 months of health plan membership, including drug benefit prior to the index date, were studied. All patients had at least one SUA and glomerular filtration rate (GFR) level measurement in the 6-month period prior to the index date and at least one SUA and one GFR in the follow-up period following the index date. Primary outcome events were at least a 30% worsening of renal function, initiation of dialysis, having a GFR of less than 15 mL/min, and undergoing a kidney transplant.

Patients with a new diagnosis of cancer were excluded from the analysis, as were those with HIV, glomerulonephritis, and/or organ transplant other than a kidney transplant.

Dr. Levy reported results from 16,186 patients who were divided into three groups: those who were never treated with urate-lowering therapy (ULT; 11,192); those who were treated with ULT less than 80% of the time from the index date to the end of follow-up period (3,902); and those who were treated with ULT 80% of the time or more from the index date to the end of the follow-up period (1,092). Of the three treatment groups, those who were treated with ULT 80% of the time or more during the study tended to be older and have more comorbid conditions, compared with the other two groups. They also began their ULT therapy earlier.

Among all patients combined, factors significantly associated with renal disease progression included having diabetes (hazard ratio, 1.96), hypertension (HR, 1.50), heart failure (HR, 1.39), previous hospitalizations (HR, 1.33), and being female (HR, 1.49) and older (HR, 1.03). The researchers found that time on ULT was not significantly associated with a reduction in renal disease progression outcome events (HR, 1.27, among those on ULT less than 80% of the time during the study vs. HR, 1.08, among those on ULT 80% of the time or more during the study). However, patients who achieved an SUA level below 6 mg/dL – a treatment goal in the 2012 ACR guidelines for management of gout – demonstrated a 37% reduction in renal disease progression (HR, 0.63; P less than .0001).

Dr. Levy acknowledged certain limitations of the study, including its retrospective design and the fact that patients with stage 4 and 5 chronic kidney disease were not included. "This is an important area, because if we can delay the worsening of renal disease in these folks, perhaps we’re abetting dialysis, which is growing by leaps and bounds in this country," he said. "Each dialysis patient now costs about $80,000 per year to take care of. If we could push that back even for a few years it would have a tremendous impact."

Dr. Levy had no relevant financial conflicts to disclose.

[email protected]

SAN DIEGO – Patients who achieve a serum uric acid level of less than 6 mg/dL based on current gout management guidelines demonstrated a 37% reduction in progression of renal disease, a large retrospective study showed.

"There are numerous studies showing that people with renal disease can develop hyperuricemia," Dr. Gerald D. Levy said during a press briefing at the annual meeting of the American College of Rheumatology. "Some of them will also develop gout. There are a few small studies showing that in humans, you can reverse hyperuricemia with urate lowering therapy and make an impact in renal disease. We wanted to see if this is true."

Dr. Levy of the division of rheumatology in the department of internal medicine at Kaiser Permanente Medical Group, Downey, Calif., was the lead investigators in a study of 111,992 Kaiser Permanente Southern California patients with a serum uric acid (SUA) level of 7 mg/dL or greater from Jan. 1, 2002, to Dec. 31, 2010. Patients with at least 12 months of health plan membership, including drug benefit prior to the index date, were studied. All patients had at least one SUA and glomerular filtration rate (GFR) level measurement in the 6-month period prior to the index date and at least one SUA and one GFR in the follow-up period following the index date. Primary outcome events were at least a 30% worsening of renal function, initiation of dialysis, having a GFR of less than 15 mL/min, and undergoing a kidney transplant.

Patients with a new diagnosis of cancer were excluded from the analysis, as were those with HIV, glomerulonephritis, and/or organ transplant other than a kidney transplant.

Dr. Levy reported results from 16,186 patients who were divided into three groups: those who were never treated with urate-lowering therapy (ULT; 11,192); those who were treated with ULT less than 80% of the time from the index date to the end of follow-up period (3,902); and those who were treated with ULT 80% of the time or more from the index date to the end of the follow-up period (1,092). Of the three treatment groups, those who were treated with ULT 80% of the time or more during the study tended to be older and have more comorbid conditions, compared with the other two groups. They also began their ULT therapy earlier.

Among all patients combined, factors significantly associated with renal disease progression included having diabetes (hazard ratio, 1.96), hypertension (HR, 1.50), heart failure (HR, 1.39), previous hospitalizations (HR, 1.33), and being female (HR, 1.49) and older (HR, 1.03). The researchers found that time on ULT was not significantly associated with a reduction in renal disease progression outcome events (HR, 1.27, among those on ULT less than 80% of the time during the study vs. HR, 1.08, among those on ULT 80% of the time or more during the study). However, patients who achieved an SUA level below 6 mg/dL – a treatment goal in the 2012 ACR guidelines for management of gout – demonstrated a 37% reduction in renal disease progression (HR, 0.63; P less than .0001).

Dr. Levy acknowledged certain limitations of the study, including its retrospective design and the fact that patients with stage 4 and 5 chronic kidney disease were not included. "This is an important area, because if we can delay the worsening of renal disease in these folks, perhaps we’re abetting dialysis, which is growing by leaps and bounds in this country," he said. "Each dialysis patient now costs about $80,000 per year to take care of. If we could push that back even for a few years it would have a tremendous impact."

Dr. Levy had no relevant financial conflicts to disclose.

[email protected]

SAN DIEGO – Patients who achieve a serum uric acid level of less than 6 mg/dL based on current gout management guidelines demonstrated a 37% reduction in progression of renal disease, a large retrospective study showed.

"There are numerous studies showing that people with renal disease can develop hyperuricemia," Dr. Gerald D. Levy said during a press briefing at the annual meeting of the American College of Rheumatology. "Some of them will also develop gout. There are a few small studies showing that in humans, you can reverse hyperuricemia with urate lowering therapy and make an impact in renal disease. We wanted to see if this is true."

Dr. Levy of the division of rheumatology in the department of internal medicine at Kaiser Permanente Medical Group, Downey, Calif., was the lead investigators in a study of 111,992 Kaiser Permanente Southern California patients with a serum uric acid (SUA) level of 7 mg/dL or greater from Jan. 1, 2002, to Dec. 31, 2010. Patients with at least 12 months of health plan membership, including drug benefit prior to the index date, were studied. All patients had at least one SUA and glomerular filtration rate (GFR) level measurement in the 6-month period prior to the index date and at least one SUA and one GFR in the follow-up period following the index date. Primary outcome events were at least a 30% worsening of renal function, initiation of dialysis, having a GFR of less than 15 mL/min, and undergoing a kidney transplant.

Patients with a new diagnosis of cancer were excluded from the analysis, as were those with HIV, glomerulonephritis, and/or organ transplant other than a kidney transplant.

Dr. Levy reported results from 16,186 patients who were divided into three groups: those who were never treated with urate-lowering therapy (ULT; 11,192); those who were treated with ULT less than 80% of the time from the index date to the end of follow-up period (3,902); and those who were treated with ULT 80% of the time or more from the index date to the end of the follow-up period (1,092). Of the three treatment groups, those who were treated with ULT 80% of the time or more during the study tended to be older and have more comorbid conditions, compared with the other two groups. They also began their ULT therapy earlier.

Among all patients combined, factors significantly associated with renal disease progression included having diabetes (hazard ratio, 1.96), hypertension (HR, 1.50), heart failure (HR, 1.39), previous hospitalizations (HR, 1.33), and being female (HR, 1.49) and older (HR, 1.03). The researchers found that time on ULT was not significantly associated with a reduction in renal disease progression outcome events (HR, 1.27, among those on ULT less than 80% of the time during the study vs. HR, 1.08, among those on ULT 80% of the time or more during the study). However, patients who achieved an SUA level below 6 mg/dL – a treatment goal in the 2012 ACR guidelines for management of gout – demonstrated a 37% reduction in renal disease progression (HR, 0.63; P less than .0001).

Dr. Levy acknowledged certain limitations of the study, including its retrospective design and the fact that patients with stage 4 and 5 chronic kidney disease were not included. "This is an important area, because if we can delay the worsening of renal disease in these folks, perhaps we’re abetting dialysis, which is growing by leaps and bounds in this country," he said. "Each dialysis patient now costs about $80,000 per year to take care of. If we could push that back even for a few years it would have a tremendous impact."

Dr. Levy had no relevant financial conflicts to disclose.

[email protected]

SAN DIEGO – A high percentage of gout patients treated by rheumatologists do not meet the treatment goals established by the American College of Rheumatology, even after 6 months of higher-dose urate-lowering therapy, results from a national survey found.

"These findings suggest that even among rheumatologists, gout management may not be optimal and may be inadequately aggressive in the most severe patients," Dr. Max Hamburger said at the annual meeting of the American College of Rheumatology. "It seems that there is further study needed to determine the long-term impact of the new ACR guidelines."

In 2012 the ACR published updated guidelines for the management of gout and hyperuricemia (Arth. Care and Res. 2012;64:1431-46). The recommendations included a call for treat-to-target serum uric acid (sUA) of below 6 mg/dL at a minimum, and below 5 mg/dL in select patients. "The intent of this treat-to-target was to durably improve signs and symptoms of gout and also to address palpable and visible tophi," said Dr. Hamburger, a rheumatologist who practices in Melville, N.Y. "The extent to which current practice among rheumatologists aligns with the guidelines is unknown. The areas in which the guidelines may help improve gout treatment also remains to be determined."

He and his associates set out to assess symptoms, treatment, and outcomes among gout patients treated by rheumatologists in the United States and to identify gaps that might exist in current practice with the new ACR recommendations. They recruited a national sample of rheumatologists to report gout patient encounters prospectively during Jan. 15 to Feb. 22, 2013. Rheumatologists were eligible for the study if they were board certified or board eligible in rheumatology, if they spent at least 70% of their time on patient care, if they were in practice for at least 2 years, and if they saw at least four gout patients per month.

The researchers collected anonymous patient data, including demographics, history with the rheumatology practice, gout symptoms and severity, rheumatologist assessment of disease control, and gout medications and treatment changes at the time of each visit. They applied the ACR working case scenarios and grouped patients by increasing level of disease severity. Patients in the scenarios 1-3 group had intermittent symptoms and no tophi (mild disease); patients in the scenarios 4-6 group had intermittent symptoms and 1 tophus or more (moderate disease), and patients in the scenarios 7-9 group had chronic tophaceous gouty arthropathy (more severe disease). Higher-dose ULT was defined as greater than 300 mg/day of allopurinol or 80 mg or more per day of febuxostat (Uloric).

Dr. Hamburger reported results from 127 rheumatologists who received 2,380 valid patient encounter forms. Most of the patients (79%) were male, their mean age was 61 years, and 72% were seen by a rheumatologist for 6 months or longer. Based on ACR scenario groupings, 68% were in the scenarios 1-3 group, 4% were in the scenarios 4-6 group, and 28% were in the scenarios 7-9 group.

Most patients in the scenarios 1-3 group were judged by the rheumatologists to have controlled disease, compared with 91% of patients in the scenarios 4-6 group and 81% of patients in the scenarios 7-9 group. In addition, 14% of patients in the scenarios 1-3 group were on higher-dose ULT, compared with 28% in the scenarios 4-6 group and 40% in the scenarios 7-9 group. Nearly one-quarter of all patients (24%) were on higher-dose ULT.

Among patients on higher-dose ULT, 45% of those in the scenarios 1-3 group had an sUA greater than 6 mg/dL, compared with 53% in the scenarios 4-6 group and 61% in the scenarios 7-9 group. "Despite elevated sUA, 45% of encounters did not result in an increased ULT dose or treatment change at this visit," Dr. Hamburger said.

Even with 6 months or more at higher-dose ULT, only 55% of patients overall had an sUA at or below guideline recommendations of 6 mg/dL, including only 40% of patients in the scenarios 7-9 group. In addition, 16% of patients overall had an sUA between 6 and 6.8 mg/dL, despite being on higher-dose ULT for 6 months or longer.

Dr. Hamburger acknowledged certain limitations of the study, including the fact that "rheumatologist participation in this market research may be biased based on willingness to participate in online data collection over the reporting period," he said. In addition, "a varying number of encounter forms were provided by each participant and based on estimated patient volume. Not all participants reported on 100% of their patients during the reporting period."

Dr. Hamburger disclosed that he is a speaker for Savient Pharmaceuticals, which markets the gout drug pegloticase (Krystexxa), and Takeda Pharmaceuticals, which markets febuxostat and colchicine (Colcrys). Funding for the market research used in the study was provided by Savient.

[email protected]

SAN DIEGO – A high percentage of gout patients treated by rheumatologists do not meet the treatment goals established by the American College of Rheumatology, even after 6 months of higher-dose urate-lowering therapy, results from a national survey found.

"These findings suggest that even among rheumatologists, gout management may not be optimal and may be inadequately aggressive in the most severe patients," Dr. Max Hamburger said at the annual meeting of the American College of Rheumatology. "It seems that there is further study needed to determine the long-term impact of the new ACR guidelines."

In 2012 the ACR published updated guidelines for the management of gout and hyperuricemia (Arth. Care and Res. 2012;64:1431-46). The recommendations included a call for treat-to-target serum uric acid (sUA) of below 6 mg/dL at a minimum, and below 5 mg/dL in select patients. "The intent of this treat-to-target was to durably improve signs and symptoms of gout and also to address palpable and visible tophi," said Dr. Hamburger, a rheumatologist who practices in Melville, N.Y. "The extent to which current practice among rheumatologists aligns with the guidelines is unknown. The areas in which the guidelines may help improve gout treatment also remains to be determined."

He and his associates set out to assess symptoms, treatment, and outcomes among gout patients treated by rheumatologists in the United States and to identify gaps that might exist in current practice with the new ACR recommendations. They recruited a national sample of rheumatologists to report gout patient encounters prospectively during Jan. 15 to Feb. 22, 2013. Rheumatologists were eligible for the study if they were board certified or board eligible in rheumatology, if they spent at least 70% of their time on patient care, if they were in practice for at least 2 years, and if they saw at least four gout patients per month.

The researchers collected anonymous patient data, including demographics, history with the rheumatology practice, gout symptoms and severity, rheumatologist assessment of disease control, and gout medications and treatment changes at the time of each visit. They applied the ACR working case scenarios and grouped patients by increasing level of disease severity. Patients in the scenarios 1-3 group had intermittent symptoms and no tophi (mild disease); patients in the scenarios 4-6 group had intermittent symptoms and 1 tophus or more (moderate disease), and patients in the scenarios 7-9 group had chronic tophaceous gouty arthropathy (more severe disease). Higher-dose ULT was defined as greater than 300 mg/day of allopurinol or 80 mg or more per day of febuxostat (Uloric).

Dr. Hamburger reported results from 127 rheumatologists who received 2,380 valid patient encounter forms. Most of the patients (79%) were male, their mean age was 61 years, and 72% were seen by a rheumatologist for 6 months or longer. Based on ACR scenario groupings, 68% were in the scenarios 1-3 group, 4% were in the scenarios 4-6 group, and 28% were in the scenarios 7-9 group.

Most patients in the scenarios 1-3 group were judged by the rheumatologists to have controlled disease, compared with 91% of patients in the scenarios 4-6 group and 81% of patients in the scenarios 7-9 group. In addition, 14% of patients in the scenarios 1-3 group were on higher-dose ULT, compared with 28% in the scenarios 4-6 group and 40% in the scenarios 7-9 group. Nearly one-quarter of all patients (24%) were on higher-dose ULT.

Among patients on higher-dose ULT, 45% of those in the scenarios 1-3 group had an sUA greater than 6 mg/dL, compared with 53% in the scenarios 4-6 group and 61% in the scenarios 7-9 group. "Despite elevated sUA, 45% of encounters did not result in an increased ULT dose or treatment change at this visit," Dr. Hamburger said.

Even with 6 months or more at higher-dose ULT, only 55% of patients overall had an sUA at or below guideline recommendations of 6 mg/dL, including only 40% of patients in the scenarios 7-9 group. In addition, 16% of patients overall had an sUA between 6 and 6.8 mg/dL, despite being on higher-dose ULT for 6 months or longer.

Dr. Hamburger acknowledged certain limitations of the study, including the fact that "rheumatologist participation in this market research may be biased based on willingness to participate in online data collection over the reporting period," he said. In addition, "a varying number of encounter forms were provided by each participant and based on estimated patient volume. Not all participants reported on 100% of their patients during the reporting period."

Dr. Hamburger disclosed that he is a speaker for Savient Pharmaceuticals, which markets the gout drug pegloticase (Krystexxa), and Takeda Pharmaceuticals, which markets febuxostat and colchicine (Colcrys). Funding for the market research used in the study was provided by Savient.

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SAN DIEGO – A high percentage of gout patients treated by rheumatologists do not meet the treatment goals established by the American College of Rheumatology, even after 6 months of higher-dose urate-lowering therapy, results from a national survey found.

"These findings suggest that even among rheumatologists, gout management may not be optimal and may be inadequately aggressive in the most severe patients," Dr. Max Hamburger said at the annual meeting of the American College of Rheumatology. "It seems that there is further study needed to determine the long-term impact of the new ACR guidelines."

In 2012 the ACR published updated guidelines for the management of gout and hyperuricemia (Arth. Care and Res. 2012;64:1431-46). The recommendations included a call for treat-to-target serum uric acid (sUA) of below 6 mg/dL at a minimum, and below 5 mg/dL in select patients. "The intent of this treat-to-target was to durably improve signs and symptoms of gout and also to address palpable and visible tophi," said Dr. Hamburger, a rheumatologist who practices in Melville, N.Y. "The extent to which current practice among rheumatologists aligns with the guidelines is unknown. The areas in which the guidelines may help improve gout treatment also remains to be determined."

He and his associates set out to assess symptoms, treatment, and outcomes among gout patients treated by rheumatologists in the United States and to identify gaps that might exist in current practice with the new ACR recommendations. They recruited a national sample of rheumatologists to report gout patient encounters prospectively during Jan. 15 to Feb. 22, 2013. Rheumatologists were eligible for the study if they were board certified or board eligible in rheumatology, if they spent at least 70% of their time on patient care, if they were in practice for at least 2 years, and if they saw at least four gout patients per month.

The researchers collected anonymous patient data, including demographics, history with the rheumatology practice, gout symptoms and severity, rheumatologist assessment of disease control, and gout medications and treatment changes at the time of each visit. They applied the ACR working case scenarios and grouped patients by increasing level of disease severity. Patients in the scenarios 1-3 group had intermittent symptoms and no tophi (mild disease); patients in the scenarios 4-6 group had intermittent symptoms and 1 tophus or more (moderate disease), and patients in the scenarios 7-9 group had chronic tophaceous gouty arthropathy (more severe disease). Higher-dose ULT was defined as greater than 300 mg/day of allopurinol or 80 mg or more per day of febuxostat (Uloric).

Dr. Hamburger reported results from 127 rheumatologists who received 2,380 valid patient encounter forms. Most of the patients (79%) were male, their mean age was 61 years, and 72% were seen by a rheumatologist for 6 months or longer. Based on ACR scenario groupings, 68% were in the scenarios 1-3 group, 4% were in the scenarios 4-6 group, and 28% were in the scenarios 7-9 group.

Most patients in the scenarios 1-3 group were judged by the rheumatologists to have controlled disease, compared with 91% of patients in the scenarios 4-6 group and 81% of patients in the scenarios 7-9 group. In addition, 14% of patients in the scenarios 1-3 group were on higher-dose ULT, compared with 28% in the scenarios 4-6 group and 40% in the scenarios 7-9 group. Nearly one-quarter of all patients (24%) were on higher-dose ULT.

Among patients on higher-dose ULT, 45% of those in the scenarios 1-3 group had an sUA greater than 6 mg/dL, compared with 53% in the scenarios 4-6 group and 61% in the scenarios 7-9 group. "Despite elevated sUA, 45% of encounters did not result in an increased ULT dose or treatment change at this visit," Dr. Hamburger said.

Even with 6 months or more at higher-dose ULT, only 55% of patients overall had an sUA at or below guideline recommendations of 6 mg/dL, including only 40% of patients in the scenarios 7-9 group. In addition, 16% of patients overall had an sUA between 6 and 6.8 mg/dL, despite being on higher-dose ULT for 6 months or longer.

Dr. Hamburger acknowledged certain limitations of the study, including the fact that "rheumatologist participation in this market research may be biased based on willingness to participate in online data collection over the reporting period," he said. In addition, "a varying number of encounter forms were provided by each participant and based on estimated patient volume. Not all participants reported on 100% of their patients during the reporting period."

Dr. Hamburger disclosed that he is a speaker for Savient Pharmaceuticals, which markets the gout drug pegloticase (Krystexxa), and Takeda Pharmaceuticals, which markets febuxostat and colchicine (Colcrys). Funding for the market research used in the study was provided by Savient.

[email protected]