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ACR guidelines employ new methods and EULAR collaboration
PARIS – When the American College of Rheumatology and the European League Against Rheumatism unveiled new joint guidelines in June for managing patients with polymyalgia rheumatica, it marked the start of two new features for ACR guideline development.
Creation of the joint polymyalgia rheumatica (PMR) guidelines using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system marked a shift for the ACR in how it generates the database for guideline development. The college’s collaboration with the European League Against Rheumatism (EULAR) on a management guideline was new as well. Both changes will carry forward, while the ACR also will step up the pace at which it puts out guidelines and guideline updates, Dr. Kenneth G. Saag said at the annual European Congress of Rheumatology.
"I’m very pleased with our first-ever joint ACR-EULAR guideline [on PMR] presented at this meeting," said Dr. Saag, professor of medicine at the University of Alabama, Birmingham, and an ACR member active in guideline development.
While preparing the PMR guideline, which took shape using the GRADE methods, he noted, the ACR "developed a new infrastructure that will allow us to do [future guidelines] more adeptly and quickly." This infrastructure is now working with an ACR panel to write updated rheumatoid arthritis management guidelines that are expected to be out next year, said Dr. Saag, who is also director of the Center for Education & Research on Therapeutics of Musculoskeletal Disorders at the university.
"GRADE has been advocated internationally as the state of the art for guidelines. It brings a higher level of transparency to the process," he said in an interview. With the switch to the GRADE method, which involved consultations with members of the Cochrane Collaboration data-review organization, the ACR is "transitioning to a process that is more similar to EULAR’s, with a centralized infrastructure. We are moving toward having more in-house expertise with the GRADE method. We hope it will allow us to update guidelines more quickly." ACR groups are reviewing the college’s existing guidelines to find ones that need updating, as well as new areas for guideline development.
Further guideline collaboration with EULAR, however, faces significant hurdles that will mean joint guidelines will only be possible for selected conditions.
Collaboration between EULAR and ACR on guidelines first began in 2003 and eventually led to joint criteria for rheumatoid arthritis remission as well as the PMR guidelines. "We have come a long way in just a few years. Joint management recommendations are not too easy because of the different health care systems in Europe and the United States, and different attitudes towards conflicts of interest," said Dr. Josef Smolen, who represented EULAR’s perspective at the session.
"The issues [in joint ACR and EULAR guidelines] were sorted out for PMR because it was easy. There are no conflicts of interest when treatment is with glucocorticoids," noted Dr. Smolen, professor and chairman of rheumatology at the Medical University of Vienna.
ACR and EULAR collaboration "has been challenging, but it doesn’t mean we can’t do it, and the fact that we now have some momentum [from the PMR guidelines] is a positive sign," Dr. Saag said.
Dr. Saag said that he has served on advisory or data safety and monitoring boards for nine drug companies, and that he has received research grants from Ardea, Amgen, Merck, and Takeda. Dr. Smolen said that he has received honoraria as a consultant or speaker for 17 drug companies.
On Twitter @mitchelzoler
PARIS – When the American College of Rheumatology and the European League Against Rheumatism unveiled new joint guidelines in June for managing patients with polymyalgia rheumatica, it marked the start of two new features for ACR guideline development.
Creation of the joint polymyalgia rheumatica (PMR) guidelines using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system marked a shift for the ACR in how it generates the database for guideline development. The college’s collaboration with the European League Against Rheumatism (EULAR) on a management guideline was new as well. Both changes will carry forward, while the ACR also will step up the pace at which it puts out guidelines and guideline updates, Dr. Kenneth G. Saag said at the annual European Congress of Rheumatology.
"I’m very pleased with our first-ever joint ACR-EULAR guideline [on PMR] presented at this meeting," said Dr. Saag, professor of medicine at the University of Alabama, Birmingham, and an ACR member active in guideline development.
While preparing the PMR guideline, which took shape using the GRADE methods, he noted, the ACR "developed a new infrastructure that will allow us to do [future guidelines] more adeptly and quickly." This infrastructure is now working with an ACR panel to write updated rheumatoid arthritis management guidelines that are expected to be out next year, said Dr. Saag, who is also director of the Center for Education & Research on Therapeutics of Musculoskeletal Disorders at the university.
"GRADE has been advocated internationally as the state of the art for guidelines. It brings a higher level of transparency to the process," he said in an interview. With the switch to the GRADE method, which involved consultations with members of the Cochrane Collaboration data-review organization, the ACR is "transitioning to a process that is more similar to EULAR’s, with a centralized infrastructure. We are moving toward having more in-house expertise with the GRADE method. We hope it will allow us to update guidelines more quickly." ACR groups are reviewing the college’s existing guidelines to find ones that need updating, as well as new areas for guideline development.
Further guideline collaboration with EULAR, however, faces significant hurdles that will mean joint guidelines will only be possible for selected conditions.
Collaboration between EULAR and ACR on guidelines first began in 2003 and eventually led to joint criteria for rheumatoid arthritis remission as well as the PMR guidelines. "We have come a long way in just a few years. Joint management recommendations are not too easy because of the different health care systems in Europe and the United States, and different attitudes towards conflicts of interest," said Dr. Josef Smolen, who represented EULAR’s perspective at the session.
"The issues [in joint ACR and EULAR guidelines] were sorted out for PMR because it was easy. There are no conflicts of interest when treatment is with glucocorticoids," noted Dr. Smolen, professor and chairman of rheumatology at the Medical University of Vienna.
ACR and EULAR collaboration "has been challenging, but it doesn’t mean we can’t do it, and the fact that we now have some momentum [from the PMR guidelines] is a positive sign," Dr. Saag said.
Dr. Saag said that he has served on advisory or data safety and monitoring boards for nine drug companies, and that he has received research grants from Ardea, Amgen, Merck, and Takeda. Dr. Smolen said that he has received honoraria as a consultant or speaker for 17 drug companies.
On Twitter @mitchelzoler
PARIS – When the American College of Rheumatology and the European League Against Rheumatism unveiled new joint guidelines in June for managing patients with polymyalgia rheumatica, it marked the start of two new features for ACR guideline development.
Creation of the joint polymyalgia rheumatica (PMR) guidelines using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system marked a shift for the ACR in how it generates the database for guideline development. The college’s collaboration with the European League Against Rheumatism (EULAR) on a management guideline was new as well. Both changes will carry forward, while the ACR also will step up the pace at which it puts out guidelines and guideline updates, Dr. Kenneth G. Saag said at the annual European Congress of Rheumatology.
"I’m very pleased with our first-ever joint ACR-EULAR guideline [on PMR] presented at this meeting," said Dr. Saag, professor of medicine at the University of Alabama, Birmingham, and an ACR member active in guideline development.
While preparing the PMR guideline, which took shape using the GRADE methods, he noted, the ACR "developed a new infrastructure that will allow us to do [future guidelines] more adeptly and quickly." This infrastructure is now working with an ACR panel to write updated rheumatoid arthritis management guidelines that are expected to be out next year, said Dr. Saag, who is also director of the Center for Education & Research on Therapeutics of Musculoskeletal Disorders at the university.
"GRADE has been advocated internationally as the state of the art for guidelines. It brings a higher level of transparency to the process," he said in an interview. With the switch to the GRADE method, which involved consultations with members of the Cochrane Collaboration data-review organization, the ACR is "transitioning to a process that is more similar to EULAR’s, with a centralized infrastructure. We are moving toward having more in-house expertise with the GRADE method. We hope it will allow us to update guidelines more quickly." ACR groups are reviewing the college’s existing guidelines to find ones that need updating, as well as new areas for guideline development.
Further guideline collaboration with EULAR, however, faces significant hurdles that will mean joint guidelines will only be possible for selected conditions.
Collaboration between EULAR and ACR on guidelines first began in 2003 and eventually led to joint criteria for rheumatoid arthritis remission as well as the PMR guidelines. "We have come a long way in just a few years. Joint management recommendations are not too easy because of the different health care systems in Europe and the United States, and different attitudes towards conflicts of interest," said Dr. Josef Smolen, who represented EULAR’s perspective at the session.
"The issues [in joint ACR and EULAR guidelines] were sorted out for PMR because it was easy. There are no conflicts of interest when treatment is with glucocorticoids," noted Dr. Smolen, professor and chairman of rheumatology at the Medical University of Vienna.
ACR and EULAR collaboration "has been challenging, but it doesn’t mean we can’t do it, and the fact that we now have some momentum [from the PMR guidelines] is a positive sign," Dr. Saag said.
Dr. Saag said that he has served on advisory or data safety and monitoring boards for nine drug companies, and that he has received research grants from Ardea, Amgen, Merck, and Takeda. Dr. Smolen said that he has received honoraria as a consultant or speaker for 17 drug companies.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE EULAR CONGRESS 2014
ACR guidelines employ new methods and EULAR collaboration
PARIS – When the American College of Rheumatology and the European League Against Rheumatism unveiled new joint guidelines in June for managing patients with polymyalgia rheumatica, it marked the start of two new features for ACR guideline development.
Creation of the joint polymyalgia rheumatica (PMR) guidelines using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system marked a shift for the ACR in how it generates the database for guideline development. The college’s collaboration with the European League Against Rheumatism (EULAR) on a management guideline was new as well. Both changes will carry forward, while the ACR also will step up the pace at which it puts out guidelines and guideline updates, Dr. Kenneth G. Saag said at the annual European Congress of Rheumatology.
"I’m very pleased with our first-ever joint ACR-EULAR guideline [on PMR] presented at this meeting," said Dr. Saag, professor of medicine at the University of Alabama, Birmingham, and an ACR member active in guideline development.
While preparing the PMR guideline, which took shape using the GRADE methods, he noted, the ACR "developed a new infrastructure that will allow us to do [future guidelines] more adeptly and quickly." This infrastructure is now working with an ACR panel to write updated rheumatoid arthritis management guidelines that are expected to be out next year, said Dr. Saag, who is also director of the Center for Education & Research on Therapeutics of Musculoskeletal Disorders at the university.
"GRADE has been advocated internationally as the state of the art for guidelines. It brings a higher level of transparency to the process," he said in an interview. With the switch to the GRADE method, which involved consultations with members of the Cochrane Collaboration data-review organization, the ACR is "transitioning to a process that is more similar to EULAR’s, with a centralized infrastructure. We are moving toward having more in-house expertise with the GRADE method. We hope it will allow us to update guidelines more quickly." ACR groups are reviewing the college’s existing guidelines to find ones that need updating, as well as new areas for guideline development.
Further guideline collaboration with EULAR, however, faces significant hurdles that will mean joint guidelines will only be possible for selected conditions.
Collaboration between EULAR and ACR on guidelines first began in 2003 and eventually led to joint criteria for rheumatoid arthritis remission as well as the PMR guidelines. "We have come a long way in just a few years. Joint management recommendations are not too easy because of the different health care systems in Europe and the United States, and different attitudes towards conflicts of interest," said Dr. Josef Smolen, who represented EULAR’s perspective at the session.
"The issues [in joint ACR and EULAR guidelines] were sorted out for PMR because it was easy. There are no conflicts of interest when treatment is with glucocorticoids," noted Dr. Smolen, professor and chairman of rheumatology at the Medical University of Vienna.
ACR and EULAR collaboration "has been challenging, but it doesn’t mean we can’t do it, and the fact that we now have some momentum [from the PMR guidelines] is a positive sign," Dr. Saag said.
Dr. Saag said that he has served on advisory or data safety and monitoring boards for nine drug companies, and that he has received research grants from Ardea, Amgen, Merck, and Takeda. Dr. Smolen said that he has received honoraria as a consultant or speaker for 17 drug companies.
On Twitter @mitchelzoler
PARIS – When the American College of Rheumatology and the European League Against Rheumatism unveiled new joint guidelines in June for managing patients with polymyalgia rheumatica, it marked the start of two new features for ACR guideline development.
Creation of the joint polymyalgia rheumatica (PMR) guidelines using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system marked a shift for the ACR in how it generates the database for guideline development. The college’s collaboration with the European League Against Rheumatism (EULAR) on a management guideline was new as well. Both changes will carry forward, while the ACR also will step up the pace at which it puts out guidelines and guideline updates, Dr. Kenneth G. Saag said at the annual European Congress of Rheumatology.
"I’m very pleased with our first-ever joint ACR-EULAR guideline [on PMR] presented at this meeting," said Dr. Saag, professor of medicine at the University of Alabama, Birmingham, and an ACR member active in guideline development.
While preparing the PMR guideline, which took shape using the GRADE methods, he noted, the ACR "developed a new infrastructure that will allow us to do [future guidelines] more adeptly and quickly." This infrastructure is now working with an ACR panel to write updated rheumatoid arthritis management guidelines that are expected to be out next year, said Dr. Saag, who is also director of the Center for Education & Research on Therapeutics of Musculoskeletal Disorders at the university.
"GRADE has been advocated internationally as the state of the art for guidelines. It brings a higher level of transparency to the process," he said in an interview. With the switch to the GRADE method, which involved consultations with members of the Cochrane Collaboration data-review organization, the ACR is "transitioning to a process that is more similar to EULAR’s, with a centralized infrastructure. We are moving toward having more in-house expertise with the GRADE method. We hope it will allow us to update guidelines more quickly." ACR groups are reviewing the college’s existing guidelines to find ones that need updating, as well as new areas for guideline development.
Further guideline collaboration with EULAR, however, faces significant hurdles that will mean joint guidelines will only be possible for selected conditions.
Collaboration between EULAR and ACR on guidelines first began in 2003 and eventually led to joint criteria for rheumatoid arthritis remission as well as the PMR guidelines. "We have come a long way in just a few years. Joint management recommendations are not too easy because of the different health care systems in Europe and the United States, and different attitudes towards conflicts of interest," said Dr. Josef Smolen, who represented EULAR’s perspective at the session.
"The issues [in joint ACR and EULAR guidelines] were sorted out for PMR because it was easy. There are no conflicts of interest when treatment is with glucocorticoids," noted Dr. Smolen, professor and chairman of rheumatology at the Medical University of Vienna.
ACR and EULAR collaboration "has been challenging, but it doesn’t mean we can’t do it, and the fact that we now have some momentum [from the PMR guidelines] is a positive sign," Dr. Saag said.
Dr. Saag said that he has served on advisory or data safety and monitoring boards for nine drug companies, and that he has received research grants from Ardea, Amgen, Merck, and Takeda. Dr. Smolen said that he has received honoraria as a consultant or speaker for 17 drug companies.
On Twitter @mitchelzoler
PARIS – When the American College of Rheumatology and the European League Against Rheumatism unveiled new joint guidelines in June for managing patients with polymyalgia rheumatica, it marked the start of two new features for ACR guideline development.
Creation of the joint polymyalgia rheumatica (PMR) guidelines using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system marked a shift for the ACR in how it generates the database for guideline development. The college’s collaboration with the European League Against Rheumatism (EULAR) on a management guideline was new as well. Both changes will carry forward, while the ACR also will step up the pace at which it puts out guidelines and guideline updates, Dr. Kenneth G. Saag said at the annual European Congress of Rheumatology.
"I’m very pleased with our first-ever joint ACR-EULAR guideline [on PMR] presented at this meeting," said Dr. Saag, professor of medicine at the University of Alabama, Birmingham, and an ACR member active in guideline development.
While preparing the PMR guideline, which took shape using the GRADE methods, he noted, the ACR "developed a new infrastructure that will allow us to do [future guidelines] more adeptly and quickly." This infrastructure is now working with an ACR panel to write updated rheumatoid arthritis management guidelines that are expected to be out next year, said Dr. Saag, who is also director of the Center for Education & Research on Therapeutics of Musculoskeletal Disorders at the university.
"GRADE has been advocated internationally as the state of the art for guidelines. It brings a higher level of transparency to the process," he said in an interview. With the switch to the GRADE method, which involved consultations with members of the Cochrane Collaboration data-review organization, the ACR is "transitioning to a process that is more similar to EULAR’s, with a centralized infrastructure. We are moving toward having more in-house expertise with the GRADE method. We hope it will allow us to update guidelines more quickly." ACR groups are reviewing the college’s existing guidelines to find ones that need updating, as well as new areas for guideline development.
Further guideline collaboration with EULAR, however, faces significant hurdles that will mean joint guidelines will only be possible for selected conditions.
Collaboration between EULAR and ACR on guidelines first began in 2003 and eventually led to joint criteria for rheumatoid arthritis remission as well as the PMR guidelines. "We have come a long way in just a few years. Joint management recommendations are not too easy because of the different health care systems in Europe and the United States, and different attitudes towards conflicts of interest," said Dr. Josef Smolen, who represented EULAR’s perspective at the session.
"The issues [in joint ACR and EULAR guidelines] were sorted out for PMR because it was easy. There are no conflicts of interest when treatment is with glucocorticoids," noted Dr. Smolen, professor and chairman of rheumatology at the Medical University of Vienna.
ACR and EULAR collaboration "has been challenging, but it doesn’t mean we can’t do it, and the fact that we now have some momentum [from the PMR guidelines] is a positive sign," Dr. Saag said.
Dr. Saag said that he has served on advisory or data safety and monitoring boards for nine drug companies, and that he has received research grants from Ardea, Amgen, Merck, and Takeda. Dr. Smolen said that he has received honoraria as a consultant or speaker for 17 drug companies.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE EULAR CONGRESS 2014
Increased risk of heart attack confirmed in Sjögren’s syndrome patients
PARIS – Patients with Sjögren’s syndrome appear to have a higher risk of myocardial infarction, but not stroke or transient ischemic attack, than does the general population, based on an analysis of administrative health data from British Columbia.
"Our findings support monitoring for coronary artery disease in addition to management and modification of cardiovascular disease risk factors to reduce the risk of MI in Sjögren’s syndrome patients," Dr. Marko Yurkovich said at the annual European Congress of Rheumatology.
An increased risk of MI and cerebrovascular accident (CVA) is already well known in more common rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, but the risk for either MI or CVA at the general population level in patients with Sjögren’s syndrome remains unknown, said Dr. Yurkovich, an internal medicine resident at the University of British Columbia, Vancouver.
The investigators used administrative health data from all people in British Columbia who had an outpatient visit or hospitalization during 1990-2010 to locate those who were older than 18 years and met the study’s criteria for a diagnosis of Sjögren’s syndrome. The criteria were two or more ICD-9-CM codes for the disease 2 or more months apart but within a 2-year period that were made by nonrheumatologists or one or more ICD-9-CM codes for the disease that were made by a rheumatologist or during a hospitalization.
The study excluded patients who had diagnoses of other inflammatory arthritides after the Sjögren’s diagnosis or cases in which an initial diagnosis of Sjögren’s by a nonrheumatologist was not confirmed by a rheumatologist at a later visit. MI and CVA diagnoses were defined from ICD-9-CM codes from hospital or death certificates.
"This diagnostic algorithm has been validated in a Canadian context and shown to have quite a high specificity and sensitivity, both over 95%," Dr. Yurkovich said.
In 1,176 patients with Sjögren’s syndrome, the investigators identified 28 MIs for an incidence rate of 7.7 per 1,000 person-years, compared with 138 MIs in 11,879 control individuals from the general population matched for birth year, sex, and calendar year of exposure. Patients with Sjögren’s had a significantly elevated risk for MI, compared with controls, with an incidence rate ratio of 2.19 (95% confidence interval, 1.40-3.31) and a multivariate relative risk of 2.36 (95% CI, 1.48-3.78), based on incidence rates of 7.7 per 1,000 person-years in patients with Sjögren’s and 3.4 per 1,000 person-years in controls. The relative risk for MI did not differ when the results were stratified by sex.
However, risk of incident CVA was not significantly higher among patients with Sjögren’s than in the controls, based on an incidence rate of 5.1 per 1,000 person-years among patients and 3.4 per 1,000 person-years in controls that yielded an incidence rate ratio of 1.49 and multivariable relative risk of 1.64.
The multivariable analysis controlled for angina, chronic obstructive pulmonary disease, obesity, Charlson Comorbidity Index, the number of hospitalizations in the year before the index date, and number of medications, including oral glucocorticoids, cardiovascular drugs, antidiabetic medication, hormone replacement therapy, contraceptives, fibrates, statins, NSAIDs, and COX-2 inhibitors.
"We found that the risk of MI was even further elevated within 1 year following initial diagnosis," with an incidence rate ratio of 3.6 before 1 year of follow-up, which decreased to 1.7 during 1-5 years of follow-up and 1.9 and after 5 years, Dr. Yurkovich said. He suggested that the increased risk of MI in the first year might occur because the acute inflammatory state in Sjögren’s is highest at the time of diagnosis or because the most susceptible patients had an MI early on and were no longer included in subsequent analyses.
The results remained statistically significant for MI and not for CVA after the investigators performed sensitivity analyses for unmeasured confounding variables using hypothetical low and high prevalences of 10% and 20% and low and high strengths of association in terms of odds ratios (1.3 and 3.0).
A member of the audience wondered whether antiphospholipid antibodies could have contributed to the increased risk for MI because patients with Sjögren’s syndrome typically don’t use medications such as glucocorticoids that increase atherosclerosis, and inflammation is not typically elevated in the condition, with normal C-reactive protein levels. Dr. Yurkovich replied that the cohort used glucocorticoids at a significantly higher rate than did the control group (20% vs. 4%), perhaps because they were put on them initially around the time of diagnosis, but nevertheless, the medication was one of the variables they adjusted for in the multivariable analysis. He noted that the investigators did not have antiphospholipid antibody data but they hope to obtain those and other autoantibody profiles for subsequent analyses.
Dr. Yurkovich had nothing to disclose.
PARIS – Patients with Sjögren’s syndrome appear to have a higher risk of myocardial infarction, but not stroke or transient ischemic attack, than does the general population, based on an analysis of administrative health data from British Columbia.
"Our findings support monitoring for coronary artery disease in addition to management and modification of cardiovascular disease risk factors to reduce the risk of MI in Sjögren’s syndrome patients," Dr. Marko Yurkovich said at the annual European Congress of Rheumatology.
An increased risk of MI and cerebrovascular accident (CVA) is already well known in more common rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, but the risk for either MI or CVA at the general population level in patients with Sjögren’s syndrome remains unknown, said Dr. Yurkovich, an internal medicine resident at the University of British Columbia, Vancouver.
The investigators used administrative health data from all people in British Columbia who had an outpatient visit or hospitalization during 1990-2010 to locate those who were older than 18 years and met the study’s criteria for a diagnosis of Sjögren’s syndrome. The criteria were two or more ICD-9-CM codes for the disease 2 or more months apart but within a 2-year period that were made by nonrheumatologists or one or more ICD-9-CM codes for the disease that were made by a rheumatologist or during a hospitalization.
The study excluded patients who had diagnoses of other inflammatory arthritides after the Sjögren’s diagnosis or cases in which an initial diagnosis of Sjögren’s by a nonrheumatologist was not confirmed by a rheumatologist at a later visit. MI and CVA diagnoses were defined from ICD-9-CM codes from hospital or death certificates.
"This diagnostic algorithm has been validated in a Canadian context and shown to have quite a high specificity and sensitivity, both over 95%," Dr. Yurkovich said.
In 1,176 patients with Sjögren’s syndrome, the investigators identified 28 MIs for an incidence rate of 7.7 per 1,000 person-years, compared with 138 MIs in 11,879 control individuals from the general population matched for birth year, sex, and calendar year of exposure. Patients with Sjögren’s had a significantly elevated risk for MI, compared with controls, with an incidence rate ratio of 2.19 (95% confidence interval, 1.40-3.31) and a multivariate relative risk of 2.36 (95% CI, 1.48-3.78), based on incidence rates of 7.7 per 1,000 person-years in patients with Sjögren’s and 3.4 per 1,000 person-years in controls. The relative risk for MI did not differ when the results were stratified by sex.
However, risk of incident CVA was not significantly higher among patients with Sjögren’s than in the controls, based on an incidence rate of 5.1 per 1,000 person-years among patients and 3.4 per 1,000 person-years in controls that yielded an incidence rate ratio of 1.49 and multivariable relative risk of 1.64.
The multivariable analysis controlled for angina, chronic obstructive pulmonary disease, obesity, Charlson Comorbidity Index, the number of hospitalizations in the year before the index date, and number of medications, including oral glucocorticoids, cardiovascular drugs, antidiabetic medication, hormone replacement therapy, contraceptives, fibrates, statins, NSAIDs, and COX-2 inhibitors.
"We found that the risk of MI was even further elevated within 1 year following initial diagnosis," with an incidence rate ratio of 3.6 before 1 year of follow-up, which decreased to 1.7 during 1-5 years of follow-up and 1.9 and after 5 years, Dr. Yurkovich said. He suggested that the increased risk of MI in the first year might occur because the acute inflammatory state in Sjögren’s is highest at the time of diagnosis or because the most susceptible patients had an MI early on and were no longer included in subsequent analyses.
The results remained statistically significant for MI and not for CVA after the investigators performed sensitivity analyses for unmeasured confounding variables using hypothetical low and high prevalences of 10% and 20% and low and high strengths of association in terms of odds ratios (1.3 and 3.0).
A member of the audience wondered whether antiphospholipid antibodies could have contributed to the increased risk for MI because patients with Sjögren’s syndrome typically don’t use medications such as glucocorticoids that increase atherosclerosis, and inflammation is not typically elevated in the condition, with normal C-reactive protein levels. Dr. Yurkovich replied that the cohort used glucocorticoids at a significantly higher rate than did the control group (20% vs. 4%), perhaps because they were put on them initially around the time of diagnosis, but nevertheless, the medication was one of the variables they adjusted for in the multivariable analysis. He noted that the investigators did not have antiphospholipid antibody data but they hope to obtain those and other autoantibody profiles for subsequent analyses.
Dr. Yurkovich had nothing to disclose.
PARIS – Patients with Sjögren’s syndrome appear to have a higher risk of myocardial infarction, but not stroke or transient ischemic attack, than does the general population, based on an analysis of administrative health data from British Columbia.
"Our findings support monitoring for coronary artery disease in addition to management and modification of cardiovascular disease risk factors to reduce the risk of MI in Sjögren’s syndrome patients," Dr. Marko Yurkovich said at the annual European Congress of Rheumatology.
An increased risk of MI and cerebrovascular accident (CVA) is already well known in more common rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, but the risk for either MI or CVA at the general population level in patients with Sjögren’s syndrome remains unknown, said Dr. Yurkovich, an internal medicine resident at the University of British Columbia, Vancouver.
The investigators used administrative health data from all people in British Columbia who had an outpatient visit or hospitalization during 1990-2010 to locate those who were older than 18 years and met the study’s criteria for a diagnosis of Sjögren’s syndrome. The criteria were two or more ICD-9-CM codes for the disease 2 or more months apart but within a 2-year period that were made by nonrheumatologists or one or more ICD-9-CM codes for the disease that were made by a rheumatologist or during a hospitalization.
The study excluded patients who had diagnoses of other inflammatory arthritides after the Sjögren’s diagnosis or cases in which an initial diagnosis of Sjögren’s by a nonrheumatologist was not confirmed by a rheumatologist at a later visit. MI and CVA diagnoses were defined from ICD-9-CM codes from hospital or death certificates.
"This diagnostic algorithm has been validated in a Canadian context and shown to have quite a high specificity and sensitivity, both over 95%," Dr. Yurkovich said.
In 1,176 patients with Sjögren’s syndrome, the investigators identified 28 MIs for an incidence rate of 7.7 per 1,000 person-years, compared with 138 MIs in 11,879 control individuals from the general population matched for birth year, sex, and calendar year of exposure. Patients with Sjögren’s had a significantly elevated risk for MI, compared with controls, with an incidence rate ratio of 2.19 (95% confidence interval, 1.40-3.31) and a multivariate relative risk of 2.36 (95% CI, 1.48-3.78), based on incidence rates of 7.7 per 1,000 person-years in patients with Sjögren’s and 3.4 per 1,000 person-years in controls. The relative risk for MI did not differ when the results were stratified by sex.
However, risk of incident CVA was not significantly higher among patients with Sjögren’s than in the controls, based on an incidence rate of 5.1 per 1,000 person-years among patients and 3.4 per 1,000 person-years in controls that yielded an incidence rate ratio of 1.49 and multivariable relative risk of 1.64.
The multivariable analysis controlled for angina, chronic obstructive pulmonary disease, obesity, Charlson Comorbidity Index, the number of hospitalizations in the year before the index date, and number of medications, including oral glucocorticoids, cardiovascular drugs, antidiabetic medication, hormone replacement therapy, contraceptives, fibrates, statins, NSAIDs, and COX-2 inhibitors.
"We found that the risk of MI was even further elevated within 1 year following initial diagnosis," with an incidence rate ratio of 3.6 before 1 year of follow-up, which decreased to 1.7 during 1-5 years of follow-up and 1.9 and after 5 years, Dr. Yurkovich said. He suggested that the increased risk of MI in the first year might occur because the acute inflammatory state in Sjögren’s is highest at the time of diagnosis or because the most susceptible patients had an MI early on and were no longer included in subsequent analyses.
The results remained statistically significant for MI and not for CVA after the investigators performed sensitivity analyses for unmeasured confounding variables using hypothetical low and high prevalences of 10% and 20% and low and high strengths of association in terms of odds ratios (1.3 and 3.0).
A member of the audience wondered whether antiphospholipid antibodies could have contributed to the increased risk for MI because patients with Sjögren’s syndrome typically don’t use medications such as glucocorticoids that increase atherosclerosis, and inflammation is not typically elevated in the condition, with normal C-reactive protein levels. Dr. Yurkovich replied that the cohort used glucocorticoids at a significantly higher rate than did the control group (20% vs. 4%), perhaps because they were put on them initially around the time of diagnosis, but nevertheless, the medication was one of the variables they adjusted for in the multivariable analysis. He noted that the investigators did not have antiphospholipid antibody data but they hope to obtain those and other autoantibody profiles for subsequent analyses.
Dr. Yurkovich had nothing to disclose.
AT THE EULAR CONGRESS 2014
Key clinical point: The findings support monitoring for coronary artery disease in patients with Sjögren’s syndrome in addition to management and modification of cardiovascular disease risk factors to reduce the risk of MI.
Major finding: Patients with Sjögren’s had a significantly elevated risk for MI, compared with controls, with an incidence rate ratio of 2.19 (95% CI, 1.40-3.31) and a multivariate relative risk of 2.36 (95% CI, 1.48-3.78).
Data source: A case-control study of 1,167 patients with Sjögren’s syndrome and 11,879 control individuals within an administrative health database.
Disclosures: Dr. Yurkovich had nothing to disclose.
SLE patients in remission safely stop immunotherapy
PARIS – When patients with lupus who were in remission on an immunosuppressant drug and a low dosage of prednisone stopped their immunosuppressant, 70% remained flare free 2 years off immunosuppressant treatment, in a review of 99 patients treated at one Canadian center.
Half of the patients were able to remain flare free off immunosuppressant treatment for at least 3 years, and patients who reached 3 years off treatment without flaring tended to remain stable, with a very low flare rate during 2 additional years of follow-up, Dr. Zahi Touma reported at the annual European Congress of Rheumatology.
The results "confirm that stopping immunosuppressants is possible in a selected group of lupus patients," Dr. Touma said in an interview. "Patients in clinical remission for at least 1 year and off corticosteroids or on small doses of 7.5 mg/day or less are appropriate candidates" for attempting to taper down and eventually withdraw immunosuppressant treatment, said Dr. Touma of the division of rheumatology at the University of Toronto.
"There are no guidelines on how or when to taper and stop immunosuppressants in lupus patients. At present, it is all individual physician preference. In the Toronto Lupus Clinic, in patients with clinically inactive lupus, we first aim to stop corticosteroids or reach a dose of no more than 7.5 mg/day before tapering immunosuppressants.
"Both physician and patient should agree on immunosuppressant withdrawal and discuss the possible consequences of this approach. In our study, among the 99 patients studied, 25 flared within 2 years, and 17 patients experienced a flare after year 2."
When a flare occurs in these patients, they usually restart standard of care treatment, with a corticosteroid or an immunosuppressant or both. The new study did not follow outcomes in patients who flared and then restarted standard treatment, but Dr. Touma noted that "in our clinical practice, we have witnessed patients who achieved remission after flaring, although this has not been specifically addressed in this study." He also was not sure how often patients in routine community practice who meet these criteria attempt to taper down and withdraw immunosuppressant treatment because of the lack of evidence supporting this approach.
The results also showed that a more gradual tapering down of the immunosuppressant dosage linked with a more durable remission once patients were completely off the immunosuppressant. "We have shown that the rate of flare after stopping immunosuppressants was lower in the group of patients who tapered gradually versus faster," Dr. Touma said. "In our center, we aim to taper by 25% from the baseline dose of immunosuppressant in stages, reducing by 25% every 3-6 months so that complete withdrawal is accomplished over 1-2 years."
The review included 1,678 patients with lupus seen at the Toronto Lupus Clinic, of whom 973 ever received immunosuppressant-drug treatment, and 99 of whom reached remission while on a prednisone dosage of 7.5 mg/day or less and also had no proteinuria or lupus-related thrombocytopenia or leucopenia. More than half of these 99 patients had been maintained on azathioprine prior to stopping their immunosuppressant drug, with smaller numbers of patients maintained on either methotrexate or mycophenolate mofetil.
After 2 years, 25 of the 99 patients had flared, which worked out to a 30% flare rate in a Kaplan-Meier analysis. In the same analysis, 46% of patients flared after 3 years off treatment, and 51% by 5 years off treatment. Patients who were serologically active at the time they stopped immunosuppressant therapy were more likely to flare, but Dr. Touma did not suggest using this as a criterion to select patients to withdraw from treatment.
Dr. Touma said that he had no disclosures.
On Twitter @mitchelzoler
PARIS – When patients with lupus who were in remission on an immunosuppressant drug and a low dosage of prednisone stopped their immunosuppressant, 70% remained flare free 2 years off immunosuppressant treatment, in a review of 99 patients treated at one Canadian center.
Half of the patients were able to remain flare free off immunosuppressant treatment for at least 3 years, and patients who reached 3 years off treatment without flaring tended to remain stable, with a very low flare rate during 2 additional years of follow-up, Dr. Zahi Touma reported at the annual European Congress of Rheumatology.
The results "confirm that stopping immunosuppressants is possible in a selected group of lupus patients," Dr. Touma said in an interview. "Patients in clinical remission for at least 1 year and off corticosteroids or on small doses of 7.5 mg/day or less are appropriate candidates" for attempting to taper down and eventually withdraw immunosuppressant treatment, said Dr. Touma of the division of rheumatology at the University of Toronto.
"There are no guidelines on how or when to taper and stop immunosuppressants in lupus patients. At present, it is all individual physician preference. In the Toronto Lupus Clinic, in patients with clinically inactive lupus, we first aim to stop corticosteroids or reach a dose of no more than 7.5 mg/day before tapering immunosuppressants.
"Both physician and patient should agree on immunosuppressant withdrawal and discuss the possible consequences of this approach. In our study, among the 99 patients studied, 25 flared within 2 years, and 17 patients experienced a flare after year 2."
When a flare occurs in these patients, they usually restart standard of care treatment, with a corticosteroid or an immunosuppressant or both. The new study did not follow outcomes in patients who flared and then restarted standard treatment, but Dr. Touma noted that "in our clinical practice, we have witnessed patients who achieved remission after flaring, although this has not been specifically addressed in this study." He also was not sure how often patients in routine community practice who meet these criteria attempt to taper down and withdraw immunosuppressant treatment because of the lack of evidence supporting this approach.
The results also showed that a more gradual tapering down of the immunosuppressant dosage linked with a more durable remission once patients were completely off the immunosuppressant. "We have shown that the rate of flare after stopping immunosuppressants was lower in the group of patients who tapered gradually versus faster," Dr. Touma said. "In our center, we aim to taper by 25% from the baseline dose of immunosuppressant in stages, reducing by 25% every 3-6 months so that complete withdrawal is accomplished over 1-2 years."
The review included 1,678 patients with lupus seen at the Toronto Lupus Clinic, of whom 973 ever received immunosuppressant-drug treatment, and 99 of whom reached remission while on a prednisone dosage of 7.5 mg/day or less and also had no proteinuria or lupus-related thrombocytopenia or leucopenia. More than half of these 99 patients had been maintained on azathioprine prior to stopping their immunosuppressant drug, with smaller numbers of patients maintained on either methotrexate or mycophenolate mofetil.
After 2 years, 25 of the 99 patients had flared, which worked out to a 30% flare rate in a Kaplan-Meier analysis. In the same analysis, 46% of patients flared after 3 years off treatment, and 51% by 5 years off treatment. Patients who were serologically active at the time they stopped immunosuppressant therapy were more likely to flare, but Dr. Touma did not suggest using this as a criterion to select patients to withdraw from treatment.
Dr. Touma said that he had no disclosures.
On Twitter @mitchelzoler
PARIS – When patients with lupus who were in remission on an immunosuppressant drug and a low dosage of prednisone stopped their immunosuppressant, 70% remained flare free 2 years off immunosuppressant treatment, in a review of 99 patients treated at one Canadian center.
Half of the patients were able to remain flare free off immunosuppressant treatment for at least 3 years, and patients who reached 3 years off treatment without flaring tended to remain stable, with a very low flare rate during 2 additional years of follow-up, Dr. Zahi Touma reported at the annual European Congress of Rheumatology.
The results "confirm that stopping immunosuppressants is possible in a selected group of lupus patients," Dr. Touma said in an interview. "Patients in clinical remission for at least 1 year and off corticosteroids or on small doses of 7.5 mg/day or less are appropriate candidates" for attempting to taper down and eventually withdraw immunosuppressant treatment, said Dr. Touma of the division of rheumatology at the University of Toronto.
"There are no guidelines on how or when to taper and stop immunosuppressants in lupus patients. At present, it is all individual physician preference. In the Toronto Lupus Clinic, in patients with clinically inactive lupus, we first aim to stop corticosteroids or reach a dose of no more than 7.5 mg/day before tapering immunosuppressants.
"Both physician and patient should agree on immunosuppressant withdrawal and discuss the possible consequences of this approach. In our study, among the 99 patients studied, 25 flared within 2 years, and 17 patients experienced a flare after year 2."
When a flare occurs in these patients, they usually restart standard of care treatment, with a corticosteroid or an immunosuppressant or both. The new study did not follow outcomes in patients who flared and then restarted standard treatment, but Dr. Touma noted that "in our clinical practice, we have witnessed patients who achieved remission after flaring, although this has not been specifically addressed in this study." He also was not sure how often patients in routine community practice who meet these criteria attempt to taper down and withdraw immunosuppressant treatment because of the lack of evidence supporting this approach.
The results also showed that a more gradual tapering down of the immunosuppressant dosage linked with a more durable remission once patients were completely off the immunosuppressant. "We have shown that the rate of flare after stopping immunosuppressants was lower in the group of patients who tapered gradually versus faster," Dr. Touma said. "In our center, we aim to taper by 25% from the baseline dose of immunosuppressant in stages, reducing by 25% every 3-6 months so that complete withdrawal is accomplished over 1-2 years."
The review included 1,678 patients with lupus seen at the Toronto Lupus Clinic, of whom 973 ever received immunosuppressant-drug treatment, and 99 of whom reached remission while on a prednisone dosage of 7.5 mg/day or less and also had no proteinuria or lupus-related thrombocytopenia or leucopenia. More than half of these 99 patients had been maintained on azathioprine prior to stopping their immunosuppressant drug, with smaller numbers of patients maintained on either methotrexate or mycophenolate mofetil.
After 2 years, 25 of the 99 patients had flared, which worked out to a 30% flare rate in a Kaplan-Meier analysis. In the same analysis, 46% of patients flared after 3 years off treatment, and 51% by 5 years off treatment. Patients who were serologically active at the time they stopped immunosuppressant therapy were more likely to flare, but Dr. Touma did not suggest using this as a criterion to select patients to withdraw from treatment.
Dr. Touma said that he had no disclosures.
On Twitter @mitchelzoler
AT THE EULAR CONGRESS 2014
Key clinical point: A majority of selected patients with lupus who stop immunosuppressant therapy do not flare within the next 2 years.
Major finding: Of 99 patients in remission on low-dose prednisone who stopped immunotherapy, 70% remained flare-free after 2 years.
Data source: Review of 1,678 patients with lupus seen at the University of Toronto Lupus Clinic.
Disclosures: Dr. Touma said that he had no disclosures.
VIDEO: Slow tapering worked best for stopping SLE immunosuppression
PARIS – When physicians withdrew immunosuppressant treatment from lupus patients in long-term remission, a gradual tapering down of their immunosuppressant treatment produced a lower rate of subsequent flares than did faster treatment withdrawal, based on experience with 99 patients treated at the University of Toronto.
"This study has answered a very important question," namely, what approach works best when taking patients with systemic lupus erythematosus who are in long-term remission on immunosuppressant therapy off their treatment, said Dr. Zahi Touma, a rheumatologist at the University of Toronto. When patients had their dose tapered down more gradually, they had a reduced rate of flares and needed less immunosuppressant therapy to restart, compared with patients who withdrew from treatment more quickly.
"This is not a validated approach. It is not yet even published," Dr. Touma cautioned during a video interview at the annual European Congress of Rheumatology. But the apparent advantage of more gradual treatment withdrawal "is something we found in this study," he said.
Dr. Touma said that he had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
PARIS – When physicians withdrew immunosuppressant treatment from lupus patients in long-term remission, a gradual tapering down of their immunosuppressant treatment produced a lower rate of subsequent flares than did faster treatment withdrawal, based on experience with 99 patients treated at the University of Toronto.
"This study has answered a very important question," namely, what approach works best when taking patients with systemic lupus erythematosus who are in long-term remission on immunosuppressant therapy off their treatment, said Dr. Zahi Touma, a rheumatologist at the University of Toronto. When patients had their dose tapered down more gradually, they had a reduced rate of flares and needed less immunosuppressant therapy to restart, compared with patients who withdrew from treatment more quickly.
"This is not a validated approach. It is not yet even published," Dr. Touma cautioned during a video interview at the annual European Congress of Rheumatology. But the apparent advantage of more gradual treatment withdrawal "is something we found in this study," he said.
Dr. Touma said that he had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
PARIS – When physicians withdrew immunosuppressant treatment from lupus patients in long-term remission, a gradual tapering down of their immunosuppressant treatment produced a lower rate of subsequent flares than did faster treatment withdrawal, based on experience with 99 patients treated at the University of Toronto.
"This study has answered a very important question," namely, what approach works best when taking patients with systemic lupus erythematosus who are in long-term remission on immunosuppressant therapy off their treatment, said Dr. Zahi Touma, a rheumatologist at the University of Toronto. When patients had their dose tapered down more gradually, they had a reduced rate of flares and needed less immunosuppressant therapy to restart, compared with patients who withdrew from treatment more quickly.
"This is not a validated approach. It is not yet even published," Dr. Touma cautioned during a video interview at the annual European Congress of Rheumatology. But the apparent advantage of more gradual treatment withdrawal "is something we found in this study," he said.
Dr. Touma said that he had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT THE EULAR CONGRESS 2014
Live births seen in half of pregnancies exposed to belimumab
PARIS – The live birth rate among women taking belimumab for systemic lupus erythematosus is similar to the background rate for women with the disorder, a study showed.
An analysis of clinical trials found that women who were taking the drug when they became pregnant had a live birth rate of 48% – in line with studies that place the rate at 55%-88%, Dr. Marcy Powell said at the annual European Congress of Rheumatology.
Although the number of pregnancies examined in the studies was small – with 80 exposed to belimumab (Benlysta) and 6 to placebo – the results were echoed by the initial findings in a recently established belimumab pregnancy registry, said Dr. Powell, director of safety evaluation and risk management at GlaxoSmithKline, which manufactures the drug.
More than 3,000 adult patients have been treated with belimumab – many for more than 10 years, but there are scant data on pregnancy outcomes. It’s a category C drug; women are advised to avoid pregnancy while taking it and for at least 4 months after stopping it. Thus, the only available pregnancy data are from inadvertent exposures in which the drug was stopped as soon as the pregnancy was discovered.
The data were drawn from the BLISS 52 and 78 studies, which enrolled more than 1,600 patients, 94% of whom were women. At baseline, the patients’ mean age was 38 years. Other medications were common in the cohort: 86% of patients were using corticosteroids, with 58% of those taking a prednisone equivalent of more than 5.7 mg/day. More than half (65%) were using antimalarials, and 49% were taking another immunosuppressant, including azathioprine, methotrexate, or mycophenolate mofetil.
Of the six pregnancies among patients assigned to placebo, there were three elective terminations, two spontaneous miscarriages, and one stillbirth, for a total fetal loss rate of 50%. The three pregnancies with fetal loss included two women who tested positive for anticardiolipin antibodies.
Among the 80 drug-exposed pregnancies, there were 21 elective terminations as well as 20 miscarriages and 1 stillbirth, yielding a total fetal loss rate of 26%. The background miscarriage rate was 12%-22%, and the background stillbirth rate was 2%-5%, both of which are similar to rates observed in the exposed pregnancies. Overall, women tested positive for anticardiolipin antibodies in 20 pregnancies exposed to belimumab, including 21% of the live births and 38% of the fetal losses.
There were 38 live births (48%). Four neonates had a congenital anomaly:
• One with Dandy-Walker syndrome.
• One with an unbalanced translocation (11 and 13) of maternal origin, a strictly genetic anomaly.
• One born at 27 weeks’ gestation with patent ductus arteriosus.
• One with bilateral enlarged kidneys with abnormal function whose mother was receiving ambrisentan, a known teratogen, for portal hypertension. (The infant was placed on dialysis and had the right kidney removed.)
The stillbirths in the placebo and belimumab patients occurred in conjunction with severe, very early third-trimester preeclampsia, Dr. Powell said. She noted that the sample size is so small that it’s unclear whether the results can be extrapolated to larger populations.
However, the Belimumab Pregnancy Registry, established by GlaxoSmithKline, could provide more reliable data, she said. So far, the registry has enrolled nine pregnancies, seven of which have been completed. Among those, there have been six live births and one miscarriage. Three of the infants were preterm, born at 32, 35, and 36 weeks’ gestation. There was one birth defect (mild Epstein’s anomaly of the tricuspid valve).
On Twitter @alz_gal
PARIS – The live birth rate among women taking belimumab for systemic lupus erythematosus is similar to the background rate for women with the disorder, a study showed.
An analysis of clinical trials found that women who were taking the drug when they became pregnant had a live birth rate of 48% – in line with studies that place the rate at 55%-88%, Dr. Marcy Powell said at the annual European Congress of Rheumatology.
Although the number of pregnancies examined in the studies was small – with 80 exposed to belimumab (Benlysta) and 6 to placebo – the results were echoed by the initial findings in a recently established belimumab pregnancy registry, said Dr. Powell, director of safety evaluation and risk management at GlaxoSmithKline, which manufactures the drug.
More than 3,000 adult patients have been treated with belimumab – many for more than 10 years, but there are scant data on pregnancy outcomes. It’s a category C drug; women are advised to avoid pregnancy while taking it and for at least 4 months after stopping it. Thus, the only available pregnancy data are from inadvertent exposures in which the drug was stopped as soon as the pregnancy was discovered.
The data were drawn from the BLISS 52 and 78 studies, which enrolled more than 1,600 patients, 94% of whom were women. At baseline, the patients’ mean age was 38 years. Other medications were common in the cohort: 86% of patients were using corticosteroids, with 58% of those taking a prednisone equivalent of more than 5.7 mg/day. More than half (65%) were using antimalarials, and 49% were taking another immunosuppressant, including azathioprine, methotrexate, or mycophenolate mofetil.
Of the six pregnancies among patients assigned to placebo, there were three elective terminations, two spontaneous miscarriages, and one stillbirth, for a total fetal loss rate of 50%. The three pregnancies with fetal loss included two women who tested positive for anticardiolipin antibodies.
Among the 80 drug-exposed pregnancies, there were 21 elective terminations as well as 20 miscarriages and 1 stillbirth, yielding a total fetal loss rate of 26%. The background miscarriage rate was 12%-22%, and the background stillbirth rate was 2%-5%, both of which are similar to rates observed in the exposed pregnancies. Overall, women tested positive for anticardiolipin antibodies in 20 pregnancies exposed to belimumab, including 21% of the live births and 38% of the fetal losses.
There were 38 live births (48%). Four neonates had a congenital anomaly:
• One with Dandy-Walker syndrome.
• One with an unbalanced translocation (11 and 13) of maternal origin, a strictly genetic anomaly.
• One born at 27 weeks’ gestation with patent ductus arteriosus.
• One with bilateral enlarged kidneys with abnormal function whose mother was receiving ambrisentan, a known teratogen, for portal hypertension. (The infant was placed on dialysis and had the right kidney removed.)
The stillbirths in the placebo and belimumab patients occurred in conjunction with severe, very early third-trimester preeclampsia, Dr. Powell said. She noted that the sample size is so small that it’s unclear whether the results can be extrapolated to larger populations.
However, the Belimumab Pregnancy Registry, established by GlaxoSmithKline, could provide more reliable data, she said. So far, the registry has enrolled nine pregnancies, seven of which have been completed. Among those, there have been six live births and one miscarriage. Three of the infants were preterm, born at 32, 35, and 36 weeks’ gestation. There was one birth defect (mild Epstein’s anomaly of the tricuspid valve).
On Twitter @alz_gal
PARIS – The live birth rate among women taking belimumab for systemic lupus erythematosus is similar to the background rate for women with the disorder, a study showed.
An analysis of clinical trials found that women who were taking the drug when they became pregnant had a live birth rate of 48% – in line with studies that place the rate at 55%-88%, Dr. Marcy Powell said at the annual European Congress of Rheumatology.
Although the number of pregnancies examined in the studies was small – with 80 exposed to belimumab (Benlysta) and 6 to placebo – the results were echoed by the initial findings in a recently established belimumab pregnancy registry, said Dr. Powell, director of safety evaluation and risk management at GlaxoSmithKline, which manufactures the drug.
More than 3,000 adult patients have been treated with belimumab – many for more than 10 years, but there are scant data on pregnancy outcomes. It’s a category C drug; women are advised to avoid pregnancy while taking it and for at least 4 months after stopping it. Thus, the only available pregnancy data are from inadvertent exposures in which the drug was stopped as soon as the pregnancy was discovered.
The data were drawn from the BLISS 52 and 78 studies, which enrolled more than 1,600 patients, 94% of whom were women. At baseline, the patients’ mean age was 38 years. Other medications were common in the cohort: 86% of patients were using corticosteroids, with 58% of those taking a prednisone equivalent of more than 5.7 mg/day. More than half (65%) were using antimalarials, and 49% were taking another immunosuppressant, including azathioprine, methotrexate, or mycophenolate mofetil.
Of the six pregnancies among patients assigned to placebo, there were three elective terminations, two spontaneous miscarriages, and one stillbirth, for a total fetal loss rate of 50%. The three pregnancies with fetal loss included two women who tested positive for anticardiolipin antibodies.
Among the 80 drug-exposed pregnancies, there were 21 elective terminations as well as 20 miscarriages and 1 stillbirth, yielding a total fetal loss rate of 26%. The background miscarriage rate was 12%-22%, and the background stillbirth rate was 2%-5%, both of which are similar to rates observed in the exposed pregnancies. Overall, women tested positive for anticardiolipin antibodies in 20 pregnancies exposed to belimumab, including 21% of the live births and 38% of the fetal losses.
There were 38 live births (48%). Four neonates had a congenital anomaly:
• One with Dandy-Walker syndrome.
• One with an unbalanced translocation (11 and 13) of maternal origin, a strictly genetic anomaly.
• One born at 27 weeks’ gestation with patent ductus arteriosus.
• One with bilateral enlarged kidneys with abnormal function whose mother was receiving ambrisentan, a known teratogen, for portal hypertension. (The infant was placed on dialysis and had the right kidney removed.)
The stillbirths in the placebo and belimumab patients occurred in conjunction with severe, very early third-trimester preeclampsia, Dr. Powell said. She noted that the sample size is so small that it’s unclear whether the results can be extrapolated to larger populations.
However, the Belimumab Pregnancy Registry, established by GlaxoSmithKline, could provide more reliable data, she said. So far, the registry has enrolled nine pregnancies, seven of which have been completed. Among those, there have been six live births and one miscarriage. Three of the infants were preterm, born at 32, 35, and 36 weeks’ gestation. There was one birth defect (mild Epstein’s anomaly of the tricuspid valve).
On Twitter @alz_gal
AT THE EULAR CONGRESS 2014
Key clinical point: Successful pregnancies are possible in SLE patients exposed to belimumab.
Major finding: The live birth rate was 48%, and the total fetal loss rate was 26%.
Data source: A cohort of 86 pregnancies and 9 additional pregnancies in a registry database.
Disclosures: Dr. Powell is director of safety evaluation and risk management at GlaxoSmithKline.
VIDEO: Sarilumab shows RA safety, efficacy in phase III trial
PARIS – Treatment with the interleukin-6–blocking drug sarilumab led to statistically significant and clinically meaningful improvements in patients with rheumatoid arthritis in a multicenter, placebo controlled, phase III trial with 1,197 patients.
The safety and efficacy results from the SARIL-RA-MOBILITY trial are the first outcomes from a panel of phase III studies of sarilumab in patients with rheumatoid arthritis, said Dr. Mark Genovese at the annual European Congress of Rheumatology. The results showed that treatment with sarilumab plus methotrexate led to less joint damage over time, compared with methotrexate plus placebo, a benefit that should result in patients feeling better, said Dr. Genovese, professor of medicine and co-chief of the division of immunology and rheumatology at Stanford (Calif.) University.
Sarilumab is the first agent to progress this far in testing from a novel class of immunosuppressive drugs that work by blocking interleukin-6. Having safe drugs from a new class available to treat patients with rheumatoid arthritis holds promise for better controlling this disease in patients who inadequately respond to existing drug options, Dr. Genovese said in a video interview.
The SARIL-RA-MOBILITY trial was sponsored by Sanofi and Regeneron, the companies developing the drug. Dr. Genovese said that he has been a consultant to and received research support from Sanofi. Several of the coauthors are employees of Sanofi or Regeneron.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
PARIS – Treatment with the interleukin-6–blocking drug sarilumab led to statistically significant and clinically meaningful improvements in patients with rheumatoid arthritis in a multicenter, placebo controlled, phase III trial with 1,197 patients.
The safety and efficacy results from the SARIL-RA-MOBILITY trial are the first outcomes from a panel of phase III studies of sarilumab in patients with rheumatoid arthritis, said Dr. Mark Genovese at the annual European Congress of Rheumatology. The results showed that treatment with sarilumab plus methotrexate led to less joint damage over time, compared with methotrexate plus placebo, a benefit that should result in patients feeling better, said Dr. Genovese, professor of medicine and co-chief of the division of immunology and rheumatology at Stanford (Calif.) University.
Sarilumab is the first agent to progress this far in testing from a novel class of immunosuppressive drugs that work by blocking interleukin-6. Having safe drugs from a new class available to treat patients with rheumatoid arthritis holds promise for better controlling this disease in patients who inadequately respond to existing drug options, Dr. Genovese said in a video interview.
The SARIL-RA-MOBILITY trial was sponsored by Sanofi and Regeneron, the companies developing the drug. Dr. Genovese said that he has been a consultant to and received research support from Sanofi. Several of the coauthors are employees of Sanofi or Regeneron.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
PARIS – Treatment with the interleukin-6–blocking drug sarilumab led to statistically significant and clinically meaningful improvements in patients with rheumatoid arthritis in a multicenter, placebo controlled, phase III trial with 1,197 patients.
The safety and efficacy results from the SARIL-RA-MOBILITY trial are the first outcomes from a panel of phase III studies of sarilumab in patients with rheumatoid arthritis, said Dr. Mark Genovese at the annual European Congress of Rheumatology. The results showed that treatment with sarilumab plus methotrexate led to less joint damage over time, compared with methotrexate plus placebo, a benefit that should result in patients feeling better, said Dr. Genovese, professor of medicine and co-chief of the division of immunology and rheumatology at Stanford (Calif.) University.
Sarilumab is the first agent to progress this far in testing from a novel class of immunosuppressive drugs that work by blocking interleukin-6. Having safe drugs from a new class available to treat patients with rheumatoid arthritis holds promise for better controlling this disease in patients who inadequately respond to existing drug options, Dr. Genovese said in a video interview.
The SARIL-RA-MOBILITY trial was sponsored by Sanofi and Regeneron, the companies developing the drug. Dr. Genovese said that he has been a consultant to and received research support from Sanofi. Several of the coauthors are employees of Sanofi or Regeneron.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT THE EULAR CONGRESS 2014
Physically demanding jobs link to worse ankylosing spondylitis progression
PARIS – Patients with ankylosing spondylitis who worked at more physically-demanding jobs showed greater radiographic progression than did patients who performed more sedentary jobs in a prospective cohort study with 136 patients.
The findings immediately raised questions about "our commonly given advice to patients with spondylarthritis to strenuously exercise. Should physically demanding labor be discouraged?" asked Dr. Sofia Ramiro at the annual European Congress of Rheumatology.
Dr. Ramiro stressed that the finding needs confirmation from studies in other cohorts of patients with ankylosing spondylitis (AS), but it raises the possibility that certain stresses and loads on the spine, from work or exercise, can worsen disease severity.
"If we can confirm that mechanical stress has an impact on radiographic progression, then I think we would have to analyze further and identify the type of activity having this impact, and then recommend the activity not be done," said Dr. Ramiro, a researcher at the Amsterdam Rheumatology Center, University of Amsterdam.
"I’m not saying that we would stop recommending exercise and that patients with AS should stay quiet at home, but perhaps we will advise against certain types of exercise," Dr. Ramiro said in an interview.
Dr. Ramiro and her associates previously reported this year that disease activity contributed longitudinally to radiographic AS progression during up to 12 years of follow-up (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2014-205178]). They further evaluated patients in the same cohort, 184 AS patients enrolled in OASIS (the Outcome in AS International Study), for additional factors that might affect radiographic progression either directly or indirectly. In addition to documenting a link between disease activity and radiographic progression, the report earlier this year had identified sex and disease duration as modifiers of the impact of disease activity. This impact on radiographic progression was greater in men, and early during the course of AS.
The new analysis looked for possible effects from smoking, and for chronic activity patterns using the surrogate marker of job type. The 184 patients in OASIS were sorted by their type of regular work, which identified 65 people with physically demanding (blue collar) jobs and 71 with relatively sedentary (white collar) jobs. The other 48 patients had either missing employment data or jobs with less clear links to activity levels, such as students or homemakers.
The findings showed that neither smoking nor job type appeared to have a direct influence on radiographic progression, but that smoking and a physically demanding job each had significant indirect effects. A physically demanding job linked with a 1.19-U increase in a measure of radiographic progression (the modified Stoke AS Spine Score, or mSASSS) for every 1-U increase in a measure of disease activity (the AS disease activity score, or ASDAS) during 2 years of follow-up, Dr. Ramiro reported. In contrast, the impact of a sedentary job was a 0.20-U rise in mSASSS for each 1-U rise in ASDAS. Smoking produced a 1.95-U rise in the mSASSS for each 1-U rise in ASDAS, significantly more than the 0.35 rate among nonsmokers.
Personal income, family income, and education each showed no statistically significant link with radiographic progression.
When the investigators analyzed job activity in subgroups divided by sex, they found that the relationship between a more physically demanding job and increased radiographic progression remained statistically significant in men, but the relationship was no longer significant in women.
The researchers could not include leisure activity or sports participation in their analysis as these data were not available. In addition, analysis by leisure activity may pose problems because baseline data on leisure activity may not extrapolate long-term, and patients can also have recall bias when reporting leisure activity, Dr. Ramiro said.
Dr. Ramiro said that she had no disclosures.
On Twitter @mitchelzoler
The relationships reported in this study between both job type and smoking and more extensive radiographic progression in patients with ankylosing spondylitis are probably true. This is not the first study of patients with ankylosing spondylitis to produce results that show these relationships, and the job-related effect is consistent with animal models of AS and the impact of chronic mechanical stress on progression.
Pain and other symptoms of AS improve with activity, but the findings by Dr. Ramiro as well as by others suggest that certain types of activity can worsen progression.
How this may apply to managing patients depends on the magnitude of the effect, and what options a patient might have. Many patients do not have a real choice about the work they do. In addition, we continue to advise patients to do what we consider therapeutic exercises, ideally 20-30 minutes daily. It is possible that therapeutic exercises could counterbalance the bad effects from work-related mechanical stress.
Dr. Martin Rudwaleit is a professor of rheumatology and nephrology at the Endokrinologikum in Berlin. He said that he has been a consultant to and has received honoraria from nine drug companies. He made these comments in an interview.
The relationships reported in this study between both job type and smoking and more extensive radiographic progression in patients with ankylosing spondylitis are probably true. This is not the first study of patients with ankylosing spondylitis to produce results that show these relationships, and the job-related effect is consistent with animal models of AS and the impact of chronic mechanical stress on progression.
Pain and other symptoms of AS improve with activity, but the findings by Dr. Ramiro as well as by others suggest that certain types of activity can worsen progression.
How this may apply to managing patients depends on the magnitude of the effect, and what options a patient might have. Many patients do not have a real choice about the work they do. In addition, we continue to advise patients to do what we consider therapeutic exercises, ideally 20-30 minutes daily. It is possible that therapeutic exercises could counterbalance the bad effects from work-related mechanical stress.
Dr. Martin Rudwaleit is a professor of rheumatology and nephrology at the Endokrinologikum in Berlin. He said that he has been a consultant to and has received honoraria from nine drug companies. He made these comments in an interview.
The relationships reported in this study between both job type and smoking and more extensive radiographic progression in patients with ankylosing spondylitis are probably true. This is not the first study of patients with ankylosing spondylitis to produce results that show these relationships, and the job-related effect is consistent with animal models of AS and the impact of chronic mechanical stress on progression.
Pain and other symptoms of AS improve with activity, but the findings by Dr. Ramiro as well as by others suggest that certain types of activity can worsen progression.
How this may apply to managing patients depends on the magnitude of the effect, and what options a patient might have. Many patients do not have a real choice about the work they do. In addition, we continue to advise patients to do what we consider therapeutic exercises, ideally 20-30 minutes daily. It is possible that therapeutic exercises could counterbalance the bad effects from work-related mechanical stress.
Dr. Martin Rudwaleit is a professor of rheumatology and nephrology at the Endokrinologikum in Berlin. He said that he has been a consultant to and has received honoraria from nine drug companies. He made these comments in an interview.
PARIS – Patients with ankylosing spondylitis who worked at more physically-demanding jobs showed greater radiographic progression than did patients who performed more sedentary jobs in a prospective cohort study with 136 patients.
The findings immediately raised questions about "our commonly given advice to patients with spondylarthritis to strenuously exercise. Should physically demanding labor be discouraged?" asked Dr. Sofia Ramiro at the annual European Congress of Rheumatology.
Dr. Ramiro stressed that the finding needs confirmation from studies in other cohorts of patients with ankylosing spondylitis (AS), but it raises the possibility that certain stresses and loads on the spine, from work or exercise, can worsen disease severity.
"If we can confirm that mechanical stress has an impact on radiographic progression, then I think we would have to analyze further and identify the type of activity having this impact, and then recommend the activity not be done," said Dr. Ramiro, a researcher at the Amsterdam Rheumatology Center, University of Amsterdam.
"I’m not saying that we would stop recommending exercise and that patients with AS should stay quiet at home, but perhaps we will advise against certain types of exercise," Dr. Ramiro said in an interview.
Dr. Ramiro and her associates previously reported this year that disease activity contributed longitudinally to radiographic AS progression during up to 12 years of follow-up (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2014-205178]). They further evaluated patients in the same cohort, 184 AS patients enrolled in OASIS (the Outcome in AS International Study), for additional factors that might affect radiographic progression either directly or indirectly. In addition to documenting a link between disease activity and radiographic progression, the report earlier this year had identified sex and disease duration as modifiers of the impact of disease activity. This impact on radiographic progression was greater in men, and early during the course of AS.
The new analysis looked for possible effects from smoking, and for chronic activity patterns using the surrogate marker of job type. The 184 patients in OASIS were sorted by their type of regular work, which identified 65 people with physically demanding (blue collar) jobs and 71 with relatively sedentary (white collar) jobs. The other 48 patients had either missing employment data or jobs with less clear links to activity levels, such as students or homemakers.
The findings showed that neither smoking nor job type appeared to have a direct influence on radiographic progression, but that smoking and a physically demanding job each had significant indirect effects. A physically demanding job linked with a 1.19-U increase in a measure of radiographic progression (the modified Stoke AS Spine Score, or mSASSS) for every 1-U increase in a measure of disease activity (the AS disease activity score, or ASDAS) during 2 years of follow-up, Dr. Ramiro reported. In contrast, the impact of a sedentary job was a 0.20-U rise in mSASSS for each 1-U rise in ASDAS. Smoking produced a 1.95-U rise in the mSASSS for each 1-U rise in ASDAS, significantly more than the 0.35 rate among nonsmokers.
Personal income, family income, and education each showed no statistically significant link with radiographic progression.
When the investigators analyzed job activity in subgroups divided by sex, they found that the relationship between a more physically demanding job and increased radiographic progression remained statistically significant in men, but the relationship was no longer significant in women.
The researchers could not include leisure activity or sports participation in their analysis as these data were not available. In addition, analysis by leisure activity may pose problems because baseline data on leisure activity may not extrapolate long-term, and patients can also have recall bias when reporting leisure activity, Dr. Ramiro said.
Dr. Ramiro said that she had no disclosures.
On Twitter @mitchelzoler
PARIS – Patients with ankylosing spondylitis who worked at more physically-demanding jobs showed greater radiographic progression than did patients who performed more sedentary jobs in a prospective cohort study with 136 patients.
The findings immediately raised questions about "our commonly given advice to patients with spondylarthritis to strenuously exercise. Should physically demanding labor be discouraged?" asked Dr. Sofia Ramiro at the annual European Congress of Rheumatology.
Dr. Ramiro stressed that the finding needs confirmation from studies in other cohorts of patients with ankylosing spondylitis (AS), but it raises the possibility that certain stresses and loads on the spine, from work or exercise, can worsen disease severity.
"If we can confirm that mechanical stress has an impact on radiographic progression, then I think we would have to analyze further and identify the type of activity having this impact, and then recommend the activity not be done," said Dr. Ramiro, a researcher at the Amsterdam Rheumatology Center, University of Amsterdam.
"I’m not saying that we would stop recommending exercise and that patients with AS should stay quiet at home, but perhaps we will advise against certain types of exercise," Dr. Ramiro said in an interview.
Dr. Ramiro and her associates previously reported this year that disease activity contributed longitudinally to radiographic AS progression during up to 12 years of follow-up (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2014-205178]). They further evaluated patients in the same cohort, 184 AS patients enrolled in OASIS (the Outcome in AS International Study), for additional factors that might affect radiographic progression either directly or indirectly. In addition to documenting a link between disease activity and radiographic progression, the report earlier this year had identified sex and disease duration as modifiers of the impact of disease activity. This impact on radiographic progression was greater in men, and early during the course of AS.
The new analysis looked for possible effects from smoking, and for chronic activity patterns using the surrogate marker of job type. The 184 patients in OASIS were sorted by their type of regular work, which identified 65 people with physically demanding (blue collar) jobs and 71 with relatively sedentary (white collar) jobs. The other 48 patients had either missing employment data or jobs with less clear links to activity levels, such as students or homemakers.
The findings showed that neither smoking nor job type appeared to have a direct influence on radiographic progression, but that smoking and a physically demanding job each had significant indirect effects. A physically demanding job linked with a 1.19-U increase in a measure of radiographic progression (the modified Stoke AS Spine Score, or mSASSS) for every 1-U increase in a measure of disease activity (the AS disease activity score, or ASDAS) during 2 years of follow-up, Dr. Ramiro reported. In contrast, the impact of a sedentary job was a 0.20-U rise in mSASSS for each 1-U rise in ASDAS. Smoking produced a 1.95-U rise in the mSASSS for each 1-U rise in ASDAS, significantly more than the 0.35 rate among nonsmokers.
Personal income, family income, and education each showed no statistically significant link with radiographic progression.
When the investigators analyzed job activity in subgroups divided by sex, they found that the relationship between a more physically demanding job and increased radiographic progression remained statistically significant in men, but the relationship was no longer significant in women.
The researchers could not include leisure activity or sports participation in their analysis as these data were not available. In addition, analysis by leisure activity may pose problems because baseline data on leisure activity may not extrapolate long-term, and patients can also have recall bias when reporting leisure activity, Dr. Ramiro said.
Dr. Ramiro said that she had no disclosures.
On Twitter @mitchelzoler
AT THE EULAR CONGRESS 2014
Key clinical point: Patients with AS who have more physically demanding jobs showed greater radiographic progression than did patients with more sedentary jobs.
Major finding: Physically demanding jobs linked with an average 1.19-U increase in mSASSS for every 1-U increase in ASDAS, compared with a 0.20-U increase in more sedentary patients.
Data source: Up to 12-year follow-up of a prospectively studied cohort with 136 evaluable patients.
Disclosures: Dr. Ramiro said that she had no disclosures.
Eurofever Project takes aim at rare autoinflammatory disorders
PARIS – A large international registry aims to gather extensive data on the presentation, complications, and treatment response of rare autoinflammatory diseases in both children and adults, according to principal investigator Dr. Marco Gattorno.
Launched in 2009, the Eurofever Project is being conducted in 67 rheumatology centers across 31 countries. So far it has accumulated nearly 3,000 patients, about 70% of whom are children. The registry has thus far generated 10 papers that involved more than 50 centers and many more studies are in the offing, Dr. Gattorno said at the annual European Congress of Rheumatology.
"The Eurofever registry gives an epidemiological overview of the distribution and prevalence of these rare disorders in Europe and other countries," he said in an interview. "The aim was to understand who the patients are and who is following them. The registry is also collecting information on the clinical manifestations and complications associated with different diseases and on the response to treatment from disease onset to enrollment."
An online survey collects information on 15 of these rare diseases. Several present very early in life as sudden-onset, recurrent fever, often accompanied by rash, serositis, lymphadenopathy, or arthritis. Disease flares are usually separated by symptom-free intervals of variable duration, characterized by complete well-being, normal growth, and normalization of acute phase reactants. This cycle can result in a considerable delay in diagnosis, the project has determined –from 5 years for children with FMF [familial Mediterranean fever] to "an incredibly astonishing delay of 18 years" for children with TRAPS [tumor necrosis factor receptor–associated periodic syndrome], CAPS [cryopyrin-associated periodic syndrome], and MKD [mevalonate kinase deficiency], said Dr. Gattorno, a pediatric rheumatologist at the IRCCS Institute Giannina Gaslini in Genoa, Italy.
Fortunately, he noted, a recent paper drawn from Eurofever data has found that these delays are shortening. Although patients born in the 1970s and 1980s typically faced decades of diagnostic confusion, children born in the 1990s and early in this century are being diagnosed much sooner – often within 5 years, he noted.
The creation of new, evidence-based diagnostic and classification criteria is also the direct result of the Eurofever registry. A paper in process is building such systems for MKD, TRAPS, CAPS, and FMF.
Primary investigator Maria Pia Sormani, Ph.D., of the University of Genoa and her colleagues, have created scoring systems for each disorder based on the presence and absence of specific demographic and clinical characteristics. Meeting or exceeding the predetermined cutoff point for each will provide a "gold standard" for diagnosis, Dr. Gattorno said.
As the Eurofever registry continues to grow, it is adding other rare disorders, he said. These include deficiency of interleukin-36 receptor antagonist (DITRA); chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE); Schnitzler syndrome (chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a low-level monoclonal immunoglobulin M gammopathy); and ADA2 deficiency, a rare syndrome of sporadic fevers, skin rashes, and recurring strokes that begins early in childhood.
Eurofever is sponsored by the Executive Agency for Health and Consumers of European Union and other EU grants, as well as unrestricted grants by Novartis and SOBI, from which Dr. Gattorno has received speakers fees. The technical expertise is provided by the Paediatric Rheumatology International Trials Organisation.
The registry is actively enrolling patients. Information on the registry and how to participate can be found at the Eurofever website.
On Twitter @alz_gal
PARIS – A large international registry aims to gather extensive data on the presentation, complications, and treatment response of rare autoinflammatory diseases in both children and adults, according to principal investigator Dr. Marco Gattorno.
Launched in 2009, the Eurofever Project is being conducted in 67 rheumatology centers across 31 countries. So far it has accumulated nearly 3,000 patients, about 70% of whom are children. The registry has thus far generated 10 papers that involved more than 50 centers and many more studies are in the offing, Dr. Gattorno said at the annual European Congress of Rheumatology.
"The Eurofever registry gives an epidemiological overview of the distribution and prevalence of these rare disorders in Europe and other countries," he said in an interview. "The aim was to understand who the patients are and who is following them. The registry is also collecting information on the clinical manifestations and complications associated with different diseases and on the response to treatment from disease onset to enrollment."
An online survey collects information on 15 of these rare diseases. Several present very early in life as sudden-onset, recurrent fever, often accompanied by rash, serositis, lymphadenopathy, or arthritis. Disease flares are usually separated by symptom-free intervals of variable duration, characterized by complete well-being, normal growth, and normalization of acute phase reactants. This cycle can result in a considerable delay in diagnosis, the project has determined –from 5 years for children with FMF [familial Mediterranean fever] to "an incredibly astonishing delay of 18 years" for children with TRAPS [tumor necrosis factor receptor–associated periodic syndrome], CAPS [cryopyrin-associated periodic syndrome], and MKD [mevalonate kinase deficiency], said Dr. Gattorno, a pediatric rheumatologist at the IRCCS Institute Giannina Gaslini in Genoa, Italy.
Fortunately, he noted, a recent paper drawn from Eurofever data has found that these delays are shortening. Although patients born in the 1970s and 1980s typically faced decades of diagnostic confusion, children born in the 1990s and early in this century are being diagnosed much sooner – often within 5 years, he noted.
The creation of new, evidence-based diagnostic and classification criteria is also the direct result of the Eurofever registry. A paper in process is building such systems for MKD, TRAPS, CAPS, and FMF.
Primary investigator Maria Pia Sormani, Ph.D., of the University of Genoa and her colleagues, have created scoring systems for each disorder based on the presence and absence of specific demographic and clinical characteristics. Meeting or exceeding the predetermined cutoff point for each will provide a "gold standard" for diagnosis, Dr. Gattorno said.
As the Eurofever registry continues to grow, it is adding other rare disorders, he said. These include deficiency of interleukin-36 receptor antagonist (DITRA); chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE); Schnitzler syndrome (chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a low-level monoclonal immunoglobulin M gammopathy); and ADA2 deficiency, a rare syndrome of sporadic fevers, skin rashes, and recurring strokes that begins early in childhood.
Eurofever is sponsored by the Executive Agency for Health and Consumers of European Union and other EU grants, as well as unrestricted grants by Novartis and SOBI, from which Dr. Gattorno has received speakers fees. The technical expertise is provided by the Paediatric Rheumatology International Trials Organisation.
The registry is actively enrolling patients. Information on the registry and how to participate can be found at the Eurofever website.
On Twitter @alz_gal
PARIS – A large international registry aims to gather extensive data on the presentation, complications, and treatment response of rare autoinflammatory diseases in both children and adults, according to principal investigator Dr. Marco Gattorno.
Launched in 2009, the Eurofever Project is being conducted in 67 rheumatology centers across 31 countries. So far it has accumulated nearly 3,000 patients, about 70% of whom are children. The registry has thus far generated 10 papers that involved more than 50 centers and many more studies are in the offing, Dr. Gattorno said at the annual European Congress of Rheumatology.
"The Eurofever registry gives an epidemiological overview of the distribution and prevalence of these rare disorders in Europe and other countries," he said in an interview. "The aim was to understand who the patients are and who is following them. The registry is also collecting information on the clinical manifestations and complications associated with different diseases and on the response to treatment from disease onset to enrollment."
An online survey collects information on 15 of these rare diseases. Several present very early in life as sudden-onset, recurrent fever, often accompanied by rash, serositis, lymphadenopathy, or arthritis. Disease flares are usually separated by symptom-free intervals of variable duration, characterized by complete well-being, normal growth, and normalization of acute phase reactants. This cycle can result in a considerable delay in diagnosis, the project has determined –from 5 years for children with FMF [familial Mediterranean fever] to "an incredibly astonishing delay of 18 years" for children with TRAPS [tumor necrosis factor receptor–associated periodic syndrome], CAPS [cryopyrin-associated periodic syndrome], and MKD [mevalonate kinase deficiency], said Dr. Gattorno, a pediatric rheumatologist at the IRCCS Institute Giannina Gaslini in Genoa, Italy.
Fortunately, he noted, a recent paper drawn from Eurofever data has found that these delays are shortening. Although patients born in the 1970s and 1980s typically faced decades of diagnostic confusion, children born in the 1990s and early in this century are being diagnosed much sooner – often within 5 years, he noted.
The creation of new, evidence-based diagnostic and classification criteria is also the direct result of the Eurofever registry. A paper in process is building such systems for MKD, TRAPS, CAPS, and FMF.
Primary investigator Maria Pia Sormani, Ph.D., of the University of Genoa and her colleagues, have created scoring systems for each disorder based on the presence and absence of specific demographic and clinical characteristics. Meeting or exceeding the predetermined cutoff point for each will provide a "gold standard" for diagnosis, Dr. Gattorno said.
As the Eurofever registry continues to grow, it is adding other rare disorders, he said. These include deficiency of interleukin-36 receptor antagonist (DITRA); chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE); Schnitzler syndrome (chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a low-level monoclonal immunoglobulin M gammopathy); and ADA2 deficiency, a rare syndrome of sporadic fevers, skin rashes, and recurring strokes that begins early in childhood.
Eurofever is sponsored by the Executive Agency for Health and Consumers of European Union and other EU grants, as well as unrestricted grants by Novartis and SOBI, from which Dr. Gattorno has received speakers fees. The technical expertise is provided by the Paediatric Rheumatology International Trials Organisation.
The registry is actively enrolling patients. Information on the registry and how to participate can be found at the Eurofever website.
On Twitter @alz_gal
AT THE EULAR CONGRESS 2014
Factors that lead to gout often differ in men and women
PARIS – Women have different predisposing risk factors for gout than do men, who more often fit the stereotypical profile of patients with gout who consume foods that increase the risk of the disease.
In the study based on data collected from participants in the Consortium of Rheumatology Researchers of North America (CORRONA) gout registry, women with gout were more likely to have taken predisposing medications and to have more gout-associated comorbidities, whereas men were more likely to consume foods linked to the disorder, such as alcohol and red meat, according to Dr. Leslie Harrold, scientific director of the CORRONA gout registry.
"We live in an era of personalized medicine," she said in an interview. "These findings speak to the need to tailor our evaluations and treatments based on the patient. There cannot be a one-size-fits-all approach. We need to approach women with gout differently than men with gout."
Patients in the gout study were enrolled in 2012-2013. Data gathered from patients and their rheumatologists at study enrollment included demographics, predisposing factors (comorbid conditions, medications, diet), gout disease characteristics, current treatments, and physical exam findings.
The 54 participating rheumatologists enrolled 1,167 gout patients (239 women). Women were significantly older than men (71 years vs. 61 years) and had higher body mass index (34 kg/m2 vs. 23 kg/m2). They also were significantly more likely to have hypertension (77% vs. 57%), diabetes (28% vs. 17%), and renal disease (25% vs. 14%).
Women also had a shorter duration of gout when enrolled (6 years vs. 11 years) and were less likely to have a crystal-proven diagnosis (26% vs. 35%).
Medication risk factors for gout, such as diuretics, were more common in women (49% vs. 22%), while dietary risk factors were more frequent in men, who consumed significantly more beer, hard liquor, beef, and pork, Dr. Harrold reported at the annual European Congress of Rheumatology.
Although the clinical features of gout were similar between the genders at the time of initial diagnosis, women reported more frequent disability. Women were more likely to have contraindications to treatment with NSAIDs or colchicine, but women with tophi or active disease – defined as two or more flares per year – used urate-lowering therapy at a rate that was not statistically different from men (78% vs. 84%).
"I think what is most interesting is that the profile of men and women with gout differs," said Dr. Harrold of the division of rheumatology at the University of Massachusetts, Worcester. "Doctors usually have a single concept of the typical patient. But instead, here we have to realize that the typical woman with gout is different than the typical man with gout. That should frame our evaluation of suspected cases."
A number of pharmaceutical companies have financially supported the CORRONA registry. In the last 5 years, Dr. Harrold has received research funding from Takeda and has a pending grant with AstraZeneca.
PARIS – Women have different predisposing risk factors for gout than do men, who more often fit the stereotypical profile of patients with gout who consume foods that increase the risk of the disease.
In the study based on data collected from participants in the Consortium of Rheumatology Researchers of North America (CORRONA) gout registry, women with gout were more likely to have taken predisposing medications and to have more gout-associated comorbidities, whereas men were more likely to consume foods linked to the disorder, such as alcohol and red meat, according to Dr. Leslie Harrold, scientific director of the CORRONA gout registry.
"We live in an era of personalized medicine," she said in an interview. "These findings speak to the need to tailor our evaluations and treatments based on the patient. There cannot be a one-size-fits-all approach. We need to approach women with gout differently than men with gout."
Patients in the gout study were enrolled in 2012-2013. Data gathered from patients and their rheumatologists at study enrollment included demographics, predisposing factors (comorbid conditions, medications, diet), gout disease characteristics, current treatments, and physical exam findings.
The 54 participating rheumatologists enrolled 1,167 gout patients (239 women). Women were significantly older than men (71 years vs. 61 years) and had higher body mass index (34 kg/m2 vs. 23 kg/m2). They also were significantly more likely to have hypertension (77% vs. 57%), diabetes (28% vs. 17%), and renal disease (25% vs. 14%).
Women also had a shorter duration of gout when enrolled (6 years vs. 11 years) and were less likely to have a crystal-proven diagnosis (26% vs. 35%).
Medication risk factors for gout, such as diuretics, were more common in women (49% vs. 22%), while dietary risk factors were more frequent in men, who consumed significantly more beer, hard liquor, beef, and pork, Dr. Harrold reported at the annual European Congress of Rheumatology.
Although the clinical features of gout were similar between the genders at the time of initial diagnosis, women reported more frequent disability. Women were more likely to have contraindications to treatment with NSAIDs or colchicine, but women with tophi or active disease – defined as two or more flares per year – used urate-lowering therapy at a rate that was not statistically different from men (78% vs. 84%).
"I think what is most interesting is that the profile of men and women with gout differs," said Dr. Harrold of the division of rheumatology at the University of Massachusetts, Worcester. "Doctors usually have a single concept of the typical patient. But instead, here we have to realize that the typical woman with gout is different than the typical man with gout. That should frame our evaluation of suspected cases."
A number of pharmaceutical companies have financially supported the CORRONA registry. In the last 5 years, Dr. Harrold has received research funding from Takeda and has a pending grant with AstraZeneca.
PARIS – Women have different predisposing risk factors for gout than do men, who more often fit the stereotypical profile of patients with gout who consume foods that increase the risk of the disease.
In the study based on data collected from participants in the Consortium of Rheumatology Researchers of North America (CORRONA) gout registry, women with gout were more likely to have taken predisposing medications and to have more gout-associated comorbidities, whereas men were more likely to consume foods linked to the disorder, such as alcohol and red meat, according to Dr. Leslie Harrold, scientific director of the CORRONA gout registry.
"We live in an era of personalized medicine," she said in an interview. "These findings speak to the need to tailor our evaluations and treatments based on the patient. There cannot be a one-size-fits-all approach. We need to approach women with gout differently than men with gout."
Patients in the gout study were enrolled in 2012-2013. Data gathered from patients and their rheumatologists at study enrollment included demographics, predisposing factors (comorbid conditions, medications, diet), gout disease characteristics, current treatments, and physical exam findings.
The 54 participating rheumatologists enrolled 1,167 gout patients (239 women). Women were significantly older than men (71 years vs. 61 years) and had higher body mass index (34 kg/m2 vs. 23 kg/m2). They also were significantly more likely to have hypertension (77% vs. 57%), diabetes (28% vs. 17%), and renal disease (25% vs. 14%).
Women also had a shorter duration of gout when enrolled (6 years vs. 11 years) and were less likely to have a crystal-proven diagnosis (26% vs. 35%).
Medication risk factors for gout, such as diuretics, were more common in women (49% vs. 22%), while dietary risk factors were more frequent in men, who consumed significantly more beer, hard liquor, beef, and pork, Dr. Harrold reported at the annual European Congress of Rheumatology.
Although the clinical features of gout were similar between the genders at the time of initial diagnosis, women reported more frequent disability. Women were more likely to have contraindications to treatment with NSAIDs or colchicine, but women with tophi or active disease – defined as two or more flares per year – used urate-lowering therapy at a rate that was not statistically different from men (78% vs. 84%).
"I think what is most interesting is that the profile of men and women with gout differs," said Dr. Harrold of the division of rheumatology at the University of Massachusetts, Worcester. "Doctors usually have a single concept of the typical patient. But instead, here we have to realize that the typical woman with gout is different than the typical man with gout. That should frame our evaluation of suspected cases."
A number of pharmaceutical companies have financially supported the CORRONA registry. In the last 5 years, Dr. Harrold has received research funding from Takeda and has a pending grant with AstraZeneca.
AT THE EULAR CONGRESS 2014
Key clinical point: Clinicians should consider the differences in the presentation of gout between women and men and tailor their evaluation and treatment accordingly.
Major finding: Medication risk factors for gout, such as diuretics, were more common in women (49% vs. 22%), while dietary risk factors were more frequent in men, who consumed significantly more beer, hard liquor, beef, and pork.
Data source: A retrospective cohort study of 1,167 patients in the CORRONA gout registry.
Disclosures: A number of pharmaceutical companies have financially supported the CORRONA registry. In the last 5 years, Dr. Harrold has received research funding from Takeda and has a pending grant with AstraZeneca.
