3e Initiative releases multinational evidence-based gout recommendations

Identification of monosodium urate crystals, either in a joint fluid sample or in a tophi aspirate, should be performed for a definite diagnosis of gout, according to new multinational evidence-based recommendations on the diagnosis and management of the disease.

When identification of monosodium urate (MSU) crystals is not possible, the diagnosis can be supported by classical clinical features such as podagra, tophi, or rapid response to colchicine, or by characteristic imaging findings, Dr. Francisca Sivera of Hospital General Universitario de Elda (Spain) and her colleagues reported on behalf of the 2011 3e (Evidence, Expertise, Exchange) Initiative. The initiative is a multinational collaboration tasked with promoting evidence-based practice in rheumatology through the development of practical recommendations that address relevant clinical issues.

The MSU identification recommendation is one of 10 recommendations developed by 474 rheumatologists from 14 countries who participated in the 2011 3e Initiative. In keeping with 3e protocol, a panel of 78 experts representing the 14 countries developed 10 key clinical questions pertinent to the diagnosis and management of gout, each of which was investigated via extensive literature review. Recommendations for each of the questions were then formulated, debated, and voted on by Initiative participants, and each recommendation was graded based on the level of evidence.

In addition to diagnosis, the gout recommendations address comorbidity screening, acute gout treatment, lifestyle counseling, urate-lowering therapy, flare prophylaxis, the effect of comorbidities on drug selection, patient monitoring, tophi treatment, and management of asymptomatic hyperuricemia (Ann. Rheum. Dis. 2013 July 18 [doi: 10.1136/annrheumdis-2013-203325]).

Specifically, with a high level of agreement that ranged from a mean of 8.1 to 9.2 on a 1-10 scale, the 3e Initiative participants recommended:

• Assessing renal function and cardiovascular risk factors in patients with gout and/or hyperuricemia.

• Treating acute gout with low-dose colchicine, nonsteroidal anti-inflammatory drugs, and/or glucocorticoids, depending on comorbidities and the risk of adverse effects.

• Advising patients about health lifestyle choices.

• Using allopurinol first-line as urate-lowering therapy, and considering uricosurics as alternatives when necessary.

• Educating patients on the risk and management of flares – and using prophylaxis – when introducing urate-lowering therapy.

• Using allopurinol with close monitoring, and starting at a low dose with slow titration, in patients with mild to moderate renal impairment.

• Setting the treatment target for serum urate at below 0.36 mmol/L (6 mg/dL) with eventual absence of gout attacks and resolution of tophi.

• Treating tophi medically by achieving a sustained reduction in serum uric acid, preferably below 0.30 mmol/L (5 mg/dL) and reserving surgery for select cases, such as those involving nerve compression, mechanical impingement, or infection.

• Forgoing pharmacological treatment of asymptomatic hyperuricemia.

The ultimate goal of these recommendations, which were based on 1a-5 evidence levels, and which received recommendation grades ranging from B to D, is to improve patient care, Dr. Sivera said in an interview. The level of evidence and grade of recommendation were made according to the Oxford Centre for Evidence-Based Medicine levels of evidence.

Gout affects up to 2% of men in Western countries, and is associated with morbidity, disability, and poorer quality of life. Despite the availability of a number of guidelines and recommendations, management of the condition is often suboptimal, she said.

"Gout is a curable disease, but evidence shows that many patients are mismanaged with regard to both treatment and diagnosis. Even in a rheumatology clinic, only about a quarter of the patients have a diagnosis of gout established by MSU crystal identification, and in a U.K. study, only one in three patients with a diagnosis of gout were taking urate-lowering therapy," she said.

Research shows that when guidelines are implemented, they improve the quality of care. Educational outreach has an effect on implementation, she said, noting that "both dissemination and education – in both gout and in evidence-based medicine – are an integral part of the 3e Initiative, so these multinational recommendations have the potential to positively influence the standard of care."

The 3e recommendations follow those published in 2012 on behalf of the American College of Rheumatology, which centered on the treatment and prophylaxis of acute gout flares and the appropriate use of urate-lowering therapy.

"Some of the recommendations provided are similar, such as treating to a target serum uric acid level, and the ‘start low, go slow’ approach to allopurinol therapy. This highlights the general consensus on many aspects of the optimal standard of gout management," Dr. Sivera said.

Where the 3e recommendation and the ACR guidelines overlap, there is, indeed, general agreement, Dr. John FitzGerald of the University of California, Los Angeles, said in an interview.

Both processes benefited from Delphi consensus methodologies and systematic literature reviews to inform decision making. However, the two diverge with respect to other aspects of the methodology and presentation, he noted.

"The RAND/UCLA methodology used by ACR resulted in guidelines that were evidence based to be the most efficacious recommendations. As noted, the RAND/UCLA methodology excludes cost of therapy (as typically there are insufficient head-to-head therapeutic cost-efficacy studies on which to base recommendations). The ACR guidelines therefore leave it to the practitioner to use the efficacy-based recommendations, along with their clinical and practical knowledge, to then provide recommendations for specific patients. As an example, allopurinol and febuxostat have relatively similar efficacy but significant cost differences," said Dr. FitzGerald, who co-led the ACR guidelines development project.

"The 3e approach incorporates that next step in decision making to provide evidence-based and practical recommendations to the practitioner," he said.

The ACR effort addressed four specific domains of gout management: treatment of acute gouty attacks, management of urate-lowering therapy, management of chronic tophaceous gout, and prophylaxis of acute gouty attacks. Although the 3e effort focused on 10 specific, clinically relevant questions, it is valuable for other reasons as well, such as the inclusion of diagnosis as part of the recommendations, and the fact that asymptomatic hyperuricemia is addressed, he said, noting that neither of these was addressed by the ACR guidelines.

The 3e recommendations also address the use of benzbromarone, a uricosuric agent that is not available in the United States.

While the 3e effort lacks the extent of detail included in the ACR guidelines, such as the inclusion of specific information on allopurinol dosing, the 3e group is to be commended for the size of the effort, Dr. FitzGerald said, stressing the value of the input from nearly 500 rheumatologists from 14 countries.

Indeed, the extensive effort by "a large group of practicing rheumatologists from many different countries in Europe, South America, and Australasia resulted in the recommendations addressing those aspects [of gout diagnosis and management] that rheumatologists found most clinically relevant," Dr. Sivera said.

She and her colleagues concluded that "the high level of agreement with the final recommendations and the multinational participation increase their utility and will hopefully facilitate their dissemination and implementation worldwide."

The 3e Gout Program was sponsored by AbbVie. Dr. Sivera reported receiving fees from Menarini for preparing educational presentations, and other authors reported receiving lecture or consulting fees and/or research grants from many companies, including AbbVie. Dr. FitzGerald reported receiving honoraria and grant support from the ACR.

Identification of monosodium urate crystals, either in a joint fluid sample or in a tophi aspirate, should be performed for a definite diagnosis of gout, according to new multinational evidence-based recommendations on the diagnosis and management of the disease.

When identification of monosodium urate (MSU) crystals is not possible, the diagnosis can be supported by classical clinical features such as podagra, tophi, or rapid response to colchicine, or by characteristic imaging findings, Dr. Francisca Sivera of Hospital General Universitario de Elda (Spain) and her colleagues reported on behalf of the 2011 3e (Evidence, Expertise, Exchange) Initiative. The initiative is a multinational collaboration tasked with promoting evidence-based practice in rheumatology through the development of practical recommendations that address relevant clinical issues.

The MSU identification recommendation is one of 10 recommendations developed by 474 rheumatologists from 14 countries who participated in the 2011 3e Initiative. In keeping with 3e protocol, a panel of 78 experts representing the 14 countries developed 10 key clinical questions pertinent to the diagnosis and management of gout, each of which was investigated via extensive literature review. Recommendations for each of the questions were then formulated, debated, and voted on by Initiative participants, and each recommendation was graded based on the level of evidence.

In addition to diagnosis, the gout recommendations address comorbidity screening, acute gout treatment, lifestyle counseling, urate-lowering therapy, flare prophylaxis, the effect of comorbidities on drug selection, patient monitoring, tophi treatment, and management of asymptomatic hyperuricemia (Ann. Rheum. Dis. 2013 July 18 [doi: 10.1136/annrheumdis-2013-203325]).

Specifically, with a high level of agreement that ranged from a mean of 8.1 to 9.2 on a 1-10 scale, the 3e Initiative participants recommended:

• Assessing renal function and cardiovascular risk factors in patients with gout and/or hyperuricemia.

• Treating acute gout with low-dose colchicine, nonsteroidal anti-inflammatory drugs, and/or glucocorticoids, depending on comorbidities and the risk of adverse effects.

• Advising patients about health lifestyle choices.

• Using allopurinol first-line as urate-lowering therapy, and considering uricosurics as alternatives when necessary.

• Educating patients on the risk and management of flares – and using prophylaxis – when introducing urate-lowering therapy.

• Using allopurinol with close monitoring, and starting at a low dose with slow titration, in patients with mild to moderate renal impairment.

• Setting the treatment target for serum urate at below 0.36 mmol/L (6 mg/dL) with eventual absence of gout attacks and resolution of tophi.

• Treating tophi medically by achieving a sustained reduction in serum uric acid, preferably below 0.30 mmol/L (5 mg/dL) and reserving surgery for select cases, such as those involving nerve compression, mechanical impingement, or infection.

• Forgoing pharmacological treatment of asymptomatic hyperuricemia.

The ultimate goal of these recommendations, which were based on 1a-5 evidence levels, and which received recommendation grades ranging from B to D, is to improve patient care, Dr. Sivera said in an interview. The level of evidence and grade of recommendation were made according to the Oxford Centre for Evidence-Based Medicine levels of evidence.

Gout affects up to 2% of men in Western countries, and is associated with morbidity, disability, and poorer quality of life. Despite the availability of a number of guidelines and recommendations, management of the condition is often suboptimal, she said.

"Gout is a curable disease, but evidence shows that many patients are mismanaged with regard to both treatment and diagnosis. Even in a rheumatology clinic, only about a quarter of the patients have a diagnosis of gout established by MSU crystal identification, and in a U.K. study, only one in three patients with a diagnosis of gout were taking urate-lowering therapy," she said.

Research shows that when guidelines are implemented, they improve the quality of care. Educational outreach has an effect on implementation, she said, noting that "both dissemination and education – in both gout and in evidence-based medicine – are an integral part of the 3e Initiative, so these multinational recommendations have the potential to positively influence the standard of care."

The 3e recommendations follow those published in 2012 on behalf of the American College of Rheumatology, which centered on the treatment and prophylaxis of acute gout flares and the appropriate use of urate-lowering therapy.

"Some of the recommendations provided are similar, such as treating to a target serum uric acid level, and the ‘start low, go slow’ approach to allopurinol therapy. This highlights the general consensus on many aspects of the optimal standard of gout management," Dr. Sivera said.

Where the 3e recommendation and the ACR guidelines overlap, there is, indeed, general agreement, Dr. John FitzGerald of the University of California, Los Angeles, said in an interview.

Both processes benefited from Delphi consensus methodologies and systematic literature reviews to inform decision making. However, the two diverge with respect to other aspects of the methodology and presentation, he noted.

"The RAND/UCLA methodology used by ACR resulted in guidelines that were evidence based to be the most efficacious recommendations. As noted, the RAND/UCLA methodology excludes cost of therapy (as typically there are insufficient head-to-head therapeutic cost-efficacy studies on which to base recommendations). The ACR guidelines therefore leave it to the practitioner to use the efficacy-based recommendations, along with their clinical and practical knowledge, to then provide recommendations for specific patients. As an example, allopurinol and febuxostat have relatively similar efficacy but significant cost differences," said Dr. FitzGerald, who co-led the ACR guidelines development project.

"The 3e approach incorporates that next step in decision making to provide evidence-based and practical recommendations to the practitioner," he said.

The ACR effort addressed four specific domains of gout management: treatment of acute gouty attacks, management of urate-lowering therapy, management of chronic tophaceous gout, and prophylaxis of acute gouty attacks. Although the 3e effort focused on 10 specific, clinically relevant questions, it is valuable for other reasons as well, such as the inclusion of diagnosis as part of the recommendations, and the fact that asymptomatic hyperuricemia is addressed, he said, noting that neither of these was addressed by the ACR guidelines.

The 3e recommendations also address the use of benzbromarone, a uricosuric agent that is not available in the United States.

While the 3e effort lacks the extent of detail included in the ACR guidelines, such as the inclusion of specific information on allopurinol dosing, the 3e group is to be commended for the size of the effort, Dr. FitzGerald said, stressing the value of the input from nearly 500 rheumatologists from 14 countries.

Indeed, the extensive effort by "a large group of practicing rheumatologists from many different countries in Europe, South America, and Australasia resulted in the recommendations addressing those aspects [of gout diagnosis and management] that rheumatologists found most clinically relevant," Dr. Sivera said.

She and her colleagues concluded that "the high level of agreement with the final recommendations and the multinational participation increase their utility and will hopefully facilitate their dissemination and implementation worldwide."

The 3e Gout Program was sponsored by AbbVie. Dr. Sivera reported receiving fees from Menarini for preparing educational presentations, and other authors reported receiving lecture or consulting fees and/or research grants from many companies, including AbbVie. Dr. FitzGerald reported receiving honoraria and grant support from the ACR.

Identification of monosodium urate crystals, either in a joint fluid sample or in a tophi aspirate, should be performed for a definite diagnosis of gout, according to new multinational evidence-based recommendations on the diagnosis and management of the disease.

When identification of monosodium urate (MSU) crystals is not possible, the diagnosis can be supported by classical clinical features such as podagra, tophi, or rapid response to colchicine, or by characteristic imaging findings, Dr. Francisca Sivera of Hospital General Universitario de Elda (Spain) and her colleagues reported on behalf of the 2011 3e (Evidence, Expertise, Exchange) Initiative. The initiative is a multinational collaboration tasked with promoting evidence-based practice in rheumatology through the development of practical recommendations that address relevant clinical issues.

The MSU identification recommendation is one of 10 recommendations developed by 474 rheumatologists from 14 countries who participated in the 2011 3e Initiative. In keeping with 3e protocol, a panel of 78 experts representing the 14 countries developed 10 key clinical questions pertinent to the diagnosis and management of gout, each of which was investigated via extensive literature review. Recommendations for each of the questions were then formulated, debated, and voted on by Initiative participants, and each recommendation was graded based on the level of evidence.

In addition to diagnosis, the gout recommendations address comorbidity screening, acute gout treatment, lifestyle counseling, urate-lowering therapy, flare prophylaxis, the effect of comorbidities on drug selection, patient monitoring, tophi treatment, and management of asymptomatic hyperuricemia (Ann. Rheum. Dis. 2013 July 18 [doi: 10.1136/annrheumdis-2013-203325]).

Specifically, with a high level of agreement that ranged from a mean of 8.1 to 9.2 on a 1-10 scale, the 3e Initiative participants recommended:

• Assessing renal function and cardiovascular risk factors in patients with gout and/or hyperuricemia.

• Treating acute gout with low-dose colchicine, nonsteroidal anti-inflammatory drugs, and/or glucocorticoids, depending on comorbidities and the risk of adverse effects.

• Advising patients about health lifestyle choices.

• Using allopurinol first-line as urate-lowering therapy, and considering uricosurics as alternatives when necessary.

• Educating patients on the risk and management of flares – and using prophylaxis – when introducing urate-lowering therapy.

• Using allopurinol with close monitoring, and starting at a low dose with slow titration, in patients with mild to moderate renal impairment.

• Setting the treatment target for serum urate at below 0.36 mmol/L (6 mg/dL) with eventual absence of gout attacks and resolution of tophi.

• Treating tophi medically by achieving a sustained reduction in serum uric acid, preferably below 0.30 mmol/L (5 mg/dL) and reserving surgery for select cases, such as those involving nerve compression, mechanical impingement, or infection.

• Forgoing pharmacological treatment of asymptomatic hyperuricemia.

The ultimate goal of these recommendations, which were based on 1a-5 evidence levels, and which received recommendation grades ranging from B to D, is to improve patient care, Dr. Sivera said in an interview. The level of evidence and grade of recommendation were made according to the Oxford Centre for Evidence-Based Medicine levels of evidence.

Gout affects up to 2% of men in Western countries, and is associated with morbidity, disability, and poorer quality of life. Despite the availability of a number of guidelines and recommendations, management of the condition is often suboptimal, she said.

"Gout is a curable disease, but evidence shows that many patients are mismanaged with regard to both treatment and diagnosis. Even in a rheumatology clinic, only about a quarter of the patients have a diagnosis of gout established by MSU crystal identification, and in a U.K. study, only one in three patients with a diagnosis of gout were taking urate-lowering therapy," she said.

Research shows that when guidelines are implemented, they improve the quality of care. Educational outreach has an effect on implementation, she said, noting that "both dissemination and education – in both gout and in evidence-based medicine – are an integral part of the 3e Initiative, so these multinational recommendations have the potential to positively influence the standard of care."

The 3e recommendations follow those published in 2012 on behalf of the American College of Rheumatology, which centered on the treatment and prophylaxis of acute gout flares and the appropriate use of urate-lowering therapy.

"Some of the recommendations provided are similar, such as treating to a target serum uric acid level, and the ‘start low, go slow’ approach to allopurinol therapy. This highlights the general consensus on many aspects of the optimal standard of gout management," Dr. Sivera said.

Where the 3e recommendation and the ACR guidelines overlap, there is, indeed, general agreement, Dr. John FitzGerald of the University of California, Los Angeles, said in an interview.

Both processes benefited from Delphi consensus methodologies and systematic literature reviews to inform decision making. However, the two diverge with respect to other aspects of the methodology and presentation, he noted.

"The RAND/UCLA methodology used by ACR resulted in guidelines that were evidence based to be the most efficacious recommendations. As noted, the RAND/UCLA methodology excludes cost of therapy (as typically there are insufficient head-to-head therapeutic cost-efficacy studies on which to base recommendations). The ACR guidelines therefore leave it to the practitioner to use the efficacy-based recommendations, along with their clinical and practical knowledge, to then provide recommendations for specific patients. As an example, allopurinol and febuxostat have relatively similar efficacy but significant cost differences," said Dr. FitzGerald, who co-led the ACR guidelines development project.

"The 3e approach incorporates that next step in decision making to provide evidence-based and practical recommendations to the practitioner," he said.

The ACR effort addressed four specific domains of gout management: treatment of acute gouty attacks, management of urate-lowering therapy, management of chronic tophaceous gout, and prophylaxis of acute gouty attacks. Although the 3e effort focused on 10 specific, clinically relevant questions, it is valuable for other reasons as well, such as the inclusion of diagnosis as part of the recommendations, and the fact that asymptomatic hyperuricemia is addressed, he said, noting that neither of these was addressed by the ACR guidelines.

The 3e recommendations also address the use of benzbromarone, a uricosuric agent that is not available in the United States.

While the 3e effort lacks the extent of detail included in the ACR guidelines, such as the inclusion of specific information on allopurinol dosing, the 3e group is to be commended for the size of the effort, Dr. FitzGerald said, stressing the value of the input from nearly 500 rheumatologists from 14 countries.

Indeed, the extensive effort by "a large group of practicing rheumatologists from many different countries in Europe, South America, and Australasia resulted in the recommendations addressing those aspects [of gout diagnosis and management] that rheumatologists found most clinically relevant," Dr. Sivera said.

She and her colleagues concluded that "the high level of agreement with the final recommendations and the multinational participation increase their utility and will hopefully facilitate their dissemination and implementation worldwide."

The 3e Gout Program was sponsored by AbbVie. Dr. Sivera reported receiving fees from Menarini for preparing educational presentations, and other authors reported receiving lecture or consulting fees and/or research grants from many companies, including AbbVie. Dr. FitzGerald reported receiving honoraria and grant support from the ACR.