Gout

After decades of increases, the prevalences of gout and hyperuricemia were steady over the past decade, according to data from an ongoing, nationally representative survey.

Findings from the National Health and Nutrition Examination Survey (NHANES) also show that only about one-third of gout patients were using urate-lowering therapies, Michael Chen-Xu, MBChB, MPH, of the Harvard T.H. Chan School of Public Health, Boston, and his associates wrote in Arthritis & Rheumatology.

“The prevalence of gout and hyperuricemia in the United States more than doubled between the 1960s and the 1990s and continued to increase steadily afterwards,” they wrote. By 2007-2008, the earliest 2-year NHANES cycle in the study, gout prevalence among adults stood at 3.9%, but after a slight dip and a rise it was 3.9% again in 2015-2016, the last cycle in the study, the investigators reported.


The prevalence of hyperuricemia – defined as a serum urate level of more than 7.0 mg/dL in males and more than 5.7 mg/dL in females – did drop from 21.4% in 2007-2008 to 20.1% in 2015-16, but the change was not significant, Dr. Chen-Xu and his associates said.

Overall use of urate-lowering therapy (ULT) among patients with gout was 32.8% over the study period, with use showing a nonsignificant increase from 33.0% in 2007-2008 to 35.5% in 2013-2014, with a dip down to 29.4% in 2011-2012. (Data on ULT use were not available for the 2015-2016 NHANES cycle.) Current ULT use among male gout patients was 35.5% in 2013-2014 and 15.5% among women, and nearly all ULT use (95.3%) consisted of allopurinol, they said.


“Although we did not find a significant change in the trends of gout or hyperuricemia prevalence from 2007 to 2016,” Dr. Chen-Xu and his associates wrote, “10 years may not be long enough to detect what might actually be a significant trend(s) over a longer period.”

The study was supported by Ironwood and Horizon. Dr. Chen-Xu had no conflicts to disclose. One of his associates has served on advisory boards for Takeda, Ironwood, Horizon, Kowa, and Selecta. Another has served on advisory boards for Pfizer, Horizon, SOBI, and Ironwood and as a study site investigator for Takeda.

[email protected]

SOURCE: Chen-Xu M et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40807.

After decades of increases, the prevalences of gout and hyperuricemia were steady over the past decade, according to data from an ongoing, nationally representative survey.

Findings from the National Health and Nutrition Examination Survey (NHANES) also show that only about one-third of gout patients were using urate-lowering therapies, Michael Chen-Xu, MBChB, MPH, of the Harvard T.H. Chan School of Public Health, Boston, and his associates wrote in Arthritis & Rheumatology.

“The prevalence of gout and hyperuricemia in the United States more than doubled between the 1960s and the 1990s and continued to increase steadily afterwards,” they wrote. By 2007-2008, the earliest 2-year NHANES cycle in the study, gout prevalence among adults stood at 3.9%, but after a slight dip and a rise it was 3.9% again in 2015-2016, the last cycle in the study, the investigators reported.


The prevalence of hyperuricemia – defined as a serum urate level of more than 7.0 mg/dL in males and more than 5.7 mg/dL in females – did drop from 21.4% in 2007-2008 to 20.1% in 2015-16, but the change was not significant, Dr. Chen-Xu and his associates said.

Overall use of urate-lowering therapy (ULT) among patients with gout was 32.8% over the study period, with use showing a nonsignificant increase from 33.0% in 2007-2008 to 35.5% in 2013-2014, with a dip down to 29.4% in 2011-2012. (Data on ULT use were not available for the 2015-2016 NHANES cycle.) Current ULT use among male gout patients was 35.5% in 2013-2014 and 15.5% among women, and nearly all ULT use (95.3%) consisted of allopurinol, they said.


“Although we did not find a significant change in the trends of gout or hyperuricemia prevalence from 2007 to 2016,” Dr. Chen-Xu and his associates wrote, “10 years may not be long enough to detect what might actually be a significant trend(s) over a longer period.”

The study was supported by Ironwood and Horizon. Dr. Chen-Xu had no conflicts to disclose. One of his associates has served on advisory boards for Takeda, Ironwood, Horizon, Kowa, and Selecta. Another has served on advisory boards for Pfizer, Horizon, SOBI, and Ironwood and as a study site investigator for Takeda.

[email protected]

SOURCE: Chen-Xu M et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40807.

After decades of increases, the prevalences of gout and hyperuricemia were steady over the past decade, according to data from an ongoing, nationally representative survey.

Findings from the National Health and Nutrition Examination Survey (NHANES) also show that only about one-third of gout patients were using urate-lowering therapies, Michael Chen-Xu, MBChB, MPH, of the Harvard T.H. Chan School of Public Health, Boston, and his associates wrote in Arthritis & Rheumatology.

“The prevalence of gout and hyperuricemia in the United States more than doubled between the 1960s and the 1990s and continued to increase steadily afterwards,” they wrote. By 2007-2008, the earliest 2-year NHANES cycle in the study, gout prevalence among adults stood at 3.9%, but after a slight dip and a rise it was 3.9% again in 2015-2016, the last cycle in the study, the investigators reported.


The prevalence of hyperuricemia – defined as a serum urate level of more than 7.0 mg/dL in males and more than 5.7 mg/dL in females – did drop from 21.4% in 2007-2008 to 20.1% in 2015-16, but the change was not significant, Dr. Chen-Xu and his associates said.

Overall use of urate-lowering therapy (ULT) among patients with gout was 32.8% over the study period, with use showing a nonsignificant increase from 33.0% in 2007-2008 to 35.5% in 2013-2014, with a dip down to 29.4% in 2011-2012. (Data on ULT use were not available for the 2015-2016 NHANES cycle.) Current ULT use among male gout patients was 35.5% in 2013-2014 and 15.5% among women, and nearly all ULT use (95.3%) consisted of allopurinol, they said.


“Although we did not find a significant change in the trends of gout or hyperuricemia prevalence from 2007 to 2016,” Dr. Chen-Xu and his associates wrote, “10 years may not be long enough to detect what might actually be a significant trend(s) over a longer period.”

The study was supported by Ironwood and Horizon. Dr. Chen-Xu had no conflicts to disclose. One of his associates has served on advisory boards for Takeda, Ironwood, Horizon, Kowa, and Selecta. Another has served on advisory boards for Pfizer, Horizon, SOBI, and Ironwood and as a study site investigator for Takeda.

[email protected]

SOURCE: Chen-Xu M et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40807.

CHICAGO – Failure to reach the therapeutic target of a serum urate level below 6 mg/dL in gout patients is an independent risk factor for all-cause mortality conferring a 139% increased risk, Fernando Perez-Ruiz, MD, PhD, said at the annual meeting of the American College of Rheumatology.

This new finding from a prospective cohort study of 1,193 gout patients constitutes a ringing endorsement that a treat-to-target approach should become the standard in the management of this disease, declared Dr. Perez-Ruiz, a rheumatologist at Hospital Universitario Cruces, Barakaldo, Spain.

“This is encouraging news. We can say to patients and clinicians that we should make every effort to reach the therapeutic target. This is a concept that’s not new in medicine. We do it for diabetes, for hypertension, for hyperlipidemia, and I think now for the first time we will do it for gout,” the rheumatologist said at a press conference highlighting the study findings.

“A lot of physicians including, unfortunately, rheumatologists don’t treat gout to target. They feel like if a patient is doing nicely, that’s good enough. But it’s like lowering cholesterol: If you’re at 400 mg/dL and you go to 300, does that mean it’s fine and you won’t get a myocardial infarction?” he asked rhetorically.

The study included 1,193 gout patients with a mean age at baseline of 60 years, 6.8 years disease duration, and an average of 3-4 flares during the previous year. Mean follow-up was 48 months, translating to 4,830 patient-years of prospective observation. Overall mortality was 13%, mostly from cardiovascular causes.

The mean baseline serum urate level was 9.1 mg/dL. Although both ACR and EULAR guidelines recommend a serum urate level below 6 mg/dL as a therapeutic target, 16.3% of subjects had a level of 6 mg/dL or more despite treatment. The crude mortality rate during follow-up was 80.9 deaths per 1,000 person-years in those with serum urate levels of 6 mg/dL or more, compared with 25.7 per 1,000 person-years in patients with serum urate levels below 6 mg/dL. In a multivariate analysis adjusted for age, prior cardiovascular events, other comorbid conditions, sex, baseline serum urate level, alcohol intake, and other potential confounders, a serum urate of 6 mg/dL or more was independently associated with a 139% increased risk of mortality during follow-up.

“I think the message we would like to give to clinicians is, ‘If you can do that [i.e., maintain the serum urate level below 6 mg/dL], do it. You have the knowledge, you have the means, make the effort. Your patient will benefit from that. Don’t take risks,’” Dr. Perez-Ruiz said.

Session moderator Shraddha Jatwani, MD, a rheumatologist at St. Vincent Hospital in Evansville, Ind., pronounced this a message she will take home to her clinical practice.

“What we usually see in clinical practice is that gout patients are among the most noncompliant. Once they stop hurting they just don’t see the need to take their medication daily. And now that we have this data, we can tell them that their gout medications are like statins, which help reduce the risk of heart attacks. Taking their gout medication will help them reduce their mortality risk. This information will help us to change patient perception,” she said.

Dr. Perez-Ruiz reported relationships with Amgen, Grünenthal, and Menarini.

[email protected]

SOURCE: Perez-Ruiz F et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 869.

CHICAGO – Failure to reach the therapeutic target of a serum urate level below 6 mg/dL in gout patients is an independent risk factor for all-cause mortality conferring a 139% increased risk, Fernando Perez-Ruiz, MD, PhD, said at the annual meeting of the American College of Rheumatology.

This new finding from a prospective cohort study of 1,193 gout patients constitutes a ringing endorsement that a treat-to-target approach should become the standard in the management of this disease, declared Dr. Perez-Ruiz, a rheumatologist at Hospital Universitario Cruces, Barakaldo, Spain.

“This is encouraging news. We can say to patients and clinicians that we should make every effort to reach the therapeutic target. This is a concept that’s not new in medicine. We do it for diabetes, for hypertension, for hyperlipidemia, and I think now for the first time we will do it for gout,” the rheumatologist said at a press conference highlighting the study findings.

“A lot of physicians including, unfortunately, rheumatologists don’t treat gout to target. They feel like if a patient is doing nicely, that’s good enough. But it’s like lowering cholesterol: If you’re at 400 mg/dL and you go to 300, does that mean it’s fine and you won’t get a myocardial infarction?” he asked rhetorically.

The study included 1,193 gout patients with a mean age at baseline of 60 years, 6.8 years disease duration, and an average of 3-4 flares during the previous year. Mean follow-up was 48 months, translating to 4,830 patient-years of prospective observation. Overall mortality was 13%, mostly from cardiovascular causes.

The mean baseline serum urate level was 9.1 mg/dL. Although both ACR and EULAR guidelines recommend a serum urate level below 6 mg/dL as a therapeutic target, 16.3% of subjects had a level of 6 mg/dL or more despite treatment. The crude mortality rate during follow-up was 80.9 deaths per 1,000 person-years in those with serum urate levels of 6 mg/dL or more, compared with 25.7 per 1,000 person-years in patients with serum urate levels below 6 mg/dL. In a multivariate analysis adjusted for age, prior cardiovascular events, other comorbid conditions, sex, baseline serum urate level, alcohol intake, and other potential confounders, a serum urate of 6 mg/dL or more was independently associated with a 139% increased risk of mortality during follow-up.

“I think the message we would like to give to clinicians is, ‘If you can do that [i.e., maintain the serum urate level below 6 mg/dL], do it. You have the knowledge, you have the means, make the effort. Your patient will benefit from that. Don’t take risks,’” Dr. Perez-Ruiz said.

Session moderator Shraddha Jatwani, MD, a rheumatologist at St. Vincent Hospital in Evansville, Ind., pronounced this a message she will take home to her clinical practice.

“What we usually see in clinical practice is that gout patients are among the most noncompliant. Once they stop hurting they just don’t see the need to take their medication daily. And now that we have this data, we can tell them that their gout medications are like statins, which help reduce the risk of heart attacks. Taking their gout medication will help them reduce their mortality risk. This information will help us to change patient perception,” she said.

Dr. Perez-Ruiz reported relationships with Amgen, Grünenthal, and Menarini.

[email protected]

SOURCE: Perez-Ruiz F et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 869.

CHICAGO – Failure to reach the therapeutic target of a serum urate level below 6 mg/dL in gout patients is an independent risk factor for all-cause mortality conferring a 139% increased risk, Fernando Perez-Ruiz, MD, PhD, said at the annual meeting of the American College of Rheumatology.

This new finding from a prospective cohort study of 1,193 gout patients constitutes a ringing endorsement that a treat-to-target approach should become the standard in the management of this disease, declared Dr. Perez-Ruiz, a rheumatologist at Hospital Universitario Cruces, Barakaldo, Spain.

“This is encouraging news. We can say to patients and clinicians that we should make every effort to reach the therapeutic target. This is a concept that’s not new in medicine. We do it for diabetes, for hypertension, for hyperlipidemia, and I think now for the first time we will do it for gout,” the rheumatologist said at a press conference highlighting the study findings.

“A lot of physicians including, unfortunately, rheumatologists don’t treat gout to target. They feel like if a patient is doing nicely, that’s good enough. But it’s like lowering cholesterol: If you’re at 400 mg/dL and you go to 300, does that mean it’s fine and you won’t get a myocardial infarction?” he asked rhetorically.

The study included 1,193 gout patients with a mean age at baseline of 60 years, 6.8 years disease duration, and an average of 3-4 flares during the previous year. Mean follow-up was 48 months, translating to 4,830 patient-years of prospective observation. Overall mortality was 13%, mostly from cardiovascular causes.

The mean baseline serum urate level was 9.1 mg/dL. Although both ACR and EULAR guidelines recommend a serum urate level below 6 mg/dL as a therapeutic target, 16.3% of subjects had a level of 6 mg/dL or more despite treatment. The crude mortality rate during follow-up was 80.9 deaths per 1,000 person-years in those with serum urate levels of 6 mg/dL or more, compared with 25.7 per 1,000 person-years in patients with serum urate levels below 6 mg/dL. In a multivariate analysis adjusted for age, prior cardiovascular events, other comorbid conditions, sex, baseline serum urate level, alcohol intake, and other potential confounders, a serum urate of 6 mg/dL or more was independently associated with a 139% increased risk of mortality during follow-up.

“I think the message we would like to give to clinicians is, ‘If you can do that [i.e., maintain the serum urate level below 6 mg/dL], do it. You have the knowledge, you have the means, make the effort. Your patient will benefit from that. Don’t take risks,’” Dr. Perez-Ruiz said.

Session moderator Shraddha Jatwani, MD, a rheumatologist at St. Vincent Hospital in Evansville, Ind., pronounced this a message she will take home to her clinical practice.

“What we usually see in clinical practice is that gout patients are among the most noncompliant. Once they stop hurting they just don’t see the need to take their medication daily. And now that we have this data, we can tell them that their gout medications are like statins, which help reduce the risk of heart attacks. Taking their gout medication will help them reduce their mortality risk. This information will help us to change patient perception,” she said.

Dr. Perez-Ruiz reported relationships with Amgen, Grünenthal, and Menarini.

[email protected]

SOURCE: Perez-Ruiz F et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 869.

Persistent and nonepisodic foot pain in hyperuricemia is associated with ultrasound features of monosodium urate deposition within joints that is responsive to urate-lowering therapy, a case-control study shows.

The research suggests that symptomatic hyperuricemia occurring prior to episodic gout could represent an earlier or alternative disease presentation, reported Yousef Mohammed Alammari, of the department of rheumatology, Tallaght University Hospital, Dublin, and associates.

Furthermore, the researchers wrote in Annals of the Rheumatic Diseases, their findings serve as “potential rationale” for reclassification of the ACR/EULAR 2015 gout classification criteria.

The research team noted that the gout classification criteria from the two rheumatology organizations require a history of a “prior episode of swelling, pain, or tenderness of a peripheral joint/bursa before confirmation either through MSU crystal identification in synovial fluid or through achieving a score of greater than 8 using a predefined scoring system of radiological, laboratory, and clinical features.”

Yet, emerging evidence suggests that foot pain could be a preclinical and clinical phase of gout that might occur prior to a first episodic gout attack, the investigators noted.

The current study involved 16 hyperuricemia individuals with persistent, nonepisodic foot pain who did not fulfill ACR/EULAR 2015 gout classification criteria but received febuxostat 80 mg once daily for 3 months. Controls were 15 individuals with asymptomatic hyperuricemia.

Results showed that double contour sign erosion and tophus occurred in 44%, 37%, and 37% of the cases, respectively, whereas no ultrasound features of gout were seen in the controls.

No significant difference in baseline serum urate was observed between the cases (450 plus or minus 18 mg/dL) and controls (426 plus or minus 7; P = nonsignificant), but at 1- and 3-month time points, serum urate fell in the cases (200 plus or minus 18; P less than 0.001 and 223 plus or minus 28; P less than less than 0.001).

In the cases, baseline 24-hour pain visual analogue score (65 plus or minus 4.9) reduced at 1 month (41 plus or minus 6.6; P = 0.001) and 3 months (33 plus or minus 7.2; P less than 0.001) of urate lowering therapy, as did the 7-day pain visual analogue score (70 plus or minus 4.7) scores (44 plus or minus 7.1; P less than 0.001 at 1 month; 38 plus or minus 8; P less than 0.001 at 3 months).

The Manchester Foot Pain and Disability Index also decreased at 1 month (21 plus or minus 2.9; P = 0.019) and 3 months (17 plus or minus 2.8; P = 0.012).

When the investigators grouped the cases according to the presence (n = 7) or absence (n = 9) of double contour sign on baseline ultrasound, no differences were observed for baseline pain scores.

However, after treatment with ultrasound, 24-hour pain visual analogue scores were significantly lower in double contour positive patients at 1 month and 3 months.

In addition, the researchers found, the 7-day pain visual analogue scores were significantly lower in double contour positive patients at 1 month and 3 months. No significant differences were seen between double contour positive and double contour negative patients in the Manchester Foot Pain and Disability Index or serum urate at 1 or 3 months of ultrasound.

The investigators noted that their findings indicated that persistent, nonepisodic foot pain in hyperuricemia was both associated with ultrasound features of monosodium urate deposition and was responsive to urate lowering therapy.

“Symptomatic hyperuricemia occurring prior to episodic gout therefore represents an earlier or alternative disease presentation,” they wrote. “Changes to the ACR/ EULAR classification criteria to include nonepisodic foot pain in the presence of [ultrasound] features of gout may increase the sensitivity of disease classification at an early stage, leading to improved future treatment strategies and long-term outcomes.”

No disclosures were declared.

SOURCE: Alammari YM et al. Ann Rheum Dis. 2018. doi: 10.1136/annrheumdis-2018-214305.
 

Persistent and nonepisodic foot pain in hyperuricemia is associated with ultrasound features of monosodium urate deposition within joints that is responsive to urate-lowering therapy, a case-control study shows.

The research suggests that symptomatic hyperuricemia occurring prior to episodic gout could represent an earlier or alternative disease presentation, reported Yousef Mohammed Alammari, of the department of rheumatology, Tallaght University Hospital, Dublin, and associates.

Furthermore, the researchers wrote in Annals of the Rheumatic Diseases, their findings serve as “potential rationale” for reclassification of the ACR/EULAR 2015 gout classification criteria.

The research team noted that the gout classification criteria from the two rheumatology organizations require a history of a “prior episode of swelling, pain, or tenderness of a peripheral joint/bursa before confirmation either through MSU crystal identification in synovial fluid or through achieving a score of greater than 8 using a predefined scoring system of radiological, laboratory, and clinical features.”

Yet, emerging evidence suggests that foot pain could be a preclinical and clinical phase of gout that might occur prior to a first episodic gout attack, the investigators noted.

The current study involved 16 hyperuricemia individuals with persistent, nonepisodic foot pain who did not fulfill ACR/EULAR 2015 gout classification criteria but received febuxostat 80 mg once daily for 3 months. Controls were 15 individuals with asymptomatic hyperuricemia.

Results showed that double contour sign erosion and tophus occurred in 44%, 37%, and 37% of the cases, respectively, whereas no ultrasound features of gout were seen in the controls.

No significant difference in baseline serum urate was observed between the cases (450 plus or minus 18 mg/dL) and controls (426 plus or minus 7; P = nonsignificant), but at 1- and 3-month time points, serum urate fell in the cases (200 plus or minus 18; P less than 0.001 and 223 plus or minus 28; P less than less than 0.001).

In the cases, baseline 24-hour pain visual analogue score (65 plus or minus 4.9) reduced at 1 month (41 plus or minus 6.6; P = 0.001) and 3 months (33 plus or minus 7.2; P less than 0.001) of urate lowering therapy, as did the 7-day pain visual analogue score (70 plus or minus 4.7) scores (44 plus or minus 7.1; P less than 0.001 at 1 month; 38 plus or minus 8; P less than 0.001 at 3 months).

The Manchester Foot Pain and Disability Index also decreased at 1 month (21 plus or minus 2.9; P = 0.019) and 3 months (17 plus or minus 2.8; P = 0.012).

When the investigators grouped the cases according to the presence (n = 7) or absence (n = 9) of double contour sign on baseline ultrasound, no differences were observed for baseline pain scores.

However, after treatment with ultrasound, 24-hour pain visual analogue scores were significantly lower in double contour positive patients at 1 month and 3 months.

In addition, the researchers found, the 7-day pain visual analogue scores were significantly lower in double contour positive patients at 1 month and 3 months. No significant differences were seen between double contour positive and double contour negative patients in the Manchester Foot Pain and Disability Index or serum urate at 1 or 3 months of ultrasound.

The investigators noted that their findings indicated that persistent, nonepisodic foot pain in hyperuricemia was both associated with ultrasound features of monosodium urate deposition and was responsive to urate lowering therapy.

“Symptomatic hyperuricemia occurring prior to episodic gout therefore represents an earlier or alternative disease presentation,” they wrote. “Changes to the ACR/ EULAR classification criteria to include nonepisodic foot pain in the presence of [ultrasound] features of gout may increase the sensitivity of disease classification at an early stage, leading to improved future treatment strategies and long-term outcomes.”

No disclosures were declared.

SOURCE: Alammari YM et al. Ann Rheum Dis. 2018. doi: 10.1136/annrheumdis-2018-214305.
 

Persistent and nonepisodic foot pain in hyperuricemia is associated with ultrasound features of monosodium urate deposition within joints that is responsive to urate-lowering therapy, a case-control study shows.

The research suggests that symptomatic hyperuricemia occurring prior to episodic gout could represent an earlier or alternative disease presentation, reported Yousef Mohammed Alammari, of the department of rheumatology, Tallaght University Hospital, Dublin, and associates.

Furthermore, the researchers wrote in Annals of the Rheumatic Diseases, their findings serve as “potential rationale” for reclassification of the ACR/EULAR 2015 gout classification criteria.

The research team noted that the gout classification criteria from the two rheumatology organizations require a history of a “prior episode of swelling, pain, or tenderness of a peripheral joint/bursa before confirmation either through MSU crystal identification in synovial fluid or through achieving a score of greater than 8 using a predefined scoring system of radiological, laboratory, and clinical features.”

Yet, emerging evidence suggests that foot pain could be a preclinical and clinical phase of gout that might occur prior to a first episodic gout attack, the investigators noted.

The current study involved 16 hyperuricemia individuals with persistent, nonepisodic foot pain who did not fulfill ACR/EULAR 2015 gout classification criteria but received febuxostat 80 mg once daily for 3 months. Controls were 15 individuals with asymptomatic hyperuricemia.

Results showed that double contour sign erosion and tophus occurred in 44%, 37%, and 37% of the cases, respectively, whereas no ultrasound features of gout were seen in the controls.

No significant difference in baseline serum urate was observed between the cases (450 plus or minus 18 mg/dL) and controls (426 plus or minus 7; P = nonsignificant), but at 1- and 3-month time points, serum urate fell in the cases (200 plus or minus 18; P less than 0.001 and 223 plus or minus 28; P less than less than 0.001).

In the cases, baseline 24-hour pain visual analogue score (65 plus or minus 4.9) reduced at 1 month (41 plus or minus 6.6; P = 0.001) and 3 months (33 plus or minus 7.2; P less than 0.001) of urate lowering therapy, as did the 7-day pain visual analogue score (70 plus or minus 4.7) scores (44 plus or minus 7.1; P less than 0.001 at 1 month; 38 plus or minus 8; P less than 0.001 at 3 months).

The Manchester Foot Pain and Disability Index also decreased at 1 month (21 plus or minus 2.9; P = 0.019) and 3 months (17 plus or minus 2.8; P = 0.012).

When the investigators grouped the cases according to the presence (n = 7) or absence (n = 9) of double contour sign on baseline ultrasound, no differences were observed for baseline pain scores.

However, after treatment with ultrasound, 24-hour pain visual analogue scores were significantly lower in double contour positive patients at 1 month and 3 months.

In addition, the researchers found, the 7-day pain visual analogue scores were significantly lower in double contour positive patients at 1 month and 3 months. No significant differences were seen between double contour positive and double contour negative patients in the Manchester Foot Pain and Disability Index or serum urate at 1 or 3 months of ultrasound.

The investigators noted that their findings indicated that persistent, nonepisodic foot pain in hyperuricemia was both associated with ultrasound features of monosodium urate deposition and was responsive to urate lowering therapy.

“Symptomatic hyperuricemia occurring prior to episodic gout therefore represents an earlier or alternative disease presentation,” they wrote. “Changes to the ACR/ EULAR classification criteria to include nonepisodic foot pain in the presence of [ultrasound] features of gout may increase the sensitivity of disease classification at an early stage, leading to improved future treatment strategies and long-term outcomes.”

No disclosures were declared.

SOURCE: Alammari YM et al. Ann Rheum Dis. 2018. doi: 10.1136/annrheumdis-2018-214305.
 

CHICAGO – Diet plays a significantly less important role than genes in the development of high serum urate levels that typically precede gout, research from New Zealand has revealed.

SilverV/Thinkstock

These findings stem from a first-ever systematic analysis of a large data set to “determine the relative contributions of inherited genetic variants and overall diet to variance in serum urate concentrations,” Tanya J. Major, PhD, of the University of Otago in Dunedin, New Zealand, and her colleagues first reported in The BMJ and then less than 2 weeks later at the annual meeting of the American College of Rheumatology.

Prior studies have estimated that genetic factors explain 25%-60% of the variability in serum urate levels, but diet also has long been considered a risk factor for gout, with certain diets such as the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet shown in studies to reduce serum urate levels and the risk of gout, the researchers noted.

The new study found that common genetic factors accounted for nearly 24% of the variation in serum urate levels, whereas  diet accounted for less than 1%.

Before these findings, the impact of diet on hyperuricemia was known to be limited, but that doesn’t mean that diet is meaningless, Michael H. Pillinger, MD, who was not involved in the study, said in an interview at the ACR annual meeting.

“What this work does from a scientific point of view is underline the genetic basis [of hyperuricemia]. What it does from a practical and clinical point of view is tell us that diet is a meaningful thing to adjust. It will provide other health benefits, but it isn’t the solution, and we know that it rarely is,” said Dr. Pillinger, professor of medicine and biochemistry and molecular pharmacology at New York University. “We shouldn’t expect a really large impact from diet, and we shouldn’t make people feel guilty about their diets, and optimally you want to manage a diet that a patient can tolerate and not one that will be impossible to sustain.”

Dr. Major had a similar message in an interview at the meeting: “By focusing on diet and treating urate levels through diet, you start to kind of get this blame element going on that the reason you’ve got gout is you’re eating the wrong foods, and so then it makes people less likely to want to go to see their doctor to start with. And then when they do try to follow their doctor’s advice about their diet, and nothing changes, then it starts to get frustrating for them as well.”

The research team analyzed dietary survey data from five U.S. cohort studies (Atherosclerosis Risk in Communities, Coronary Artery Risk Development in [Young] Adults, Cardiovascular Heart Study, Framingham Heart Study, and Third National Health and Nutrition Examination Survey [NHANES III]) that altogether included 16,760 individuals (8,414 men and 8,346 women) of European ancestry.

Participants were aged 18 years or older, did not have gout or kidney disease, and were not taking urate-lowering or diuretic drugs. Serum urate measurements, dietary survey data, and confounders such as gender, age, body mass index, smoking status, and average daily calorie intake were all recorded.

The results showed that 15 foods were significantly associated with serum urate levels. Six were established urate-modifying foods: beer, liquor, wine, soft drinks, skim milk, and meat (beef, pork, or lamb). The remaining nine foods included two less established urate-modifying foods (cheese and noncitrus fruit) and seven food items without established associations: poultry, potatoes, brown bread, peanuts, margarine, cold cereal, and eggs.

Beer and liquor had the strongest urate-raising effect, associated with a 1.38 micromol/L increase in serum urate per serving per week, equating to a 9.66 micromol/L (0.16 mg/dL) increase per daily serving.

The authors noted that the associations seen with known and confirmed serum urate–influencing foods were consistent with previously reported associations in terms of effect and magnitude. Nevertheless, they noted that “each of these established foods explained less than 1% of variation in serum urate levels within the full cohort.”

When the researchers analyzed the data according to three diet scores based on healthy diet guidelines, they found that diet explained “very little variance in serum urate levels (0.28% for the DASH diet, 0.15% for the Healthy Eating diet, 0.06% for the Mediterranean diet, and 0.16% for the data-driven diet pattern).”

However, they noted that even though their findings, along with previous research, suggest that a clinically relevant decrease in serum urate levels could be achieved with the DASH diet, the implementation of such a diet might not be “straightforward” because “the barriers to implementing this diet both at a population level and in a primary care setting are yet to be overcome.”

In contrast, when the research team looked at genes in the cohort they found that common genetic factors explained 23.9% of variation in serum urate levels in the full cohort (excluding the NHANES III study because of a lack of genotype data).

Baseline visit diet information for these cohort studies ranged from the mid-1980s to the early to mid-2000s, making it hard to account for changes in food composition over time. Dr. Major said that food compositions overall were likely to be more processed over time and contain more urate-raising foods. However, any effects of food composition changes on urate levels over time would be more likely be felt at the level of individual food products, not on diets overall, she said.

The variability in the diet scores that the investigators noted across individuals and regions in these U.S. cohort studies did not appear to affect the results, Dr. Major noted. Furthermore, adjustment within models for these diet scores did not affect the degree of variation in urate levels that genetics accounted for, whereas adjustment for genetics lowered the amount of variation that diet contributed to urate levels.

The findings also don’t have any say on the relative contribution of diet versus genetics on gout flares, which is a separate issue. Many patients would agree that they suspect certain foods trigger gout flares even if they don’t affect baseline urate levels very much, Dr. Pillinger said.

The next steps for Dr. Major and her coinvestigators may be to see if diet is influencing urate levels to the same degree in people with gout as this study shows for the general population, she said.The investigators noted that the use of different food questionnaires between the five studies is one limitation of the analysis, and there should be some caution in generalizing the results to people with gout or those of non-European ancestry.

The study was supported by the Health Research Council of New Zealand and the University of Otago. One author reported receiving consulting and speaker fees or grants from several pharmaceutical companies that manufacture urate-lowering drugs.

This article was updated 10/25/18.

SOURCE: Major TJ et al. BMJ. 2018. doi: 10.1136/bmj.k3951.

CHICAGO – Diet plays a significantly less important role than genes in the development of high serum urate levels that typically precede gout, research from New Zealand has revealed.

SilverV/Thinkstock

These findings stem from a first-ever systematic analysis of a large data set to “determine the relative contributions of inherited genetic variants and overall diet to variance in serum urate concentrations,” Tanya J. Major, PhD, of the University of Otago in Dunedin, New Zealand, and her colleagues first reported in The BMJ and then less than 2 weeks later at the annual meeting of the American College of Rheumatology.

Prior studies have estimated that genetic factors explain 25%-60% of the variability in serum urate levels, but diet also has long been considered a risk factor for gout, with certain diets such as the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet shown in studies to reduce serum urate levels and the risk of gout, the researchers noted.

The new study found that common genetic factors accounted for nearly 24% of the variation in serum urate levels, whereas  diet accounted for less than 1%.

Before these findings, the impact of diet on hyperuricemia was known to be limited, but that doesn’t mean that diet is meaningless, Michael H. Pillinger, MD, who was not involved in the study, said in an interview at the ACR annual meeting.

“What this work does from a scientific point of view is underline the genetic basis [of hyperuricemia]. What it does from a practical and clinical point of view is tell us that diet is a meaningful thing to adjust. It will provide other health benefits, but it isn’t the solution, and we know that it rarely is,” said Dr. Pillinger, professor of medicine and biochemistry and molecular pharmacology at New York University. “We shouldn’t expect a really large impact from diet, and we shouldn’t make people feel guilty about their diets, and optimally you want to manage a diet that a patient can tolerate and not one that will be impossible to sustain.”

Dr. Major had a similar message in an interview at the meeting: “By focusing on diet and treating urate levels through diet, you start to kind of get this blame element going on that the reason you’ve got gout is you’re eating the wrong foods, and so then it makes people less likely to want to go to see their doctor to start with. And then when they do try to follow their doctor’s advice about their diet, and nothing changes, then it starts to get frustrating for them as well.”

The research team analyzed dietary survey data from five U.S. cohort studies (Atherosclerosis Risk in Communities, Coronary Artery Risk Development in [Young] Adults, Cardiovascular Heart Study, Framingham Heart Study, and Third National Health and Nutrition Examination Survey [NHANES III]) that altogether included 16,760 individuals (8,414 men and 8,346 women) of European ancestry.

Participants were aged 18 years or older, did not have gout or kidney disease, and were not taking urate-lowering or diuretic drugs. Serum urate measurements, dietary survey data, and confounders such as gender, age, body mass index, smoking status, and average daily calorie intake were all recorded.

The results showed that 15 foods were significantly associated with serum urate levels. Six were established urate-modifying foods: beer, liquor, wine, soft drinks, skim milk, and meat (beef, pork, or lamb). The remaining nine foods included two less established urate-modifying foods (cheese and noncitrus fruit) and seven food items without established associations: poultry, potatoes, brown bread, peanuts, margarine, cold cereal, and eggs.

Beer and liquor had the strongest urate-raising effect, associated with a 1.38 micromol/L increase in serum urate per serving per week, equating to a 9.66 micromol/L (0.16 mg/dL) increase per daily serving.

The authors noted that the associations seen with known and confirmed serum urate–influencing foods were consistent with previously reported associations in terms of effect and magnitude. Nevertheless, they noted that “each of these established foods explained less than 1% of variation in serum urate levels within the full cohort.”

When the researchers analyzed the data according to three diet scores based on healthy diet guidelines, they found that diet explained “very little variance in serum urate levels (0.28% for the DASH diet, 0.15% for the Healthy Eating diet, 0.06% for the Mediterranean diet, and 0.16% for the data-driven diet pattern).”

However, they noted that even though their findings, along with previous research, suggest that a clinically relevant decrease in serum urate levels could be achieved with the DASH diet, the implementation of such a diet might not be “straightforward” because “the barriers to implementing this diet both at a population level and in a primary care setting are yet to be overcome.”

In contrast, when the research team looked at genes in the cohort they found that common genetic factors explained 23.9% of variation in serum urate levels in the full cohort (excluding the NHANES III study because of a lack of genotype data).

Baseline visit diet information for these cohort studies ranged from the mid-1980s to the early to mid-2000s, making it hard to account for changes in food composition over time. Dr. Major said that food compositions overall were likely to be more processed over time and contain more urate-raising foods. However, any effects of food composition changes on urate levels over time would be more likely be felt at the level of individual food products, not on diets overall, she said.

The variability in the diet scores that the investigators noted across individuals and regions in these U.S. cohort studies did not appear to affect the results, Dr. Major noted. Furthermore, adjustment within models for these diet scores did not affect the degree of variation in urate levels that genetics accounted for, whereas adjustment for genetics lowered the amount of variation that diet contributed to urate levels.

The findings also don’t have any say on the relative contribution of diet versus genetics on gout flares, which is a separate issue. Many patients would agree that they suspect certain foods trigger gout flares even if they don’t affect baseline urate levels very much, Dr. Pillinger said.

The next steps for Dr. Major and her coinvestigators may be to see if diet is influencing urate levels to the same degree in people with gout as this study shows for the general population, she said.The investigators noted that the use of different food questionnaires between the five studies is one limitation of the analysis, and there should be some caution in generalizing the results to people with gout or those of non-European ancestry.

The study was supported by the Health Research Council of New Zealand and the University of Otago. One author reported receiving consulting and speaker fees or grants from several pharmaceutical companies that manufacture urate-lowering drugs.

This article was updated 10/25/18.

SOURCE: Major TJ et al. BMJ. 2018. doi: 10.1136/bmj.k3951.

CHICAGO – Diet plays a significantly less important role than genes in the development of high serum urate levels that typically precede gout, research from New Zealand has revealed.

SilverV/Thinkstock

These findings stem from a first-ever systematic analysis of a large data set to “determine the relative contributions of inherited genetic variants and overall diet to variance in serum urate concentrations,” Tanya J. Major, PhD, of the University of Otago in Dunedin, New Zealand, and her colleagues first reported in The BMJ and then less than 2 weeks later at the annual meeting of the American College of Rheumatology.

Prior studies have estimated that genetic factors explain 25%-60% of the variability in serum urate levels, but diet also has long been considered a risk factor for gout, with certain diets such as the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet shown in studies to reduce serum urate levels and the risk of gout, the researchers noted.

The new study found that common genetic factors accounted for nearly 24% of the variation in serum urate levels, whereas  diet accounted for less than 1%.

Before these findings, the impact of diet on hyperuricemia was known to be limited, but that doesn’t mean that diet is meaningless, Michael H. Pillinger, MD, who was not involved in the study, said in an interview at the ACR annual meeting.

“What this work does from a scientific point of view is underline the genetic basis [of hyperuricemia]. What it does from a practical and clinical point of view is tell us that diet is a meaningful thing to adjust. It will provide other health benefits, but it isn’t the solution, and we know that it rarely is,” said Dr. Pillinger, professor of medicine and biochemistry and molecular pharmacology at New York University. “We shouldn’t expect a really large impact from diet, and we shouldn’t make people feel guilty about their diets, and optimally you want to manage a diet that a patient can tolerate and not one that will be impossible to sustain.”

Dr. Major had a similar message in an interview at the meeting: “By focusing on diet and treating urate levels through diet, you start to kind of get this blame element going on that the reason you’ve got gout is you’re eating the wrong foods, and so then it makes people less likely to want to go to see their doctor to start with. And then when they do try to follow their doctor’s advice about their diet, and nothing changes, then it starts to get frustrating for them as well.”

The research team analyzed dietary survey data from five U.S. cohort studies (Atherosclerosis Risk in Communities, Coronary Artery Risk Development in [Young] Adults, Cardiovascular Heart Study, Framingham Heart Study, and Third National Health and Nutrition Examination Survey [NHANES III]) that altogether included 16,760 individuals (8,414 men and 8,346 women) of European ancestry.

Participants were aged 18 years or older, did not have gout or kidney disease, and were not taking urate-lowering or diuretic drugs. Serum urate measurements, dietary survey data, and confounders such as gender, age, body mass index, smoking status, and average daily calorie intake were all recorded.

The results showed that 15 foods were significantly associated with serum urate levels. Six were established urate-modifying foods: beer, liquor, wine, soft drinks, skim milk, and meat (beef, pork, or lamb). The remaining nine foods included two less established urate-modifying foods (cheese and noncitrus fruit) and seven food items without established associations: poultry, potatoes, brown bread, peanuts, margarine, cold cereal, and eggs.

Beer and liquor had the strongest urate-raising effect, associated with a 1.38 micromol/L increase in serum urate per serving per week, equating to a 9.66 micromol/L (0.16 mg/dL) increase per daily serving.

The authors noted that the associations seen with known and confirmed serum urate–influencing foods were consistent with previously reported associations in terms of effect and magnitude. Nevertheless, they noted that “each of these established foods explained less than 1% of variation in serum urate levels within the full cohort.”

When the researchers analyzed the data according to three diet scores based on healthy diet guidelines, they found that diet explained “very little variance in serum urate levels (0.28% for the DASH diet, 0.15% for the Healthy Eating diet, 0.06% for the Mediterranean diet, and 0.16% for the data-driven diet pattern).”

However, they noted that even though their findings, along with previous research, suggest that a clinically relevant decrease in serum urate levels could be achieved with the DASH diet, the implementation of such a diet might not be “straightforward” because “the barriers to implementing this diet both at a population level and in a primary care setting are yet to be overcome.”

In contrast, when the research team looked at genes in the cohort they found that common genetic factors explained 23.9% of variation in serum urate levels in the full cohort (excluding the NHANES III study because of a lack of genotype data).

Baseline visit diet information for these cohort studies ranged from the mid-1980s to the early to mid-2000s, making it hard to account for changes in food composition over time. Dr. Major said that food compositions overall were likely to be more processed over time and contain more urate-raising foods. However, any effects of food composition changes on urate levels over time would be more likely be felt at the level of individual food products, not on diets overall, she said.

The variability in the diet scores that the investigators noted across individuals and regions in these U.S. cohort studies did not appear to affect the results, Dr. Major noted. Furthermore, adjustment within models for these diet scores did not affect the degree of variation in urate levels that genetics accounted for, whereas adjustment for genetics lowered the amount of variation that diet contributed to urate levels.

The findings also don’t have any say on the relative contribution of diet versus genetics on gout flares, which is a separate issue. Many patients would agree that they suspect certain foods trigger gout flares even if they don’t affect baseline urate levels very much, Dr. Pillinger said.

The next steps for Dr. Major and her coinvestigators may be to see if diet is influencing urate levels to the same degree in people with gout as this study shows for the general population, she said.The investigators noted that the use of different food questionnaires between the five studies is one limitation of the analysis, and there should be some caution in generalizing the results to people with gout or those of non-European ancestry.

The study was supported by the Health Research Council of New Zealand and the University of Otago. One author reported receiving consulting and speaker fees or grants from several pharmaceutical companies that manufacture urate-lowering drugs.

This article was updated 10/25/18.

SOURCE: Major TJ et al. BMJ. 2018. doi: 10.1136/bmj.k3951.

In patients with gout, at least 300 mg of allopurinol daily may reduce the risk of renal function decline, according to a new study.

London_England/Thinkstock

Since no evidence supports allopurinol nephrotoxicity and usage does not appear to worsen chronic kidney disease (CKD), clinicians should consider other causes of declining renal function, according to lead author Ana Beatriz Vargas-Santos, MD, of the rheumatology unit at the State University of Rio de Janeiro and her colleagues.

These findings reinforce the American College of Rheumatology’s 2012 treatment recommendation that the dose of allopurinol, a urate-lowering therapy (ULT), “can be raised above 300 mg daily, even with renal impairment, as long as it is accompanied by adequate patient education and monitoring for drug toxicity may worsen renal function.”*

“Renal-dosing of allopurinol compounds the poor management of gout and adds to the perception that allopurinol may be detrimental for renal function,” the investigators wrote in JAMA Internal Medicine. “In contrast, recent studies provide support for starting allopurinol at a low dose with gradual dose escalation to serum urate target with close monitoring, even among patients with renal insufficiency, without increased risk of allopurinol hypersensitivity syndrome (AHS). Further, there is emerging evidence that ULT may be beneficial for kidney dysfunction.”

Building upon these developments, the investigators “aimed to assess the relation of allopurinol initiation to the risk of developing CKD stage 3 or higher among people with newly diagnosed gout.”

Patients for the cohort study were drawn from the Health Improvement Network (THIN), a database of records from general practitioners in the United Kingdom. Included patients were recently diagnosed with gout but did not have stage 3 or higher chronic kidney disease or ULT usage within a year prior to diagnosis. After screening, 4,760 allopurinol users were matched with 4,760 allopurinol nonusers. Overall, 71% of patients had CKD stage 2, while the remaining 29% had CKD stage 1 or normal kidney function.

The primary outcome of CKD stage 3 or higher was defined as glomerular filtration rate below 60 mL/min (recorded at least twice in 1 year with a 3-month interval between readings and GFR never exceeding 75 mL/min during the intervening period), kidney transplant, or dialysis. The mean follow-up time was 5 years for allopurinol users and 4 years for nonusers.

The investigators found that 579 allopurinol users developed CKD stage 3 or higher, compared with 623 nonusers, suggesting that allopurinol reduced risk of CKD stage 3 or higher by 13%. Allopurinol doses of at least 300 mg/day were associated with a hazard ratio of 0.87, but lower doses did not share this association (HR = 1.02).

In defense of their findings, Dr. Vargas-Santos and her associates evaluated the relevance of their study, compared with previous allopurinol studies.

“This study is one of few that have evaluated the relation of allopurinol to renal function among patients with gout and normal or near-normal kidney function at baseline,” the authors wrote, noting that most gout patients do not have severe kidney disease.

Previous studies have suggested that allopurinol worsens kidney function, but these studies were often conducted in nongout populations, with patients exhibiting CKD stage 3 or higher, they noted. Instead of allopurinol-induced kidney damage, renal decline in gout patients is likely multifactorial.

“Because people with gout have intrinsic differences compared with those with asymptomatic hyperuricemia, including higher mortality, more comorbidities, and more NSAID use, these studies’ results are not directly applicable to gout patients,” the investigators wrote.

“At minimum, allopurinol does not seem to have a detrimental effect on renal function in individuals with gout,” Dr. Vargas-Santos and her associates concluded. “Clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.”
The authors reported funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Ministry of Science, Technology and Innovation of Brazil; and National Institutes of Health. Dr Vargas-Santos has received speaking fees and support for international medical events from Grünenthal. No other disclosures were reported.

SOURCE: Vargas-Santos AB et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4463

*Correction, 11/5/2018: An earlier version of this story incorrectly stated the American College of Rheumatology’s 2012 gout treatment recommendation for using allopurinol in patients with renal impairment.

In patients with gout, at least 300 mg of allopurinol daily may reduce the risk of renal function decline, according to a new study.

London_England/Thinkstock

Since no evidence supports allopurinol nephrotoxicity and usage does not appear to worsen chronic kidney disease (CKD), clinicians should consider other causes of declining renal function, according to lead author Ana Beatriz Vargas-Santos, MD, of the rheumatology unit at the State University of Rio de Janeiro and her colleagues.

These findings reinforce the American College of Rheumatology’s 2012 treatment recommendation that the dose of allopurinol, a urate-lowering therapy (ULT), “can be raised above 300 mg daily, even with renal impairment, as long as it is accompanied by adequate patient education and monitoring for drug toxicity may worsen renal function.”*

“Renal-dosing of allopurinol compounds the poor management of gout and adds to the perception that allopurinol may be detrimental for renal function,” the investigators wrote in JAMA Internal Medicine. “In contrast, recent studies provide support for starting allopurinol at a low dose with gradual dose escalation to serum urate target with close monitoring, even among patients with renal insufficiency, without increased risk of allopurinol hypersensitivity syndrome (AHS). Further, there is emerging evidence that ULT may be beneficial for kidney dysfunction.”

Building upon these developments, the investigators “aimed to assess the relation of allopurinol initiation to the risk of developing CKD stage 3 or higher among people with newly diagnosed gout.”

Patients for the cohort study were drawn from the Health Improvement Network (THIN), a database of records from general practitioners in the United Kingdom. Included patients were recently diagnosed with gout but did not have stage 3 or higher chronic kidney disease or ULT usage within a year prior to diagnosis. After screening, 4,760 allopurinol users were matched with 4,760 allopurinol nonusers. Overall, 71% of patients had CKD stage 2, while the remaining 29% had CKD stage 1 or normal kidney function.

The primary outcome of CKD stage 3 or higher was defined as glomerular filtration rate below 60 mL/min (recorded at least twice in 1 year with a 3-month interval between readings and GFR never exceeding 75 mL/min during the intervening period), kidney transplant, or dialysis. The mean follow-up time was 5 years for allopurinol users and 4 years for nonusers.

The investigators found that 579 allopurinol users developed CKD stage 3 or higher, compared with 623 nonusers, suggesting that allopurinol reduced risk of CKD stage 3 or higher by 13%. Allopurinol doses of at least 300 mg/day were associated with a hazard ratio of 0.87, but lower doses did not share this association (HR = 1.02).

In defense of their findings, Dr. Vargas-Santos and her associates evaluated the relevance of their study, compared with previous allopurinol studies.

“This study is one of few that have evaluated the relation of allopurinol to renal function among patients with gout and normal or near-normal kidney function at baseline,” the authors wrote, noting that most gout patients do not have severe kidney disease.

Previous studies have suggested that allopurinol worsens kidney function, but these studies were often conducted in nongout populations, with patients exhibiting CKD stage 3 or higher, they noted. Instead of allopurinol-induced kidney damage, renal decline in gout patients is likely multifactorial.

“Because people with gout have intrinsic differences compared with those with asymptomatic hyperuricemia, including higher mortality, more comorbidities, and more NSAID use, these studies’ results are not directly applicable to gout patients,” the investigators wrote.

“At minimum, allopurinol does not seem to have a detrimental effect on renal function in individuals with gout,” Dr. Vargas-Santos and her associates concluded. “Clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.”
The authors reported funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Ministry of Science, Technology and Innovation of Brazil; and National Institutes of Health. Dr Vargas-Santos has received speaking fees and support for international medical events from Grünenthal. No other disclosures were reported.

SOURCE: Vargas-Santos AB et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4463

*Correction, 11/5/2018: An earlier version of this story incorrectly stated the American College of Rheumatology’s 2012 gout treatment recommendation for using allopurinol in patients with renal impairment.

In patients with gout, at least 300 mg of allopurinol daily may reduce the risk of renal function decline, according to a new study.

London_England/Thinkstock

Since no evidence supports allopurinol nephrotoxicity and usage does not appear to worsen chronic kidney disease (CKD), clinicians should consider other causes of declining renal function, according to lead author Ana Beatriz Vargas-Santos, MD, of the rheumatology unit at the State University of Rio de Janeiro and her colleagues.

These findings reinforce the American College of Rheumatology’s 2012 treatment recommendation that the dose of allopurinol, a urate-lowering therapy (ULT), “can be raised above 300 mg daily, even with renal impairment, as long as it is accompanied by adequate patient education and monitoring for drug toxicity may worsen renal function.”*

“Renal-dosing of allopurinol compounds the poor management of gout and adds to the perception that allopurinol may be detrimental for renal function,” the investigators wrote in JAMA Internal Medicine. “In contrast, recent studies provide support for starting allopurinol at a low dose with gradual dose escalation to serum urate target with close monitoring, even among patients with renal insufficiency, without increased risk of allopurinol hypersensitivity syndrome (AHS). Further, there is emerging evidence that ULT may be beneficial for kidney dysfunction.”

Building upon these developments, the investigators “aimed to assess the relation of allopurinol initiation to the risk of developing CKD stage 3 or higher among people with newly diagnosed gout.”

Patients for the cohort study were drawn from the Health Improvement Network (THIN), a database of records from general practitioners in the United Kingdom. Included patients were recently diagnosed with gout but did not have stage 3 or higher chronic kidney disease or ULT usage within a year prior to diagnosis. After screening, 4,760 allopurinol users were matched with 4,760 allopurinol nonusers. Overall, 71% of patients had CKD stage 2, while the remaining 29% had CKD stage 1 or normal kidney function.

The primary outcome of CKD stage 3 or higher was defined as glomerular filtration rate below 60 mL/min (recorded at least twice in 1 year with a 3-month interval between readings and GFR never exceeding 75 mL/min during the intervening period), kidney transplant, or dialysis. The mean follow-up time was 5 years for allopurinol users and 4 years for nonusers.

The investigators found that 579 allopurinol users developed CKD stage 3 or higher, compared with 623 nonusers, suggesting that allopurinol reduced risk of CKD stage 3 or higher by 13%. Allopurinol doses of at least 300 mg/day were associated with a hazard ratio of 0.87, but lower doses did not share this association (HR = 1.02).

In defense of their findings, Dr. Vargas-Santos and her associates evaluated the relevance of their study, compared with previous allopurinol studies.

“This study is one of few that have evaluated the relation of allopurinol to renal function among patients with gout and normal or near-normal kidney function at baseline,” the authors wrote, noting that most gout patients do not have severe kidney disease.

Previous studies have suggested that allopurinol worsens kidney function, but these studies were often conducted in nongout populations, with patients exhibiting CKD stage 3 or higher, they noted. Instead of allopurinol-induced kidney damage, renal decline in gout patients is likely multifactorial.

“Because people with gout have intrinsic differences compared with those with asymptomatic hyperuricemia, including higher mortality, more comorbidities, and more NSAID use, these studies’ results are not directly applicable to gout patients,” the investigators wrote.

“At minimum, allopurinol does not seem to have a detrimental effect on renal function in individuals with gout,” Dr. Vargas-Santos and her associates concluded. “Clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.”
The authors reported funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Ministry of Science, Technology and Innovation of Brazil; and National Institutes of Health. Dr Vargas-Santos has received speaking fees and support for international medical events from Grünenthal. No other disclosures were reported.

SOURCE: Vargas-Santos AB et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4463

*Correction, 11/5/2018: An earlier version of this story incorrectly stated the American College of Rheumatology’s 2012 gout treatment recommendation for using allopurinol in patients with renal impairment.

LAS VEGAS – Brian F. Mandell, MD, PhD, of Cleveland Clinic, has a message about one of the most devastating conditions that rheumatologists see: Gout isn’t just a treatable disease. It’s a curable one.

Still, research shows time and time again that physicians manage gout “horrendously,” he told colleagues at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “The problem really lies with us,” he said. “We need to do a better job.”

At issue, he believes, is a failure to consider the basic workings of gout when making treatment decisions and advising patients. Lowering serum uric acid (SUA) via medication works, he said, but physicians too frequently don’t go far enough with this approach.

Gout appears to be on the rise in the United States, reflecting increases in related conditions such as obesity and diabetes. A study published this year found that the rate of new-onset gout more than doubled in Olmsted County, Minn., from 1989-1992 to 2009-2010, reaching an adjusted rate of 137/100,000 (J Rheumatol. 2018 Apr;45[4]:574-9).

According to Dr. Mandell, various mysteries regarding gout still need to be cleared up. For one, does resolution of gout also resolve conditions related to hyperuricemia, such as onset of hypertension, progressive chronic kidney disease, and nonalcoholic fatty liver along with higher all-cause mortality?

“We don’t know from interventional studies whether these are as reversible as the gouty arthritis,” he said.

It’s also unknown why so many hyperuricemic patients don’t get flares, with one study estimating that about 50% don’t get them over 15 years (Arthritis Rheumatol. 2017;69[Suppl 10]: Abstract 2843).

One fascinating theory, Dr. Mandell said, suggests “the microbiome is playing a huge [role] in the body’s response to deposits of crystals.”

Fortunately, he said, other mysteries about gout are being solved.

It’s now clear that lowering SUA below 6 mg/dL with medication will reduce flares, Dr. Mandell said. He pointed to a 2017 study of 314 patients with early gout that found 63% of patients who took febuxostat (Uloric) lowered their SUA below 6 mg/dL, compared with just 6% of the placebo group. The overall percentage of patients who had at least one gout flare over 2 years was 29% in the febuxostat group vs. 41% in the placebo group (Arthritis Rheumatol. 2017;69[12]:2386‐95).

It’s also clear that maintenance of lower SUA levels is crucial to prevent recurrence, Dr. Mandell said.

So why is management of hyperuricemia so poor? He ticked off various possible explanations: Maybe it’s the medications. Or perhaps patient compliance is low.

But the drugs are fine, he said, although he cautioned that too-rapid lowering of SUA levels can provoke attacks. He pointed to a 2014 study that suggests allopurinol can help nearly all patients get their SUA below 6 mg/dL, and in the study, the drug was “generally well tolerated” (Semin Arthritis Rheum. 2014 Aug;44[1]:25-30).

As for compliance, Dr. Mandell said, it can be boosted by patient education. The problem, he said, is that physicians are failing patients by not up-titrating allopurinol despite evidence that this approach works.

He added that hyperuricemia can be managed even in patients on diuretic therapy (Arthritis Res Ther. 2018;20:53).

What about patients who are intolerant to allopurinol or don’t fully respond to it on the SUA front? Dr. Mandell said he likes to try febuxostat, although he noted that it’s tremendously more expensive than allopurinol in the United States with a price that could be 10 times higher.

The nonscored design of febuxostat pills makes dose adjustment difficult in patients, he said, and there are concerns about heart-related and all-cause deaths.

Lesinurad (Zurampic) may be helpful for patients with hyperuricemia that doesn’t response to high doses of xanthine oxidase inhibitors (XOI) or if they’re intolerant to lower inadequate doses, he said. Avoid the drug in patients with chronic kidney disease, he cautioned, and be aware that it’s not approved as a monotherapy. Instead, it’s approved by the Food and Drug Administration for use with an XOI.

As for other gout issues, Dr. Mandell said pegloticase (Krystexxa) via infusion can help patients who don’t respond to an XOI but infusion reactions can occur (mainly in nonresponders), and it’s extremely expensive (about $20,000 per month).

He added that anti–IL-1 therapy is effective in hospitalized patients with gout and doesn’t exacerbate other conditions.

Dr. Mandell disclosed various links to drug makers that produce treatments for gout. He has served as clinical investigator for Horizon, has been a consultant to AstraZeneca, Ironwood, and Horizon, and has received honoraria (unrestricted grants) for continuing medical education activities from Takeda and Horizon. He also reported soliciting advertisements for a journal and educational grants for CME activities.

Global Academy for Medical Education and this news organization are owned by the same parent company.

LAS VEGAS – Brian F. Mandell, MD, PhD, of Cleveland Clinic, has a message about one of the most devastating conditions that rheumatologists see: Gout isn’t just a treatable disease. It’s a curable one.

Still, research shows time and time again that physicians manage gout “horrendously,” he told colleagues at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “The problem really lies with us,” he said. “We need to do a better job.”

At issue, he believes, is a failure to consider the basic workings of gout when making treatment decisions and advising patients. Lowering serum uric acid (SUA) via medication works, he said, but physicians too frequently don’t go far enough with this approach.

Gout appears to be on the rise in the United States, reflecting increases in related conditions such as obesity and diabetes. A study published this year found that the rate of new-onset gout more than doubled in Olmsted County, Minn., from 1989-1992 to 2009-2010, reaching an adjusted rate of 137/100,000 (J Rheumatol. 2018 Apr;45[4]:574-9).

According to Dr. Mandell, various mysteries regarding gout still need to be cleared up. For one, does resolution of gout also resolve conditions related to hyperuricemia, such as onset of hypertension, progressive chronic kidney disease, and nonalcoholic fatty liver along with higher all-cause mortality?

“We don’t know from interventional studies whether these are as reversible as the gouty arthritis,” he said.

It’s also unknown why so many hyperuricemic patients don’t get flares, with one study estimating that about 50% don’t get them over 15 years (Arthritis Rheumatol. 2017;69[Suppl 10]: Abstract 2843).

One fascinating theory, Dr. Mandell said, suggests “the microbiome is playing a huge [role] in the body’s response to deposits of crystals.”

Fortunately, he said, other mysteries about gout are being solved.

It’s now clear that lowering SUA below 6 mg/dL with medication will reduce flares, Dr. Mandell said. He pointed to a 2017 study of 314 patients with early gout that found 63% of patients who took febuxostat (Uloric) lowered their SUA below 6 mg/dL, compared with just 6% of the placebo group. The overall percentage of patients who had at least one gout flare over 2 years was 29% in the febuxostat group vs. 41% in the placebo group (Arthritis Rheumatol. 2017;69[12]:2386‐95).

It’s also clear that maintenance of lower SUA levels is crucial to prevent recurrence, Dr. Mandell said.

So why is management of hyperuricemia so poor? He ticked off various possible explanations: Maybe it’s the medications. Or perhaps patient compliance is low.

But the drugs are fine, he said, although he cautioned that too-rapid lowering of SUA levels can provoke attacks. He pointed to a 2014 study that suggests allopurinol can help nearly all patients get their SUA below 6 mg/dL, and in the study, the drug was “generally well tolerated” (Semin Arthritis Rheum. 2014 Aug;44[1]:25-30).

As for compliance, Dr. Mandell said, it can be boosted by patient education. The problem, he said, is that physicians are failing patients by not up-titrating allopurinol despite evidence that this approach works.

He added that hyperuricemia can be managed even in patients on diuretic therapy (Arthritis Res Ther. 2018;20:53).

What about patients who are intolerant to allopurinol or don’t fully respond to it on the SUA front? Dr. Mandell said he likes to try febuxostat, although he noted that it’s tremendously more expensive than allopurinol in the United States with a price that could be 10 times higher.

The nonscored design of febuxostat pills makes dose adjustment difficult in patients, he said, and there are concerns about heart-related and all-cause deaths.

Lesinurad (Zurampic) may be helpful for patients with hyperuricemia that doesn’t response to high doses of xanthine oxidase inhibitors (XOI) or if they’re intolerant to lower inadequate doses, he said. Avoid the drug in patients with chronic kidney disease, he cautioned, and be aware that it’s not approved as a monotherapy. Instead, it’s approved by the Food and Drug Administration for use with an XOI.

As for other gout issues, Dr. Mandell said pegloticase (Krystexxa) via infusion can help patients who don’t respond to an XOI but infusion reactions can occur (mainly in nonresponders), and it’s extremely expensive (about $20,000 per month).

He added that anti–IL-1 therapy is effective in hospitalized patients with gout and doesn’t exacerbate other conditions.

Dr. Mandell disclosed various links to drug makers that produce treatments for gout. He has served as clinical investigator for Horizon, has been a consultant to AstraZeneca, Ironwood, and Horizon, and has received honoraria (unrestricted grants) for continuing medical education activities from Takeda and Horizon. He also reported soliciting advertisements for a journal and educational grants for CME activities.

Global Academy for Medical Education and this news organization are owned by the same parent company.

LAS VEGAS – Brian F. Mandell, MD, PhD, of Cleveland Clinic, has a message about one of the most devastating conditions that rheumatologists see: Gout isn’t just a treatable disease. It’s a curable one.

Still, research shows time and time again that physicians manage gout “horrendously,” he told colleagues at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “The problem really lies with us,” he said. “We need to do a better job.”

At issue, he believes, is a failure to consider the basic workings of gout when making treatment decisions and advising patients. Lowering serum uric acid (SUA) via medication works, he said, but physicians too frequently don’t go far enough with this approach.

Gout appears to be on the rise in the United States, reflecting increases in related conditions such as obesity and diabetes. A study published this year found that the rate of new-onset gout more than doubled in Olmsted County, Minn., from 1989-1992 to 2009-2010, reaching an adjusted rate of 137/100,000 (J Rheumatol. 2018 Apr;45[4]:574-9).

According to Dr. Mandell, various mysteries regarding gout still need to be cleared up. For one, does resolution of gout also resolve conditions related to hyperuricemia, such as onset of hypertension, progressive chronic kidney disease, and nonalcoholic fatty liver along with higher all-cause mortality?

“We don’t know from interventional studies whether these are as reversible as the gouty arthritis,” he said.

It’s also unknown why so many hyperuricemic patients don’t get flares, with one study estimating that about 50% don’t get them over 15 years (Arthritis Rheumatol. 2017;69[Suppl 10]: Abstract 2843).

One fascinating theory, Dr. Mandell said, suggests “the microbiome is playing a huge [role] in the body’s response to deposits of crystals.”

Fortunately, he said, other mysteries about gout are being solved.

It’s now clear that lowering SUA below 6 mg/dL with medication will reduce flares, Dr. Mandell said. He pointed to a 2017 study of 314 patients with early gout that found 63% of patients who took febuxostat (Uloric) lowered their SUA below 6 mg/dL, compared with just 6% of the placebo group. The overall percentage of patients who had at least one gout flare over 2 years was 29% in the febuxostat group vs. 41% in the placebo group (Arthritis Rheumatol. 2017;69[12]:2386‐95).

It’s also clear that maintenance of lower SUA levels is crucial to prevent recurrence, Dr. Mandell said.

So why is management of hyperuricemia so poor? He ticked off various possible explanations: Maybe it’s the medications. Or perhaps patient compliance is low.

But the drugs are fine, he said, although he cautioned that too-rapid lowering of SUA levels can provoke attacks. He pointed to a 2014 study that suggests allopurinol can help nearly all patients get their SUA below 6 mg/dL, and in the study, the drug was “generally well tolerated” (Semin Arthritis Rheum. 2014 Aug;44[1]:25-30).

As for compliance, Dr. Mandell said, it can be boosted by patient education. The problem, he said, is that physicians are failing patients by not up-titrating allopurinol despite evidence that this approach works.

He added that hyperuricemia can be managed even in patients on diuretic therapy (Arthritis Res Ther. 2018;20:53).

What about patients who are intolerant to allopurinol or don’t fully respond to it on the SUA front? Dr. Mandell said he likes to try febuxostat, although he noted that it’s tremendously more expensive than allopurinol in the United States with a price that could be 10 times higher.

The nonscored design of febuxostat pills makes dose adjustment difficult in patients, he said, and there are concerns about heart-related and all-cause deaths.

Lesinurad (Zurampic) may be helpful for patients with hyperuricemia that doesn’t response to high doses of xanthine oxidase inhibitors (XOI) or if they’re intolerant to lower inadequate doses, he said. Avoid the drug in patients with chronic kidney disease, he cautioned, and be aware that it’s not approved as a monotherapy. Instead, it’s approved by the Food and Drug Administration for use with an XOI.

As for other gout issues, Dr. Mandell said pegloticase (Krystexxa) via infusion can help patients who don’t respond to an XOI but infusion reactions can occur (mainly in nonresponders), and it’s extremely expensive (about $20,000 per month).

He added that anti–IL-1 therapy is effective in hospitalized patients with gout and doesn’t exacerbate other conditions.

Dr. Mandell disclosed various links to drug makers that produce treatments for gout. He has served as clinical investigator for Horizon, has been a consultant to AstraZeneca, Ironwood, and Horizon, and has received honoraria (unrestricted grants) for continuing medical education activities from Takeda and Horizon. He also reported soliciting advertisements for a journal and educational grants for CME activities.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Canakinumab, an interleukin-1–beta blocker, reduced the risk of a gout attack by 52% when administered every 3 months, according to a secondary exploratory analysis of data from the multicenter, randomized, double-blind, placebo-controlled CANTOS trial (NCT01327846). The results of this analysis were published Sept. 17 in the Annals of Internal Medicine (doi: 10.7326/M18-1167).

We covered this story before it was published in the journal. Find our conference coverage at the links below.

Canakinumab, an interleukin-1–beta blocker, reduced the risk of a gout attack by 52% when administered every 3 months, according to a secondary exploratory analysis of data from the multicenter, randomized, double-blind, placebo-controlled CANTOS trial (NCT01327846). The results of this analysis were published Sept. 17 in the Annals of Internal Medicine (doi: 10.7326/M18-1167).

We covered this story before it was published in the journal. Find our conference coverage at the links below.

Canakinumab, an interleukin-1–beta blocker, reduced the risk of a gout attack by 52% when administered every 3 months, according to a secondary exploratory analysis of data from the multicenter, randomized, double-blind, placebo-controlled CANTOS trial (NCT01327846). The results of this analysis were published Sept. 17 in the Annals of Internal Medicine (doi: 10.7326/M18-1167).

We covered this story before it was published in the journal. Find our conference coverage at the links below.

Adults with obstructive sleep apnea are approximately twice as likely as are those without it to develop gout, according to data from a large, retrospective study with a median 5-year follow-up.

copyright designer491/Thinkstock

Data from previous studies have shown an increased risk in developing gout within the first year of an obstructive sleep apnea (OSA) diagnosis, wrote Milica Blagojevic-Bucknall, PhD, of Keele (England) University, and her colleagues.

In a study published in Arthritis & Rheumatology, the researchers compared 15,879 patients with OSA and 63,296 without.

Overall, 4.9% of OSA patients and 2.6% non‐OSA controls developed gout over a median follow‐up period of 5.8 years. The incidence rate for gout per 1,000 person‐years was 7.83 among patients with OSA and 4.03 for controls (adjusted hazard ratio, 1.42). The greatest risk for gout in the OSA patients occurred approximately 1-2 years after their diagnosis.

The researchers also found significant associations between body mass index and gout risk in sleep apnea across all BMI categories, but the strongest association occurred in the normal BMI group (HR 2.02) at 2-5 years after the index date of OSA.

“The novelty of this study lies in assessing both the short- and long-term association of OSA with incident gout in a large primary care-based population,” the researchers said. They proposed that the most likely explanation for the events was that “intermittent hypoxia increases nucleotide turnover which enhances endogenous uric acid production.”

The study findings were limited by several factors including potential misclassification of OSA and the impact of confounding variables such as genetics and diet, they noted.

However, the results support the association between sleep apnea and gout, but also serve to highlight that clinicians should “consider the possibility of gout in patients with sleep apnea regardless of obesity,” the researchers wrote.

The National Institute for Health Research funded the study. The authors have no conflicts of interest to declare.

SOURCE: Blagojevic-Bucknall M et al. Arthritis Rheumatol. 2018 Aug 30. doi: 10.1002/art.40662.

Adults with obstructive sleep apnea are approximately twice as likely as are those without it to develop gout, according to data from a large, retrospective study with a median 5-year follow-up.

copyright designer491/Thinkstock

Data from previous studies have shown an increased risk in developing gout within the first year of an obstructive sleep apnea (OSA) diagnosis, wrote Milica Blagojevic-Bucknall, PhD, of Keele (England) University, and her colleagues.

In a study published in Arthritis & Rheumatology, the researchers compared 15,879 patients with OSA and 63,296 without.

Overall, 4.9% of OSA patients and 2.6% non‐OSA controls developed gout over a median follow‐up period of 5.8 years. The incidence rate for gout per 1,000 person‐years was 7.83 among patients with OSA and 4.03 for controls (adjusted hazard ratio, 1.42). The greatest risk for gout in the OSA patients occurred approximately 1-2 years after their diagnosis.

The researchers also found significant associations between body mass index and gout risk in sleep apnea across all BMI categories, but the strongest association occurred in the normal BMI group (HR 2.02) at 2-5 years after the index date of OSA.

“The novelty of this study lies in assessing both the short- and long-term association of OSA with incident gout in a large primary care-based population,” the researchers said. They proposed that the most likely explanation for the events was that “intermittent hypoxia increases nucleotide turnover which enhances endogenous uric acid production.”

The study findings were limited by several factors including potential misclassification of OSA and the impact of confounding variables such as genetics and diet, they noted.

However, the results support the association between sleep apnea and gout, but also serve to highlight that clinicians should “consider the possibility of gout in patients with sleep apnea regardless of obesity,” the researchers wrote.

The National Institute for Health Research funded the study. The authors have no conflicts of interest to declare.

SOURCE: Blagojevic-Bucknall M et al. Arthritis Rheumatol. 2018 Aug 30. doi: 10.1002/art.40662.

Adults with obstructive sleep apnea are approximately twice as likely as are those without it to develop gout, according to data from a large, retrospective study with a median 5-year follow-up.

copyright designer491/Thinkstock

Data from previous studies have shown an increased risk in developing gout within the first year of an obstructive sleep apnea (OSA) diagnosis, wrote Milica Blagojevic-Bucknall, PhD, of Keele (England) University, and her colleagues.

In a study published in Arthritis & Rheumatology, the researchers compared 15,879 patients with OSA and 63,296 without.

Overall, 4.9% of OSA patients and 2.6% non‐OSA controls developed gout over a median follow‐up period of 5.8 years. The incidence rate for gout per 1,000 person‐years was 7.83 among patients with OSA and 4.03 for controls (adjusted hazard ratio, 1.42). The greatest risk for gout in the OSA patients occurred approximately 1-2 years after their diagnosis.

The researchers also found significant associations between body mass index and gout risk in sleep apnea across all BMI categories, but the strongest association occurred in the normal BMI group (HR 2.02) at 2-5 years after the index date of OSA.

“The novelty of this study lies in assessing both the short- and long-term association of OSA with incident gout in a large primary care-based population,” the researchers said. They proposed that the most likely explanation for the events was that “intermittent hypoxia increases nucleotide turnover which enhances endogenous uric acid production.”

The study findings were limited by several factors including potential misclassification of OSA and the impact of confounding variables such as genetics and diet, they noted.

However, the results support the association between sleep apnea and gout, but also serve to highlight that clinicians should “consider the possibility of gout in patients with sleep apnea regardless of obesity,” the researchers wrote.

The National Institute for Health Research funded the study. The authors have no conflicts of interest to declare.

SOURCE: Blagojevic-Bucknall M et al. Arthritis Rheumatol. 2018 Aug 30. doi: 10.1002/art.40662.

AMSTERDAM – Results from the longitudinal NOR-GOUT study show that ultrasound can help visualize decreasing levels of uric acid deposits that occur during a treat-to-target approach with urate-lowering therapy.

“We used a treat-to-target approach with the medication,” Dr. Hammer explained. The aim was to get uric acid levels to 360 micromol/L or lower, or to less than 300 micromol/L (5.0 mg/dL) if clinical tophi were present. “The medication was optimized by monthly follow-up by a study nurse until the treatment target was met,” she added.

Patients underwent an extensive ultrasound assessment at study entry and again after 3, 6, and 12 months of urate-lowering therapy. This included bilateral assessment of all relevant joints and the presence of crystals semiquantitatively scored from 0 to 3, the latter signifying many deposits. The sum of scores for the three key OMERACT definitions were calculated each time the patients were assessed, with a total score for all three also calculated.

Mean serum urate levels dropped from a baseline of 487 to 312 micromol/L (from 8.2 to 5.3 mg/dL) at 12 months (P less than .001), Dr. Hammer reported. The percentage of patients achieving a urate target of less than 360 micromol/L increased from 71% at 3 months to 81% at 6 months and to 84% at 12 months, she said.

Ultrasound scores decreased with decreasing urate levels at 3, 6, and 12 months, with the highest numeric difference from baseline seen at 12 months for DC (3.1, 2.3, and 1.2; all P less than .001 vs. baseline of 4.2). The respective values for tophi were 6.3, 5.4, and 4.2 versus a baseline of 6.5; for aggregates, the values were 8.8, 7.9, and 6.7 versus a baseline of 9.1.

SOURCE: Hammer HB et al. Ann Rheum Dis. 2018;77(Suppl 2):154-5. Abstract OP0211.

AMSTERDAM – Results from the longitudinal NOR-GOUT study show that ultrasound can help visualize decreasing levels of uric acid deposits that occur during a treat-to-target approach with urate-lowering therapy.

“We used a treat-to-target approach with the medication,” Dr. Hammer explained. The aim was to get uric acid levels to 360 micromol/L or lower, or to less than 300 micromol/L (5.0 mg/dL) if clinical tophi were present. “The medication was optimized by monthly follow-up by a study nurse until the treatment target was met,” she added.

Patients underwent an extensive ultrasound assessment at study entry and again after 3, 6, and 12 months of urate-lowering therapy. This included bilateral assessment of all relevant joints and the presence of crystals semiquantitatively scored from 0 to 3, the latter signifying many deposits. The sum of scores for the three key OMERACT definitions were calculated each time the patients were assessed, with a total score for all three also calculated.

Mean serum urate levels dropped from a baseline of 487 to 312 micromol/L (from 8.2 to 5.3 mg/dL) at 12 months (P less than .001), Dr. Hammer reported. The percentage of patients achieving a urate target of less than 360 micromol/L increased from 71% at 3 months to 81% at 6 months and to 84% at 12 months, she said.

Ultrasound scores decreased with decreasing urate levels at 3, 6, and 12 months, with the highest numeric difference from baseline seen at 12 months for DC (3.1, 2.3, and 1.2; all P less than .001 vs. baseline of 4.2). The respective values for tophi were 6.3, 5.4, and 4.2 versus a baseline of 6.5; for aggregates, the values were 8.8, 7.9, and 6.7 versus a baseline of 9.1.

SOURCE: Hammer HB et al. Ann Rheum Dis. 2018;77(Suppl 2):154-5. Abstract OP0211.

AMSTERDAM – Results from the longitudinal NOR-GOUT study show that ultrasound can help visualize decreasing levels of uric acid deposits that occur during a treat-to-target approach with urate-lowering therapy.

“We used a treat-to-target approach with the medication,” Dr. Hammer explained. The aim was to get uric acid levels to 360 micromol/L or lower, or to less than 300 micromol/L (5.0 mg/dL) if clinical tophi were present. “The medication was optimized by monthly follow-up by a study nurse until the treatment target was met,” she added.

Patients underwent an extensive ultrasound assessment at study entry and again after 3, 6, and 12 months of urate-lowering therapy. This included bilateral assessment of all relevant joints and the presence of crystals semiquantitatively scored from 0 to 3, the latter signifying many deposits. The sum of scores for the three key OMERACT definitions were calculated each time the patients were assessed, with a total score for all three also calculated.

Mean serum urate levels dropped from a baseline of 487 to 312 micromol/L (from 8.2 to 5.3 mg/dL) at 12 months (P less than .001), Dr. Hammer reported. The percentage of patients achieving a urate target of less than 360 micromol/L increased from 71% at 3 months to 81% at 6 months and to 84% at 12 months, she said.

Ultrasound scores decreased with decreasing urate levels at 3, 6, and 12 months, with the highest numeric difference from baseline seen at 12 months for DC (3.1, 2.3, and 1.2; all P less than .001 vs. baseline of 4.2). The respective values for tophi were 6.3, 5.4, and 4.2 versus a baseline of 6.5; for aggregates, the values were 8.8, 7.9, and 6.7 versus a baseline of 9.1.

SOURCE: Hammer HB et al. Ann Rheum Dis. 2018;77(Suppl 2):154-5. Abstract OP0211.

AMSTERDAM – Treatment with the anti-inflammatory, interleukin-1 blocking drug canakinumab roughly halves gout attacks in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.

While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks, Daniel H. Solomon, MD, said at the European Congress of Rheumatology.

“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.

The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).

It’s also unclear that canakinumab (Ilaris) is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study (N Engl J Med. 2017 Sept 21;377[12]:1119-31). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.

In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.

Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.

[email protected]

SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. Abstract OP0014.

AMSTERDAM – Treatment with the anti-inflammatory, interleukin-1 blocking drug canakinumab roughly halves gout attacks in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.

While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks, Daniel H. Solomon, MD, said at the European Congress of Rheumatology.

“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.

The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).

It’s also unclear that canakinumab (Ilaris) is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study (N Engl J Med. 2017 Sept 21;377[12]:1119-31). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.

In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.

Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.

[email protected]

SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. Abstract OP0014.

AMSTERDAM – Treatment with the anti-inflammatory, interleukin-1 blocking drug canakinumab roughly halves gout attacks in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.

While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks, Daniel H. Solomon, MD, said at the European Congress of Rheumatology.

“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.

The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).

It’s also unclear that canakinumab (Ilaris) is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study (N Engl J Med. 2017 Sept 21;377[12]:1119-31). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.

In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.

Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.

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SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. Abstract OP0014.