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Alcohol consumption habits can predict gout tophi
The more years a person drinks alcohol, the kind of alcohol consumed, and the amount consumed can help to predict gout tophi, researchers say in a newly published paper in Arthritis Care and Research.
The study, led by Lin Han, PhD, of the gout laboratory, Shandong provincial clinical research center for immune diseases and gout, Affiliated Hospital of Qingdao (China) University, helps clarify the already-established relationship between alcohol consumption and gout tophi.
Additionally, the effects of drinking alcohol on ultrasound (US)–detected tophi and subcutaneous tophi (subtophi) were evaluated separately for the first time in this work, the authors say.
Tophi may be underdiagnosed because they are hard to find with only a physical exam. US can help with early detection, especially with small clusters of crystals or those found deep in the tissues, and offers good diagnostic accuracy with high specificity.
“Unlike subtophi, which represent long-term subcutaneous MSU [monosodium urate] deposition over many years, US-detected tophi represent the early stage of tophi in both intra- and extra-articular settings,” the authors write.
This cross-sectional study in China included 554 patients with gout who had joint ultrasound and physical exams through the Affiliated Hospital of Qingdao University. Physicians gathered medical histories using the Biobank Information Management System.
Physicians also tracked alcohol consumption patterns through the biobank information, which included answers to a detailed drinking questionnaire.
Patients were classified as either nondrinkers (no history of drinking; n = 141), former drinkers (n = 60), or current regular drinkers (n = 353). Current regular drinkers were asked further questions about their drinking patterns, including how long they have been drinking, type of alcohol they drink, and how much and how often they drink. In China, the average drink is considered to contain 10 g of alcohol, according to the World Health Organization.
Results from US and clinically detected tophi
Compared with nondrinkers, excessive drinkers (more than 70 g/week); long-term drinkers (at least 10 years), and spirits drinkers had a greater proportion, size, and number of US-detected tophi and subtophi (all P < .05).
After adjusting for confounders, the researchers found that excessive drinking was significantly associated with having US-detected tophi (odds ratio, 1.79) and subtophi (OR, 2.00). Similar associations were found for consumption of alcohol for at least 10 years (OR, 1.96 for US-detected tophi; OR, 2.17 for sub-tophi) and drinking spirits (OR, 1.81 for US-detected tophi; OR, 2.10 for subtophi). All comparisons were P < .05.
Among patients who already have US-detected tophi or subtophi, moderate drinking (70 g/week or less) was linked with larger or multiple tophi (all P < .05).
Angelo Gaffo, MD, section chief of rheumatology at the Birmingham VA Medical Center and associate professor of medicine in the division of rheumatology at the University of Alabama at Birmingham, said in an interview that the results are likely generalizable.
“I wouldn’t expect them to be specific to the Chinese population,” he said.
Most of the 554 patients were male (97.8%) and had no family history of gout (79.8%). The median duration of gout was 4 years, and the average age was 45.1 years.
Dr. Gaffo noted the population age was fairly young and the average duration of gout in these patients was fairly short. He also noted most had small tophi that were detected only by ultrasound and small numbers of tophi overall.
“I would like to see how these results will replicate in a population that has had gout for, say, 10 years on average,” he said.
Dr. Gaffo says he explores alcohol history with his patients with gout. If they are frequent drinkers, he encourages them to cut back.
“At the very least,” he said, “you have to restrict your intake to no more than 1-2 servings per week,” he said. “For some patients, even minimal amounts of alcohol intake can be associated with the development of flares.”
Still, research like this, he says, can help physicians point to evidence in their advice to patients about alcohol use.
He noted that the authors found the association between different types of alcohol and tophi was independent of serum urate level.
“That surprised me,” Dr. Gaffo said. “That’s a very unique finding.”
This work was supported by grants from the National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province, Qingdao applied basic research project, National College Students’ Innovation and Entrepreneurship Training Program, and Shandong Provincial Science Foundation for Outstanding Youth Scholars.
The authors of the study and Dr. Gaffo report no relevant financial relationships.
The more years a person drinks alcohol, the kind of alcohol consumed, and the amount consumed can help to predict gout tophi, researchers say in a newly published paper in Arthritis Care and Research.
The study, led by Lin Han, PhD, of the gout laboratory, Shandong provincial clinical research center for immune diseases and gout, Affiliated Hospital of Qingdao (China) University, helps clarify the already-established relationship between alcohol consumption and gout tophi.
Additionally, the effects of drinking alcohol on ultrasound (US)–detected tophi and subcutaneous tophi (subtophi) were evaluated separately for the first time in this work, the authors say.
Tophi may be underdiagnosed because they are hard to find with only a physical exam. US can help with early detection, especially with small clusters of crystals or those found deep in the tissues, and offers good diagnostic accuracy with high specificity.
“Unlike subtophi, which represent long-term subcutaneous MSU [monosodium urate] deposition over many years, US-detected tophi represent the early stage of tophi in both intra- and extra-articular settings,” the authors write.
This cross-sectional study in China included 554 patients with gout who had joint ultrasound and physical exams through the Affiliated Hospital of Qingdao University. Physicians gathered medical histories using the Biobank Information Management System.
Physicians also tracked alcohol consumption patterns through the biobank information, which included answers to a detailed drinking questionnaire.
Patients were classified as either nondrinkers (no history of drinking; n = 141), former drinkers (n = 60), or current regular drinkers (n = 353). Current regular drinkers were asked further questions about their drinking patterns, including how long they have been drinking, type of alcohol they drink, and how much and how often they drink. In China, the average drink is considered to contain 10 g of alcohol, according to the World Health Organization.
Results from US and clinically detected tophi
Compared with nondrinkers, excessive drinkers (more than 70 g/week); long-term drinkers (at least 10 years), and spirits drinkers had a greater proportion, size, and number of US-detected tophi and subtophi (all P < .05).
After adjusting for confounders, the researchers found that excessive drinking was significantly associated with having US-detected tophi (odds ratio, 1.79) and subtophi (OR, 2.00). Similar associations were found for consumption of alcohol for at least 10 years (OR, 1.96 for US-detected tophi; OR, 2.17 for sub-tophi) and drinking spirits (OR, 1.81 for US-detected tophi; OR, 2.10 for subtophi). All comparisons were P < .05.
Among patients who already have US-detected tophi or subtophi, moderate drinking (70 g/week or less) was linked with larger or multiple tophi (all P < .05).
Angelo Gaffo, MD, section chief of rheumatology at the Birmingham VA Medical Center and associate professor of medicine in the division of rheumatology at the University of Alabama at Birmingham, said in an interview that the results are likely generalizable.
“I wouldn’t expect them to be specific to the Chinese population,” he said.
Most of the 554 patients were male (97.8%) and had no family history of gout (79.8%). The median duration of gout was 4 years, and the average age was 45.1 years.
Dr. Gaffo noted the population age was fairly young and the average duration of gout in these patients was fairly short. He also noted most had small tophi that were detected only by ultrasound and small numbers of tophi overall.
“I would like to see how these results will replicate in a population that has had gout for, say, 10 years on average,” he said.
Dr. Gaffo says he explores alcohol history with his patients with gout. If they are frequent drinkers, he encourages them to cut back.
“At the very least,” he said, “you have to restrict your intake to no more than 1-2 servings per week,” he said. “For some patients, even minimal amounts of alcohol intake can be associated with the development of flares.”
Still, research like this, he says, can help physicians point to evidence in their advice to patients about alcohol use.
He noted that the authors found the association between different types of alcohol and tophi was independent of serum urate level.
“That surprised me,” Dr. Gaffo said. “That’s a very unique finding.”
This work was supported by grants from the National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province, Qingdao applied basic research project, National College Students’ Innovation and Entrepreneurship Training Program, and Shandong Provincial Science Foundation for Outstanding Youth Scholars.
The authors of the study and Dr. Gaffo report no relevant financial relationships.
The more years a person drinks alcohol, the kind of alcohol consumed, and the amount consumed can help to predict gout tophi, researchers say in a newly published paper in Arthritis Care and Research.
The study, led by Lin Han, PhD, of the gout laboratory, Shandong provincial clinical research center for immune diseases and gout, Affiliated Hospital of Qingdao (China) University, helps clarify the already-established relationship between alcohol consumption and gout tophi.
Additionally, the effects of drinking alcohol on ultrasound (US)–detected tophi and subcutaneous tophi (subtophi) were evaluated separately for the first time in this work, the authors say.
Tophi may be underdiagnosed because they are hard to find with only a physical exam. US can help with early detection, especially with small clusters of crystals or those found deep in the tissues, and offers good diagnostic accuracy with high specificity.
“Unlike subtophi, which represent long-term subcutaneous MSU [monosodium urate] deposition over many years, US-detected tophi represent the early stage of tophi in both intra- and extra-articular settings,” the authors write.
This cross-sectional study in China included 554 patients with gout who had joint ultrasound and physical exams through the Affiliated Hospital of Qingdao University. Physicians gathered medical histories using the Biobank Information Management System.
Physicians also tracked alcohol consumption patterns through the biobank information, which included answers to a detailed drinking questionnaire.
Patients were classified as either nondrinkers (no history of drinking; n = 141), former drinkers (n = 60), or current regular drinkers (n = 353). Current regular drinkers were asked further questions about their drinking patterns, including how long they have been drinking, type of alcohol they drink, and how much and how often they drink. In China, the average drink is considered to contain 10 g of alcohol, according to the World Health Organization.
Results from US and clinically detected tophi
Compared with nondrinkers, excessive drinkers (more than 70 g/week); long-term drinkers (at least 10 years), and spirits drinkers had a greater proportion, size, and number of US-detected tophi and subtophi (all P < .05).
After adjusting for confounders, the researchers found that excessive drinking was significantly associated with having US-detected tophi (odds ratio, 1.79) and subtophi (OR, 2.00). Similar associations were found for consumption of alcohol for at least 10 years (OR, 1.96 for US-detected tophi; OR, 2.17 for sub-tophi) and drinking spirits (OR, 1.81 for US-detected tophi; OR, 2.10 for subtophi). All comparisons were P < .05.
Among patients who already have US-detected tophi or subtophi, moderate drinking (70 g/week or less) was linked with larger or multiple tophi (all P < .05).
Angelo Gaffo, MD, section chief of rheumatology at the Birmingham VA Medical Center and associate professor of medicine in the division of rheumatology at the University of Alabama at Birmingham, said in an interview that the results are likely generalizable.
“I wouldn’t expect them to be specific to the Chinese population,” he said.
Most of the 554 patients were male (97.8%) and had no family history of gout (79.8%). The median duration of gout was 4 years, and the average age was 45.1 years.
Dr. Gaffo noted the population age was fairly young and the average duration of gout in these patients was fairly short. He also noted most had small tophi that were detected only by ultrasound and small numbers of tophi overall.
“I would like to see how these results will replicate in a population that has had gout for, say, 10 years on average,” he said.
Dr. Gaffo says he explores alcohol history with his patients with gout. If they are frequent drinkers, he encourages them to cut back.
“At the very least,” he said, “you have to restrict your intake to no more than 1-2 servings per week,” he said. “For some patients, even minimal amounts of alcohol intake can be associated with the development of flares.”
Still, research like this, he says, can help physicians point to evidence in their advice to patients about alcohol use.
He noted that the authors found the association between different types of alcohol and tophi was independent of serum urate level.
“That surprised me,” Dr. Gaffo said. “That’s a very unique finding.”
This work was supported by grants from the National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province, Qingdao applied basic research project, National College Students’ Innovation and Entrepreneurship Training Program, and Shandong Provincial Science Foundation for Outstanding Youth Scholars.
The authors of the study and Dr. Gaffo report no relevant financial relationships.
FROM ARTHRITIS CARE AND RESEARCH
Methotrexate enhances pegloticase response in uncontrolled gout
In patients with uncontrolled gout, response rates were increased by 32% when methotrexate was used in conjunction with pegloticase versus pegloticase plus a placebo, it was reported at the annual European Congress of Rheumatology.
In the phase 4 MIRROR trial, 71% of patients who received pretreatment with methotrexate and then the combination of methotrexate and pegloticase achieved uric-acid levels lower than 6 mg/dL for more than 80% of the time during weeks 20-24 of the 52-week study. By comparison, only 39% of those treated with pegloticase plus a placebo achieved this primary endpoint (P < .0001).
“This trial confirms not only improved efficacy but improved safety in patients treated with pegloticase in combination with methotrexate 15 mg orally once weekly,” study investigator John K. Botson, MD, RPh, CCD, said in reporting the trial’s findings.
This is good news for patients, suggested two rheumatologists who were not involved in the study. The combination appears “useful for a select group of gout patients,” observed Christian Ammitzbøll, MD, PhD, from Aarhus University Hospital, Denmark.
“Very promising in refractory gout,” agreed Emre Bilgin, MD, from Ankara, Turkey.
Rationale for using methotrexate
“Oral urate lowering agents are the mainstay of treatment of gout, but there are patients that just don’t respond to oral agents,” said Dr. Botson, a rheumatologist in private practice from Anchorage, Alaska.
“These patients are very difficult to treat,” he added. “They have a lot of physical disabilities, they have high medical comorbidities, and they have a low quality of life. Their treatment options are extremely limited.”
One of the few options they have is pegloticase, a pegylated uric acid specific enzyme sold under the brand name Krystexxa for the past 12 years. It lowers serum uric acid by converting it to allantoin, which is more water soluble and thus is easier to excrete from the body.
However, one of the problems of using the drug is that anti-drug antibodies frequently develop, meaning that discontinuation rates can be as high as 50%, with around a quarter of patients at high risk of experiencing an infusion reaction.
“Methotrexate is a medication we’re very familiar with for other rheumatologic conditions that use biologic medications, and we use this to prevent anti-drug antibodies. So, the MIRROR RCT was a study we performed to examine the pegloticase therapy in combination with methotrexate co therapy,” explained Dr. Botson.
In fact, co-administration of methotrexate and pegloticase was associated with fewer infusion reactions than using pegloticase alone (3% vs. 31%).
Study design and results
A total of 152 patients were included in the trial and were treated with methotrexate at a weekly dose of 15 mg for 2 weeks before being randomized, 2:1, to either continue methotrexate and then receive intravenous pegloticase or receive the latter with a placebo. Pegloticase was given at a dose of 8 mg every 2 weeks. Treatment was for 52 weeks, with the primary endpoint of serum uric acid response tested at 6 months.
The reason for the 2-week run-in period with methotrexate was to check that patients would be able to tolerate it, Dr. Botson explained.
The mean age of patients was around 54 years, the majority (> 84%) were male and were White (69%). The average duration of gout was about 14 years, with over 74% having tophi present at screening and experiencing 10-11 flares in the previous year. Baseline serum uric acid averaged at about 9 mg/dL.
Almost three-quarters of the 100 patients (73%) who were treated with the combination completed treatment to week 24 while the corresponding percentage in the placebo arm (n = 52) was 39%. The main reason for stopping was due to lack of efficacy (27% and 61% of cases, respectively), defined as having serum uric acid levels above 6 mg/dL on two consecutive measurements.
The median time to discontinuation was 69 days for those in the placebo arm; “it was non-estimable” in the methotrexate arm, Dr. Botson reported.
The mean change in serum uric acid through to week 24 was higher in the methotrexate than placebo arm, at a respective 7.66 and 5.23 mg/dL, giving a significant mean difference of 2.43 mg/dL.
There was a “dramatic resolution of tophaceous deposits,” Dr. Botson said. Complete resolution of tophi was seen in 34.6% of methotrexate-treated patients versus 13.8% of pegloticase-placebo–treated patients (P = .043).
One of the most common adverse events associated with pegloticase treatment is gout flare, which occurred in about 70% of participants in both study arms. Overall, the addition of methotrexate did not increase the risk for adverse events in general, and of the two deaths seen in the study – both in methotrexate-treated patients – one was because of a heart attack and another due COVID-19, so they were unrelated to study treatment.
In patients with renal insufficiency
Concern was raised during the discussion, however, on how to handle methotrexate use in patients with renal insufficiency.
“That’s been a debate that we’ve had in this study and others,” said Dr. Botson, acknowledging that “methotrexate is often a concern for the nephrologist that we’re co-treating these patients with.” However, no dose adjustments were needed in the study.
“There are some other studies with other immunomodulators that do suggest that other agents could be used that may be a little less potentially renal toxic, but we didn’t see any toxicity in the patients that we had, even in those that had a reduced [glomerular filtration rate],” he added.
Dr. Botson has received research support from Horizon and Radius Health. He also acknowledged receiving speakers fees from AbbVie, Amgen, Aurinia, ChemoCentryx*, Horizon, Eli Lilly, and Novartis.
Correction, 6/7/22: The name of the company ChemoCentryx was misstated.
In patients with uncontrolled gout, response rates were increased by 32% when methotrexate was used in conjunction with pegloticase versus pegloticase plus a placebo, it was reported at the annual European Congress of Rheumatology.
In the phase 4 MIRROR trial, 71% of patients who received pretreatment with methotrexate and then the combination of methotrexate and pegloticase achieved uric-acid levels lower than 6 mg/dL for more than 80% of the time during weeks 20-24 of the 52-week study. By comparison, only 39% of those treated with pegloticase plus a placebo achieved this primary endpoint (P < .0001).
“This trial confirms not only improved efficacy but improved safety in patients treated with pegloticase in combination with methotrexate 15 mg orally once weekly,” study investigator John K. Botson, MD, RPh, CCD, said in reporting the trial’s findings.
This is good news for patients, suggested two rheumatologists who were not involved in the study. The combination appears “useful for a select group of gout patients,” observed Christian Ammitzbøll, MD, PhD, from Aarhus University Hospital, Denmark.
“Very promising in refractory gout,” agreed Emre Bilgin, MD, from Ankara, Turkey.
Rationale for using methotrexate
“Oral urate lowering agents are the mainstay of treatment of gout, but there are patients that just don’t respond to oral agents,” said Dr. Botson, a rheumatologist in private practice from Anchorage, Alaska.
“These patients are very difficult to treat,” he added. “They have a lot of physical disabilities, they have high medical comorbidities, and they have a low quality of life. Their treatment options are extremely limited.”
One of the few options they have is pegloticase, a pegylated uric acid specific enzyme sold under the brand name Krystexxa for the past 12 years. It lowers serum uric acid by converting it to allantoin, which is more water soluble and thus is easier to excrete from the body.
However, one of the problems of using the drug is that anti-drug antibodies frequently develop, meaning that discontinuation rates can be as high as 50%, with around a quarter of patients at high risk of experiencing an infusion reaction.
“Methotrexate is a medication we’re very familiar with for other rheumatologic conditions that use biologic medications, and we use this to prevent anti-drug antibodies. So, the MIRROR RCT was a study we performed to examine the pegloticase therapy in combination with methotrexate co therapy,” explained Dr. Botson.
In fact, co-administration of methotrexate and pegloticase was associated with fewer infusion reactions than using pegloticase alone (3% vs. 31%).
Study design and results
A total of 152 patients were included in the trial and were treated with methotrexate at a weekly dose of 15 mg for 2 weeks before being randomized, 2:1, to either continue methotrexate and then receive intravenous pegloticase or receive the latter with a placebo. Pegloticase was given at a dose of 8 mg every 2 weeks. Treatment was for 52 weeks, with the primary endpoint of serum uric acid response tested at 6 months.
The reason for the 2-week run-in period with methotrexate was to check that patients would be able to tolerate it, Dr. Botson explained.
The mean age of patients was around 54 years, the majority (> 84%) were male and were White (69%). The average duration of gout was about 14 years, with over 74% having tophi present at screening and experiencing 10-11 flares in the previous year. Baseline serum uric acid averaged at about 9 mg/dL.
Almost three-quarters of the 100 patients (73%) who were treated with the combination completed treatment to week 24 while the corresponding percentage in the placebo arm (n = 52) was 39%. The main reason for stopping was due to lack of efficacy (27% and 61% of cases, respectively), defined as having serum uric acid levels above 6 mg/dL on two consecutive measurements.
The median time to discontinuation was 69 days for those in the placebo arm; “it was non-estimable” in the methotrexate arm, Dr. Botson reported.
The mean change in serum uric acid through to week 24 was higher in the methotrexate than placebo arm, at a respective 7.66 and 5.23 mg/dL, giving a significant mean difference of 2.43 mg/dL.
There was a “dramatic resolution of tophaceous deposits,” Dr. Botson said. Complete resolution of tophi was seen in 34.6% of methotrexate-treated patients versus 13.8% of pegloticase-placebo–treated patients (P = .043).
One of the most common adverse events associated with pegloticase treatment is gout flare, which occurred in about 70% of participants in both study arms. Overall, the addition of methotrexate did not increase the risk for adverse events in general, and of the two deaths seen in the study – both in methotrexate-treated patients – one was because of a heart attack and another due COVID-19, so they were unrelated to study treatment.
In patients with renal insufficiency
Concern was raised during the discussion, however, on how to handle methotrexate use in patients with renal insufficiency.
“That’s been a debate that we’ve had in this study and others,” said Dr. Botson, acknowledging that “methotrexate is often a concern for the nephrologist that we’re co-treating these patients with.” However, no dose adjustments were needed in the study.
“There are some other studies with other immunomodulators that do suggest that other agents could be used that may be a little less potentially renal toxic, but we didn’t see any toxicity in the patients that we had, even in those that had a reduced [glomerular filtration rate],” he added.
Dr. Botson has received research support from Horizon and Radius Health. He also acknowledged receiving speakers fees from AbbVie, Amgen, Aurinia, ChemoCentryx*, Horizon, Eli Lilly, and Novartis.
Correction, 6/7/22: The name of the company ChemoCentryx was misstated.
In patients with uncontrolled gout, response rates were increased by 32% when methotrexate was used in conjunction with pegloticase versus pegloticase plus a placebo, it was reported at the annual European Congress of Rheumatology.
In the phase 4 MIRROR trial, 71% of patients who received pretreatment with methotrexate and then the combination of methotrexate and pegloticase achieved uric-acid levels lower than 6 mg/dL for more than 80% of the time during weeks 20-24 of the 52-week study. By comparison, only 39% of those treated with pegloticase plus a placebo achieved this primary endpoint (P < .0001).
“This trial confirms not only improved efficacy but improved safety in patients treated with pegloticase in combination with methotrexate 15 mg orally once weekly,” study investigator John K. Botson, MD, RPh, CCD, said in reporting the trial’s findings.
This is good news for patients, suggested two rheumatologists who were not involved in the study. The combination appears “useful for a select group of gout patients,” observed Christian Ammitzbøll, MD, PhD, from Aarhus University Hospital, Denmark.
“Very promising in refractory gout,” agreed Emre Bilgin, MD, from Ankara, Turkey.
Rationale for using methotrexate
“Oral urate lowering agents are the mainstay of treatment of gout, but there are patients that just don’t respond to oral agents,” said Dr. Botson, a rheumatologist in private practice from Anchorage, Alaska.
“These patients are very difficult to treat,” he added. “They have a lot of physical disabilities, they have high medical comorbidities, and they have a low quality of life. Their treatment options are extremely limited.”
One of the few options they have is pegloticase, a pegylated uric acid specific enzyme sold under the brand name Krystexxa for the past 12 years. It lowers serum uric acid by converting it to allantoin, which is more water soluble and thus is easier to excrete from the body.
However, one of the problems of using the drug is that anti-drug antibodies frequently develop, meaning that discontinuation rates can be as high as 50%, with around a quarter of patients at high risk of experiencing an infusion reaction.
“Methotrexate is a medication we’re very familiar with for other rheumatologic conditions that use biologic medications, and we use this to prevent anti-drug antibodies. So, the MIRROR RCT was a study we performed to examine the pegloticase therapy in combination with methotrexate co therapy,” explained Dr. Botson.
In fact, co-administration of methotrexate and pegloticase was associated with fewer infusion reactions than using pegloticase alone (3% vs. 31%).
Study design and results
A total of 152 patients were included in the trial and were treated with methotrexate at a weekly dose of 15 mg for 2 weeks before being randomized, 2:1, to either continue methotrexate and then receive intravenous pegloticase or receive the latter with a placebo. Pegloticase was given at a dose of 8 mg every 2 weeks. Treatment was for 52 weeks, with the primary endpoint of serum uric acid response tested at 6 months.
The reason for the 2-week run-in period with methotrexate was to check that patients would be able to tolerate it, Dr. Botson explained.
The mean age of patients was around 54 years, the majority (> 84%) were male and were White (69%). The average duration of gout was about 14 years, with over 74% having tophi present at screening and experiencing 10-11 flares in the previous year. Baseline serum uric acid averaged at about 9 mg/dL.
Almost three-quarters of the 100 patients (73%) who were treated with the combination completed treatment to week 24 while the corresponding percentage in the placebo arm (n = 52) was 39%. The main reason for stopping was due to lack of efficacy (27% and 61% of cases, respectively), defined as having serum uric acid levels above 6 mg/dL on two consecutive measurements.
The median time to discontinuation was 69 days for those in the placebo arm; “it was non-estimable” in the methotrexate arm, Dr. Botson reported.
The mean change in serum uric acid through to week 24 was higher in the methotrexate than placebo arm, at a respective 7.66 and 5.23 mg/dL, giving a significant mean difference of 2.43 mg/dL.
There was a “dramatic resolution of tophaceous deposits,” Dr. Botson said. Complete resolution of tophi was seen in 34.6% of methotrexate-treated patients versus 13.8% of pegloticase-placebo–treated patients (P = .043).
One of the most common adverse events associated with pegloticase treatment is gout flare, which occurred in about 70% of participants in both study arms. Overall, the addition of methotrexate did not increase the risk for adverse events in general, and of the two deaths seen in the study – both in methotrexate-treated patients – one was because of a heart attack and another due COVID-19, so they were unrelated to study treatment.
In patients with renal insufficiency
Concern was raised during the discussion, however, on how to handle methotrexate use in patients with renal insufficiency.
“That’s been a debate that we’ve had in this study and others,” said Dr. Botson, acknowledging that “methotrexate is often a concern for the nephrologist that we’re co-treating these patients with.” However, no dose adjustments were needed in the study.
“There are some other studies with other immunomodulators that do suggest that other agents could be used that may be a little less potentially renal toxic, but we didn’t see any toxicity in the patients that we had, even in those that had a reduced [glomerular filtration rate],” he added.
Dr. Botson has received research support from Horizon and Radius Health. He also acknowledged receiving speakers fees from AbbVie, Amgen, Aurinia, ChemoCentryx*, Horizon, Eli Lilly, and Novartis.
Correction, 6/7/22: The name of the company ChemoCentryx was misstated.
FROM THE EULAR 2022 CONGRESS
Gout app improves treat to target, reduces flares
Self-management of gout using a smartphone app to record self-test urate levels and flares, and communicate those results to clinicians, could see more patients reaching target urate levels and even reducing flare frequency, a study has found.
Writing in The Lancet Rheumatology, Philip Riches, PhD, of the rheumatic disease unit at Western General Hospital in Edinburgh, and coauthors presented the findings of their randomized, controlled feasibility study of a new gout self-management approach aimed at helping patients treat to target.
While current rheumatology guidelines stress the importance of keeping urate below target levels to reduce flares and improve clinical outcomes, this isn’t always achieved in clinical practice. A previous trial of a nurse-led treat-to-target intervention did show a reduced incidence of flares and tophaceous disease, but the authors said, despite its cost-effectiveness, this approach has yet to be implemented in the United Kingdom.
Dr. Riches and colleagues developed a self-management strategy in which all 60 patients in the study self-tested their urate levels and were prompted to enter that data into the GoutSMART smartphone app once a month or opportunistically, along with information on disease severity and quality of life. All patients had been recommended for initiation or escalation of urate-lowering therapy, and had a serum urate of 0.36 mmol/L (6 mg/dL) or higher at baseline, and all received a gout management plan at the start of the study.
Patients in the intervention group who recorded a urate level above 0.30 mmol/L (5 mg/dL) via the app during the study were prompted to do a self-test every 2 weeks and given daily reminders in the app. Their urate levels were transmitted securely to the study team who then advised on dose escalation or treatment change. Those in the usual-care group also used the app but it only prompted them to record gout flares, keep quality of life diaries, or message the researchers.
At 24 weeks after the start of the study, 73% of 40 participants in the self-management group had reached the urate target of 0.30 mmol/L or below, compared with 15% of the 20 participants in the usual-care group (P < .0001).
The difference between the two groups was sustained even 1 year after starting the intervention, when 80% of those in the self-management group had reached that target, compared with 45% of those in the usual-care group.
Patients in the intervention group also had fewer flares, experiencing a mean of 2.03 flares in the first 24 weeks, compared with a mean of 3 among the control group, although the study didn’t report any difference in the rates of tophaceous disease.
Those in the self-management group had fewer medical appointments, but were prescribed higher doses of allopurinol at the 24- and 52-week visits.
“Qualitative feedback suggests that the self-monitoring approach was accepted by most participants and was enthusiastically endorsed by many,” the authors wrote. “The approach empowers patients and provides feedback on the effect of medication.”
It will be important to determine if the success of this self-management intervention can be replicated in an even broader patient population, Lisa K. Stamp, MBChB, PhD, of University of Otago, Christchurch, New Zealand, and Angelo L. Gaffo, MD, of University of Alabama at Birmingham, noted in an accompanying editorial. They wrote it was encouraging that only 7% of the 92 people screened for the trial did not have a smartphone and that it the patient sample had a mean age of 53 years. However, the trial did not include people with chronic kidney disease who make up nearly a quarter of all people with gout.
“It remains unknown whether the characteristics of those who did not reach target urate are the same or different as those who did, and a head-to-head comparison of these interventions would be of interest,” Dr. Stamp and Dr. Gaffo wrote. “A key challenge in managing gout is to determine which treatment strategy will be best suited to an individual with gout and to identify those for whom more support might be required.”
This study was supported by the University of Edinburgh and funded by NHS Lothian Health Foundation. No conflicts of interest were declared.
Self-management of gout using a smartphone app to record self-test urate levels and flares, and communicate those results to clinicians, could see more patients reaching target urate levels and even reducing flare frequency, a study has found.
Writing in The Lancet Rheumatology, Philip Riches, PhD, of the rheumatic disease unit at Western General Hospital in Edinburgh, and coauthors presented the findings of their randomized, controlled feasibility study of a new gout self-management approach aimed at helping patients treat to target.
While current rheumatology guidelines stress the importance of keeping urate below target levels to reduce flares and improve clinical outcomes, this isn’t always achieved in clinical practice. A previous trial of a nurse-led treat-to-target intervention did show a reduced incidence of flares and tophaceous disease, but the authors said, despite its cost-effectiveness, this approach has yet to be implemented in the United Kingdom.
Dr. Riches and colleagues developed a self-management strategy in which all 60 patients in the study self-tested their urate levels and were prompted to enter that data into the GoutSMART smartphone app once a month or opportunistically, along with information on disease severity and quality of life. All patients had been recommended for initiation or escalation of urate-lowering therapy, and had a serum urate of 0.36 mmol/L (6 mg/dL) or higher at baseline, and all received a gout management plan at the start of the study.
Patients in the intervention group who recorded a urate level above 0.30 mmol/L (5 mg/dL) via the app during the study were prompted to do a self-test every 2 weeks and given daily reminders in the app. Their urate levels were transmitted securely to the study team who then advised on dose escalation or treatment change. Those in the usual-care group also used the app but it only prompted them to record gout flares, keep quality of life diaries, or message the researchers.
At 24 weeks after the start of the study, 73% of 40 participants in the self-management group had reached the urate target of 0.30 mmol/L or below, compared with 15% of the 20 participants in the usual-care group (P < .0001).
The difference between the two groups was sustained even 1 year after starting the intervention, when 80% of those in the self-management group had reached that target, compared with 45% of those in the usual-care group.
Patients in the intervention group also had fewer flares, experiencing a mean of 2.03 flares in the first 24 weeks, compared with a mean of 3 among the control group, although the study didn’t report any difference in the rates of tophaceous disease.
Those in the self-management group had fewer medical appointments, but were prescribed higher doses of allopurinol at the 24- and 52-week visits.
“Qualitative feedback suggests that the self-monitoring approach was accepted by most participants and was enthusiastically endorsed by many,” the authors wrote. “The approach empowers patients and provides feedback on the effect of medication.”
It will be important to determine if the success of this self-management intervention can be replicated in an even broader patient population, Lisa K. Stamp, MBChB, PhD, of University of Otago, Christchurch, New Zealand, and Angelo L. Gaffo, MD, of University of Alabama at Birmingham, noted in an accompanying editorial. They wrote it was encouraging that only 7% of the 92 people screened for the trial did not have a smartphone and that it the patient sample had a mean age of 53 years. However, the trial did not include people with chronic kidney disease who make up nearly a quarter of all people with gout.
“It remains unknown whether the characteristics of those who did not reach target urate are the same or different as those who did, and a head-to-head comparison of these interventions would be of interest,” Dr. Stamp and Dr. Gaffo wrote. “A key challenge in managing gout is to determine which treatment strategy will be best suited to an individual with gout and to identify those for whom more support might be required.”
This study was supported by the University of Edinburgh and funded by NHS Lothian Health Foundation. No conflicts of interest were declared.
Self-management of gout using a smartphone app to record self-test urate levels and flares, and communicate those results to clinicians, could see more patients reaching target urate levels and even reducing flare frequency, a study has found.
Writing in The Lancet Rheumatology, Philip Riches, PhD, of the rheumatic disease unit at Western General Hospital in Edinburgh, and coauthors presented the findings of their randomized, controlled feasibility study of a new gout self-management approach aimed at helping patients treat to target.
While current rheumatology guidelines stress the importance of keeping urate below target levels to reduce flares and improve clinical outcomes, this isn’t always achieved in clinical practice. A previous trial of a nurse-led treat-to-target intervention did show a reduced incidence of flares and tophaceous disease, but the authors said, despite its cost-effectiveness, this approach has yet to be implemented in the United Kingdom.
Dr. Riches and colleagues developed a self-management strategy in which all 60 patients in the study self-tested their urate levels and were prompted to enter that data into the GoutSMART smartphone app once a month or opportunistically, along with information on disease severity and quality of life. All patients had been recommended for initiation or escalation of urate-lowering therapy, and had a serum urate of 0.36 mmol/L (6 mg/dL) or higher at baseline, and all received a gout management plan at the start of the study.
Patients in the intervention group who recorded a urate level above 0.30 mmol/L (5 mg/dL) via the app during the study were prompted to do a self-test every 2 weeks and given daily reminders in the app. Their urate levels were transmitted securely to the study team who then advised on dose escalation or treatment change. Those in the usual-care group also used the app but it only prompted them to record gout flares, keep quality of life diaries, or message the researchers.
At 24 weeks after the start of the study, 73% of 40 participants in the self-management group had reached the urate target of 0.30 mmol/L or below, compared with 15% of the 20 participants in the usual-care group (P < .0001).
The difference between the two groups was sustained even 1 year after starting the intervention, when 80% of those in the self-management group had reached that target, compared with 45% of those in the usual-care group.
Patients in the intervention group also had fewer flares, experiencing a mean of 2.03 flares in the first 24 weeks, compared with a mean of 3 among the control group, although the study didn’t report any difference in the rates of tophaceous disease.
Those in the self-management group had fewer medical appointments, but were prescribed higher doses of allopurinol at the 24- and 52-week visits.
“Qualitative feedback suggests that the self-monitoring approach was accepted by most participants and was enthusiastically endorsed by many,” the authors wrote. “The approach empowers patients and provides feedback on the effect of medication.”
It will be important to determine if the success of this self-management intervention can be replicated in an even broader patient population, Lisa K. Stamp, MBChB, PhD, of University of Otago, Christchurch, New Zealand, and Angelo L. Gaffo, MD, of University of Alabama at Birmingham, noted in an accompanying editorial. They wrote it was encouraging that only 7% of the 92 people screened for the trial did not have a smartphone and that it the patient sample had a mean age of 53 years. However, the trial did not include people with chronic kidney disease who make up nearly a quarter of all people with gout.
“It remains unknown whether the characteristics of those who did not reach target urate are the same or different as those who did, and a head-to-head comparison of these interventions would be of interest,” Dr. Stamp and Dr. Gaffo wrote. “A key challenge in managing gout is to determine which treatment strategy will be best suited to an individual with gout and to identify those for whom more support might be required.”
This study was supported by the University of Edinburgh and funded by NHS Lothian Health Foundation. No conflicts of interest were declared.
FROM THE LANCET RHEUMATOLOGY
EULAR CVD management guidance focuses on gout, lupus, vasculitis
New recommendations from the European Alliance of Associations for Rheumatology provide both broad and detailed advice for cardiovascular risk management in various rheumatic and musculoskeletal diseases (RMDs), many of which can lead to an increased possibility of cardiovascular disease (CVD).
“The panel believes that these recommendations will enable health care providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving cardiovascular health in RMDs,” write George C. Drosos, National and Kapodistrian University of Athens, and colleagues. The recommendations were published in February in Annals of the Rheumatic Diseases).
EULAR assembled a task force to generate best practices for preventing CVD in patients with gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS).
The cardiovascular risk management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis was covered in prior EULAR recommendations.
The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 EMEUNET (Emerging EULAR Network) members. One group of task force members conducted a systematic literature review of 105 articles about gout, vasculitis, SSc, myositis, MCTD, and SS, and another group evaluated 75 articles about SLE and APS. Together, they decided on four overarching principles:
Clinicians need to be aware of increased cardiovascular risk in patients with RMDs, with disease reduction likely decreasing risk.
Rheumatologists – in tandem with other health care providers – are responsible for their patients’ cardiovascular risk assessment and management.
Screening for cardiovascular risk should be performed regularly in all patients with RMDs, with an emphasis on factors like smoking and blood pressure management.
Patient education and counseling on cardiovascular risk, including important lifestyle modifications, is key for RMD patients.
Specific recommendations from the gout, vasculitis, SSc, myositis, MCTD, and SS group include deploying existing cardiovascular prediction tools as they are used in the general population, with the European Vasculitis Society model suggesting to supplement the Framingham Risk Score for patients with antineutrophil cytoplasmic antibody–associated vasculitis. They also recommended avoiding diuretics in patients with gout and beta-blockers in patients with SSc, as well as following the same blood pressure and lipid management strategies that are used among the general population.
Recommendations from the SLE and APS group include thoroughly assessing traditional cardiovascular risk factors in all patients, following typical blood pressure management strategies in patients with APS, and setting a blood pressure target of less than 130/80 mm Hg in patients with SLE. They also recommended administering the lowest possible glucocorticoid dose in patients with SLE, along with treatment with hydroxychloroquine – unless contraindicated – and even common preventive strategies like low-dose aspirin if it suits their cardiovascular risk profile.
As for next steps, the task force noted several areas where additional focus is needed, such as identifying patient subgroups with increased cardiovascular risk. This could include patients with a longer disease duration or more flare-ups, older patients, and those with certain disease characteristics like antiphospholipid positivity in SLE.
Can EULAR’s recommendations be implemented in U.S. rheumatology practices?
“We have been hearing for years that patients with rheumatic diseases have an increased risk of cardiovascular disease,” Ali A. Duarte Garcia, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told this news organization. “That has been consistently published for more than a decade now. But any further guidance about it has not been issued. I think there was a void there.”
“Certainly, cardiovascular disease risk in rheumatoid and psoriatic arthritis has been front of mind for the last decade or so,” Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, said when asked to comment on the recommendations. “But in some of these other conditions, it hasn’t been.”
When asked if rheumatologists would be ready and willing to implement these recommendations, Dr. Duarte Garcia acknowledged that it could be challenging for some.
“It’s a different workflow,” he said. “You’ve been trained traditionally to assess inflammation, to keep the disease under control, which is something they recommend, by the way. If you control the disease, patients do better. But I think lipid screening, for example, and testing for cholesterol, smoking cessation, those well-established programs are harder to bring to a rheumatology clinic. It’s doable, but it’s something that needs to be implemented within the current workflows and could take a few years to take hold.”
Dr. Bartels, however, noted that her group has done extensive work over the last 5 years incorporating certain interventions into practice, including sending patients with high blood pressure back to primary care.
“It’s a sustainable intervention in our clinic that basically our medical assistants and nurses do as a routine operation,” she said. “Our primary care providers are grateful to get these patients back. Our patients are grateful because otherwise when they come to the rheumatologist, get their blood pressure measured, and don’t get feedback, they assume they’re OK. So, we’re giving them a false signal.
“We have a similar intervention with smoking,” she added. “Often our patients aren’t even aware that they’re at increased risk of cardiovascular disease or that smoking might make their rheumatic disease and their cardiovascular outcomes worse. No one has had that conversation with them. They really welcome engaging in those discussions.
“Our tobacco intervention takes 90 seconds at point of care. Our blood pressure intervention at point of care, we’ve timed it, takes 3 minutes. There are ways that we can hardwire this into care.”
Along those lines, Dr. Duarte Garcia stated that the recommendations – although released by EULAR – are largely intuitive and should be very adaptable to an American health care context. He also recognized this moment as an opportunity for rheumatologists to consider patient outcomes beyond what they usually encounter firsthand.
“I don’t think we have many rheumatologists with patients who get a stroke or heart attack because if that happens, it’s in a hospital context or they go see a cardiologist,” he said. “You may see it once it happens if they survive and come and see you – or perhaps if you’re in a more integrated practice – but I don’t think it’s as apparent in our clinics because it is a predominantly outpatient practice and many times those are emergencies or inpatient complications.
“The bottom line,” he added, “is these are practical guidelines. It’s a push in the right direction, but there is still work to be done. And hopefully some of the recommendations, like measuring high blood pressure and addressing it just as in the general population, are something we can start to implement.”
Dr. Duarte Garcia reported receiving grant funding from the Rheumatology Research Foundation and the Centers for Disease Control and Prevention. Dr. Bartels reported that her group’s tobacco cessation work is funded by Pfizer’s Independent Grants for Learning and Change.
A version of this article first appeared on Medscape.com.
New recommendations from the European Alliance of Associations for Rheumatology provide both broad and detailed advice for cardiovascular risk management in various rheumatic and musculoskeletal diseases (RMDs), many of which can lead to an increased possibility of cardiovascular disease (CVD).
“The panel believes that these recommendations will enable health care providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving cardiovascular health in RMDs,” write George C. Drosos, National and Kapodistrian University of Athens, and colleagues. The recommendations were published in February in Annals of the Rheumatic Diseases).
EULAR assembled a task force to generate best practices for preventing CVD in patients with gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS).
The cardiovascular risk management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis was covered in prior EULAR recommendations.
The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 EMEUNET (Emerging EULAR Network) members. One group of task force members conducted a systematic literature review of 105 articles about gout, vasculitis, SSc, myositis, MCTD, and SS, and another group evaluated 75 articles about SLE and APS. Together, they decided on four overarching principles:
Clinicians need to be aware of increased cardiovascular risk in patients with RMDs, with disease reduction likely decreasing risk.
Rheumatologists – in tandem with other health care providers – are responsible for their patients’ cardiovascular risk assessment and management.
Screening for cardiovascular risk should be performed regularly in all patients with RMDs, with an emphasis on factors like smoking and blood pressure management.
Patient education and counseling on cardiovascular risk, including important lifestyle modifications, is key for RMD patients.
Specific recommendations from the gout, vasculitis, SSc, myositis, MCTD, and SS group include deploying existing cardiovascular prediction tools as they are used in the general population, with the European Vasculitis Society model suggesting to supplement the Framingham Risk Score for patients with antineutrophil cytoplasmic antibody–associated vasculitis. They also recommended avoiding diuretics in patients with gout and beta-blockers in patients with SSc, as well as following the same blood pressure and lipid management strategies that are used among the general population.
Recommendations from the SLE and APS group include thoroughly assessing traditional cardiovascular risk factors in all patients, following typical blood pressure management strategies in patients with APS, and setting a blood pressure target of less than 130/80 mm Hg in patients with SLE. They also recommended administering the lowest possible glucocorticoid dose in patients with SLE, along with treatment with hydroxychloroquine – unless contraindicated – and even common preventive strategies like low-dose aspirin if it suits their cardiovascular risk profile.
As for next steps, the task force noted several areas where additional focus is needed, such as identifying patient subgroups with increased cardiovascular risk. This could include patients with a longer disease duration or more flare-ups, older patients, and those with certain disease characteristics like antiphospholipid positivity in SLE.
Can EULAR’s recommendations be implemented in U.S. rheumatology practices?
“We have been hearing for years that patients with rheumatic diseases have an increased risk of cardiovascular disease,” Ali A. Duarte Garcia, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told this news organization. “That has been consistently published for more than a decade now. But any further guidance about it has not been issued. I think there was a void there.”
“Certainly, cardiovascular disease risk in rheumatoid and psoriatic arthritis has been front of mind for the last decade or so,” Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, said when asked to comment on the recommendations. “But in some of these other conditions, it hasn’t been.”
When asked if rheumatologists would be ready and willing to implement these recommendations, Dr. Duarte Garcia acknowledged that it could be challenging for some.
“It’s a different workflow,” he said. “You’ve been trained traditionally to assess inflammation, to keep the disease under control, which is something they recommend, by the way. If you control the disease, patients do better. But I think lipid screening, for example, and testing for cholesterol, smoking cessation, those well-established programs are harder to bring to a rheumatology clinic. It’s doable, but it’s something that needs to be implemented within the current workflows and could take a few years to take hold.”
Dr. Bartels, however, noted that her group has done extensive work over the last 5 years incorporating certain interventions into practice, including sending patients with high blood pressure back to primary care.
“It’s a sustainable intervention in our clinic that basically our medical assistants and nurses do as a routine operation,” she said. “Our primary care providers are grateful to get these patients back. Our patients are grateful because otherwise when they come to the rheumatologist, get their blood pressure measured, and don’t get feedback, they assume they’re OK. So, we’re giving them a false signal.
“We have a similar intervention with smoking,” she added. “Often our patients aren’t even aware that they’re at increased risk of cardiovascular disease or that smoking might make their rheumatic disease and their cardiovascular outcomes worse. No one has had that conversation with them. They really welcome engaging in those discussions.
“Our tobacco intervention takes 90 seconds at point of care. Our blood pressure intervention at point of care, we’ve timed it, takes 3 minutes. There are ways that we can hardwire this into care.”
Along those lines, Dr. Duarte Garcia stated that the recommendations – although released by EULAR – are largely intuitive and should be very adaptable to an American health care context. He also recognized this moment as an opportunity for rheumatologists to consider patient outcomes beyond what they usually encounter firsthand.
“I don’t think we have many rheumatologists with patients who get a stroke or heart attack because if that happens, it’s in a hospital context or they go see a cardiologist,” he said. “You may see it once it happens if they survive and come and see you – or perhaps if you’re in a more integrated practice – but I don’t think it’s as apparent in our clinics because it is a predominantly outpatient practice and many times those are emergencies or inpatient complications.
“The bottom line,” he added, “is these are practical guidelines. It’s a push in the right direction, but there is still work to be done. And hopefully some of the recommendations, like measuring high blood pressure and addressing it just as in the general population, are something we can start to implement.”
Dr. Duarte Garcia reported receiving grant funding from the Rheumatology Research Foundation and the Centers for Disease Control and Prevention. Dr. Bartels reported that her group’s tobacco cessation work is funded by Pfizer’s Independent Grants for Learning and Change.
A version of this article first appeared on Medscape.com.
New recommendations from the European Alliance of Associations for Rheumatology provide both broad and detailed advice for cardiovascular risk management in various rheumatic and musculoskeletal diseases (RMDs), many of which can lead to an increased possibility of cardiovascular disease (CVD).
“The panel believes that these recommendations will enable health care providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving cardiovascular health in RMDs,” write George C. Drosos, National and Kapodistrian University of Athens, and colleagues. The recommendations were published in February in Annals of the Rheumatic Diseases).
EULAR assembled a task force to generate best practices for preventing CVD in patients with gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS).
The cardiovascular risk management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis was covered in prior EULAR recommendations.
The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 EMEUNET (Emerging EULAR Network) members. One group of task force members conducted a systematic literature review of 105 articles about gout, vasculitis, SSc, myositis, MCTD, and SS, and another group evaluated 75 articles about SLE and APS. Together, they decided on four overarching principles:
Clinicians need to be aware of increased cardiovascular risk in patients with RMDs, with disease reduction likely decreasing risk.
Rheumatologists – in tandem with other health care providers – are responsible for their patients’ cardiovascular risk assessment and management.
Screening for cardiovascular risk should be performed regularly in all patients with RMDs, with an emphasis on factors like smoking and blood pressure management.
Patient education and counseling on cardiovascular risk, including important lifestyle modifications, is key for RMD patients.
Specific recommendations from the gout, vasculitis, SSc, myositis, MCTD, and SS group include deploying existing cardiovascular prediction tools as they are used in the general population, with the European Vasculitis Society model suggesting to supplement the Framingham Risk Score for patients with antineutrophil cytoplasmic antibody–associated vasculitis. They also recommended avoiding diuretics in patients with gout and beta-blockers in patients with SSc, as well as following the same blood pressure and lipid management strategies that are used among the general population.
Recommendations from the SLE and APS group include thoroughly assessing traditional cardiovascular risk factors in all patients, following typical blood pressure management strategies in patients with APS, and setting a blood pressure target of less than 130/80 mm Hg in patients with SLE. They also recommended administering the lowest possible glucocorticoid dose in patients with SLE, along with treatment with hydroxychloroquine – unless contraindicated – and even common preventive strategies like low-dose aspirin if it suits their cardiovascular risk profile.
As for next steps, the task force noted several areas where additional focus is needed, such as identifying patient subgroups with increased cardiovascular risk. This could include patients with a longer disease duration or more flare-ups, older patients, and those with certain disease characteristics like antiphospholipid positivity in SLE.
Can EULAR’s recommendations be implemented in U.S. rheumatology practices?
“We have been hearing for years that patients with rheumatic diseases have an increased risk of cardiovascular disease,” Ali A. Duarte Garcia, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told this news organization. “That has been consistently published for more than a decade now. But any further guidance about it has not been issued. I think there was a void there.”
“Certainly, cardiovascular disease risk in rheumatoid and psoriatic arthritis has been front of mind for the last decade or so,” Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, said when asked to comment on the recommendations. “But in some of these other conditions, it hasn’t been.”
When asked if rheumatologists would be ready and willing to implement these recommendations, Dr. Duarte Garcia acknowledged that it could be challenging for some.
“It’s a different workflow,” he said. “You’ve been trained traditionally to assess inflammation, to keep the disease under control, which is something they recommend, by the way. If you control the disease, patients do better. But I think lipid screening, for example, and testing for cholesterol, smoking cessation, those well-established programs are harder to bring to a rheumatology clinic. It’s doable, but it’s something that needs to be implemented within the current workflows and could take a few years to take hold.”
Dr. Bartels, however, noted that her group has done extensive work over the last 5 years incorporating certain interventions into practice, including sending patients with high blood pressure back to primary care.
“It’s a sustainable intervention in our clinic that basically our medical assistants and nurses do as a routine operation,” she said. “Our primary care providers are grateful to get these patients back. Our patients are grateful because otherwise when they come to the rheumatologist, get their blood pressure measured, and don’t get feedback, they assume they’re OK. So, we’re giving them a false signal.
“We have a similar intervention with smoking,” she added. “Often our patients aren’t even aware that they’re at increased risk of cardiovascular disease or that smoking might make their rheumatic disease and their cardiovascular outcomes worse. No one has had that conversation with them. They really welcome engaging in those discussions.
“Our tobacco intervention takes 90 seconds at point of care. Our blood pressure intervention at point of care, we’ve timed it, takes 3 minutes. There are ways that we can hardwire this into care.”
Along those lines, Dr. Duarte Garcia stated that the recommendations – although released by EULAR – are largely intuitive and should be very adaptable to an American health care context. He also recognized this moment as an opportunity for rheumatologists to consider patient outcomes beyond what they usually encounter firsthand.
“I don’t think we have many rheumatologists with patients who get a stroke or heart attack because if that happens, it’s in a hospital context or they go see a cardiologist,” he said. “You may see it once it happens if they survive and come and see you – or perhaps if you’re in a more integrated practice – but I don’t think it’s as apparent in our clinics because it is a predominantly outpatient practice and many times those are emergencies or inpatient complications.
“The bottom line,” he added, “is these are practical guidelines. It’s a push in the right direction, but there is still work to be done. And hopefully some of the recommendations, like measuring high blood pressure and addressing it just as in the general population, are something we can start to implement.”
Dr. Duarte Garcia reported receiving grant funding from the Rheumatology Research Foundation and the Centers for Disease Control and Prevention. Dr. Bartels reported that her group’s tobacco cessation work is funded by Pfizer’s Independent Grants for Learning and Change.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF THE RHEUMATIC DISEASES
A range of healthy dietary patterns can reduce risk of gout in women
A new study of thousands of women has found that sticking to recommended healthy dietary patterns can lessen the risk of new-onset gout.
“The identification of multiple patterns of eating that can similarly reduce a woman’s risk of incident gout in our study allows more choice for potential personalization of dietary recommendations according to culinary traditions and personal preferences to enhance adherence,” Chio Yokose, MD, of Harvard Medical School, Boston, and coauthors wrote. The study was published Jan. 31, 2022, in JAMA Internal Medicine.
To determine whether consistent healthy eating plays a role in preventing gout in women, the authors launched a prospective cohort study tied to the Nurses’ Health Study, an ongoing endeavor that has been questioning its participants’ food and beverage intake since 1984. Based on the 2020 to 2025 Dietary Guidelines for Americans, four healthy eating patterns were identified for assessment: the Dietary Approaches to Stop Hypertension (DASH), the Mediterranean diet, the Alternative Healthy Eating Index, and the Prudent diet, as well as the unhealthy Western dietary pattern for comparison.
Over 34 years of follow-up, the researchers identified 3,890 cases of gout among 80,039 women with an average age of 50.5 and an average body mass index (BMI) of 25.0 kg/m2. Women who strongly adhered to either of the four healthy dietary patterns had a significantly lower risk of gout, especially those who stuck to DASH (multivariable hazard ratio, 0.68; 95% confidence interval, 0.61-0.76) and Prudent (HR, 0.75; 95% CI, 0.73-0.90). In contrast, women with high Western diet scores had a 49% increased risk of gout (HR, 1.49; 95% CI, 1.33-1.68), compared with those who had low scores.
After additional analysis that factored in variables like diuretic use, alcohol use, and obesity, the associations between each diet and their risk of gout persisted in almost every instance. In particular, the most DASH-adherent women with normal BMI had a 68% lower risk of gout (HR, 0.32; 95% CI, 0.26-0.38), compared with the least-adherent women who were overweight or obese. Strong DASH adherence and no diuretic use also led to a 65% gout risk reduction (HR, 0.35; 95% CI, 0.30-0.41).
Healthy eating offers broad benefits for gout patients
“These results are consistent with a lot of the conversations we have on a day-to-day basis with patients,” Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha, said in an interview. “But I will say, I don’t get a lot of patients coming in saying: ‘Hey, what can I do to prevent gout?’ You’re usually seeing them after the fact.”
“These results shouldn’t be confused with that,” he said. “In other words, I wouldn’t want people interpreting this study to mean diet is always a satisfactory treatment for someone with established gout. The fact of the matter is, often it’s not. We need medication to effectively treat gout. I think this and other studies like it call for future research that can look at these dietary interventions as either standalone or probably adjuvant therapies in gout treatment.”
But, he added, that doesn’t mean conversations about diet aren’t of the utmost importance for gout patients.
“That shouldn’t stop clinicians from talking to patients about dietary changes that holistically are going to have positive benefits,” he said. “By the time you meet them, gout patients often already have other health conditions: high blood pressure, diabetes, obesity. The dietary changes that these authors studied are going to have a holistic benefit that goes well beyond gout risk, and that’s important. That’s a conversation that physicians and health care providers can and should be having right now with their patients.”
The authors acknowledged their study’s limitations, including the unmeasured or residual confounding that could come with any observational study as well as these rates of gout and these dietary patterns not necessarily being representative of a random sample of American women. “Future research could examine the population contributions of diets and other risk factors for incident female gout, as done in men.”
The study was funded by the National Institutes of Health. The authors reported several potential conflicts of interest, including receiving grants from the NIH and grants and personal fees from other organizations and pharmaceutical companies. Dr. Mikuls reported receiving past funding from Horizon Therapeutics and serving for them in a consulting capacity.
A new study of thousands of women has found that sticking to recommended healthy dietary patterns can lessen the risk of new-onset gout.
“The identification of multiple patterns of eating that can similarly reduce a woman’s risk of incident gout in our study allows more choice for potential personalization of dietary recommendations according to culinary traditions and personal preferences to enhance adherence,” Chio Yokose, MD, of Harvard Medical School, Boston, and coauthors wrote. The study was published Jan. 31, 2022, in JAMA Internal Medicine.
To determine whether consistent healthy eating plays a role in preventing gout in women, the authors launched a prospective cohort study tied to the Nurses’ Health Study, an ongoing endeavor that has been questioning its participants’ food and beverage intake since 1984. Based on the 2020 to 2025 Dietary Guidelines for Americans, four healthy eating patterns were identified for assessment: the Dietary Approaches to Stop Hypertension (DASH), the Mediterranean diet, the Alternative Healthy Eating Index, and the Prudent diet, as well as the unhealthy Western dietary pattern for comparison.
Over 34 years of follow-up, the researchers identified 3,890 cases of gout among 80,039 women with an average age of 50.5 and an average body mass index (BMI) of 25.0 kg/m2. Women who strongly adhered to either of the four healthy dietary patterns had a significantly lower risk of gout, especially those who stuck to DASH (multivariable hazard ratio, 0.68; 95% confidence interval, 0.61-0.76) and Prudent (HR, 0.75; 95% CI, 0.73-0.90). In contrast, women with high Western diet scores had a 49% increased risk of gout (HR, 1.49; 95% CI, 1.33-1.68), compared with those who had low scores.
After additional analysis that factored in variables like diuretic use, alcohol use, and obesity, the associations between each diet and their risk of gout persisted in almost every instance. In particular, the most DASH-adherent women with normal BMI had a 68% lower risk of gout (HR, 0.32; 95% CI, 0.26-0.38), compared with the least-adherent women who were overweight or obese. Strong DASH adherence and no diuretic use also led to a 65% gout risk reduction (HR, 0.35; 95% CI, 0.30-0.41).
Healthy eating offers broad benefits for gout patients
“These results are consistent with a lot of the conversations we have on a day-to-day basis with patients,” Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha, said in an interview. “But I will say, I don’t get a lot of patients coming in saying: ‘Hey, what can I do to prevent gout?’ You’re usually seeing them after the fact.”
“These results shouldn’t be confused with that,” he said. “In other words, I wouldn’t want people interpreting this study to mean diet is always a satisfactory treatment for someone with established gout. The fact of the matter is, often it’s not. We need medication to effectively treat gout. I think this and other studies like it call for future research that can look at these dietary interventions as either standalone or probably adjuvant therapies in gout treatment.”
But, he added, that doesn’t mean conversations about diet aren’t of the utmost importance for gout patients.
“That shouldn’t stop clinicians from talking to patients about dietary changes that holistically are going to have positive benefits,” he said. “By the time you meet them, gout patients often already have other health conditions: high blood pressure, diabetes, obesity. The dietary changes that these authors studied are going to have a holistic benefit that goes well beyond gout risk, and that’s important. That’s a conversation that physicians and health care providers can and should be having right now with their patients.”
The authors acknowledged their study’s limitations, including the unmeasured or residual confounding that could come with any observational study as well as these rates of gout and these dietary patterns not necessarily being representative of a random sample of American women. “Future research could examine the population contributions of diets and other risk factors for incident female gout, as done in men.”
The study was funded by the National Institutes of Health. The authors reported several potential conflicts of interest, including receiving grants from the NIH and grants and personal fees from other organizations and pharmaceutical companies. Dr. Mikuls reported receiving past funding from Horizon Therapeutics and serving for them in a consulting capacity.
A new study of thousands of women has found that sticking to recommended healthy dietary patterns can lessen the risk of new-onset gout.
“The identification of multiple patterns of eating that can similarly reduce a woman’s risk of incident gout in our study allows more choice for potential personalization of dietary recommendations according to culinary traditions and personal preferences to enhance adherence,” Chio Yokose, MD, of Harvard Medical School, Boston, and coauthors wrote. The study was published Jan. 31, 2022, in JAMA Internal Medicine.
To determine whether consistent healthy eating plays a role in preventing gout in women, the authors launched a prospective cohort study tied to the Nurses’ Health Study, an ongoing endeavor that has been questioning its participants’ food and beverage intake since 1984. Based on the 2020 to 2025 Dietary Guidelines for Americans, four healthy eating patterns were identified for assessment: the Dietary Approaches to Stop Hypertension (DASH), the Mediterranean diet, the Alternative Healthy Eating Index, and the Prudent diet, as well as the unhealthy Western dietary pattern for comparison.
Over 34 years of follow-up, the researchers identified 3,890 cases of gout among 80,039 women with an average age of 50.5 and an average body mass index (BMI) of 25.0 kg/m2. Women who strongly adhered to either of the four healthy dietary patterns had a significantly lower risk of gout, especially those who stuck to DASH (multivariable hazard ratio, 0.68; 95% confidence interval, 0.61-0.76) and Prudent (HR, 0.75; 95% CI, 0.73-0.90). In contrast, women with high Western diet scores had a 49% increased risk of gout (HR, 1.49; 95% CI, 1.33-1.68), compared with those who had low scores.
After additional analysis that factored in variables like diuretic use, alcohol use, and obesity, the associations between each diet and their risk of gout persisted in almost every instance. In particular, the most DASH-adherent women with normal BMI had a 68% lower risk of gout (HR, 0.32; 95% CI, 0.26-0.38), compared with the least-adherent women who were overweight or obese. Strong DASH adherence and no diuretic use also led to a 65% gout risk reduction (HR, 0.35; 95% CI, 0.30-0.41).
Healthy eating offers broad benefits for gout patients
“These results are consistent with a lot of the conversations we have on a day-to-day basis with patients,” Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha, said in an interview. “But I will say, I don’t get a lot of patients coming in saying: ‘Hey, what can I do to prevent gout?’ You’re usually seeing them after the fact.”
“These results shouldn’t be confused with that,” he said. “In other words, I wouldn’t want people interpreting this study to mean diet is always a satisfactory treatment for someone with established gout. The fact of the matter is, often it’s not. We need medication to effectively treat gout. I think this and other studies like it call for future research that can look at these dietary interventions as either standalone or probably adjuvant therapies in gout treatment.”
But, he added, that doesn’t mean conversations about diet aren’t of the utmost importance for gout patients.
“That shouldn’t stop clinicians from talking to patients about dietary changes that holistically are going to have positive benefits,” he said. “By the time you meet them, gout patients often already have other health conditions: high blood pressure, diabetes, obesity. The dietary changes that these authors studied are going to have a holistic benefit that goes well beyond gout risk, and that’s important. That’s a conversation that physicians and health care providers can and should be having right now with their patients.”
The authors acknowledged their study’s limitations, including the unmeasured or residual confounding that could come with any observational study as well as these rates of gout and these dietary patterns not necessarily being representative of a random sample of American women. “Future research could examine the population contributions of diets and other risk factors for incident female gout, as done in men.”
The study was funded by the National Institutes of Health. The authors reported several potential conflicts of interest, including receiving grants from the NIH and grants and personal fees from other organizations and pharmaceutical companies. Dr. Mikuls reported receiving past funding from Horizon Therapeutics and serving for them in a consulting capacity.
FROM JAMA INTERNAL MEDICINE
Allopurinol found safe in patients with concomitant gout, CKD
Allopurinol treatment is not associated with increased mortality in patients with gout and chronic kidney disease even at 5 years after starting treatment, a study has found.
Around one in five patients with gout also have chronic kidney disease, and previous research suggests that hyperuricemia is itself a contributor to renal disease, which is why there has been interest in the use of serum urate–lowering medication in patients with both conditions.
Since the publication of two earlier randomized controlled trials suggested a twofold increase in mortality among patients with renal disease who were treated with allopurinol in an attempt to slow progression, there has been wariness about the drug in patients with compromised renal function.
In a study published in Annals of Internal Medicine, Jie Wei, PhD, of Xiangya Hospital at Central South University in Changsha, China, and coauthors report the results of their retrospective, population-based study of 5,277 adults aged 40 and older with gout and moderate to severe chronic kidney disease who were initiated on allopurinol and 5,277 matched individuals not on allopurinol.
At 5 years after the patients started allopurinol, the study found that mortality was a statistically significant 15% lower (hazard ratio, 0.85; 95% confidence interval, 0.77-0.93) among those on allopurinol, compared with those not taking the drug. The rate was 4.9 deaths per 100 person-years among those on allopurinol, compared with 5.8 among those not taking it.
The researchers also created two simulated randomized clinical trials from the data for initiators of allopurinol, replicating each initiator twice. The first trial assigned patient replicates either to achieving a target serum urate level of less than 0.36 mmol/L within a year or not achieving it. The second assigned patient replicates to either an allopurinol dose-escalation group or no dose escalation.
For the target serum urate level study, 1,484 achieved the target, and this was associated with a 13% lower hazard ratio for mortality that just missed statistical significance (HR, 0.87; 95% confidence interval, 0.75-1.01).
In the dose-escalation study, there were 773 participants who increased their dose of allopurinol in the first year after initiation – from a median of 100 mg/day to a median final dose of 300 mg/day – and 2,923 who didn’t. Those who escalated their dose had a nonsignificant 12% lower risk of mortality (HR, 0.88; 95% CI, 0.73-1.07), compared with those who didn’t.
The authors suggest that this could be the result of confounding, as patients who achieved target serum urate levels may have been of better health generally than those who didn’t, which could also have contributed to lower mortality.
Coauthor of the study Yuqing Zhang, DSc, of Massachusetts General Hospital and Harvard Medical School, Boston, said there had previously been a theory that allopurinol could protect against progression of renal disease. However, the two randomized, controlled trials in patients with chronic kidney disease but not gout published in 2020 suggested that allopurinol was instead associated with a doubling of mortality in this group.
“This study really shows convincing evidence that among gout patients with renal disease, allopurinol does not increase mortality,” Dr. Zhang told this news organization. He suggested the reason that the earlier studies had found higher mortality among patients on allopurinol was because those patients did not have gout. Given that gout can increase mortality, treating it effectively with allopurinol may therefore reduce mortality even in patients with concurrent chronic kidney disease.
Commenting on the study, Angelo Gaffo, MD, from the Birmingham VA Medical Center and the division of rheumatology at the University of Alabama at Birmingham, said that, while there had been data suggesting increased mortality, the findings from this “very well-done” study were reassuring and even suggested a possible decrease in mortality associated with allopurinol.
“I wouldn’t scream it out loud because it needs confirmation, but it’s something also that we have a sense that could be true,” he said.
Dr. Gaffo noted that patients treated with allopurinol tended to be those with fewer comorbidities. “Patients who have a lot of comorbidities probably are less likely to have their dose of allopurinol started or increased because of some concerns that practitioners may have about putting them on another medicine or increasing the dose of that medicine,” he said.
He also stressed that the findings still need replication in other large database studies, given that a prospective, randomized clinical trial addressing such a question would be difficult to conduct.
The study was supported by the Project Program of National Clinical Research Center for Geriatric Disorders, the National Natural Science Foundation of China, and the U.S. National Institutes of Health. Two authors reported consulting fees from the pharmaceutical sector unrelated to the study. No other conflicts of interest were declared.
A version of this article first appeared on Medscape.com.
Allopurinol treatment is not associated with increased mortality in patients with gout and chronic kidney disease even at 5 years after starting treatment, a study has found.
Around one in five patients with gout also have chronic kidney disease, and previous research suggests that hyperuricemia is itself a contributor to renal disease, which is why there has been interest in the use of serum urate–lowering medication in patients with both conditions.
Since the publication of two earlier randomized controlled trials suggested a twofold increase in mortality among patients with renal disease who were treated with allopurinol in an attempt to slow progression, there has been wariness about the drug in patients with compromised renal function.
In a study published in Annals of Internal Medicine, Jie Wei, PhD, of Xiangya Hospital at Central South University in Changsha, China, and coauthors report the results of their retrospective, population-based study of 5,277 adults aged 40 and older with gout and moderate to severe chronic kidney disease who were initiated on allopurinol and 5,277 matched individuals not on allopurinol.
At 5 years after the patients started allopurinol, the study found that mortality was a statistically significant 15% lower (hazard ratio, 0.85; 95% confidence interval, 0.77-0.93) among those on allopurinol, compared with those not taking the drug. The rate was 4.9 deaths per 100 person-years among those on allopurinol, compared with 5.8 among those not taking it.
The researchers also created two simulated randomized clinical trials from the data for initiators of allopurinol, replicating each initiator twice. The first trial assigned patient replicates either to achieving a target serum urate level of less than 0.36 mmol/L within a year or not achieving it. The second assigned patient replicates to either an allopurinol dose-escalation group or no dose escalation.
For the target serum urate level study, 1,484 achieved the target, and this was associated with a 13% lower hazard ratio for mortality that just missed statistical significance (HR, 0.87; 95% confidence interval, 0.75-1.01).
In the dose-escalation study, there were 773 participants who increased their dose of allopurinol in the first year after initiation – from a median of 100 mg/day to a median final dose of 300 mg/day – and 2,923 who didn’t. Those who escalated their dose had a nonsignificant 12% lower risk of mortality (HR, 0.88; 95% CI, 0.73-1.07), compared with those who didn’t.
The authors suggest that this could be the result of confounding, as patients who achieved target serum urate levels may have been of better health generally than those who didn’t, which could also have contributed to lower mortality.
Coauthor of the study Yuqing Zhang, DSc, of Massachusetts General Hospital and Harvard Medical School, Boston, said there had previously been a theory that allopurinol could protect against progression of renal disease. However, the two randomized, controlled trials in patients with chronic kidney disease but not gout published in 2020 suggested that allopurinol was instead associated with a doubling of mortality in this group.
“This study really shows convincing evidence that among gout patients with renal disease, allopurinol does not increase mortality,” Dr. Zhang told this news organization. He suggested the reason that the earlier studies had found higher mortality among patients on allopurinol was because those patients did not have gout. Given that gout can increase mortality, treating it effectively with allopurinol may therefore reduce mortality even in patients with concurrent chronic kidney disease.
Commenting on the study, Angelo Gaffo, MD, from the Birmingham VA Medical Center and the division of rheumatology at the University of Alabama at Birmingham, said that, while there had been data suggesting increased mortality, the findings from this “very well-done” study were reassuring and even suggested a possible decrease in mortality associated with allopurinol.
“I wouldn’t scream it out loud because it needs confirmation, but it’s something also that we have a sense that could be true,” he said.
Dr. Gaffo noted that patients treated with allopurinol tended to be those with fewer comorbidities. “Patients who have a lot of comorbidities probably are less likely to have their dose of allopurinol started or increased because of some concerns that practitioners may have about putting them on another medicine or increasing the dose of that medicine,” he said.
He also stressed that the findings still need replication in other large database studies, given that a prospective, randomized clinical trial addressing such a question would be difficult to conduct.
The study was supported by the Project Program of National Clinical Research Center for Geriatric Disorders, the National Natural Science Foundation of China, and the U.S. National Institutes of Health. Two authors reported consulting fees from the pharmaceutical sector unrelated to the study. No other conflicts of interest were declared.
A version of this article first appeared on Medscape.com.
Allopurinol treatment is not associated with increased mortality in patients with gout and chronic kidney disease even at 5 years after starting treatment, a study has found.
Around one in five patients with gout also have chronic kidney disease, and previous research suggests that hyperuricemia is itself a contributor to renal disease, which is why there has been interest in the use of serum urate–lowering medication in patients with both conditions.
Since the publication of two earlier randomized controlled trials suggested a twofold increase in mortality among patients with renal disease who were treated with allopurinol in an attempt to slow progression, there has been wariness about the drug in patients with compromised renal function.
In a study published in Annals of Internal Medicine, Jie Wei, PhD, of Xiangya Hospital at Central South University in Changsha, China, and coauthors report the results of their retrospective, population-based study of 5,277 adults aged 40 and older with gout and moderate to severe chronic kidney disease who were initiated on allopurinol and 5,277 matched individuals not on allopurinol.
At 5 years after the patients started allopurinol, the study found that mortality was a statistically significant 15% lower (hazard ratio, 0.85; 95% confidence interval, 0.77-0.93) among those on allopurinol, compared with those not taking the drug. The rate was 4.9 deaths per 100 person-years among those on allopurinol, compared with 5.8 among those not taking it.
The researchers also created two simulated randomized clinical trials from the data for initiators of allopurinol, replicating each initiator twice. The first trial assigned patient replicates either to achieving a target serum urate level of less than 0.36 mmol/L within a year or not achieving it. The second assigned patient replicates to either an allopurinol dose-escalation group or no dose escalation.
For the target serum urate level study, 1,484 achieved the target, and this was associated with a 13% lower hazard ratio for mortality that just missed statistical significance (HR, 0.87; 95% confidence interval, 0.75-1.01).
In the dose-escalation study, there were 773 participants who increased their dose of allopurinol in the first year after initiation – from a median of 100 mg/day to a median final dose of 300 mg/day – and 2,923 who didn’t. Those who escalated their dose had a nonsignificant 12% lower risk of mortality (HR, 0.88; 95% CI, 0.73-1.07), compared with those who didn’t.
The authors suggest that this could be the result of confounding, as patients who achieved target serum urate levels may have been of better health generally than those who didn’t, which could also have contributed to lower mortality.
Coauthor of the study Yuqing Zhang, DSc, of Massachusetts General Hospital and Harvard Medical School, Boston, said there had previously been a theory that allopurinol could protect against progression of renal disease. However, the two randomized, controlled trials in patients with chronic kidney disease but not gout published in 2020 suggested that allopurinol was instead associated with a doubling of mortality in this group.
“This study really shows convincing evidence that among gout patients with renal disease, allopurinol does not increase mortality,” Dr. Zhang told this news organization. He suggested the reason that the earlier studies had found higher mortality among patients on allopurinol was because those patients did not have gout. Given that gout can increase mortality, treating it effectively with allopurinol may therefore reduce mortality even in patients with concurrent chronic kidney disease.
Commenting on the study, Angelo Gaffo, MD, from the Birmingham VA Medical Center and the division of rheumatology at the University of Alabama at Birmingham, said that, while there had been data suggesting increased mortality, the findings from this “very well-done” study were reassuring and even suggested a possible decrease in mortality associated with allopurinol.
“I wouldn’t scream it out loud because it needs confirmation, but it’s something also that we have a sense that could be true,” he said.
Dr. Gaffo noted that patients treated with allopurinol tended to be those with fewer comorbidities. “Patients who have a lot of comorbidities probably are less likely to have their dose of allopurinol started or increased because of some concerns that practitioners may have about putting them on another medicine or increasing the dose of that medicine,” he said.
He also stressed that the findings still need replication in other large database studies, given that a prospective, randomized clinical trial addressing such a question would be difficult to conduct.
The study was supported by the Project Program of National Clinical Research Center for Geriatric Disorders, the National Natural Science Foundation of China, and the U.S. National Institutes of Health. Two authors reported consulting fees from the pharmaceutical sector unrelated to the study. No other conflicts of interest were declared.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Super-low uric acid may not be best for erosive gout
Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.
Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.
Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.
The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.
Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.
“It is reassuring that the approach of treating to target is a good approach,” Dr. Gaffo said. “The very, very low targets were not better than the [standard target].”
The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.
Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.
Fewer in intensive group hit target
The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).
The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).
Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).
Rates of adverse and serious adverse events were similar between the groups.
The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.
“However, improved erosion scores were not observed in this study,” the authors noted.
The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.
They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.
Pegloticase not available outside United States
However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.
Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.
Managing gout is a long-term process
Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.
“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Dr. Baraf said.
He agreed with Dr. Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.
He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”
He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.
“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Dr. Baraf.
It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.
“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.
The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”
Dr. Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Dr. Gaffo reported no relevant financial relationships. Dr. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.
Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.
Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.
Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.
The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.
Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.
“It is reassuring that the approach of treating to target is a good approach,” Dr. Gaffo said. “The very, very low targets were not better than the [standard target].”
The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.
Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.
Fewer in intensive group hit target
The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).
The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).
Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).
Rates of adverse and serious adverse events were similar between the groups.
The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.
“However, improved erosion scores were not observed in this study,” the authors noted.
The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.
They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.
Pegloticase not available outside United States
However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.
Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.
Managing gout is a long-term process
Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.
“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Dr. Baraf said.
He agreed with Dr. Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.
He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”
He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.
“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Dr. Baraf.
It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.
“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.
The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”
Dr. Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Dr. Gaffo reported no relevant financial relationships. Dr. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.
Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.
Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.
Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.
The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.
Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.
“It is reassuring that the approach of treating to target is a good approach,” Dr. Gaffo said. “The very, very low targets were not better than the [standard target].”
The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.
Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.
Fewer in intensive group hit target
The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).
The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).
Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).
Rates of adverse and serious adverse events were similar between the groups.
The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.
“However, improved erosion scores were not observed in this study,” the authors noted.
The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.
They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.
Pegloticase not available outside United States
However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.
Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.
Managing gout is a long-term process
Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.
“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Dr. Baraf said.
He agreed with Dr. Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.
He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”
He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.
“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Dr. Baraf.
It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.
“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.
The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”
Dr. Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Dr. Gaffo reported no relevant financial relationships. Dr. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.
FROM ARTHRITIS & RHEUMATOLOGY
‘Misleading’ results in colchicine COVID-19 trials meta-analysis
A new meta-analysis appears to show that colchicine has no benefit as a treatment for COVID-19, but its inclusion of trials studying differing patient populations and testing different outcomes led to “misleading” results, says a researcher involved in one of the trials.
The meta-analysis, which includes data from the recent Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, was published Nov. 22 in RMD Open.
Kedar Gautambhai Mehta, MBBS, MD, of the GMERS Medical College Gotri in Vadodara, India, and colleagues included outcomes from six studies of 16,148 patients with COVID-19 who received colchicine or supportive care. They evaluated the efficacy outcomes of mortality, need for ventilation, intensive care unit admission, and length of stay in hospital, as well as safety outcomes of adverse events, serious adverse events, and diarrhea.
The studies in the meta-analysis included a randomized, controlled trial (RCT) of 105 patients hospitalized with COVID-19 in Greece, the international, open-label RECOVERY RCT of 11,340 patients hospitalized with COVID-19, an RCT of 72 hospitalized patients with moderate or severe COVID-19 in Brazil, an RCT of 100 patients hospitalized with COVID-19 in Iran, the international COLCORONA trial of 4,488 patients with COVID-19 who were treated with colchicine or placebo on an outpatient basis, and the randomized COLORIT trial of 43 patients hospitalized with COVID-19 in Russia.
Studies “asked very different questions” about colchicine
Commenting on the meta-analysis, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology with New York University, said the authors combined studies “that are not comparable and that asked very different questions.” Two of the studies in the meta-analysis are very large, and four are very small, which skews the results, he explained.
“The larger studies therefore drive the outcome, and while the small studies are potentially insight providing, the large studies are the only ones worth giving our attention to in the context of the meta-analysis,” he said. The two largest studies – RECOVERY and COLCORONA – taken together show no benefit for colchicine as a treatment, even though the former demonstrated no benefit and the latter did show a benefit, explained Dr. Pillinger, a co–principal investigator for the COLCORONA trial in the United States.
The studies were designed differently and should not have been included in the same analysis, Dr. Pillinger argued. In the case of COLCORONA, early treatment with colchicine was the intervention, whereas RECOVERY focused on hospitalized patients.
“In designing [COLCORONA], the author group (of whom I was a member) expressly rejected the idea that colchicine might be useful for the sicker hospitalized patients, based on the long experience with colchicine of some of us as rheumatologists,” Dr. Pillinger said.
“In short, COLCORONA proved a benefit of colchicine in outpatient COVID-19, and its authors presumed there would be no inpatient benefit; RECOVERY went ahead and proved a lack of inpatient benefit, at least when high-dose steroids were also given,” he said. “While there is no conflict between these results, the combination of the two studies in this meta-analysis suggests there might be no benefit for colchicine overall, which is misleading and can lead physicians to reject the potential of outpatient colchicine, even for future studies.”
Dr. Pillinger said he still believes colchicine has potential value as a COVID-19 treatment option for patients with mild disease, “especially for low–vaccine rate, resource-starved countries.
“It would be unfortunate if meta-analyses such as this one would put a stop to colchicine’s use, or at least its further investigation,” he said.
Study details
The authors of the study assessed heterogeneity of the trials’ data across the outcomes using an I2 test. They evaluated the quality of the evidence for the outcomes using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE).
The results of their meta-analysis showed that colchicine offered no significant improvement in mortality in six studies (risk difference, –0.0; 95% confidence interval, –0.01 to 0.01; I2 = 15%). It showed no benefit with respect to requiring ventilatory support in five studies of 15,519 patients (risk ratio, 0.67; 95% CI, 0.38-1.21; I2 = 47%); being admitted to the ICU in three studies with 220 patients (RR, 0.49; 95% CI, 0.19-1.25; I2 = 34%); and length of stay while in the hospital in four studies of 11,560 patients (mean difference, –1.17; 95% CI, –3.02 to 0.67; I2 = 77%).
There was no difference in serious adverse events in three studies with 4,665 patients (RD, –0.01; 95% CI, –0.02 to 0.00; I2 = 28%) for patients who received colchicine, compared with supportive care alone. Patients who received colchicine were more likely to have a higher rate of adverse events (RR, 1.58; 95% CI, 1.07-2.33; I2 = 81%) and to experience diarrhea (RR, 1.93; 95% CI, 1.62-2.29; I2 = 0%) than were patients who received supportive care alone. The researchers note that for most outcomes, the GRADE quality of evidence was moderate.
“Our findings on colchicine should be interpreted cautiously due to the inclusion of open-labeled, randomized clinical trials,” Dr. Mehta and colleagues write. “The analysis of efficacy and safety outcomes are based on a small number of RCTs in control interventions.”
The authors reported no relevant financial relationships. Dr. Pillinger is co–principal investigator of the U.S. component of the COLCORONA trial; he reported no other relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
A new meta-analysis appears to show that colchicine has no benefit as a treatment for COVID-19, but its inclusion of trials studying differing patient populations and testing different outcomes led to “misleading” results, says a researcher involved in one of the trials.
The meta-analysis, which includes data from the recent Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, was published Nov. 22 in RMD Open.
Kedar Gautambhai Mehta, MBBS, MD, of the GMERS Medical College Gotri in Vadodara, India, and colleagues included outcomes from six studies of 16,148 patients with COVID-19 who received colchicine or supportive care. They evaluated the efficacy outcomes of mortality, need for ventilation, intensive care unit admission, and length of stay in hospital, as well as safety outcomes of adverse events, serious adverse events, and diarrhea.
The studies in the meta-analysis included a randomized, controlled trial (RCT) of 105 patients hospitalized with COVID-19 in Greece, the international, open-label RECOVERY RCT of 11,340 patients hospitalized with COVID-19, an RCT of 72 hospitalized patients with moderate or severe COVID-19 in Brazil, an RCT of 100 patients hospitalized with COVID-19 in Iran, the international COLCORONA trial of 4,488 patients with COVID-19 who were treated with colchicine or placebo on an outpatient basis, and the randomized COLORIT trial of 43 patients hospitalized with COVID-19 in Russia.
Studies “asked very different questions” about colchicine
Commenting on the meta-analysis, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology with New York University, said the authors combined studies “that are not comparable and that asked very different questions.” Two of the studies in the meta-analysis are very large, and four are very small, which skews the results, he explained.
“The larger studies therefore drive the outcome, and while the small studies are potentially insight providing, the large studies are the only ones worth giving our attention to in the context of the meta-analysis,” he said. The two largest studies – RECOVERY and COLCORONA – taken together show no benefit for colchicine as a treatment, even though the former demonstrated no benefit and the latter did show a benefit, explained Dr. Pillinger, a co–principal investigator for the COLCORONA trial in the United States.
The studies were designed differently and should not have been included in the same analysis, Dr. Pillinger argued. In the case of COLCORONA, early treatment with colchicine was the intervention, whereas RECOVERY focused on hospitalized patients.
“In designing [COLCORONA], the author group (of whom I was a member) expressly rejected the idea that colchicine might be useful for the sicker hospitalized patients, based on the long experience with colchicine of some of us as rheumatologists,” Dr. Pillinger said.
“In short, COLCORONA proved a benefit of colchicine in outpatient COVID-19, and its authors presumed there would be no inpatient benefit; RECOVERY went ahead and proved a lack of inpatient benefit, at least when high-dose steroids were also given,” he said. “While there is no conflict between these results, the combination of the two studies in this meta-analysis suggests there might be no benefit for colchicine overall, which is misleading and can lead physicians to reject the potential of outpatient colchicine, even for future studies.”
Dr. Pillinger said he still believes colchicine has potential value as a COVID-19 treatment option for patients with mild disease, “especially for low–vaccine rate, resource-starved countries.
“It would be unfortunate if meta-analyses such as this one would put a stop to colchicine’s use, or at least its further investigation,” he said.
Study details
The authors of the study assessed heterogeneity of the trials’ data across the outcomes using an I2 test. They evaluated the quality of the evidence for the outcomes using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE).
The results of their meta-analysis showed that colchicine offered no significant improvement in mortality in six studies (risk difference, –0.0; 95% confidence interval, –0.01 to 0.01; I2 = 15%). It showed no benefit with respect to requiring ventilatory support in five studies of 15,519 patients (risk ratio, 0.67; 95% CI, 0.38-1.21; I2 = 47%); being admitted to the ICU in three studies with 220 patients (RR, 0.49; 95% CI, 0.19-1.25; I2 = 34%); and length of stay while in the hospital in four studies of 11,560 patients (mean difference, –1.17; 95% CI, –3.02 to 0.67; I2 = 77%).
There was no difference in serious adverse events in three studies with 4,665 patients (RD, –0.01; 95% CI, –0.02 to 0.00; I2 = 28%) for patients who received colchicine, compared with supportive care alone. Patients who received colchicine were more likely to have a higher rate of adverse events (RR, 1.58; 95% CI, 1.07-2.33; I2 = 81%) and to experience diarrhea (RR, 1.93; 95% CI, 1.62-2.29; I2 = 0%) than were patients who received supportive care alone. The researchers note that for most outcomes, the GRADE quality of evidence was moderate.
“Our findings on colchicine should be interpreted cautiously due to the inclusion of open-labeled, randomized clinical trials,” Dr. Mehta and colleagues write. “The analysis of efficacy and safety outcomes are based on a small number of RCTs in control interventions.”
The authors reported no relevant financial relationships. Dr. Pillinger is co–principal investigator of the U.S. component of the COLCORONA trial; he reported no other relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
A new meta-analysis appears to show that colchicine has no benefit as a treatment for COVID-19, but its inclusion of trials studying differing patient populations and testing different outcomes led to “misleading” results, says a researcher involved in one of the trials.
The meta-analysis, which includes data from the recent Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, was published Nov. 22 in RMD Open.
Kedar Gautambhai Mehta, MBBS, MD, of the GMERS Medical College Gotri in Vadodara, India, and colleagues included outcomes from six studies of 16,148 patients with COVID-19 who received colchicine or supportive care. They evaluated the efficacy outcomes of mortality, need for ventilation, intensive care unit admission, and length of stay in hospital, as well as safety outcomes of adverse events, serious adverse events, and diarrhea.
The studies in the meta-analysis included a randomized, controlled trial (RCT) of 105 patients hospitalized with COVID-19 in Greece, the international, open-label RECOVERY RCT of 11,340 patients hospitalized with COVID-19, an RCT of 72 hospitalized patients with moderate or severe COVID-19 in Brazil, an RCT of 100 patients hospitalized with COVID-19 in Iran, the international COLCORONA trial of 4,488 patients with COVID-19 who were treated with colchicine or placebo on an outpatient basis, and the randomized COLORIT trial of 43 patients hospitalized with COVID-19 in Russia.
Studies “asked very different questions” about colchicine
Commenting on the meta-analysis, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology with New York University, said the authors combined studies “that are not comparable and that asked very different questions.” Two of the studies in the meta-analysis are very large, and four are very small, which skews the results, he explained.
“The larger studies therefore drive the outcome, and while the small studies are potentially insight providing, the large studies are the only ones worth giving our attention to in the context of the meta-analysis,” he said. The two largest studies – RECOVERY and COLCORONA – taken together show no benefit for colchicine as a treatment, even though the former demonstrated no benefit and the latter did show a benefit, explained Dr. Pillinger, a co–principal investigator for the COLCORONA trial in the United States.
The studies were designed differently and should not have been included in the same analysis, Dr. Pillinger argued. In the case of COLCORONA, early treatment with colchicine was the intervention, whereas RECOVERY focused on hospitalized patients.
“In designing [COLCORONA], the author group (of whom I was a member) expressly rejected the idea that colchicine might be useful for the sicker hospitalized patients, based on the long experience with colchicine of some of us as rheumatologists,” Dr. Pillinger said.
“In short, COLCORONA proved a benefit of colchicine in outpatient COVID-19, and its authors presumed there would be no inpatient benefit; RECOVERY went ahead and proved a lack of inpatient benefit, at least when high-dose steroids were also given,” he said. “While there is no conflict between these results, the combination of the two studies in this meta-analysis suggests there might be no benefit for colchicine overall, which is misleading and can lead physicians to reject the potential of outpatient colchicine, even for future studies.”
Dr. Pillinger said he still believes colchicine has potential value as a COVID-19 treatment option for patients with mild disease, “especially for low–vaccine rate, resource-starved countries.
“It would be unfortunate if meta-analyses such as this one would put a stop to colchicine’s use, or at least its further investigation,” he said.
Study details
The authors of the study assessed heterogeneity of the trials’ data across the outcomes using an I2 test. They evaluated the quality of the evidence for the outcomes using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE).
The results of their meta-analysis showed that colchicine offered no significant improvement in mortality in six studies (risk difference, –0.0; 95% confidence interval, –0.01 to 0.01; I2 = 15%). It showed no benefit with respect to requiring ventilatory support in five studies of 15,519 patients (risk ratio, 0.67; 95% CI, 0.38-1.21; I2 = 47%); being admitted to the ICU in three studies with 220 patients (RR, 0.49; 95% CI, 0.19-1.25; I2 = 34%); and length of stay while in the hospital in four studies of 11,560 patients (mean difference, –1.17; 95% CI, –3.02 to 0.67; I2 = 77%).
There was no difference in serious adverse events in three studies with 4,665 patients (RD, –0.01; 95% CI, –0.02 to 0.00; I2 = 28%) for patients who received colchicine, compared with supportive care alone. Patients who received colchicine were more likely to have a higher rate of adverse events (RR, 1.58; 95% CI, 1.07-2.33; I2 = 81%) and to experience diarrhea (RR, 1.93; 95% CI, 1.62-2.29; I2 = 0%) than were patients who received supportive care alone. The researchers note that for most outcomes, the GRADE quality of evidence was moderate.
“Our findings on colchicine should be interpreted cautiously due to the inclusion of open-labeled, randomized clinical trials,” Dr. Mehta and colleagues write. “The analysis of efficacy and safety outcomes are based on a small number of RCTs in control interventions.”
The authors reported no relevant financial relationships. Dr. Pillinger is co–principal investigator of the U.S. component of the COLCORONA trial; he reported no other relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Allopurinol proves noninferior to febuxostat for gout relief
Allopurinol may finally start to get the respect that many rheumatologists feel it deserves as a first-line urate-lowering treatment for gout, following results of a randomized trial showing that it was noninferior to febuxostat both in the overall trial population and in patients with stage 3 chronic kidney disease (CKD).
In the multicenter, randomized, double-blinded comparison trial that used a treat-to-target strategy, allopurinol met the primary outcome of noninferiority to febuxostat for preventing gout flare during the observation phase of therapy, reported James O’Dell, MD, chief of the division of rheumatology and vice chair for education in the department of internal medicine at the University of Nebraska Medical Center in Omaha.
“Both agents were well tolerated, with or without CKD. Most importantly, both agents were highly effective when used in a treat-to-target protocol in getting patients to target urate levels,” he said in an oral abstract presentation during the American College of Rheumatology (ACR) 2021 Annual Meeting, which was held online.
And although febuxostat contains a boxed warning about the risks of cardiovascular adverse events with its use, there were no signals for increased cardiovascular toxicity with febuxostat compared with allopurinol, the investigators found.
The trial is the first to compare allopurinol, a decades-old drug, with febuxostat, approved in 2009, in a treat-to-target approach, Dr. O’Dell said.
American College of Physicians’ guideline ‘antiquated’
The results of the study “will hopefully teach doctors how to treat gout better by encouraging them to use higher doses of gout medications safely than they’re actually using at this time,” said Donald Thomas Jr., MD, in private practice in Greenbelt, Md., and associate professor of medicine at the Uniformed Services University of the Health Sciences in Bethesda, Md.
Dr. Thomas, who moderated a media briefing where Dr. O’Dell discussed the results of the trial, said that he had recently read the 2017 gout guideline by the American College of Physicians (ACP), which he called “antiquated.”
The ACP recommends the use of corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or low-dose colchicine to treat patients with acute gout. The ACP also recommends “against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.”
The guideline recommends that clinicians discuss potential benefits, risks, costs, and personal preferences before starting patients on urate-lowering therapy in patients with recurrent gout attacks.
The 2017 guidelines also state, however, that “[e]vidence was insufficient to conclude whether the benefits of escalating urate-lowering therapy to reach a serum urate target (‘treat to target’) outweigh the harms associated with repeated monitoring and medication escalation.”
“I’ve been a proud member of the American College of Physicians for years, I’m a master of the ACP, and they do a lot of great things, but this is one case where their insistence that they’re not going to have a guideline that isn’t completely based in evidence from studies is getting in the way of common sense,” Dr. O’Dell said.
“Their contention is that what matters to a gout patient is a gout flare, and how do we know that gout flares are less if you treat to target or not – and that’s a fair question,” he continued, “except for the fact that in uric acid metabolism we know physiologically that there’s a magic number and that’s 6.8 mg/dL, and anything above that, every day uric acid is above 6.8, you are literally putting crystal out into all places in your body.”
In contrast, the ACR’s 2020 guideline for the management of gout strongly recommends starting urate-lowering therapy for all patients with tophaceous gout, radiographic damage because of gout, or frequent gout flares. It also advises using allopurinol as the preferred first-line urate-lowering therapy, including for those with stage 3 or greater CKD, and using a low starting dose of allopurinol of 100 mg/day or less (lower in CKD) or febuxostat at 40 mg/day or less. It endorses a treat-to-target management strategy that aims for serum urate < 6 mg/dL with dose titration of urate-lowering agents guided by serial serum urate measurements.
Dr. Thomas and Dr. O’Dell expressed hope that the results of this clinical trial will put the issue to rest, and that the ACP will update its guideline accordingly.
VA-sponsored trial
The study was conducted at 19 Veterans Affairs medical centers and two non-VA sites. The trial was divided into dose-titration, maintenance, and observation phases, each lasting 24 weeks.
A total of 950 participants with gout and a serum urate concentration 6.8 mg/dL or greater were randomly assigned on a 1:1 basis to receive allopurinol 100-800 mg or febuxostat 40 mg to 80/120 mg daily. In 2019, the Food and Drug Administration requested that the maximum titrated dose of febuxostat in the trial be capped at 80 mg daily. All patients stopped prophylaxis with NSAIDs, colchicine, or prednisone before the observation phase.
Patients with persistent hyperuricemia despite treatment with allopurinol were eligible, and these patients were started in the titration phase at their current dose.
The mean patient age was 62.9 years in the allopurinol arm and 61.3 years in the febuxostat arm. Men comprised 98% of patients in each study arm.
The racial/ethnic distribution of patients was similar between the groups. In all, 38.7% of patients assigned to allopurinol and 36% assigned to febuxostat had CKD stages 1-3. (Patients with stage 4 or 5 CKD were excluded from the study.)
A gout flare occurred if a participants reported three or more symptoms of tender, warm, swollen joints, or gout flare, or if the participant reported use of medication for gout flare in the observation phase during weeks 49-72.
As noted before, the trial met its primary endpoint, with 36.5% of patients on allopurinol reporting gout flare in the observation phase, compared with 43.5% on febuxostat (P for noninferiority < .001).
Among patients with CKD stage 3, the respective percentages of patients reporting at least one gout flare in the observation phase were 31.9% and 45.3% (P for noninferiority < .001).
Approximately 80% of patients in each arm had mean serum urate concentrations less than 6.0 mg/dL during the maintenance phase (weeks 36, 42, and 48).
In each arm, about 20% of patients left the study before completing 72 weeks of follow-up. Serious adverse events occurred in 26.7% of patients assigned to allopurinol and 26.1% of patients assigned to febuxostat.
Cardiovascular adverse events occurred in 8.1% and 6.8%, respectively. There were three cases of cardiovascular death in the allopurinol arm and one in the febuxostat arm. Nonfatal myocardial infarction occurred in two and four patients, respectively, stroke in one and two, and unstable angina requiring urgent revascularization in four and three patients.
In the question-and-answer session of the briefing, this news organization asked Dr. Thomas whether he would use the agents interchangeably in his practice. He replied “no, I start off with allopurinol in all of my patients, even those with chronic kidney disease, because it has been shown to be safe. I start off at a very low dose, go up slowly, [and] if they have a reaction, I change it to febuxostat.”
The study was supported by the U.S. Department of Veterans Affairs. Dr. O’Dell and Dr. Thomas have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Allopurinol may finally start to get the respect that many rheumatologists feel it deserves as a first-line urate-lowering treatment for gout, following results of a randomized trial showing that it was noninferior to febuxostat both in the overall trial population and in patients with stage 3 chronic kidney disease (CKD).
In the multicenter, randomized, double-blinded comparison trial that used a treat-to-target strategy, allopurinol met the primary outcome of noninferiority to febuxostat for preventing gout flare during the observation phase of therapy, reported James O’Dell, MD, chief of the division of rheumatology and vice chair for education in the department of internal medicine at the University of Nebraska Medical Center in Omaha.
“Both agents were well tolerated, with or without CKD. Most importantly, both agents were highly effective when used in a treat-to-target protocol in getting patients to target urate levels,” he said in an oral abstract presentation during the American College of Rheumatology (ACR) 2021 Annual Meeting, which was held online.
And although febuxostat contains a boxed warning about the risks of cardiovascular adverse events with its use, there were no signals for increased cardiovascular toxicity with febuxostat compared with allopurinol, the investigators found.
The trial is the first to compare allopurinol, a decades-old drug, with febuxostat, approved in 2009, in a treat-to-target approach, Dr. O’Dell said.
American College of Physicians’ guideline ‘antiquated’
The results of the study “will hopefully teach doctors how to treat gout better by encouraging them to use higher doses of gout medications safely than they’re actually using at this time,” said Donald Thomas Jr., MD, in private practice in Greenbelt, Md., and associate professor of medicine at the Uniformed Services University of the Health Sciences in Bethesda, Md.
Dr. Thomas, who moderated a media briefing where Dr. O’Dell discussed the results of the trial, said that he had recently read the 2017 gout guideline by the American College of Physicians (ACP), which he called “antiquated.”
The ACP recommends the use of corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or low-dose colchicine to treat patients with acute gout. The ACP also recommends “against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.”
The guideline recommends that clinicians discuss potential benefits, risks, costs, and personal preferences before starting patients on urate-lowering therapy in patients with recurrent gout attacks.
The 2017 guidelines also state, however, that “[e]vidence was insufficient to conclude whether the benefits of escalating urate-lowering therapy to reach a serum urate target (‘treat to target’) outweigh the harms associated with repeated monitoring and medication escalation.”
“I’ve been a proud member of the American College of Physicians for years, I’m a master of the ACP, and they do a lot of great things, but this is one case where their insistence that they’re not going to have a guideline that isn’t completely based in evidence from studies is getting in the way of common sense,” Dr. O’Dell said.
“Their contention is that what matters to a gout patient is a gout flare, and how do we know that gout flares are less if you treat to target or not – and that’s a fair question,” he continued, “except for the fact that in uric acid metabolism we know physiologically that there’s a magic number and that’s 6.8 mg/dL, and anything above that, every day uric acid is above 6.8, you are literally putting crystal out into all places in your body.”
In contrast, the ACR’s 2020 guideline for the management of gout strongly recommends starting urate-lowering therapy for all patients with tophaceous gout, radiographic damage because of gout, or frequent gout flares. It also advises using allopurinol as the preferred first-line urate-lowering therapy, including for those with stage 3 or greater CKD, and using a low starting dose of allopurinol of 100 mg/day or less (lower in CKD) or febuxostat at 40 mg/day or less. It endorses a treat-to-target management strategy that aims for serum urate < 6 mg/dL with dose titration of urate-lowering agents guided by serial serum urate measurements.
Dr. Thomas and Dr. O’Dell expressed hope that the results of this clinical trial will put the issue to rest, and that the ACP will update its guideline accordingly.
VA-sponsored trial
The study was conducted at 19 Veterans Affairs medical centers and two non-VA sites. The trial was divided into dose-titration, maintenance, and observation phases, each lasting 24 weeks.
A total of 950 participants with gout and a serum urate concentration 6.8 mg/dL or greater were randomly assigned on a 1:1 basis to receive allopurinol 100-800 mg or febuxostat 40 mg to 80/120 mg daily. In 2019, the Food and Drug Administration requested that the maximum titrated dose of febuxostat in the trial be capped at 80 mg daily. All patients stopped prophylaxis with NSAIDs, colchicine, or prednisone before the observation phase.
Patients with persistent hyperuricemia despite treatment with allopurinol were eligible, and these patients were started in the titration phase at their current dose.
The mean patient age was 62.9 years in the allopurinol arm and 61.3 years in the febuxostat arm. Men comprised 98% of patients in each study arm.
The racial/ethnic distribution of patients was similar between the groups. In all, 38.7% of patients assigned to allopurinol and 36% assigned to febuxostat had CKD stages 1-3. (Patients with stage 4 or 5 CKD were excluded from the study.)
A gout flare occurred if a participants reported three or more symptoms of tender, warm, swollen joints, or gout flare, or if the participant reported use of medication for gout flare in the observation phase during weeks 49-72.
As noted before, the trial met its primary endpoint, with 36.5% of patients on allopurinol reporting gout flare in the observation phase, compared with 43.5% on febuxostat (P for noninferiority < .001).
Among patients with CKD stage 3, the respective percentages of patients reporting at least one gout flare in the observation phase were 31.9% and 45.3% (P for noninferiority < .001).
Approximately 80% of patients in each arm had mean serum urate concentrations less than 6.0 mg/dL during the maintenance phase (weeks 36, 42, and 48).
In each arm, about 20% of patients left the study before completing 72 weeks of follow-up. Serious adverse events occurred in 26.7% of patients assigned to allopurinol and 26.1% of patients assigned to febuxostat.
Cardiovascular adverse events occurred in 8.1% and 6.8%, respectively. There were three cases of cardiovascular death in the allopurinol arm and one in the febuxostat arm. Nonfatal myocardial infarction occurred in two and four patients, respectively, stroke in one and two, and unstable angina requiring urgent revascularization in four and three patients.
In the question-and-answer session of the briefing, this news organization asked Dr. Thomas whether he would use the agents interchangeably in his practice. He replied “no, I start off with allopurinol in all of my patients, even those with chronic kidney disease, because it has been shown to be safe. I start off at a very low dose, go up slowly, [and] if they have a reaction, I change it to febuxostat.”
The study was supported by the U.S. Department of Veterans Affairs. Dr. O’Dell and Dr. Thomas have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Allopurinol may finally start to get the respect that many rheumatologists feel it deserves as a first-line urate-lowering treatment for gout, following results of a randomized trial showing that it was noninferior to febuxostat both in the overall trial population and in patients with stage 3 chronic kidney disease (CKD).
In the multicenter, randomized, double-blinded comparison trial that used a treat-to-target strategy, allopurinol met the primary outcome of noninferiority to febuxostat for preventing gout flare during the observation phase of therapy, reported James O’Dell, MD, chief of the division of rheumatology and vice chair for education in the department of internal medicine at the University of Nebraska Medical Center in Omaha.
“Both agents were well tolerated, with or without CKD. Most importantly, both agents were highly effective when used in a treat-to-target protocol in getting patients to target urate levels,” he said in an oral abstract presentation during the American College of Rheumatology (ACR) 2021 Annual Meeting, which was held online.
And although febuxostat contains a boxed warning about the risks of cardiovascular adverse events with its use, there were no signals for increased cardiovascular toxicity with febuxostat compared with allopurinol, the investigators found.
The trial is the first to compare allopurinol, a decades-old drug, with febuxostat, approved in 2009, in a treat-to-target approach, Dr. O’Dell said.
American College of Physicians’ guideline ‘antiquated’
The results of the study “will hopefully teach doctors how to treat gout better by encouraging them to use higher doses of gout medications safely than they’re actually using at this time,” said Donald Thomas Jr., MD, in private practice in Greenbelt, Md., and associate professor of medicine at the Uniformed Services University of the Health Sciences in Bethesda, Md.
Dr. Thomas, who moderated a media briefing where Dr. O’Dell discussed the results of the trial, said that he had recently read the 2017 gout guideline by the American College of Physicians (ACP), which he called “antiquated.”
The ACP recommends the use of corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or low-dose colchicine to treat patients with acute gout. The ACP also recommends “against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.”
The guideline recommends that clinicians discuss potential benefits, risks, costs, and personal preferences before starting patients on urate-lowering therapy in patients with recurrent gout attacks.
The 2017 guidelines also state, however, that “[e]vidence was insufficient to conclude whether the benefits of escalating urate-lowering therapy to reach a serum urate target (‘treat to target’) outweigh the harms associated with repeated monitoring and medication escalation.”
“I’ve been a proud member of the American College of Physicians for years, I’m a master of the ACP, and they do a lot of great things, but this is one case where their insistence that they’re not going to have a guideline that isn’t completely based in evidence from studies is getting in the way of common sense,” Dr. O’Dell said.
“Their contention is that what matters to a gout patient is a gout flare, and how do we know that gout flares are less if you treat to target or not – and that’s a fair question,” he continued, “except for the fact that in uric acid metabolism we know physiologically that there’s a magic number and that’s 6.8 mg/dL, and anything above that, every day uric acid is above 6.8, you are literally putting crystal out into all places in your body.”
In contrast, the ACR’s 2020 guideline for the management of gout strongly recommends starting urate-lowering therapy for all patients with tophaceous gout, radiographic damage because of gout, or frequent gout flares. It also advises using allopurinol as the preferred first-line urate-lowering therapy, including for those with stage 3 or greater CKD, and using a low starting dose of allopurinol of 100 mg/day or less (lower in CKD) or febuxostat at 40 mg/day or less. It endorses a treat-to-target management strategy that aims for serum urate < 6 mg/dL with dose titration of urate-lowering agents guided by serial serum urate measurements.
Dr. Thomas and Dr. O’Dell expressed hope that the results of this clinical trial will put the issue to rest, and that the ACP will update its guideline accordingly.
VA-sponsored trial
The study was conducted at 19 Veterans Affairs medical centers and two non-VA sites. The trial was divided into dose-titration, maintenance, and observation phases, each lasting 24 weeks.
A total of 950 participants with gout and a serum urate concentration 6.8 mg/dL or greater were randomly assigned on a 1:1 basis to receive allopurinol 100-800 mg or febuxostat 40 mg to 80/120 mg daily. In 2019, the Food and Drug Administration requested that the maximum titrated dose of febuxostat in the trial be capped at 80 mg daily. All patients stopped prophylaxis with NSAIDs, colchicine, or prednisone before the observation phase.
Patients with persistent hyperuricemia despite treatment with allopurinol were eligible, and these patients were started in the titration phase at their current dose.
The mean patient age was 62.9 years in the allopurinol arm and 61.3 years in the febuxostat arm. Men comprised 98% of patients in each study arm.
The racial/ethnic distribution of patients was similar between the groups. In all, 38.7% of patients assigned to allopurinol and 36% assigned to febuxostat had CKD stages 1-3. (Patients with stage 4 or 5 CKD were excluded from the study.)
A gout flare occurred if a participants reported three or more symptoms of tender, warm, swollen joints, or gout flare, or if the participant reported use of medication for gout flare in the observation phase during weeks 49-72.
As noted before, the trial met its primary endpoint, with 36.5% of patients on allopurinol reporting gout flare in the observation phase, compared with 43.5% on febuxostat (P for noninferiority < .001).
Among patients with CKD stage 3, the respective percentages of patients reporting at least one gout flare in the observation phase were 31.9% and 45.3% (P for noninferiority < .001).
Approximately 80% of patients in each arm had mean serum urate concentrations less than 6.0 mg/dL during the maintenance phase (weeks 36, 42, and 48).
In each arm, about 20% of patients left the study before completing 72 weeks of follow-up. Serious adverse events occurred in 26.7% of patients assigned to allopurinol and 26.1% of patients assigned to febuxostat.
Cardiovascular adverse events occurred in 8.1% and 6.8%, respectively. There were three cases of cardiovascular death in the allopurinol arm and one in the febuxostat arm. Nonfatal myocardial infarction occurred in two and four patients, respectively, stroke in one and two, and unstable angina requiring urgent revascularization in four and three patients.
In the question-and-answer session of the briefing, this news organization asked Dr. Thomas whether he would use the agents interchangeably in his practice. He replied “no, I start off with allopurinol in all of my patients, even those with chronic kidney disease, because it has been shown to be safe. I start off at a very low dose, go up slowly, [and] if they have a reaction, I change it to febuxostat.”
The study was supported by the U.S. Department of Veterans Affairs. Dr. O’Dell and Dr. Thomas have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACR 2021
U.S. arthritis prevalence continues steady rise; activity limitations grow more rapidly
Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.
“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”
The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
Activity limitations rose faster than predicted
According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.
The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.
“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”
Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).
The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”
The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).
Comments on latest findings
Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”
As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”
It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”
Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”
The authors and LaValley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.
“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”
The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
Activity limitations rose faster than predicted
According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.
The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.
“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”
Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).
The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”
The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).
Comments on latest findings
Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”
As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”
It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”
Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”
The authors and LaValley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.
“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”
The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
Activity limitations rose faster than predicted
According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.
The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.
“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”
Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).
The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”
The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).
Comments on latest findings
Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”
As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”
It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”
Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”
The authors and LaValley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.