Rheumatoid Arthritis

Warnings about the potential risk of hepatotoxicity associated with the use of diclofenac have been added to the labels of all products containing the nonsteroidal anti-inflammatory drug, the Food and Drug Administration announced.

A notice on the FDA's MedWatch site said that the manufacturers—Endo Pharmaceuticals Inc. and Novartis Consumer Health Inc.—had revised the “hepatic effects” section of the diclofenac topical gel label to include new warnings and precautions about the potential for elevated liver function tests during treatment with diclofenac products, including the formulation marketed as Voltaren Gel 1%.

There have been postmarketing reports of severe hepatic reactions including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure in patients treated with diclofenac, according to the FDA. Some cases have been fatal or have resulted in liver transplantation.

Because severe hepatoxicity may be asymptomatic, the FDA and the revised label both recommend that clinicians periodically measure transaminase levels in patients taking diclofenac long term. Levels should be monitored within 4-8 weeks after initiating treatment, according to the FDA notice.

The labeling changes are summarized in a Dear Health Care Professional letter issued by the manufacturers.

For more information, call 800-452-0051. The MedWatch notice and letter can be viewed at www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm

Warnings about the potential risk of hepatotoxicity associated with the use of diclofenac have been added to the labels of all products containing the nonsteroidal anti-inflammatory drug, the Food and Drug Administration announced.

A notice on the FDA's MedWatch site said that the manufacturers—Endo Pharmaceuticals Inc. and Novartis Consumer Health Inc.—had revised the “hepatic effects” section of the diclofenac topical gel label to include new warnings and precautions about the potential for elevated liver function tests during treatment with diclofenac products, including the formulation marketed as Voltaren Gel 1%.

There have been postmarketing reports of severe hepatic reactions including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure in patients treated with diclofenac, according to the FDA. Some cases have been fatal or have resulted in liver transplantation.

Because severe hepatoxicity may be asymptomatic, the FDA and the revised label both recommend that clinicians periodically measure transaminase levels in patients taking diclofenac long term. Levels should be monitored within 4-8 weeks after initiating treatment, according to the FDA notice.

The labeling changes are summarized in a Dear Health Care Professional letter issued by the manufacturers.

For more information, call 800-452-0051. The MedWatch notice and letter can be viewed at www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm

Warnings about the potential risk of hepatotoxicity associated with the use of diclofenac have been added to the labels of all products containing the nonsteroidal anti-inflammatory drug, the Food and Drug Administration announced.

A notice on the FDA's MedWatch site said that the manufacturers—Endo Pharmaceuticals Inc. and Novartis Consumer Health Inc.—had revised the “hepatic effects” section of the diclofenac topical gel label to include new warnings and precautions about the potential for elevated liver function tests during treatment with diclofenac products, including the formulation marketed as Voltaren Gel 1%.

There have been postmarketing reports of severe hepatic reactions including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure in patients treated with diclofenac, according to the FDA. Some cases have been fatal or have resulted in liver transplantation.

Because severe hepatoxicity may be asymptomatic, the FDA and the revised label both recommend that clinicians periodically measure transaminase levels in patients taking diclofenac long term. Levels should be monitored within 4-8 weeks after initiating treatment, according to the FDA notice.

The labeling changes are summarized in a Dear Health Care Professional letter issued by the manufacturers.

For more information, call 800-452-0051. The MedWatch notice and letter can be viewed at www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm

PHILADELPHIA — Patients with moderately active rheumatoid arthritis had a high prevalence of vitamin D insufficiency and deficiency in a prospective study of 1,160 patients in the Veterans Health Administration system.

Based on this finding, the “testing of vitamin D levels is mandatory” in patients with RA, Dr. Gail S. Kerr said at the annual meeting of the American College of Rheumatology.

In addition, although “more evidence is needed to determine the exact role of vitamin D in patients with rheumatoid arthritis, we advocate vitamin D replacement as an additional, non-DMARD [disease-modifying antirheumatic drug] component of RA management,” said Dr. Kerr, chief of rheumatology at the Washington D.C. VA Medical Center.

The study used patients who were enrolled in the U.S. VARA (Veterans With RA) registry, which began in 2002 at eight VHA centers around the United States. The registry protocol included drawing a blood specimen from patients at the time of their enrollment. Patients entered the registry at similar rates throughout the year, which meant that no seasonal bias skewed their vitamin D levels.

The VHA provides medical care to more than 67,000 people with RA. Investigators plan to expand the registry to enroll 12,000 patients eventually.

The current analysis focused on the 1,160 enrolled patients for whom vitamin D levels were available. Measurement of serum vitamin D was by a radioimmunoassay. Insufficiency was defined as a level of 30 ng/mL or lower; deficiency was 20 ng/mL or lower.

Patients' average age was 64 years; 91% were men, 77% were white, and 17% were black. Their average duration of RA was 12 years, and they generally had moderately active disease. Their average body mass index was 28 kg/m

Low vitamin D levels were common, with 85% of the patients meeting the definition of insufficiency, and 45% with a deficient level.

The average vitamin D level for the entire group was 22 ng/mL.

A multivariate analysis showed that patients who were younger and not white, as well as those with higher tender joint counts and higher body mass index, had a higher risk for having vitamin D insufficiency or deficiency.

Low vitamin D levels were also significantly linked with being positive for anti–cyclic citrullinated protein antibodies, and with a higher number of comorbidities, Dr. Kerr concluded.

PHILADELPHIA — Patients with moderately active rheumatoid arthritis had a high prevalence of vitamin D insufficiency and deficiency in a prospective study of 1,160 patients in the Veterans Health Administration system.

Based on this finding, the “testing of vitamin D levels is mandatory” in patients with RA, Dr. Gail S. Kerr said at the annual meeting of the American College of Rheumatology.

In addition, although “more evidence is needed to determine the exact role of vitamin D in patients with rheumatoid arthritis, we advocate vitamin D replacement as an additional, non-DMARD [disease-modifying antirheumatic drug] component of RA management,” said Dr. Kerr, chief of rheumatology at the Washington D.C. VA Medical Center.

The study used patients who were enrolled in the U.S. VARA (Veterans With RA) registry, which began in 2002 at eight VHA centers around the United States. The registry protocol included drawing a blood specimen from patients at the time of their enrollment. Patients entered the registry at similar rates throughout the year, which meant that no seasonal bias skewed their vitamin D levels.

The VHA provides medical care to more than 67,000 people with RA. Investigators plan to expand the registry to enroll 12,000 patients eventually.

The current analysis focused on the 1,160 enrolled patients for whom vitamin D levels were available. Measurement of serum vitamin D was by a radioimmunoassay. Insufficiency was defined as a level of 30 ng/mL or lower; deficiency was 20 ng/mL or lower.

Patients' average age was 64 years; 91% were men, 77% were white, and 17% were black. Their average duration of RA was 12 years, and they generally had moderately active disease. Their average body mass index was 28 kg/m

Low vitamin D levels were common, with 85% of the patients meeting the definition of insufficiency, and 45% with a deficient level.

The average vitamin D level for the entire group was 22 ng/mL.

A multivariate analysis showed that patients who were younger and not white, as well as those with higher tender joint counts and higher body mass index, had a higher risk for having vitamin D insufficiency or deficiency.

Low vitamin D levels were also significantly linked with being positive for anti–cyclic citrullinated protein antibodies, and with a higher number of comorbidities, Dr. Kerr concluded.

PHILADELPHIA — Patients with moderately active rheumatoid arthritis had a high prevalence of vitamin D insufficiency and deficiency in a prospective study of 1,160 patients in the Veterans Health Administration system.

Based on this finding, the “testing of vitamin D levels is mandatory” in patients with RA, Dr. Gail S. Kerr said at the annual meeting of the American College of Rheumatology.

In addition, although “more evidence is needed to determine the exact role of vitamin D in patients with rheumatoid arthritis, we advocate vitamin D replacement as an additional, non-DMARD [disease-modifying antirheumatic drug] component of RA management,” said Dr. Kerr, chief of rheumatology at the Washington D.C. VA Medical Center.

The study used patients who were enrolled in the U.S. VARA (Veterans With RA) registry, which began in 2002 at eight VHA centers around the United States. The registry protocol included drawing a blood specimen from patients at the time of their enrollment. Patients entered the registry at similar rates throughout the year, which meant that no seasonal bias skewed their vitamin D levels.

The VHA provides medical care to more than 67,000 people with RA. Investigators plan to expand the registry to enroll 12,000 patients eventually.

The current analysis focused on the 1,160 enrolled patients for whom vitamin D levels were available. Measurement of serum vitamin D was by a radioimmunoassay. Insufficiency was defined as a level of 30 ng/mL or lower; deficiency was 20 ng/mL or lower.

Patients' average age was 64 years; 91% were men, 77% were white, and 17% were black. Their average duration of RA was 12 years, and they generally had moderately active disease. Their average body mass index was 28 kg/m

Low vitamin D levels were common, with 85% of the patients meeting the definition of insufficiency, and 45% with a deficient level.

The average vitamin D level for the entire group was 22 ng/mL.

A multivariate analysis showed that patients who were younger and not white, as well as those with higher tender joint counts and higher body mass index, had a higher risk for having vitamin D insufficiency or deficiency.

Low vitamin D levels were also significantly linked with being positive for anti–cyclic citrullinated protein antibodies, and with a higher number of comorbidities, Dr. Kerr concluded.

Chronic musculoskeletal pain raises elderly people's risk of falling, independent of their underlying pathologies or the medications they may be taking for the pain, according to a study of more than 700 elders living independently.

The finding that pain is “an overlooked and potentially important risk factor for falls” suggests that “the common complaint of aches and pains of old age is related to a greater hazard than previously thought,” Suzanne G. Leveille, Ph.D., R.N., of the University of Massachusetts, Boston, and her associates wrote (JAMA 2009;302:2214-21).

“Daily discomfort may accompany not only difficulties in performing daily activities but equally as important may be a risk for falls and possibly fall-related injuries in the older population,” the authors wrote.

Dr. Leveille and her colleagues used data from the MOBILIZE Boston study to identify new strategies for preventing falls. (The study's title stands for Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly.) The researchers assessed data on 749 men and women aged 70 and older who were living in a variety of urban and suburban settings.

The study participants were evaluated during home and clinic visits at the beginning of the study. The researchers noted the severity and location of musculoskeletal pain, as well as its interference with daily activities. Monthly for up to 18 months thereafter, the participants reported pain symptoms and all falls on postcards.

This study design enabled the researchers to track the risk of falls over time in relation to baseline chronic pain and pain reported periodically.

Overall, 40% of the study subjects reported chronic polyarticular pain, and another 24% reported chronic pain in just one joint area. A total of 1,029 falls occurred during follow-up, with 405 subjects (54%) falling at least once during the study.

Compared with participants who did not report chronic pain, those who did had a significantly higher rate of falls, regardless of whether their pain was measured by location, severity, or degree of interference with daily life, Dr. Leveille and her colleagues said.

Chronic pain was persistently associated with fall risk after the data were adjusted to account for coexisting chronic conditions, other risk factors for falling, baseline balance and mobility, the use of psychotherapeutic medications, and the use of analgesics.

There also was a strong, graded relationship between monthly pain-severity ratings and the risk for falling during the subsequent month.

“For example, among persons who reported severe or very severe pain for any given month on their calendar postcard, there was a 77% increased likelihood for a fall in the subsequent month, compared with those who reported no pain,” the investigators said.

“Persons reporting even very mild pain also had an elevated risk of falling in any given month,” they added.

There are three possible mechanisms underlying the link between pain and falling, according to the researchers. First, joint pathology may cause both pain and the instability that can lead to falling.

However, Dr. Leveille and her colleagues deemed that explanation unlikely because the association in this study was independent of hand and knee osteoarthritis and of mobility.

Second, the neuromuscular effects of pain could cause muscle weakness, slowed responses to an impending fall, or gait alterations, all of which can lead to falling. Third, said the researchers, chronic pain may distract patients or otherwise interfere with the cognitive activity needed to prevent falling.

Other studies have shown that patients with chronic pain show decreased executive function and attention. Moreover, avoiding or interrupting a fall “typically requires a cognitively mediated physical maneuver,” Dr. Leveille and her associates noted.

A randomized controlled trial might determine whether improved pain control could reduce the risk for falling in elderly patients, the researchers said.

Disclosures: Dr. Leveille reported no financial conflict of interest. The MOBILIZE Boston study was supported in part by a grant from Pfizer Inc.

Chronic musculoskeletal pain raises elderly people's risk of falling, independent of their underlying pathologies or the medications they may be taking for the pain, according to a study of more than 700 elders living independently.

The finding that pain is “an overlooked and potentially important risk factor for falls” suggests that “the common complaint of aches and pains of old age is related to a greater hazard than previously thought,” Suzanne G. Leveille, Ph.D., R.N., of the University of Massachusetts, Boston, and her associates wrote (JAMA 2009;302:2214-21).

“Daily discomfort may accompany not only difficulties in performing daily activities but equally as important may be a risk for falls and possibly fall-related injuries in the older population,” the authors wrote.

Dr. Leveille and her colleagues used data from the MOBILIZE Boston study to identify new strategies for preventing falls. (The study's title stands for Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly.) The researchers assessed data on 749 men and women aged 70 and older who were living in a variety of urban and suburban settings.

The study participants were evaluated during home and clinic visits at the beginning of the study. The researchers noted the severity and location of musculoskeletal pain, as well as its interference with daily activities. Monthly for up to 18 months thereafter, the participants reported pain symptoms and all falls on postcards.

This study design enabled the researchers to track the risk of falls over time in relation to baseline chronic pain and pain reported periodically.

Overall, 40% of the study subjects reported chronic polyarticular pain, and another 24% reported chronic pain in just one joint area. A total of 1,029 falls occurred during follow-up, with 405 subjects (54%) falling at least once during the study.

Compared with participants who did not report chronic pain, those who did had a significantly higher rate of falls, regardless of whether their pain was measured by location, severity, or degree of interference with daily life, Dr. Leveille and her colleagues said.

Chronic pain was persistently associated with fall risk after the data were adjusted to account for coexisting chronic conditions, other risk factors for falling, baseline balance and mobility, the use of psychotherapeutic medications, and the use of analgesics.

There also was a strong, graded relationship between monthly pain-severity ratings and the risk for falling during the subsequent month.

“For example, among persons who reported severe or very severe pain for any given month on their calendar postcard, there was a 77% increased likelihood for a fall in the subsequent month, compared with those who reported no pain,” the investigators said.

“Persons reporting even very mild pain also had an elevated risk of falling in any given month,” they added.

There are three possible mechanisms underlying the link between pain and falling, according to the researchers. First, joint pathology may cause both pain and the instability that can lead to falling.

However, Dr. Leveille and her colleagues deemed that explanation unlikely because the association in this study was independent of hand and knee osteoarthritis and of mobility.

Second, the neuromuscular effects of pain could cause muscle weakness, slowed responses to an impending fall, or gait alterations, all of which can lead to falling. Third, said the researchers, chronic pain may distract patients or otherwise interfere with the cognitive activity needed to prevent falling.

Other studies have shown that patients with chronic pain show decreased executive function and attention. Moreover, avoiding or interrupting a fall “typically requires a cognitively mediated physical maneuver,” Dr. Leveille and her associates noted.

A randomized controlled trial might determine whether improved pain control could reduce the risk for falling in elderly patients, the researchers said.

Disclosures: Dr. Leveille reported no financial conflict of interest. The MOBILIZE Boston study was supported in part by a grant from Pfizer Inc.

Chronic musculoskeletal pain raises elderly people's risk of falling, independent of their underlying pathologies or the medications they may be taking for the pain, according to a study of more than 700 elders living independently.

The finding that pain is “an overlooked and potentially important risk factor for falls” suggests that “the common complaint of aches and pains of old age is related to a greater hazard than previously thought,” Suzanne G. Leveille, Ph.D., R.N., of the University of Massachusetts, Boston, and her associates wrote (JAMA 2009;302:2214-21).

“Daily discomfort may accompany not only difficulties in performing daily activities but equally as important may be a risk for falls and possibly fall-related injuries in the older population,” the authors wrote.

Dr. Leveille and her colleagues used data from the MOBILIZE Boston study to identify new strategies for preventing falls. (The study's title stands for Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly.) The researchers assessed data on 749 men and women aged 70 and older who were living in a variety of urban and suburban settings.

The study participants were evaluated during home and clinic visits at the beginning of the study. The researchers noted the severity and location of musculoskeletal pain, as well as its interference with daily activities. Monthly for up to 18 months thereafter, the participants reported pain symptoms and all falls on postcards.

This study design enabled the researchers to track the risk of falls over time in relation to baseline chronic pain and pain reported periodically.

Overall, 40% of the study subjects reported chronic polyarticular pain, and another 24% reported chronic pain in just one joint area. A total of 1,029 falls occurred during follow-up, with 405 subjects (54%) falling at least once during the study.

Compared with participants who did not report chronic pain, those who did had a significantly higher rate of falls, regardless of whether their pain was measured by location, severity, or degree of interference with daily life, Dr. Leveille and her colleagues said.

Chronic pain was persistently associated with fall risk after the data were adjusted to account for coexisting chronic conditions, other risk factors for falling, baseline balance and mobility, the use of psychotherapeutic medications, and the use of analgesics.

There also was a strong, graded relationship between monthly pain-severity ratings and the risk for falling during the subsequent month.

“For example, among persons who reported severe or very severe pain for any given month on their calendar postcard, there was a 77% increased likelihood for a fall in the subsequent month, compared with those who reported no pain,” the investigators said.

“Persons reporting even very mild pain also had an elevated risk of falling in any given month,” they added.

There are three possible mechanisms underlying the link between pain and falling, according to the researchers. First, joint pathology may cause both pain and the instability that can lead to falling.

However, Dr. Leveille and her colleagues deemed that explanation unlikely because the association in this study was independent of hand and knee osteoarthritis and of mobility.

Second, the neuromuscular effects of pain could cause muscle weakness, slowed responses to an impending fall, or gait alterations, all of which can lead to falling. Third, said the researchers, chronic pain may distract patients or otherwise interfere with the cognitive activity needed to prevent falling.

Other studies have shown that patients with chronic pain show decreased executive function and attention. Moreover, avoiding or interrupting a fall “typically requires a cognitively mediated physical maneuver,” Dr. Leveille and her associates noted.

A randomized controlled trial might determine whether improved pain control could reduce the risk for falling in elderly patients, the researchers said.

Disclosures: Dr. Leveille reported no financial conflict of interest. The MOBILIZE Boston study was supported in part by a grant from Pfizer Inc.

PHILADELPHIA — Using MRI to help classify spondyloarthritis poses a significant risk for error, according to findings from a multicenter study that evaluated 85 MRI scans.

A panel of five rheumatologists and radiologists specially trained in MRI assessment of lesions associated with spondyloarthritis (SpA) in the sacroiliac joint misclassified 6 of 85 cases based on their MRI scans, Dr. Ulrich Weber said at the annual meeting of the American College of Rheumatology.

The finding underscores the importance of establishing reliable thresholds for diagnosing significant SpA-associated pathology in MRI scans of sacroiliac joints, said Dr. Weber, a rheumatologist at the Balgrist University Clinic in Zurich, Switzerland. “MRI will never be 100% accurate for confirming a diagnosis of SpA. Low-grade active and chronic abnormalities [on MRI] are seen in up to a third of healthy volunteers and patients with non-specific back pain.”

The findings, “underscore the limitations of reading MRI, even in the hands of trained readers,” commented Dr. John D. Reveille, professor of internal medicine and director of the division of rheumatology and clinical immunogenetics at the University of Texas Medical School at Houston.

Although sacroiliitis identified by plain radiography has been the traditional method for classifying SpA, MRI has been increasingly used. MRI's role for classifying SpA solidified in 2009 with the publication of the SpA classification criteria of the Assessment of Spondyloarthritis International Society (ASAS) (Ann Rheum Dis. 2009;68:777-83). In this paper, ASAS said that MRI scans showing “active (acute) inflammation of sacroiliac joints … highly suggestive of sacroiliitis associated with SpA” could substitute for radiographic evidence when classifying a patient as having SpA.

To examine the consequences of MRI assessment, Dr. Weber and his associates developed a training program to teach rheumatologists and radiologists to identify sacroiliac joint pathology indicative of SpA. The classification criteria focused on four features of active inflammation: bone marrow edema, erosion, fatty infiltration, and ankylosis. They then had a panel of two radiologists and three rheumatologists who underwent training review MRI scans from 59 asymptomatic healthy volunteers and 26 patients with nonspecific back pain of mechanical origin. All subjects were age 45 years or younger.

Among the 59 healthy volunteers, one or more of the panel members misclassified four (7%) as having MRI features indicative of SpA. When reviewing the 26 patients with mechanically induced lower back pain, panel members misclassified two (8%) as having SpA.

The error rate was even higher for some of the individual assessment elements. At least two panel members identified some degree of bone marrow edema in 22% of the healthy volunteers and in 38% of the patients with nonspecific, mechanical back pain.

Two panel members scored the bone marrow edema clinically relevant in 12% of the healthy volunteers and in 23% of the patients with mechanically triggered back pain.

Roughly similar mistake rates occurred when the panelists scored the MRIs for bone erosions and for fatty infiltrations.

The physicians who read MRI scans of back pain patients need careful training and clear guidance on what constitutes SpA lesions in sacroiliac joints, accordng to Dr. Weber.

Disclosures: Dr. Weber said that he and his associates had no financial disclosures relevant to his presentation on SpA and MRI.

'MRI will never be 100% accurate for confirming a diagnosis of SpA.'

Source DR. WEBER

My Take

Knowing How to Use MRI Is Key

I would agree that the isolated use of an MRI evaluation of the sacroiliac joint would be subject to false-positive error for the diagnosis of ankylosing spondylitis. The value of the MRI findings needs to be used in combination with the other features that are seen with AS, which is why the diagnosis is based upon multiple criteria. Nevertheless, in conjunction with other findings the ability to recognize inflammation of the sacroiliac joint in particular with negative radiographs has been well reported to improve the diagnostic yield significantly.

I would agree that an experienced radiologist needs to interpret the significance of the MRI findings as is evidenced by Dr. Ulrich Weber's findings. The false positives reported may well have been avoided in experienced radiologist's hands. In fact, sensitivity of MRI is always an issue. That does not mean it is a bad tool. Like driving a race car, you have to know how to handle and interpret the high tech equipment you are utilizing.

NORMAN B. GAYLIS, M.D., president of the International Society of Extremity MRI in Rheumatology, is in private practice in Aventura, Fla. He has written and lectured widely on in-office use of imaging in rheumatology. Dr. Gaylis reports financial relationships with numerous pharmaceutical companies.

DR. GAYLI

PHILADELPHIA — Using MRI to help classify spondyloarthritis poses a significant risk for error, according to findings from a multicenter study that evaluated 85 MRI scans.

A panel of five rheumatologists and radiologists specially trained in MRI assessment of lesions associated with spondyloarthritis (SpA) in the sacroiliac joint misclassified 6 of 85 cases based on their MRI scans, Dr. Ulrich Weber said at the annual meeting of the American College of Rheumatology.

The finding underscores the importance of establishing reliable thresholds for diagnosing significant SpA-associated pathology in MRI scans of sacroiliac joints, said Dr. Weber, a rheumatologist at the Balgrist University Clinic in Zurich, Switzerland. “MRI will never be 100% accurate for confirming a diagnosis of SpA. Low-grade active and chronic abnormalities [on MRI] are seen in up to a third of healthy volunteers and patients with non-specific back pain.”

The findings, “underscore the limitations of reading MRI, even in the hands of trained readers,” commented Dr. John D. Reveille, professor of internal medicine and director of the division of rheumatology and clinical immunogenetics at the University of Texas Medical School at Houston.

Although sacroiliitis identified by plain radiography has been the traditional method for classifying SpA, MRI has been increasingly used. MRI's role for classifying SpA solidified in 2009 with the publication of the SpA classification criteria of the Assessment of Spondyloarthritis International Society (ASAS) (Ann Rheum Dis. 2009;68:777-83). In this paper, ASAS said that MRI scans showing “active (acute) inflammation of sacroiliac joints … highly suggestive of sacroiliitis associated with SpA” could substitute for radiographic evidence when classifying a patient as having SpA.

To examine the consequences of MRI assessment, Dr. Weber and his associates developed a training program to teach rheumatologists and radiologists to identify sacroiliac joint pathology indicative of SpA. The classification criteria focused on four features of active inflammation: bone marrow edema, erosion, fatty infiltration, and ankylosis. They then had a panel of two radiologists and three rheumatologists who underwent training review MRI scans from 59 asymptomatic healthy volunteers and 26 patients with nonspecific back pain of mechanical origin. All subjects were age 45 years or younger.

Among the 59 healthy volunteers, one or more of the panel members misclassified four (7%) as having MRI features indicative of SpA. When reviewing the 26 patients with mechanically induced lower back pain, panel members misclassified two (8%) as having SpA.

The error rate was even higher for some of the individual assessment elements. At least two panel members identified some degree of bone marrow edema in 22% of the healthy volunteers and in 38% of the patients with nonspecific, mechanical back pain.

Two panel members scored the bone marrow edema clinically relevant in 12% of the healthy volunteers and in 23% of the patients with mechanically triggered back pain.

Roughly similar mistake rates occurred when the panelists scored the MRIs for bone erosions and for fatty infiltrations.

The physicians who read MRI scans of back pain patients need careful training and clear guidance on what constitutes SpA lesions in sacroiliac joints, accordng to Dr. Weber.

Disclosures: Dr. Weber said that he and his associates had no financial disclosures relevant to his presentation on SpA and MRI.

'MRI will never be 100% accurate for confirming a diagnosis of SpA.'

Source DR. WEBER

My Take

Knowing How to Use MRI Is Key

I would agree that the isolated use of an MRI evaluation of the sacroiliac joint would be subject to false-positive error for the diagnosis of ankylosing spondylitis. The value of the MRI findings needs to be used in combination with the other features that are seen with AS, which is why the diagnosis is based upon multiple criteria. Nevertheless, in conjunction with other findings the ability to recognize inflammation of the sacroiliac joint in particular with negative radiographs has been well reported to improve the diagnostic yield significantly.

I would agree that an experienced radiologist needs to interpret the significance of the MRI findings as is evidenced by Dr. Ulrich Weber's findings. The false positives reported may well have been avoided in experienced radiologist's hands. In fact, sensitivity of MRI is always an issue. That does not mean it is a bad tool. Like driving a race car, you have to know how to handle and interpret the high tech equipment you are utilizing.

NORMAN B. GAYLIS, M.D., president of the International Society of Extremity MRI in Rheumatology, is in private practice in Aventura, Fla. He has written and lectured widely on in-office use of imaging in rheumatology. Dr. Gaylis reports financial relationships with numerous pharmaceutical companies.

DR. GAYLI

PHILADELPHIA — Using MRI to help classify spondyloarthritis poses a significant risk for error, according to findings from a multicenter study that evaluated 85 MRI scans.

A panel of five rheumatologists and radiologists specially trained in MRI assessment of lesions associated with spondyloarthritis (SpA) in the sacroiliac joint misclassified 6 of 85 cases based on their MRI scans, Dr. Ulrich Weber said at the annual meeting of the American College of Rheumatology.

The finding underscores the importance of establishing reliable thresholds for diagnosing significant SpA-associated pathology in MRI scans of sacroiliac joints, said Dr. Weber, a rheumatologist at the Balgrist University Clinic in Zurich, Switzerland. “MRI will never be 100% accurate for confirming a diagnosis of SpA. Low-grade active and chronic abnormalities [on MRI] are seen in up to a third of healthy volunteers and patients with non-specific back pain.”

The findings, “underscore the limitations of reading MRI, even in the hands of trained readers,” commented Dr. John D. Reveille, professor of internal medicine and director of the division of rheumatology and clinical immunogenetics at the University of Texas Medical School at Houston.

Although sacroiliitis identified by plain radiography has been the traditional method for classifying SpA, MRI has been increasingly used. MRI's role for classifying SpA solidified in 2009 with the publication of the SpA classification criteria of the Assessment of Spondyloarthritis International Society (ASAS) (Ann Rheum Dis. 2009;68:777-83). In this paper, ASAS said that MRI scans showing “active (acute) inflammation of sacroiliac joints … highly suggestive of sacroiliitis associated with SpA” could substitute for radiographic evidence when classifying a patient as having SpA.

To examine the consequences of MRI assessment, Dr. Weber and his associates developed a training program to teach rheumatologists and radiologists to identify sacroiliac joint pathology indicative of SpA. The classification criteria focused on four features of active inflammation: bone marrow edema, erosion, fatty infiltration, and ankylosis. They then had a panel of two radiologists and three rheumatologists who underwent training review MRI scans from 59 asymptomatic healthy volunteers and 26 patients with nonspecific back pain of mechanical origin. All subjects were age 45 years or younger.

Among the 59 healthy volunteers, one or more of the panel members misclassified four (7%) as having MRI features indicative of SpA. When reviewing the 26 patients with mechanically induced lower back pain, panel members misclassified two (8%) as having SpA.

The error rate was even higher for some of the individual assessment elements. At least two panel members identified some degree of bone marrow edema in 22% of the healthy volunteers and in 38% of the patients with nonspecific, mechanical back pain.

Two panel members scored the bone marrow edema clinically relevant in 12% of the healthy volunteers and in 23% of the patients with mechanically triggered back pain.

Roughly similar mistake rates occurred when the panelists scored the MRIs for bone erosions and for fatty infiltrations.

The physicians who read MRI scans of back pain patients need careful training and clear guidance on what constitutes SpA lesions in sacroiliac joints, accordng to Dr. Weber.

Disclosures: Dr. Weber said that he and his associates had no financial disclosures relevant to his presentation on SpA and MRI.

'MRI will never be 100% accurate for confirming a diagnosis of SpA.'

Source DR. WEBER

My Take

Knowing How to Use MRI Is Key

I would agree that the isolated use of an MRI evaluation of the sacroiliac joint would be subject to false-positive error for the diagnosis of ankylosing spondylitis. The value of the MRI findings needs to be used in combination with the other features that are seen with AS, which is why the diagnosis is based upon multiple criteria. Nevertheless, in conjunction with other findings the ability to recognize inflammation of the sacroiliac joint in particular with negative radiographs has been well reported to improve the diagnostic yield significantly.

I would agree that an experienced radiologist needs to interpret the significance of the MRI findings as is evidenced by Dr. Ulrich Weber's findings. The false positives reported may well have been avoided in experienced radiologist's hands. In fact, sensitivity of MRI is always an issue. That does not mean it is a bad tool. Like driving a race car, you have to know how to handle and interpret the high tech equipment you are utilizing.

NORMAN B. GAYLIS, M.D., president of the International Society of Extremity MRI in Rheumatology, is in private practice in Aventura, Fla. He has written and lectured widely on in-office use of imaging in rheumatology. Dr. Gaylis reports financial relationships with numerous pharmaceutical companies.

DR. GAYLI

PHILADELPHIA — Vaccination rates in patients with rheumatoid arthritis and other rheumatic diseases continued to lag behind recommendations in two reports at the annual meeting of the American College of Rheumatology.

Although the Centers for Disease Control and Prevention and other infectious disease organizations recommend annual influenza vaccination and current pneumonia vaccination for all adults with chronic illness, including rheumatoid arthritis and other rheumatic diseases, both studies found vaccination rates of roughly 50%.

One report, by researchers from the CDC, used data collected in 2007 by the Behavioral Risk Factor Surveillance System, which conducted more than 400,000 random telephone surveys of U.S. adults. The researchers identified respondents as having arthritis if they had ever been told by a doctor that they had arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia.

Among the survey respondents who self-identified as having arthritis, 52% reported receiving an influenza vaccination by either injection or nasal spray in the prior 12 months; the flu vaccination rate was 31% in the other adults surveyed, Jennifer Hootman, Ph.D., and her colleague reported in a poster at the meeting.

In an analysis that adjusted for demographics and general health indicators, people with arthritis were 40% more likely to have had an influenza vaccination, compared with the other adults surveyed, said Dr. Hootman, a CDC epidemiologist.

Several factors correlated with the prevalence of vaccination among the people with arthritis. Age was a particularly strong factor, even though influenza vaccination is recommended for all adults with a chronic illness like arthritis regardless of their age. People who self-reported arthritis and were aged 65 years or older were more than fourfold as likely to have had flu vaccination as were those aged 18-44 years. People with arthritis who were aged 45-64 years were about 60% more likely to have received vaccine, compared with the younger adults.

Another significant determinant in people with arthritis were state of residence. Arthritis patients living in South Carolina had a vaccination prevalence lower than 40%, and arthritis patients living in Arkansas, Indianapolis, and Texas had a rate of 40%-45%. Racial and ethnic minorities, smokers, people who were obese, and people with a low education level also had a significantly lower vaccination rate than did people with arthritis in comparator groups, Dr. Hootman reported in her poster.

The second report looked at rates of vaccination for influenza, pneumonia, and herpes zoster during 2007-2008 among 10,481 patients with arthritis who were enrolled in the National Data Bank for Rheumatic Diseases.

The study population included patients with rheumatoid arthritis (70%), fibromyalgia (10%), systemic lupus erythematosus (8%), and noninflammatory rheumatic diseases (12%). Health authorities also recommend regular pneumococcal vaccination for adults with a chronic disease such as arthritis, but no recommendation exists for the herpes zoster vaccine.

The results again showed that vaccination rates for influenza and pneumonia were very age dependent. Patients reported influenza vaccination during the prior year at a rate of 41% in those aged younger than 40 years, 56% in those aged 40-64 years, and 70% in those aged 65 or older, said Kalab Michaud, Ph.D., a rheumatology researcher at the University of Nebraska in Omaha.

The rates for ever having a pneumococcal vaccination were 30% in patients younger than 40 years, 45% in those aged 45-64, and 78% in patients 65 or older. The rates for a pneumococcal vaccination within the prior 5 years were 24%, 37%, and 66% respectively in the three age groups.

Patients aged 65 years or older also reported a 9% rate of ever having vaccination for herpes zoster.

The vaccination rates for both influenza and pneumonia were significantly higher in patients with lupus, and higher for pneumonia in patients with rheumatoid arthritis, compared with patients with noninflammatory rheumatoid disease. The immunization rates for both infections were significantly lower in patients with fibromyalgia.

Other significant determinants of vaccination rates in these patients included an education level lower than high school graduation, which reduced the rate, and the presence of comorbidities such as diabetes, heart disease, or pulmonary disease, which increased the rate.

The researchers on both studies reported no financial disclosures.

Influenza vaccination rates were 41% (younger than age 40), 56% (40-64), and 70% (65 or older).

Source DR. MICHAUD

PHILADELPHIA — Vaccination rates in patients with rheumatoid arthritis and other rheumatic diseases continued to lag behind recommendations in two reports at the annual meeting of the American College of Rheumatology.

Although the Centers for Disease Control and Prevention and other infectious disease organizations recommend annual influenza vaccination and current pneumonia vaccination for all adults with chronic illness, including rheumatoid arthritis and other rheumatic diseases, both studies found vaccination rates of roughly 50%.

One report, by researchers from the CDC, used data collected in 2007 by the Behavioral Risk Factor Surveillance System, which conducted more than 400,000 random telephone surveys of U.S. adults. The researchers identified respondents as having arthritis if they had ever been told by a doctor that they had arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia.

Among the survey respondents who self-identified as having arthritis, 52% reported receiving an influenza vaccination by either injection or nasal spray in the prior 12 months; the flu vaccination rate was 31% in the other adults surveyed, Jennifer Hootman, Ph.D., and her colleague reported in a poster at the meeting.

In an analysis that adjusted for demographics and general health indicators, people with arthritis were 40% more likely to have had an influenza vaccination, compared with the other adults surveyed, said Dr. Hootman, a CDC epidemiologist.

Several factors correlated with the prevalence of vaccination among the people with arthritis. Age was a particularly strong factor, even though influenza vaccination is recommended for all adults with a chronic illness like arthritis regardless of their age. People who self-reported arthritis and were aged 65 years or older were more than fourfold as likely to have had flu vaccination as were those aged 18-44 years. People with arthritis who were aged 45-64 years were about 60% more likely to have received vaccine, compared with the younger adults.

Another significant determinant in people with arthritis were state of residence. Arthritis patients living in South Carolina had a vaccination prevalence lower than 40%, and arthritis patients living in Arkansas, Indianapolis, and Texas had a rate of 40%-45%. Racial and ethnic minorities, smokers, people who were obese, and people with a low education level also had a significantly lower vaccination rate than did people with arthritis in comparator groups, Dr. Hootman reported in her poster.

The second report looked at rates of vaccination for influenza, pneumonia, and herpes zoster during 2007-2008 among 10,481 patients with arthritis who were enrolled in the National Data Bank for Rheumatic Diseases.

The study population included patients with rheumatoid arthritis (70%), fibromyalgia (10%), systemic lupus erythematosus (8%), and noninflammatory rheumatic diseases (12%). Health authorities also recommend regular pneumococcal vaccination for adults with a chronic disease such as arthritis, but no recommendation exists for the herpes zoster vaccine.

The results again showed that vaccination rates for influenza and pneumonia were very age dependent. Patients reported influenza vaccination during the prior year at a rate of 41% in those aged younger than 40 years, 56% in those aged 40-64 years, and 70% in those aged 65 or older, said Kalab Michaud, Ph.D., a rheumatology researcher at the University of Nebraska in Omaha.

The rates for ever having a pneumococcal vaccination were 30% in patients younger than 40 years, 45% in those aged 45-64, and 78% in patients 65 or older. The rates for a pneumococcal vaccination within the prior 5 years were 24%, 37%, and 66% respectively in the three age groups.

Patients aged 65 years or older also reported a 9% rate of ever having vaccination for herpes zoster.

The vaccination rates for both influenza and pneumonia were significantly higher in patients with lupus, and higher for pneumonia in patients with rheumatoid arthritis, compared with patients with noninflammatory rheumatoid disease. The immunization rates for both infections were significantly lower in patients with fibromyalgia.

Other significant determinants of vaccination rates in these patients included an education level lower than high school graduation, which reduced the rate, and the presence of comorbidities such as diabetes, heart disease, or pulmonary disease, which increased the rate.

The researchers on both studies reported no financial disclosures.

Influenza vaccination rates were 41% (younger than age 40), 56% (40-64), and 70% (65 or older).

Source DR. MICHAUD

PHILADELPHIA — Vaccination rates in patients with rheumatoid arthritis and other rheumatic diseases continued to lag behind recommendations in two reports at the annual meeting of the American College of Rheumatology.

Although the Centers for Disease Control and Prevention and other infectious disease organizations recommend annual influenza vaccination and current pneumonia vaccination for all adults with chronic illness, including rheumatoid arthritis and other rheumatic diseases, both studies found vaccination rates of roughly 50%.

One report, by researchers from the CDC, used data collected in 2007 by the Behavioral Risk Factor Surveillance System, which conducted more than 400,000 random telephone surveys of U.S. adults. The researchers identified respondents as having arthritis if they had ever been told by a doctor that they had arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia.

Among the survey respondents who self-identified as having arthritis, 52% reported receiving an influenza vaccination by either injection or nasal spray in the prior 12 months; the flu vaccination rate was 31% in the other adults surveyed, Jennifer Hootman, Ph.D., and her colleague reported in a poster at the meeting.

In an analysis that adjusted for demographics and general health indicators, people with arthritis were 40% more likely to have had an influenza vaccination, compared with the other adults surveyed, said Dr. Hootman, a CDC epidemiologist.

Several factors correlated with the prevalence of vaccination among the people with arthritis. Age was a particularly strong factor, even though influenza vaccination is recommended for all adults with a chronic illness like arthritis regardless of their age. People who self-reported arthritis and were aged 65 years or older were more than fourfold as likely to have had flu vaccination as were those aged 18-44 years. People with arthritis who were aged 45-64 years were about 60% more likely to have received vaccine, compared with the younger adults.

Another significant determinant in people with arthritis were state of residence. Arthritis patients living in South Carolina had a vaccination prevalence lower than 40%, and arthritis patients living in Arkansas, Indianapolis, and Texas had a rate of 40%-45%. Racial and ethnic minorities, smokers, people who were obese, and people with a low education level also had a significantly lower vaccination rate than did people with arthritis in comparator groups, Dr. Hootman reported in her poster.

The second report looked at rates of vaccination for influenza, pneumonia, and herpes zoster during 2007-2008 among 10,481 patients with arthritis who were enrolled in the National Data Bank for Rheumatic Diseases.

The study population included patients with rheumatoid arthritis (70%), fibromyalgia (10%), systemic lupus erythematosus (8%), and noninflammatory rheumatic diseases (12%). Health authorities also recommend regular pneumococcal vaccination for adults with a chronic disease such as arthritis, but no recommendation exists for the herpes zoster vaccine.

The results again showed that vaccination rates for influenza and pneumonia were very age dependent. Patients reported influenza vaccination during the prior year at a rate of 41% in those aged younger than 40 years, 56% in those aged 40-64 years, and 70% in those aged 65 or older, said Kalab Michaud, Ph.D., a rheumatology researcher at the University of Nebraska in Omaha.

The rates for ever having a pneumococcal vaccination were 30% in patients younger than 40 years, 45% in those aged 45-64, and 78% in patients 65 or older. The rates for a pneumococcal vaccination within the prior 5 years were 24%, 37%, and 66% respectively in the three age groups.

Patients aged 65 years or older also reported a 9% rate of ever having vaccination for herpes zoster.

The vaccination rates for both influenza and pneumonia were significantly higher in patients with lupus, and higher for pneumonia in patients with rheumatoid arthritis, compared with patients with noninflammatory rheumatoid disease. The immunization rates for both infections were significantly lower in patients with fibromyalgia.

Other significant determinants of vaccination rates in these patients included an education level lower than high school graduation, which reduced the rate, and the presence of comorbidities such as diabetes, heart disease, or pulmonary disease, which increased the rate.

The researchers on both studies reported no financial disclosures.

Influenza vaccination rates were 41% (younger than age 40), 56% (40-64), and 70% (65 or older).

Source DR. MICHAUD

PHILADELPHIA — The Framingham risk score does a poor job of estimating future risk for cardiovascular events in patients with rheumatoid arthritis, according to a review of 550 unselected patients drawn from the general population.

Results from a second study reported at the annual meeting of the American College of Rheumatology suggested that adding three more risk markers (carotid disease assessment with ultrasound, erythrocyte sedimentation rate, and cumulative steroid dose) to the standard Framingham risk score (FRS) could significantly improve prognostic accuracy for coronary disease in patients with RA. And findings from a third study presented at the meeting indicated that treatment with methotrexate is an effective way to cut coronary disease risk in RA patients.

To assess the prognostic value of the FRS, Cynthia S. Crowson and her associates at the Mayo Clinic in Rochester, Minn., used data collected for the Rochester Epidemiology Project from residents of Olmsted County, Minn. They included 550 people who presented during 1988-2008 with incident RA that matched the 1987 RA criteria of the American College of Rheumatology and who also had no history of cardiovascular disease at the time of their initial RA diagnosis. The researchers calculated an FRS for each of these patients based on their medical records and using a revised FRS (introduced in 2008) that predicted risk for cardiovascular disease events including stroke and peripheral artery disease as well as coronary disease (Circulation 2008;117:743-53).

The Mayo researchers then compared the predicted rate of cardiovascular disease events against the actual rate observed during the first 10 years following RA diagnosis. The study group included 491 RA patients who were aged 30-74 years, and 59 others who were aged 75 years or older. The FRS is designed for application to adults younger than 75.

Among the 341 women aged 30-74 years, the average predicted event rate was 5%, and the actual observed rate was 11%. Among the 150 men in this age range, the predicted rate was 12% and the observed rate was 26%, reported Ms. Crowson in a poster. She is a biostatistician at the Mayo Clinic. The researchers used a regression model to calculate a standard incidence ratio, in which the ratio of actual to expected events was 79% in women and 56% in men. Both differences were statistically significant. Further analysis showed that the largest differences between observed and expected rates were in women aged 55 years or older and in men aged 45 or older.

Although the FRS is not designed for use on people older than 74 years, Ms. Crowson and her associates applied the same analysis to 59 RA patients in this age group. The results again showed a significant excess of observed events over expected events. In women, the observed event rate was 57%, compared with an expected 14% rate. In men, the observed rate was 87%, compared with an expected rate of 37%. The findings “underscore the need for [a more] accurate tool to predict the risk of cardiovascular disease in RA patients.”

One way to improve cardiovascular risk assessment in RA patients may be to add additional risk factors to the FRS, an idea explored in a poster presented by Dr. Inmaculada del Rincon, a rheumatologist at the University of Texas Health Sciences Center in San Antonio, and her associates. They compared the correlation between standard FRS assessment and an enhanced assessment model for predicting the risk of acute coronary syndrome events in 599 RA patients. None of the patients in the study had a history of cardiovascular disease at the time the study began. During an average 5-year follow-up, 66 patients had acute coronary syndrome events.

To enhance the FRS predictive power, they added measures of carotid plaque and intima-media thickness by carotid ultrasonography, erythrocyte sedimentation rate, and cumulative glucocorticoid dose. The analysis showed that the standard FRS accounted for 70% of the events observed in the patients. The three additional risk markers boosted this rate to 76%, a statistically significant improvement, reported Dr. del Rincon and her associates in their poster.

A third poster reviewed the ability of methotrexate to reduce cardiovascular risk in RA patients. Dr. Janice Gupta, a rheumatologist at Tufts Medical Center in Boston, and her associates reviewed the medical literature for studies that compared the ability of methotrexate to lower cardiovascular events against other RA treatments. They identified six studies published during 2002-2007 that made this comparison. The studies involved a total of about 162,000 RA patients. The results showed a consistent pattern of reduced cardiovascular events in the patients who received methotrexate. The event risk was generally reduced by 15%-20%, compared with other RA treatments; the researchers did not calculate an overall summary risk-reduction rate.

Disclosures: All of the study investigators and their associates reported having no relevant financial relationships.

PHILADELPHIA — The Framingham risk score does a poor job of estimating future risk for cardiovascular events in patients with rheumatoid arthritis, according to a review of 550 unselected patients drawn from the general population.

Results from a second study reported at the annual meeting of the American College of Rheumatology suggested that adding three more risk markers (carotid disease assessment with ultrasound, erythrocyte sedimentation rate, and cumulative steroid dose) to the standard Framingham risk score (FRS) could significantly improve prognostic accuracy for coronary disease in patients with RA. And findings from a third study presented at the meeting indicated that treatment with methotrexate is an effective way to cut coronary disease risk in RA patients.

To assess the prognostic value of the FRS, Cynthia S. Crowson and her associates at the Mayo Clinic in Rochester, Minn., used data collected for the Rochester Epidemiology Project from residents of Olmsted County, Minn. They included 550 people who presented during 1988-2008 with incident RA that matched the 1987 RA criteria of the American College of Rheumatology and who also had no history of cardiovascular disease at the time of their initial RA diagnosis. The researchers calculated an FRS for each of these patients based on their medical records and using a revised FRS (introduced in 2008) that predicted risk for cardiovascular disease events including stroke and peripheral artery disease as well as coronary disease (Circulation 2008;117:743-53).

The Mayo researchers then compared the predicted rate of cardiovascular disease events against the actual rate observed during the first 10 years following RA diagnosis. The study group included 491 RA patients who were aged 30-74 years, and 59 others who were aged 75 years or older. The FRS is designed for application to adults younger than 75.

Among the 341 women aged 30-74 years, the average predicted event rate was 5%, and the actual observed rate was 11%. Among the 150 men in this age range, the predicted rate was 12% and the observed rate was 26%, reported Ms. Crowson in a poster. She is a biostatistician at the Mayo Clinic. The researchers used a regression model to calculate a standard incidence ratio, in which the ratio of actual to expected events was 79% in women and 56% in men. Both differences were statistically significant. Further analysis showed that the largest differences between observed and expected rates were in women aged 55 years or older and in men aged 45 or older.

Although the FRS is not designed for use on people older than 74 years, Ms. Crowson and her associates applied the same analysis to 59 RA patients in this age group. The results again showed a significant excess of observed events over expected events. In women, the observed event rate was 57%, compared with an expected 14% rate. In men, the observed rate was 87%, compared with an expected rate of 37%. The findings “underscore the need for [a more] accurate tool to predict the risk of cardiovascular disease in RA patients.”

One way to improve cardiovascular risk assessment in RA patients may be to add additional risk factors to the FRS, an idea explored in a poster presented by Dr. Inmaculada del Rincon, a rheumatologist at the University of Texas Health Sciences Center in San Antonio, and her associates. They compared the correlation between standard FRS assessment and an enhanced assessment model for predicting the risk of acute coronary syndrome events in 599 RA patients. None of the patients in the study had a history of cardiovascular disease at the time the study began. During an average 5-year follow-up, 66 patients had acute coronary syndrome events.

To enhance the FRS predictive power, they added measures of carotid plaque and intima-media thickness by carotid ultrasonography, erythrocyte sedimentation rate, and cumulative glucocorticoid dose. The analysis showed that the standard FRS accounted for 70% of the events observed in the patients. The three additional risk markers boosted this rate to 76%, a statistically significant improvement, reported Dr. del Rincon and her associates in their poster.

A third poster reviewed the ability of methotrexate to reduce cardiovascular risk in RA patients. Dr. Janice Gupta, a rheumatologist at Tufts Medical Center in Boston, and her associates reviewed the medical literature for studies that compared the ability of methotrexate to lower cardiovascular events against other RA treatments. They identified six studies published during 2002-2007 that made this comparison. The studies involved a total of about 162,000 RA patients. The results showed a consistent pattern of reduced cardiovascular events in the patients who received methotrexate. The event risk was generally reduced by 15%-20%, compared with other RA treatments; the researchers did not calculate an overall summary risk-reduction rate.

Disclosures: All of the study investigators and their associates reported having no relevant financial relationships.

PHILADELPHIA — The Framingham risk score does a poor job of estimating future risk for cardiovascular events in patients with rheumatoid arthritis, according to a review of 550 unselected patients drawn from the general population.

Results from a second study reported at the annual meeting of the American College of Rheumatology suggested that adding three more risk markers (carotid disease assessment with ultrasound, erythrocyte sedimentation rate, and cumulative steroid dose) to the standard Framingham risk score (FRS) could significantly improve prognostic accuracy for coronary disease in patients with RA. And findings from a third study presented at the meeting indicated that treatment with methotrexate is an effective way to cut coronary disease risk in RA patients.

To assess the prognostic value of the FRS, Cynthia S. Crowson and her associates at the Mayo Clinic in Rochester, Minn., used data collected for the Rochester Epidemiology Project from residents of Olmsted County, Minn. They included 550 people who presented during 1988-2008 with incident RA that matched the 1987 RA criteria of the American College of Rheumatology and who also had no history of cardiovascular disease at the time of their initial RA diagnosis. The researchers calculated an FRS for each of these patients based on their medical records and using a revised FRS (introduced in 2008) that predicted risk for cardiovascular disease events including stroke and peripheral artery disease as well as coronary disease (Circulation 2008;117:743-53).

The Mayo researchers then compared the predicted rate of cardiovascular disease events against the actual rate observed during the first 10 years following RA diagnosis. The study group included 491 RA patients who were aged 30-74 years, and 59 others who were aged 75 years or older. The FRS is designed for application to adults younger than 75.

Among the 341 women aged 30-74 years, the average predicted event rate was 5%, and the actual observed rate was 11%. Among the 150 men in this age range, the predicted rate was 12% and the observed rate was 26%, reported Ms. Crowson in a poster. She is a biostatistician at the Mayo Clinic. The researchers used a regression model to calculate a standard incidence ratio, in which the ratio of actual to expected events was 79% in women and 56% in men. Both differences were statistically significant. Further analysis showed that the largest differences between observed and expected rates were in women aged 55 years or older and in men aged 45 or older.

Although the FRS is not designed for use on people older than 74 years, Ms. Crowson and her associates applied the same analysis to 59 RA patients in this age group. The results again showed a significant excess of observed events over expected events. In women, the observed event rate was 57%, compared with an expected 14% rate. In men, the observed rate was 87%, compared with an expected rate of 37%. The findings “underscore the need for [a more] accurate tool to predict the risk of cardiovascular disease in RA patients.”

One way to improve cardiovascular risk assessment in RA patients may be to add additional risk factors to the FRS, an idea explored in a poster presented by Dr. Inmaculada del Rincon, a rheumatologist at the University of Texas Health Sciences Center in San Antonio, and her associates. They compared the correlation between standard FRS assessment and an enhanced assessment model for predicting the risk of acute coronary syndrome events in 599 RA patients. None of the patients in the study had a history of cardiovascular disease at the time the study began. During an average 5-year follow-up, 66 patients had acute coronary syndrome events.

To enhance the FRS predictive power, they added measures of carotid plaque and intima-media thickness by carotid ultrasonography, erythrocyte sedimentation rate, and cumulative glucocorticoid dose. The analysis showed that the standard FRS accounted for 70% of the events observed in the patients. The three additional risk markers boosted this rate to 76%, a statistically significant improvement, reported Dr. del Rincon and her associates in their poster.

A third poster reviewed the ability of methotrexate to reduce cardiovascular risk in RA patients. Dr. Janice Gupta, a rheumatologist at Tufts Medical Center in Boston, and her associates reviewed the medical literature for studies that compared the ability of methotrexate to lower cardiovascular events against other RA treatments. They identified six studies published during 2002-2007 that made this comparison. The studies involved a total of about 162,000 RA patients. The results showed a consistent pattern of reduced cardiovascular events in the patients who received methotrexate. The event risk was generally reduced by 15%-20%, compared with other RA treatments; the researchers did not calculate an overall summary risk-reduction rate.

Disclosures: All of the study investigators and their associates reported having no relevant financial relationships.

SANTA MONICA, CALIF. — Progression of early rheumatoid arthritis is likely in any woman who smokes, has active disease at the time of presentation, and is positive for both rheumatoid factor and anti–cyclic citrullinated peptide antibodies.

Sex and clinical disease activity are the most frequent risk factors for progression of rheumatoid arthritis (RA), and rheumatoid factor and anti–cyclic citrullinated peptide (anti-CCP) antibodies are the most frequent tests that physicians use to assess the likelihood of such progression. Other genetic tests that offer information about progression risk, such as that for HLA-DRB1, are not widely used. And yet other tests for genetic determinants of treatment response and the likelihood of developing adverse events in response to treatment are encouraging, but remain largely in the realm of research, according to Dr. Daniel E. Furst, who is the Carl M. Pearson Professor of Rheumatology at the University of California, Los Angeles.

No single marker can absolutely predict disease progression, at least in part because RA is probably more than one disease, dependent on the presence or absence of anti-CCP antibodies. Anti-CCP antibodies are the result of a genetic predisposition and a systemic stress, such as smoking. However, Dr. Furst pointed out that even among all anti-CCP antibody–positive people, the course of RA may vary because of the effects of environmental stimuli, immune events, and interventions (Annu. Rev. Immunol. 2008;26:651-75).

Citrullination is present in a wide range of inflammatory tissues, suggesting that this process is a nonspecific response to inflammation, rather than a disease-specific response, Dr. Furst noted at a meeting sponsored by

Subset analyses of data from the PROMPT (Probable Rheumatoid Arthritis: Methotrexate vs. Placebo Treatment) study, presented by Dr. Henrike Van Dongen of Leiden (the Netherlands) University Medical Center at the 2006 congress of the European League Against Rheumatism (EULAR), demonstrated that the presence of anti-CCP determined response to methotrexate. Responses at 15 months after diagnosis in a group of 27 anti-CCP antibody–positive patients were below 10% in those on placebo, but were close to 50% in those on methotrexate. There was no treatment effect in a group of 83 anti-CCP–negative patients (Arthritis Rheum. 2007; 56:1424).

The HLA-DRB1 gene is associated with extra-articular manifestations of RA and the development of Felty's syndrome. That syndrome occurs in fewer than 1% of RA patients and is considered to be a complication of long-standing disease. It involves a triad of conditions: RA, splenomegaly, and an abnormally low white blood count. Findings from an unpublished study show that Felty's syndrome was associated with HLA-DRB1.0401.

Other extra-articular manifestations of RA (such as pericarditis, vasculitis, interstitial lung disease, and neurologic involvement) were seen not with individual alleles, but with DRB1.04SE double-dose genotypes.

Findings from numerous other studies show that multiple single nucleotide polymorphisms (SNPs) of the PTPN22 gene have a significant association with RA, as does TRAF1-C5 (on chromosome 9).

Smoking and anti-CCP antibody status seem to be associated in RA, but PTPN22 is an independent risk factor for developing RA, according to Dr. Furst. Although not yet directly applicable to clinical care, attempts are being made to predict response to RA medications using genetic signatures or gene SNPs.

For now, other factors are more practical predictors of good response.

SDEF and this news organization are owned by Elsevier.

For a video interview with Dr. Furst, go to www.youtube.com/rheumatologynews

Disclosures: Dr. Furst reported financial relationships with numerous pharmaceutical companies and the National Institutes of Health.

Dr. Daniel E. Furst noted that anti-CCP antibodies are the result of a genetic predisposition and a systemic stress.

Source Sally Kubetin/Elsevier Global Medical News

SANTA MONICA, CALIF. — Progression of early rheumatoid arthritis is likely in any woman who smokes, has active disease at the time of presentation, and is positive for both rheumatoid factor and anti–cyclic citrullinated peptide antibodies.

Sex and clinical disease activity are the most frequent risk factors for progression of rheumatoid arthritis (RA), and rheumatoid factor and anti–cyclic citrullinated peptide (anti-CCP) antibodies are the most frequent tests that physicians use to assess the likelihood of such progression. Other genetic tests that offer information about progression risk, such as that for HLA-DRB1, are not widely used. And yet other tests for genetic determinants of treatment response and the likelihood of developing adverse events in response to treatment are encouraging, but remain largely in the realm of research, according to Dr. Daniel E. Furst, who is the Carl M. Pearson Professor of Rheumatology at the University of California, Los Angeles.

No single marker can absolutely predict disease progression, at least in part because RA is probably more than one disease, dependent on the presence or absence of anti-CCP antibodies. Anti-CCP antibodies are the result of a genetic predisposition and a systemic stress, such as smoking. However, Dr. Furst pointed out that even among all anti-CCP antibody–positive people, the course of RA may vary because of the effects of environmental stimuli, immune events, and interventions (Annu. Rev. Immunol. 2008;26:651-75).

Citrullination is present in a wide range of inflammatory tissues, suggesting that this process is a nonspecific response to inflammation, rather than a disease-specific response, Dr. Furst noted at a meeting sponsored by

Subset analyses of data from the PROMPT (Probable Rheumatoid Arthritis: Methotrexate vs. Placebo Treatment) study, presented by Dr. Henrike Van Dongen of Leiden (the Netherlands) University Medical Center at the 2006 congress of the European League Against Rheumatism (EULAR), demonstrated that the presence of anti-CCP determined response to methotrexate. Responses at 15 months after diagnosis in a group of 27 anti-CCP antibody–positive patients were below 10% in those on placebo, but were close to 50% in those on methotrexate. There was no treatment effect in a group of 83 anti-CCP–negative patients (Arthritis Rheum. 2007; 56:1424).

The HLA-DRB1 gene is associated with extra-articular manifestations of RA and the development of Felty's syndrome. That syndrome occurs in fewer than 1% of RA patients and is considered to be a complication of long-standing disease. It involves a triad of conditions: RA, splenomegaly, and an abnormally low white blood count. Findings from an unpublished study show that Felty's syndrome was associated with HLA-DRB1.0401.

Other extra-articular manifestations of RA (such as pericarditis, vasculitis, interstitial lung disease, and neurologic involvement) were seen not with individual alleles, but with DRB1.04SE double-dose genotypes.

Findings from numerous other studies show that multiple single nucleotide polymorphisms (SNPs) of the PTPN22 gene have a significant association with RA, as does TRAF1-C5 (on chromosome 9).

Smoking and anti-CCP antibody status seem to be associated in RA, but PTPN22 is an independent risk factor for developing RA, according to Dr. Furst. Although not yet directly applicable to clinical care, attempts are being made to predict response to RA medications using genetic signatures or gene SNPs.

For now, other factors are more practical predictors of good response.

SDEF and this news organization are owned by Elsevier.

For a video interview with Dr. Furst, go to www.youtube.com/rheumatologynews

Disclosures: Dr. Furst reported financial relationships with numerous pharmaceutical companies and the National Institutes of Health.

Dr. Daniel E. Furst noted that anti-CCP antibodies are the result of a genetic predisposition and a systemic stress.

Source Sally Kubetin/Elsevier Global Medical News

SANTA MONICA, CALIF. — Progression of early rheumatoid arthritis is likely in any woman who smokes, has active disease at the time of presentation, and is positive for both rheumatoid factor and anti–cyclic citrullinated peptide antibodies.

Sex and clinical disease activity are the most frequent risk factors for progression of rheumatoid arthritis (RA), and rheumatoid factor and anti–cyclic citrullinated peptide (anti-CCP) antibodies are the most frequent tests that physicians use to assess the likelihood of such progression. Other genetic tests that offer information about progression risk, such as that for HLA-DRB1, are not widely used. And yet other tests for genetic determinants of treatment response and the likelihood of developing adverse events in response to treatment are encouraging, but remain largely in the realm of research, according to Dr. Daniel E. Furst, who is the Carl M. Pearson Professor of Rheumatology at the University of California, Los Angeles.

No single marker can absolutely predict disease progression, at least in part because RA is probably more than one disease, dependent on the presence or absence of anti-CCP antibodies. Anti-CCP antibodies are the result of a genetic predisposition and a systemic stress, such as smoking. However, Dr. Furst pointed out that even among all anti-CCP antibody–positive people, the course of RA may vary because of the effects of environmental stimuli, immune events, and interventions (Annu. Rev. Immunol. 2008;26:651-75).

Citrullination is present in a wide range of inflammatory tissues, suggesting that this process is a nonspecific response to inflammation, rather than a disease-specific response, Dr. Furst noted at a meeting sponsored by

Subset analyses of data from the PROMPT (Probable Rheumatoid Arthritis: Methotrexate vs. Placebo Treatment) study, presented by Dr. Henrike Van Dongen of Leiden (the Netherlands) University Medical Center at the 2006 congress of the European League Against Rheumatism (EULAR), demonstrated that the presence of anti-CCP determined response to methotrexate. Responses at 15 months after diagnosis in a group of 27 anti-CCP antibody–positive patients were below 10% in those on placebo, but were close to 50% in those on methotrexate. There was no treatment effect in a group of 83 anti-CCP–negative patients (Arthritis Rheum. 2007; 56:1424).

The HLA-DRB1 gene is associated with extra-articular manifestations of RA and the development of Felty's syndrome. That syndrome occurs in fewer than 1% of RA patients and is considered to be a complication of long-standing disease. It involves a triad of conditions: RA, splenomegaly, and an abnormally low white blood count. Findings from an unpublished study show that Felty's syndrome was associated with HLA-DRB1.0401.

Other extra-articular manifestations of RA (such as pericarditis, vasculitis, interstitial lung disease, and neurologic involvement) were seen not with individual alleles, but with DRB1.04SE double-dose genotypes.

Findings from numerous other studies show that multiple single nucleotide polymorphisms (SNPs) of the PTPN22 gene have a significant association with RA, as does TRAF1-C5 (on chromosome 9).

Smoking and anti-CCP antibody status seem to be associated in RA, but PTPN22 is an independent risk factor for developing RA, according to Dr. Furst. Although not yet directly applicable to clinical care, attempts are being made to predict response to RA medications using genetic signatures or gene SNPs.

For now, other factors are more practical predictors of good response.

SDEF and this news organization are owned by Elsevier.

For a video interview with Dr. Furst, go to www.youtube.com/rheumatologynews

Disclosures: Dr. Furst reported financial relationships with numerous pharmaceutical companies and the National Institutes of Health.

Dr. Daniel E. Furst noted that anti-CCP antibodies are the result of a genetic predisposition and a systemic stress.

Source Sally Kubetin/Elsevier Global Medical News

PHILADELPHIA — Treatment with an investigational, oral, immune-modulating drug led to significant improvement in patients with active rheumatoid arthritis refractory to methotrexate in a phase II study in more than 400 patients.

“These results confirm our earlier observations of the effect of this drug on a background of methotrexate,” Dr. Michael E. Weinblatt said at the annual meeting of the American College of Rheumatology.

The two tested dosages of R788 (fostamatinib disodium), 150 mg once daily and 100 mg b.i.d., each led to significantly higher rates of ACR20 responses compared with placebo, the study's primary end point, said Dr. Weinblatt, a professor of medicine at Harvard University and codirector of clinical rheumatology at Brigham and Women's Hospital in Boston.

However, the story may be different in patients with active RA who have failed a biologic. In a second phase II study with the same agent in 219 such patients, administration of R788 at 100 mg b.i.d. did not produce an ACR20 response that was significantly better than placebo, reported Dr. Mark C. Genovese, a professor of medicine/immunology and rheumatology at Stanford (Calif.) University. He noted that this negative, second study seemed potentially flawed because its placebo group had an “exceptionally high placebo response rate.”

R788 is a selective inhibitor of Syk kinase, an important immuno-regulating enzyme that affects mast cells, macrophages, neutrophils, and B cells. Prior studies showed that Syk kinase was present in the synovial fluid of RA patients.

The trial enrolled patients with active RA and at least 6 (out of 28) painful and swollen joints and either a C-reactive protein level above the upper limit of normal or an erythrocyte sedimentation rate greater than 28 mm/hr. Patients also had to be on a methotrexate regimen of at least 10 mg/week for at least 3 months and with a stable dosage for at least 6 weeks. Patients could also be on stable dosages of low-dose prednisone and/or NSAIDs, but other disease modifying antirheumatic drugs, including any biologic, had to be washed out. Their average age was 53 years, about 85% were women, and their mean disease duration was 9 years. Each patient had an average of 12 painful and swollen joints.

After 6 months, an ACR20 response rate occurred in 66% of 152 patients randomized to 100 mg b.i.d., in 57% of 152 patients randomized to 150 mg once daily, and in 35% of 153 placebo patients, analyzed on an intention-to-treat basis. The differences between each of the two active arms and the placebo group were statistically significant. The 100 mg b.i.d. patients also had significantly better improvements in their ACR50 and ACR70 responses compared with placebo, as well as a significantly better rate of patients with a disease activity score (DAS)-28 of less than 2.6. Patients on 150 mg once daily also fared significantly better than the placebo group for the ACR50 and DAS-28 responses, but their ACR70 response did not significant surpass the placebo group.

The incidence of serious adverse events was similar in all three groups, with 7 in the placebo arm, 5 in patients getting 150 mg daily, and 13 in those getting 100 mg b.i.d. No patient died or had an opportunistic infection. The most common adverse event on treatment was diarrhea in 3% of placebo patients, in 12% of patients on 150 mg once daily, and in 19% of patients getting 100 mg b.i.d.

Patients receiving R788 also showed small increases in the rates of neutropenia and in elevations of liver enzymes, compared with the placebo patients. The rate of patients who had a reduction in their dosage because of an adverse event was 14% in each of the R788 arms and 4% in placebo patients. Discontinuations were for blood pressure elevations, liver enzyme elevations greater than three times the upper limit of normal, neutropenia, or gastrointestinal events.

The second study included 219 patients with active RA who previously failed to respond to or tolerate a biologic treatment. Their average age was 56 years, 80% were women, and their average disease duration was 12 years. After 3 months of treatment, the 146 patients getting 100 mg R788 b.i.d. did not have a significantly better response than 73 placebo patients for any ACR response or DAS28 measure. The patients on R788 did have significantly greater reductions in their level of C reactive protein and in their erythrocyte sedimentation rate than those on placebo.

One serious adverse event, an infection, occurred in the placebo patients. Patients on R788 had 13 serious adverse events, including 3 infections, none of them opportunistic. In the placebo group, 3% of patients had to lower their dose due to adverse events as did 14% of those on the active drug.

Disclosures: Rigel Pharmaceuticals, the company developing R788, sponsored both studies. Dr. Weinblatt and Dr. Genovese served as consultants to Rigel, and two of their associates on the study are full-time employees of the company.

R788 led to significantly higher rates of ACR20 responses, compared with placebo.

Source DR. WEINBLATT

PHILADELPHIA — Treatment with an investigational, oral, immune-modulating drug led to significant improvement in patients with active rheumatoid arthritis refractory to methotrexate in a phase II study in more than 400 patients.

“These results confirm our earlier observations of the effect of this drug on a background of methotrexate,” Dr. Michael E. Weinblatt said at the annual meeting of the American College of Rheumatology.

The two tested dosages of R788 (fostamatinib disodium), 150 mg once daily and 100 mg b.i.d., each led to significantly higher rates of ACR20 responses compared with placebo, the study's primary end point, said Dr. Weinblatt, a professor of medicine at Harvard University and codirector of clinical rheumatology at Brigham and Women's Hospital in Boston.

However, the story may be different in patients with active RA who have failed a biologic. In a second phase II study with the same agent in 219 such patients, administration of R788 at 100 mg b.i.d. did not produce an ACR20 response that was significantly better than placebo, reported Dr. Mark C. Genovese, a professor of medicine/immunology and rheumatology at Stanford (Calif.) University. He noted that this negative, second study seemed potentially flawed because its placebo group had an “exceptionally high placebo response rate.”

R788 is a selective inhibitor of Syk kinase, an important immuno-regulating enzyme that affects mast cells, macrophages, neutrophils, and B cells. Prior studies showed that Syk kinase was present in the synovial fluid of RA patients.

The trial enrolled patients with active RA and at least 6 (out of 28) painful and swollen joints and either a C-reactive protein level above the upper limit of normal or an erythrocyte sedimentation rate greater than 28 mm/hr. Patients also had to be on a methotrexate regimen of at least 10 mg/week for at least 3 months and with a stable dosage for at least 6 weeks. Patients could also be on stable dosages of low-dose prednisone and/or NSAIDs, but other disease modifying antirheumatic drugs, including any biologic, had to be washed out. Their average age was 53 years, about 85% were women, and their mean disease duration was 9 years. Each patient had an average of 12 painful and swollen joints.

After 6 months, an ACR20 response rate occurred in 66% of 152 patients randomized to 100 mg b.i.d., in 57% of 152 patients randomized to 150 mg once daily, and in 35% of 153 placebo patients, analyzed on an intention-to-treat basis. The differences between each of the two active arms and the placebo group were statistically significant. The 100 mg b.i.d. patients also had significantly better improvements in their ACR50 and ACR70 responses compared with placebo, as well as a significantly better rate of patients with a disease activity score (DAS)-28 of less than 2.6. Patients on 150 mg once daily also fared significantly better than the placebo group for the ACR50 and DAS-28 responses, but their ACR70 response did not significant surpass the placebo group.

The incidence of serious adverse events was similar in all three groups, with 7 in the placebo arm, 5 in patients getting 150 mg daily, and 13 in those getting 100 mg b.i.d. No patient died or had an opportunistic infection. The most common adverse event on treatment was diarrhea in 3% of placebo patients, in 12% of patients on 150 mg once daily, and in 19% of patients getting 100 mg b.i.d.

Patients receiving R788 also showed small increases in the rates of neutropenia and in elevations of liver enzymes, compared with the placebo patients. The rate of patients who had a reduction in their dosage because of an adverse event was 14% in each of the R788 arms and 4% in placebo patients. Discontinuations were for blood pressure elevations, liver enzyme elevations greater than three times the upper limit of normal, neutropenia, or gastrointestinal events.

The second study included 219 patients with active RA who previously failed to respond to or tolerate a biologic treatment. Their average age was 56 years, 80% were women, and their average disease duration was 12 years. After 3 months of treatment, the 146 patients getting 100 mg R788 b.i.d. did not have a significantly better response than 73 placebo patients for any ACR response or DAS28 measure. The patients on R788 did have significantly greater reductions in their level of C reactive protein and in their erythrocyte sedimentation rate than those on placebo.

One serious adverse event, an infection, occurred in the placebo patients. Patients on R788 had 13 serious adverse events, including 3 infections, none of them opportunistic. In the placebo group, 3% of patients had to lower their dose due to adverse events as did 14% of those on the active drug.

Disclosures: Rigel Pharmaceuticals, the company developing R788, sponsored both studies. Dr. Weinblatt and Dr. Genovese served as consultants to Rigel, and two of their associates on the study are full-time employees of the company.

R788 led to significantly higher rates of ACR20 responses, compared with placebo.

Source DR. WEINBLATT

PHILADELPHIA — Treatment with an investigational, oral, immune-modulating drug led to significant improvement in patients with active rheumatoid arthritis refractory to methotrexate in a phase II study in more than 400 patients.

“These results confirm our earlier observations of the effect of this drug on a background of methotrexate,” Dr. Michael E. Weinblatt said at the annual meeting of the American College of Rheumatology.

The two tested dosages of R788 (fostamatinib disodium), 150 mg once daily and 100 mg b.i.d., each led to significantly higher rates of ACR20 responses compared with placebo, the study's primary end point, said Dr. Weinblatt, a professor of medicine at Harvard University and codirector of clinical rheumatology at Brigham and Women's Hospital in Boston.

However, the story may be different in patients with active RA who have failed a biologic. In a second phase II study with the same agent in 219 such patients, administration of R788 at 100 mg b.i.d. did not produce an ACR20 response that was significantly better than placebo, reported Dr. Mark C. Genovese, a professor of medicine/immunology and rheumatology at Stanford (Calif.) University. He noted that this negative, second study seemed potentially flawed because its placebo group had an “exceptionally high placebo response rate.”

R788 is a selective inhibitor of Syk kinase, an important immuno-regulating enzyme that affects mast cells, macrophages, neutrophils, and B cells. Prior studies showed that Syk kinase was present in the synovial fluid of RA patients.

The trial enrolled patients with active RA and at least 6 (out of 28) painful and swollen joints and either a C-reactive protein level above the upper limit of normal or an erythrocyte sedimentation rate greater than 28 mm/hr. Patients also had to be on a methotrexate regimen of at least 10 mg/week for at least 3 months and with a stable dosage for at least 6 weeks. Patients could also be on stable dosages of low-dose prednisone and/or NSAIDs, but other disease modifying antirheumatic drugs, including any biologic, had to be washed out. Their average age was 53 years, about 85% were women, and their mean disease duration was 9 years. Each patient had an average of 12 painful and swollen joints.

After 6 months, an ACR20 response rate occurred in 66% of 152 patients randomized to 100 mg b.i.d., in 57% of 152 patients randomized to 150 mg once daily, and in 35% of 153 placebo patients, analyzed on an intention-to-treat basis. The differences between each of the two active arms and the placebo group were statistically significant. The 100 mg b.i.d. patients also had significantly better improvements in their ACR50 and ACR70 responses compared with placebo, as well as a significantly better rate of patients with a disease activity score (DAS)-28 of less than 2.6. Patients on 150 mg once daily also fared significantly better than the placebo group for the ACR50 and DAS-28 responses, but their ACR70 response did not significant surpass the placebo group.

The incidence of serious adverse events was similar in all three groups, with 7 in the placebo arm, 5 in patients getting 150 mg daily, and 13 in those getting 100 mg b.i.d. No patient died or had an opportunistic infection. The most common adverse event on treatment was diarrhea in 3% of placebo patients, in 12% of patients on 150 mg once daily, and in 19% of patients getting 100 mg b.i.d.

Patients receiving R788 also showed small increases in the rates of neutropenia and in elevations of liver enzymes, compared with the placebo patients. The rate of patients who had a reduction in their dosage because of an adverse event was 14% in each of the R788 arms and 4% in placebo patients. Discontinuations were for blood pressure elevations, liver enzyme elevations greater than three times the upper limit of normal, neutropenia, or gastrointestinal events.

The second study included 219 patients with active RA who previously failed to respond to or tolerate a biologic treatment. Their average age was 56 years, 80% were women, and their average disease duration was 12 years. After 3 months of treatment, the 146 patients getting 100 mg R788 b.i.d. did not have a significantly better response than 73 placebo patients for any ACR response or DAS28 measure. The patients on R788 did have significantly greater reductions in their level of C reactive protein and in their erythrocyte sedimentation rate than those on placebo.

One serious adverse event, an infection, occurred in the placebo patients. Patients on R788 had 13 serious adverse events, including 3 infections, none of them opportunistic. In the placebo group, 3% of patients had to lower their dose due to adverse events as did 14% of those on the active drug.

Disclosures: Rigel Pharmaceuticals, the company developing R788, sponsored both studies. Dr. Weinblatt and Dr. Genovese served as consultants to Rigel, and two of their associates on the study are full-time employees of the company.

R788 led to significantly higher rates of ACR20 responses, compared with placebo.

Source DR. WEINBLATT

SANTA MONICA, CALIF. — Although good drugs are available, it takes more than medications to manage fibromyalgia, according to Dr. Chad S. Boomershine.

“I recommend that fibromyalgia patients perform stretches every morning and, on alternating days, engage in aerobic and resistance exercise a total of 6 days per week,” counseled Dr. Boomershine, a rheumatologist at Vanderbilt University, Nashville, Tenn., where he specializes in treating fibromyalgia in collaboration with the Vanderbilt Center for Integrative Health and the Vanderbilt Dayani Center.

“The combination of aerobic and resistance exercise is particularly effective in improving symptoms. Since many patients don't live near an exercise facility, I provide patients with instructional handouts and [professional elastic resistance bands] for resistance exercise on their initial visit so they can exercise at home,” Dr. Boomershine said at a meeting sponsored by

Dr. Boomershine said he refers his patients to the exercise guide on the National Institute on Aging Web site (www.nia.nih.gov/HealthInformation/Publications/ExerciseGuide

He also recommends the National Center on Physical Activity and Disability Web site's exercise fact sheet (www.ncpad.org/exercise/fact_sheet.php?sheet=259

Additionally, he recommends that patients learn more about fibromyalgia and find support groups in their area. “Due to the severity of their symptoms, patients are often afraid they have a terminal illness,” he noted. “Understanding that fibromyalgia is not progressive and realizing they can manage their symptoms by learning self-help techniques is empowering and necessary if patients are to have lasting symptom improvement.”

The Web sites www.knowfibro.comwww.fmaware.org

Between 2% and 4% of the U.S. population meet the fibromyalgia classification criteria issued in 1990 by the American College of Rheumatology. However, the true prevalence is estimated to be about twice as high, and—as prevalence increases with age—fibromyalgia is expected to become increasingly common with the aging of the population, he said.

Of those who have the condition, the reported 9:1 ratio of women to men is incorrect, as women have more tender points and men are more likely to self-medicate rather than to seek medical care.

There are no official figures on how many people are unable to work due to fibromyalgia because the Social Security Adminustration does not recognize it as a cause of disability.

SDEF and this news organization are owned by Elsevier.

SANTA MONICA, CALIF. — Although good drugs are available, it takes more than medications to manage fibromyalgia, according to Dr. Chad S. Boomershine.

“I recommend that fibromyalgia patients perform stretches every morning and, on alternating days, engage in aerobic and resistance exercise a total of 6 days per week,” counseled Dr. Boomershine, a rheumatologist at Vanderbilt University, Nashville, Tenn., where he specializes in treating fibromyalgia in collaboration with the Vanderbilt Center for Integrative Health and the Vanderbilt Dayani Center.

“The combination of aerobic and resistance exercise is particularly effective in improving symptoms. Since many patients don't live near an exercise facility, I provide patients with instructional handouts and [professional elastic resistance bands] for resistance exercise on their initial visit so they can exercise at home,” Dr. Boomershine said at a meeting sponsored by

Dr. Boomershine said he refers his patients to the exercise guide on the National Institute on Aging Web site (www.nia.nih.gov/HealthInformation/Publications/ExerciseGuide

He also recommends the National Center on Physical Activity and Disability Web site's exercise fact sheet (www.ncpad.org/exercise/fact_sheet.php?sheet=259

Additionally, he recommends that patients learn more about fibromyalgia and find support groups in their area. “Due to the severity of their symptoms, patients are often afraid they have a terminal illness,” he noted. “Understanding that fibromyalgia is not progressive and realizing they can manage their symptoms by learning self-help techniques is empowering and necessary if patients are to have lasting symptom improvement.”

The Web sites www.knowfibro.comwww.fmaware.org

Between 2% and 4% of the U.S. population meet the fibromyalgia classification criteria issued in 1990 by the American College of Rheumatology. However, the true prevalence is estimated to be about twice as high, and—as prevalence increases with age—fibromyalgia is expected to become increasingly common with the aging of the population, he said.

Of those who have the condition, the reported 9:1 ratio of women to men is incorrect, as women have more tender points and men are more likely to self-medicate rather than to seek medical care.

There are no official figures on how many people are unable to work due to fibromyalgia because the Social Security Adminustration does not recognize it as a cause of disability.

SDEF and this news organization are owned by Elsevier.

SANTA MONICA, CALIF. — Although good drugs are available, it takes more than medications to manage fibromyalgia, according to Dr. Chad S. Boomershine.

“I recommend that fibromyalgia patients perform stretches every morning and, on alternating days, engage in aerobic and resistance exercise a total of 6 days per week,” counseled Dr. Boomershine, a rheumatologist at Vanderbilt University, Nashville, Tenn., where he specializes in treating fibromyalgia in collaboration with the Vanderbilt Center for Integrative Health and the Vanderbilt Dayani Center.

“The combination of aerobic and resistance exercise is particularly effective in improving symptoms. Since many patients don't live near an exercise facility, I provide patients with instructional handouts and [professional elastic resistance bands] for resistance exercise on their initial visit so they can exercise at home,” Dr. Boomershine said at a meeting sponsored by

Dr. Boomershine said he refers his patients to the exercise guide on the National Institute on Aging Web site (www.nia.nih.gov/HealthInformation/Publications/ExerciseGuide

He also recommends the National Center on Physical Activity and Disability Web site's exercise fact sheet (www.ncpad.org/exercise/fact_sheet.php?sheet=259

Additionally, he recommends that patients learn more about fibromyalgia and find support groups in their area. “Due to the severity of their symptoms, patients are often afraid they have a terminal illness,” he noted. “Understanding that fibromyalgia is not progressive and realizing they can manage their symptoms by learning self-help techniques is empowering and necessary if patients are to have lasting symptom improvement.”

The Web sites www.knowfibro.comwww.fmaware.org

Between 2% and 4% of the U.S. population meet the fibromyalgia classification criteria issued in 1990 by the American College of Rheumatology. However, the true prevalence is estimated to be about twice as high, and—as prevalence increases with age—fibromyalgia is expected to become increasingly common with the aging of the population, he said.

Of those who have the condition, the reported 9:1 ratio of women to men is incorrect, as women have more tender points and men are more likely to self-medicate rather than to seek medical care.

There are no official figures on how many people are unable to work due to fibromyalgia because the Social Security Adminustration does not recognize it as a cause of disability.

SDEF and this news organization are owned by Elsevier.

Major Finding: Fibromyalgia therapies need to be used in combination, and sometimes at doses other than those recommended by the manufacturer, depending upon the overarching symptom of the individual patient.

Source of Data: Expert opinion.

Disclosures: Dr. Boomershine reported that he is an investigator for Pfizer Inc. and the National Institutes of Health, and is a consultant for Pfizer, Eli Lilly & Co., Forest Pharmaceuticals Inc., and Takeda Pharmaceutical Co.

SANTA MONICA, CALIF. — Effective treatments exist for fibromyalgia syndrome, but many physicians still do a poor job of treating affected patients, Dr. Chad S. Boomershine said at a meeting sponsored by

Could it be that these physicians don't consider fibromyalgia to be a “real” disease, that they perceive affected patients as being too time consuming and unlikely to get better? asked Dr. Boomershine, a rheumatologist at Vanderbilt University in Nashville, Tenn., where he specializes in treating fibromyalgia in collaboration with the Vanderbilt Center for Integrative Health and the Vanderbilt Dayani Center.

About 2%-4% of the U.S. population meets the fibromyalgia classification criteria issued in 1990 by the ACR. The true prevalence is estimated to be about twice as high, and—as prevalence increases with age—fibromyalgia is expected to become more common with the aging of the population.

The ACR classification criteria for fibromyalgia include widespread pain for at least 3 months' duration, and pain at a minimum of 11 of 18 specified tender points when enough pressure to just blanch the examiner's thumbnail is applied. The reported 9:1 ratio of women to men with the condition is incorrect, he said, as women have more tender points and men are more likely to self-medicate rather than to seek medical care.

Fibromyalgia typically involves symptoms other than pain, which Dr. Boomershine teaches using the FIBRO mnemonic (F for fatigue and 'fibrofog' [cognitive dysfunction], I for insomnia [nonrestorative sleep], B for blues [depression and anxiety], R for rigidity [muscle and joint stiffness], and O for Ow! [pain and work disability]). Nevertheless, pharmacologic management should start by treating pain because it is the one symptom common to all fibromyalgia patients, he said.

When choosing among the three indicated medications, a physician should individualize therapy based on the associated symptom that is most disabling for the patient, he recommended.

Pain associated with insomnia is best treated with pregabalin (Lyrica), he said. The label states that pregabalin should be given in two divided doses daily beginning with a total of 150 mg/day and increasing to as much as 450 mg/day if needed. In an effort to avoid the typical side effects of dizziness, somnolence, fatigue, and cognitive dysfunction, however, Dr. Boomershine recommends beginning with 25-75 mg once daily at bedtime and titrating up to 150-225 mg at night before adding a morning dose.

Pain with depression and/or anxiety is best managed with duloxetine (Cymbalta) every morning, he said. The label states that the recommended dosage for fibromyalgia is 60 mg/day, but Dr. Boomershine recommends starting with 20-30 mg and increasing to 60 mg only if necessary. Trial data indicate that many patients do well on lower doses, he noted, and higher doses are associated with increased risk for side effects, including nausea, headache, and insomnia.

For pain associated with fatigue or fibrofog, the treatment of choice is milnacipran (Savella), he said. The label for this agent recommends starting at a dose of 12.5 mg once daily and gradually working up to 50 mg twice daily after 1 week and a maximum dosage of 100 mg twice daily if needed. Dr. Boomershine said he recommends a more gradual up-titration and noted that the dose should be increased only if needed because of the patient's symptoms. Milnacipran is available in 12.5-, 25-, 50- and 100-mg tablets, allowing for dosing flexibility.

Physicians with years of experience in successfully managing fibromyalgia are accustomed to using other drugs that lack Food and Drug Administration approval specifically for use in fibromyalgia.

Amitriptyline given as a 25-mg dose at bedtime in combination with fluoxetine (20 mg) in the morning is a “particularly good combination,” said Dr. Boomershine. He noted that the combination has shown good efficacy and likely provides balanced norepinephrine and serotonin reuptake inhibition similar to that provided by duloxetine and milnacipran, but at a much lower cost.

Dr. Boomershine recommends avoiding the use of narcotics, benzodiazepines, or steroids in treating fibromyalgia symptoms.

SDEF and this news organization are owned by Elsevier.

For a video interview with Dr. Boomershine, go to www.youtube.com/rheumatologynews

Treatment needs to address the fact that pain is only one symptom of fibromyalgia, Dr. Chad S. Boomershine said.

Source Sally Kubetin/Elsevier Global Medical News

Major Finding: Fibromyalgia therapies need to be used in combination, and sometimes at doses other than those recommended by the manufacturer, depending upon the overarching symptom of the individual patient.

Source of Data: Expert opinion.

Disclosures: Dr. Boomershine reported that he is an investigator for Pfizer Inc. and the National Institutes of Health, and is a consultant for Pfizer, Eli Lilly & Co., Forest Pharmaceuticals Inc., and Takeda Pharmaceutical Co.

SANTA MONICA, CALIF. — Effective treatments exist for fibromyalgia syndrome, but many physicians still do a poor job of treating affected patients, Dr. Chad S. Boomershine said at a meeting sponsored by

Could it be that these physicians don't consider fibromyalgia to be a “real” disease, that they perceive affected patients as being too time consuming and unlikely to get better? asked Dr. Boomershine, a rheumatologist at Vanderbilt University in Nashville, Tenn., where he specializes in treating fibromyalgia in collaboration with the Vanderbilt Center for Integrative Health and the Vanderbilt Dayani Center.

About 2%-4% of the U.S. population meets the fibromyalgia classification criteria issued in 1990 by the ACR. The true prevalence is estimated to be about twice as high, and—as prevalence increases with age—fibromyalgia is expected to become more common with the aging of the population.

The ACR classification criteria for fibromyalgia include widespread pain for at least 3 months' duration, and pain at a minimum of 11 of 18 specified tender points when enough pressure to just blanch the examiner's thumbnail is applied. The reported 9:1 ratio of women to men with the condition is incorrect, he said, as women have more tender points and men are more likely to self-medicate rather than to seek medical care.

Fibromyalgia typically involves symptoms other than pain, which Dr. Boomershine teaches using the FIBRO mnemonic (F for fatigue and 'fibrofog' [cognitive dysfunction], I for insomnia [nonrestorative sleep], B for blues [depression and anxiety], R for rigidity [muscle and joint stiffness], and O for Ow! [pain and work disability]). Nevertheless, pharmacologic management should start by treating pain because it is the one symptom common to all fibromyalgia patients, he said.

When choosing among the three indicated medications, a physician should individualize therapy based on the associated symptom that is most disabling for the patient, he recommended.

Pain associated with insomnia is best treated with pregabalin (Lyrica), he said. The label states that pregabalin should be given in two divided doses daily beginning with a total of 150 mg/day and increasing to as much as 450 mg/day if needed. In an effort to avoid the typical side effects of dizziness, somnolence, fatigue, and cognitive dysfunction, however, Dr. Boomershine recommends beginning with 25-75 mg once daily at bedtime and titrating up to 150-225 mg at night before adding a morning dose.

Pain with depression and/or anxiety is best managed with duloxetine (Cymbalta) every morning, he said. The label states that the recommended dosage for fibromyalgia is 60 mg/day, but Dr. Boomershine recommends starting with 20-30 mg and increasing to 60 mg only if necessary. Trial data indicate that many patients do well on lower doses, he noted, and higher doses are associated with increased risk for side effects, including nausea, headache, and insomnia.

For pain associated with fatigue or fibrofog, the treatment of choice is milnacipran (Savella), he said. The label for this agent recommends starting at a dose of 12.5 mg once daily and gradually working up to 50 mg twice daily after 1 week and a maximum dosage of 100 mg twice daily if needed. Dr. Boomershine said he recommends a more gradual up-titration and noted that the dose should be increased only if needed because of the patient's symptoms. Milnacipran is available in 12.5-, 25-, 50- and 100-mg tablets, allowing for dosing flexibility.

Physicians with years of experience in successfully managing fibromyalgia are accustomed to using other drugs that lack Food and Drug Administration approval specifically for use in fibromyalgia.

Amitriptyline given as a 25-mg dose at bedtime in combination with fluoxetine (20 mg) in the morning is a “particularly good combination,” said Dr. Boomershine. He noted that the combination has shown good efficacy and likely provides balanced norepinephrine and serotonin reuptake inhibition similar to that provided by duloxetine and milnacipran, but at a much lower cost.

Dr. Boomershine recommends avoiding the use of narcotics, benzodiazepines, or steroids in treating fibromyalgia symptoms.

SDEF and this news organization are owned by Elsevier.

For a video interview with Dr. Boomershine, go to www.youtube.com/rheumatologynews

Treatment needs to address the fact that pain is only one symptom of fibromyalgia, Dr. Chad S. Boomershine said.

Source Sally Kubetin/Elsevier Global Medical News

Major Finding: Fibromyalgia therapies need to be used in combination, and sometimes at doses other than those recommended by the manufacturer, depending upon the overarching symptom of the individual patient.

Source of Data: Expert opinion.

Disclosures: Dr. Boomershine reported that he is an investigator for Pfizer Inc. and the National Institutes of Health, and is a consultant for Pfizer, Eli Lilly & Co., Forest Pharmaceuticals Inc., and Takeda Pharmaceutical Co.

SANTA MONICA, CALIF. — Effective treatments exist for fibromyalgia syndrome, but many physicians still do a poor job of treating affected patients, Dr. Chad S. Boomershine said at a meeting sponsored by

Could it be that these physicians don't consider fibromyalgia to be a “real” disease, that they perceive affected patients as being too time consuming and unlikely to get better? asked Dr. Boomershine, a rheumatologist at Vanderbilt University in Nashville, Tenn., where he specializes in treating fibromyalgia in collaboration with the Vanderbilt Center for Integrative Health and the Vanderbilt Dayani Center.

About 2%-4% of the U.S. population meets the fibromyalgia classification criteria issued in 1990 by the ACR. The true prevalence is estimated to be about twice as high, and—as prevalence increases with age—fibromyalgia is expected to become more common with the aging of the population.

The ACR classification criteria for fibromyalgia include widespread pain for at least 3 months' duration, and pain at a minimum of 11 of 18 specified tender points when enough pressure to just blanch the examiner's thumbnail is applied. The reported 9:1 ratio of women to men with the condition is incorrect, he said, as women have more tender points and men are more likely to self-medicate rather than to seek medical care.

Fibromyalgia typically involves symptoms other than pain, which Dr. Boomershine teaches using the FIBRO mnemonic (F for fatigue and 'fibrofog' [cognitive dysfunction], I for insomnia [nonrestorative sleep], B for blues [depression and anxiety], R for rigidity [muscle and joint stiffness], and O for Ow! [pain and work disability]). Nevertheless, pharmacologic management should start by treating pain because it is the one symptom common to all fibromyalgia patients, he said.

When choosing among the three indicated medications, a physician should individualize therapy based on the associated symptom that is most disabling for the patient, he recommended.

Pain associated with insomnia is best treated with pregabalin (Lyrica), he said. The label states that pregabalin should be given in two divided doses daily beginning with a total of 150 mg/day and increasing to as much as 450 mg/day if needed. In an effort to avoid the typical side effects of dizziness, somnolence, fatigue, and cognitive dysfunction, however, Dr. Boomershine recommends beginning with 25-75 mg once daily at bedtime and titrating up to 150-225 mg at night before adding a morning dose.

Pain with depression and/or anxiety is best managed with duloxetine (Cymbalta) every morning, he said. The label states that the recommended dosage for fibromyalgia is 60 mg/day, but Dr. Boomershine recommends starting with 20-30 mg and increasing to 60 mg only if necessary. Trial data indicate that many patients do well on lower doses, he noted, and higher doses are associated with increased risk for side effects, including nausea, headache, and insomnia.

For pain associated with fatigue or fibrofog, the treatment of choice is milnacipran (Savella), he said. The label for this agent recommends starting at a dose of 12.5 mg once daily and gradually working up to 50 mg twice daily after 1 week and a maximum dosage of 100 mg twice daily if needed. Dr. Boomershine said he recommends a more gradual up-titration and noted that the dose should be increased only if needed because of the patient's symptoms. Milnacipran is available in 12.5-, 25-, 50- and 100-mg tablets, allowing for dosing flexibility.

Physicians with years of experience in successfully managing fibromyalgia are accustomed to using other drugs that lack Food and Drug Administration approval specifically for use in fibromyalgia.

Amitriptyline given as a 25-mg dose at bedtime in combination with fluoxetine (20 mg) in the morning is a “particularly good combination,” said Dr. Boomershine. He noted that the combination has shown good efficacy and likely provides balanced norepinephrine and serotonin reuptake inhibition similar to that provided by duloxetine and milnacipran, but at a much lower cost.

Dr. Boomershine recommends avoiding the use of narcotics, benzodiazepines, or steroids in treating fibromyalgia symptoms.

SDEF and this news organization are owned by Elsevier.

For a video interview with Dr. Boomershine, go to www.youtube.com/rheumatologynews

Treatment needs to address the fact that pain is only one symptom of fibromyalgia, Dr. Chad S. Boomershine said.

Source Sally Kubetin/Elsevier Global Medical News