Rheumatoid Arthritis

Major Finding: Among women aged 50-79 years who drink tea, the odds ratio for incident RA was 1.40, compared with women who do not drink tea.

Data Source: Epidemiologic study based on self-reported tea drinking among 76,643 in the Women's Health Initiative

Disclosures: The study was funded by NIH. Dr. Collins reported having no disclosures.

Tea drinking slightly increased the risk of rheumatoid arthritis in older women, a new finding at odds with earlier studies showing it has no, or even a protective, effect.

Among women who drink tea, the study found the odds ratio for incident rheumatoid arthritis (RA) was 1.40, compared with women who do not drink tea, with a 95% confidence interval (CI) of 1.01-1.93 and a P value of .04.

The results come from the Women's Health Initiative observational study (WHI-OS), which includes 76,643 women aged 50-79 years.

The women filled out a dietary habit questionnaire at enrollment. Three years later, 185 had developed RA; the tea-drinking habits of those women were analyzed and compared to their RA-free peers.

The odds ratio increased with increasing consumption, with a P value of .03. Among women drinking four or more cups per day, the odds ratio of developing RA was 1.78, though only seven women who developed RA said they drank that much tea, and the finding was not statistically significant.

“I'm not saying anyone should stop drinking tea,” noted lead investigator Dr. Christopher Collins, of the Washington Hospital Center, and the Georgetown University School of Medicine.

The effects of tea drinking on the risk of RA were modest, the incidence of RA in the study low, and the WHI-OS dietary questionnaire vague on the question of tea drinking, asking women only if they drank tea, and if so, how many cups a day.

It did not ask what kind of tea they drank, though black tea accounts for 85% of tea drunk in the United States, Dr. Collins reported.

He presented the findings at a June meeting of the European League Against Rheumatism. They were published in a recent supplement to the Annals of the Rheumatic Diseases (2010;69[Suppl. 3]:350).

The findings contradict results of two earlier epidemiological studies; one that found tea drinking protected against RA, the other that it had no effect (Arthritis Rheum. 2002;46:83-91 and Arthritis Rheum. 2003;48:3055-60).

If tea does increase the risk of RA, the flavanoids present in the beverage offer a possible mechanism, according to Dr. Collins. Flavanoid consumption has been linked with RA risk (Am. J. Clin. Nutr. 2002;76:560-8).

Tea drinking slightly increased RA risk in older women.

Source ©Lilyana Vynogradova/iStockphoto.com

Major Finding: Among women aged 50-79 years who drink tea, the odds ratio for incident RA was 1.40, compared with women who do not drink tea.

Data Source: Epidemiologic study based on self-reported tea drinking among 76,643 in the Women's Health Initiative

Disclosures: The study was funded by NIH. Dr. Collins reported having no disclosures.

Tea drinking slightly increased the risk of rheumatoid arthritis in older women, a new finding at odds with earlier studies showing it has no, or even a protective, effect.

Among women who drink tea, the study found the odds ratio for incident rheumatoid arthritis (RA) was 1.40, compared with women who do not drink tea, with a 95% confidence interval (CI) of 1.01-1.93 and a P value of .04.

The results come from the Women's Health Initiative observational study (WHI-OS), which includes 76,643 women aged 50-79 years.

The women filled out a dietary habit questionnaire at enrollment. Three years later, 185 had developed RA; the tea-drinking habits of those women were analyzed and compared to their RA-free peers.

The odds ratio increased with increasing consumption, with a P value of .03. Among women drinking four or more cups per day, the odds ratio of developing RA was 1.78, though only seven women who developed RA said they drank that much tea, and the finding was not statistically significant.

“I'm not saying anyone should stop drinking tea,” noted lead investigator Dr. Christopher Collins, of the Washington Hospital Center, and the Georgetown University School of Medicine.

The effects of tea drinking on the risk of RA were modest, the incidence of RA in the study low, and the WHI-OS dietary questionnaire vague on the question of tea drinking, asking women only if they drank tea, and if so, how many cups a day.

It did not ask what kind of tea they drank, though black tea accounts for 85% of tea drunk in the United States, Dr. Collins reported.

He presented the findings at a June meeting of the European League Against Rheumatism. They were published in a recent supplement to the Annals of the Rheumatic Diseases (2010;69[Suppl. 3]:350).

The findings contradict results of two earlier epidemiological studies; one that found tea drinking protected against RA, the other that it had no effect (Arthritis Rheum. 2002;46:83-91 and Arthritis Rheum. 2003;48:3055-60).

If tea does increase the risk of RA, the flavanoids present in the beverage offer a possible mechanism, according to Dr. Collins. Flavanoid consumption has been linked with RA risk (Am. J. Clin. Nutr. 2002;76:560-8).

Tea drinking slightly increased RA risk in older women.

Source ©Lilyana Vynogradova/iStockphoto.com

Major Finding: Among women aged 50-79 years who drink tea, the odds ratio for incident RA was 1.40, compared with women who do not drink tea.

Data Source: Epidemiologic study based on self-reported tea drinking among 76,643 in the Women's Health Initiative

Disclosures: The study was funded by NIH. Dr. Collins reported having no disclosures.

Tea drinking slightly increased the risk of rheumatoid arthritis in older women, a new finding at odds with earlier studies showing it has no, or even a protective, effect.

Among women who drink tea, the study found the odds ratio for incident rheumatoid arthritis (RA) was 1.40, compared with women who do not drink tea, with a 95% confidence interval (CI) of 1.01-1.93 and a P value of .04.

The results come from the Women's Health Initiative observational study (WHI-OS), which includes 76,643 women aged 50-79 years.

The women filled out a dietary habit questionnaire at enrollment. Three years later, 185 had developed RA; the tea-drinking habits of those women were analyzed and compared to their RA-free peers.

The odds ratio increased with increasing consumption, with a P value of .03. Among women drinking four or more cups per day, the odds ratio of developing RA was 1.78, though only seven women who developed RA said they drank that much tea, and the finding was not statistically significant.

“I'm not saying anyone should stop drinking tea,” noted lead investigator Dr. Christopher Collins, of the Washington Hospital Center, and the Georgetown University School of Medicine.

The effects of tea drinking on the risk of RA were modest, the incidence of RA in the study low, and the WHI-OS dietary questionnaire vague on the question of tea drinking, asking women only if they drank tea, and if so, how many cups a day.

It did not ask what kind of tea they drank, though black tea accounts for 85% of tea drunk in the United States, Dr. Collins reported.

He presented the findings at a June meeting of the European League Against Rheumatism. They were published in a recent supplement to the Annals of the Rheumatic Diseases (2010;69[Suppl. 3]:350).

The findings contradict results of two earlier epidemiological studies; one that found tea drinking protected against RA, the other that it had no effect (Arthritis Rheum. 2002;46:83-91 and Arthritis Rheum. 2003;48:3055-60).

If tea does increase the risk of RA, the flavanoids present in the beverage offer a possible mechanism, according to Dr. Collins. Flavanoid consumption has been linked with RA risk (Am. J. Clin. Nutr. 2002;76:560-8).

Tea drinking slightly increased RA risk in older women.

Source ©Lilyana Vynogradova/iStockphoto.com

ROME — Candidate international consensus criteria for diagnosis of polymyalgia rheumatica performed well in their first large prospective validation study. But there's room for further improvement with tweaking of the criteria, according to Dr. Bhaskar Dasgupta, the project leader.

The core diagnostic criteria under consideration in a joint ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) project exhibited an overall 85% specificity and 68% sensitivity in discriminating the multitude of conditions that mimic polymyalgia rheumatica (PMR) from true PMR.

Not bad. But the 94% specificity for discriminating rotator cuff tears and other shoulder conditions from PMR was substantially better than the 78% specificity for discriminating rheumatoid arthritis from PMR. And a small percentage of patients—less than 5%—were consistently misclassified using the candidate diagnostic algorithm, Dr. Dasgupta noted at the congress.

“What this means is we have a group of patients—both PMR cases and controls—who are currently unclassifiable. So we need to do more work,” said Dr. Dasgupta, director of rheumatology at Southend University Hospital in Westcliff-on-Sea, England.

He stressed that the consensus diagnostic criteria are still evolving and remain very much a work in progress.

Preliminary results from the study suggest ultrasound could well end up in the final diagnostic algorithm. For the 89 PMR patients and 117 controls whose ultrasound results have been analyzed to date, a finding of bicipital tenosynovitis was present in 68% of the PMR group and 49% of controls.

Subdeltoid bursitis was identified in 60% of PMR patients compared with 35% of controls. Both differences were significant.

Ultrasound had particular value in separating PMR from rheumatoid arthritis, an area where the core diagnostic criteria need shoring up. Subdeltoid bursitis was present in 60% of the PMR group but only 35% with rheumatoid arthritis, according to Dr. Dasgupta.

For all these reasons, the rheumatologist continued, “PMR is a very, very important condition to get right.”

The ACR/EULAR prospective study includes 120 patients with new-onset presumptive PMR as agreed by experts plus 240 controls with new-onset proximal shoulder pain due to various PMR mimickers. These mimicking disorders include myeloma and other malignancies, active infections, fibromyalgia and other chronic pain conditions, osteoarthritis, adhesive capsulitis and other shoulder conditions, rheumatoid arthritis, thyroid disease and other endocrinopathies, and Parkinson's disease. Participants were followed via clinical examinations and lab tests at 1, 4, 12, and 24 weeks.

Seventy-three percent of PMR patients presented with all three of the following features: bilateral shoulder aching, morning stiffness lasting more than 45 minutes, and an elevated C-reactive protein level or erythrocyte sedimentation rate. That was the case for only 29% of controls. All three of these features made it into the core diagnostic inclusion criteria.

Along the way, numerous candidate diagnostic criteria have been weeded out as insufficiently discriminatory to make the short list of core criteria. These include gender, weight loss, neck pain, and limitation of movement.

Features that best discriminated rheumatoid arthritis from PMR included an abnormal rheumatoid factor or anti-citrullinated protein antibody test and peripheral synovitis lasting more than 6 weeks. In contrast, synovitis lasting less than 6 weeks pointed more toward PMR.

The committee is developing a stepwise approach to the diagnosis of PMR. Fully establishing the diagnosis in this way takes 4-6 weeks.

▸ Step 1 of the diagnostic algorithm requires that a patient meet all of the core inclusion criteria: age 50 years or more, bilateral shoulder and/or bilateral pelvic girdle ache, morning stiffness lasting more than 45 minutes, duration of symptoms greater than 2 weeks, and an acute phase response in the form of an elevated erythrocyte sedimentation rate and/or C-reactive protein level.

▸ Step 2 involves evaluating the patient who has successfully passed step 1 for the core exclusion criteria, including active infection, neoplasia, and giant cell arteritis.

▸ Step 3 is a brief therapeutic trial of low-dose steroids; that is, 15-20 mg/day of prednisone. A positive result consistent with a diagnosis of PMR is a clinical response within 1 week marked by at least 70% global improvement, plus laboratory resolution of the acute phase response in 3-4 weeks.

The proposed algorithm calls for a series of lab tests to be done prior to giving low-dose steroids. These include dipstick urinalysis, a full blood count, rheumatoid factor, liver function tests, a bone profile, and measurements of thyroid-stimulating hormone, anti-cyclic citrullinated peptide antibody, and creatine kinase. Selectively ordering a chest x-ray in those patients with systemic symptoms is deemed appropriate, but use of chest computed tomography to screen for malignancies is not, Dr. Dasgupta said.

▸ Step 4, the final stage in the diagnostic process, is follow-up at 4-6 weeks to make sure no alternative diagnoses have come to the fore.

When it comes to distinguishing PMR from seronegative arthropathies, there are two useful clues. First, keep in mind that synovitis of more than 6 weeks' duration is more likely to be an inflammatory arthropathy. Second, a patient who has both bilateral shoulder pain and bilateral hip pain is more likely to have PMR, Dr. Dasgupta said in response to a question from the audience.

But when it's really tough to make the distinction, the most practical issue is simply whether the patient in question responds to low-dose steroids.

“If a patient like this hasn't responded to 5 or 6 weeks of prednisone at 15-20 mg/day, you—d probably want to consider starting a DMARD,” he said.

Disclosures: Dr. Dasgupta's study is funded by grants from both the ACR and EULAR.

'We have a group of patients …who are currently unclassifiable. So we need to do more work.'

Source DR. DASGUPTA

ROME — Candidate international consensus criteria for diagnosis of polymyalgia rheumatica performed well in their first large prospective validation study. But there's room for further improvement with tweaking of the criteria, according to Dr. Bhaskar Dasgupta, the project leader.

The core diagnostic criteria under consideration in a joint ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) project exhibited an overall 85% specificity and 68% sensitivity in discriminating the multitude of conditions that mimic polymyalgia rheumatica (PMR) from true PMR.

Not bad. But the 94% specificity for discriminating rotator cuff tears and other shoulder conditions from PMR was substantially better than the 78% specificity for discriminating rheumatoid arthritis from PMR. And a small percentage of patients—less than 5%—were consistently misclassified using the candidate diagnostic algorithm, Dr. Dasgupta noted at the congress.

“What this means is we have a group of patients—both PMR cases and controls—who are currently unclassifiable. So we need to do more work,” said Dr. Dasgupta, director of rheumatology at Southend University Hospital in Westcliff-on-Sea, England.

He stressed that the consensus diagnostic criteria are still evolving and remain very much a work in progress.

Preliminary results from the study suggest ultrasound could well end up in the final diagnostic algorithm. For the 89 PMR patients and 117 controls whose ultrasound results have been analyzed to date, a finding of bicipital tenosynovitis was present in 68% of the PMR group and 49% of controls.

Subdeltoid bursitis was identified in 60% of PMR patients compared with 35% of controls. Both differences were significant.

Ultrasound had particular value in separating PMR from rheumatoid arthritis, an area where the core diagnostic criteria need shoring up. Subdeltoid bursitis was present in 60% of the PMR group but only 35% with rheumatoid arthritis, according to Dr. Dasgupta.

For all these reasons, the rheumatologist continued, “PMR is a very, very important condition to get right.”

The ACR/EULAR prospective study includes 120 patients with new-onset presumptive PMR as agreed by experts plus 240 controls with new-onset proximal shoulder pain due to various PMR mimickers. These mimicking disorders include myeloma and other malignancies, active infections, fibromyalgia and other chronic pain conditions, osteoarthritis, adhesive capsulitis and other shoulder conditions, rheumatoid arthritis, thyroid disease and other endocrinopathies, and Parkinson's disease. Participants were followed via clinical examinations and lab tests at 1, 4, 12, and 24 weeks.

Seventy-three percent of PMR patients presented with all three of the following features: bilateral shoulder aching, morning stiffness lasting more than 45 minutes, and an elevated C-reactive protein level or erythrocyte sedimentation rate. That was the case for only 29% of controls. All three of these features made it into the core diagnostic inclusion criteria.

Along the way, numerous candidate diagnostic criteria have been weeded out as insufficiently discriminatory to make the short list of core criteria. These include gender, weight loss, neck pain, and limitation of movement.

Features that best discriminated rheumatoid arthritis from PMR included an abnormal rheumatoid factor or anti-citrullinated protein antibody test and peripheral synovitis lasting more than 6 weeks. In contrast, synovitis lasting less than 6 weeks pointed more toward PMR.

The committee is developing a stepwise approach to the diagnosis of PMR. Fully establishing the diagnosis in this way takes 4-6 weeks.

▸ Step 1 of the diagnostic algorithm requires that a patient meet all of the core inclusion criteria: age 50 years or more, bilateral shoulder and/or bilateral pelvic girdle ache, morning stiffness lasting more than 45 minutes, duration of symptoms greater than 2 weeks, and an acute phase response in the form of an elevated erythrocyte sedimentation rate and/or C-reactive protein level.

▸ Step 2 involves evaluating the patient who has successfully passed step 1 for the core exclusion criteria, including active infection, neoplasia, and giant cell arteritis.

▸ Step 3 is a brief therapeutic trial of low-dose steroids; that is, 15-20 mg/day of prednisone. A positive result consistent with a diagnosis of PMR is a clinical response within 1 week marked by at least 70% global improvement, plus laboratory resolution of the acute phase response in 3-4 weeks.

The proposed algorithm calls for a series of lab tests to be done prior to giving low-dose steroids. These include dipstick urinalysis, a full blood count, rheumatoid factor, liver function tests, a bone profile, and measurements of thyroid-stimulating hormone, anti-cyclic citrullinated peptide antibody, and creatine kinase. Selectively ordering a chest x-ray in those patients with systemic symptoms is deemed appropriate, but use of chest computed tomography to screen for malignancies is not, Dr. Dasgupta said.

▸ Step 4, the final stage in the diagnostic process, is follow-up at 4-6 weeks to make sure no alternative diagnoses have come to the fore.

When it comes to distinguishing PMR from seronegative arthropathies, there are two useful clues. First, keep in mind that synovitis of more than 6 weeks' duration is more likely to be an inflammatory arthropathy. Second, a patient who has both bilateral shoulder pain and bilateral hip pain is more likely to have PMR, Dr. Dasgupta said in response to a question from the audience.

But when it's really tough to make the distinction, the most practical issue is simply whether the patient in question responds to low-dose steroids.

“If a patient like this hasn't responded to 5 or 6 weeks of prednisone at 15-20 mg/day, you—d probably want to consider starting a DMARD,” he said.

Disclosures: Dr. Dasgupta's study is funded by grants from both the ACR and EULAR.

'We have a group of patients …who are currently unclassifiable. So we need to do more work.'

Source DR. DASGUPTA

ROME — Candidate international consensus criteria for diagnosis of polymyalgia rheumatica performed well in their first large prospective validation study. But there's room for further improvement with tweaking of the criteria, according to Dr. Bhaskar Dasgupta, the project leader.

The core diagnostic criteria under consideration in a joint ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) project exhibited an overall 85% specificity and 68% sensitivity in discriminating the multitude of conditions that mimic polymyalgia rheumatica (PMR) from true PMR.

Not bad. But the 94% specificity for discriminating rotator cuff tears and other shoulder conditions from PMR was substantially better than the 78% specificity for discriminating rheumatoid arthritis from PMR. And a small percentage of patients—less than 5%—were consistently misclassified using the candidate diagnostic algorithm, Dr. Dasgupta noted at the congress.

“What this means is we have a group of patients—both PMR cases and controls—who are currently unclassifiable. So we need to do more work,” said Dr. Dasgupta, director of rheumatology at Southend University Hospital in Westcliff-on-Sea, England.

He stressed that the consensus diagnostic criteria are still evolving and remain very much a work in progress.

Preliminary results from the study suggest ultrasound could well end up in the final diagnostic algorithm. For the 89 PMR patients and 117 controls whose ultrasound results have been analyzed to date, a finding of bicipital tenosynovitis was present in 68% of the PMR group and 49% of controls.

Subdeltoid bursitis was identified in 60% of PMR patients compared with 35% of controls. Both differences were significant.

Ultrasound had particular value in separating PMR from rheumatoid arthritis, an area where the core diagnostic criteria need shoring up. Subdeltoid bursitis was present in 60% of the PMR group but only 35% with rheumatoid arthritis, according to Dr. Dasgupta.

For all these reasons, the rheumatologist continued, “PMR is a very, very important condition to get right.”

The ACR/EULAR prospective study includes 120 patients with new-onset presumptive PMR as agreed by experts plus 240 controls with new-onset proximal shoulder pain due to various PMR mimickers. These mimicking disorders include myeloma and other malignancies, active infections, fibromyalgia and other chronic pain conditions, osteoarthritis, adhesive capsulitis and other shoulder conditions, rheumatoid arthritis, thyroid disease and other endocrinopathies, and Parkinson's disease. Participants were followed via clinical examinations and lab tests at 1, 4, 12, and 24 weeks.

Seventy-three percent of PMR patients presented with all three of the following features: bilateral shoulder aching, morning stiffness lasting more than 45 minutes, and an elevated C-reactive protein level or erythrocyte sedimentation rate. That was the case for only 29% of controls. All three of these features made it into the core diagnostic inclusion criteria.

Along the way, numerous candidate diagnostic criteria have been weeded out as insufficiently discriminatory to make the short list of core criteria. These include gender, weight loss, neck pain, and limitation of movement.

Features that best discriminated rheumatoid arthritis from PMR included an abnormal rheumatoid factor or anti-citrullinated protein antibody test and peripheral synovitis lasting more than 6 weeks. In contrast, synovitis lasting less than 6 weeks pointed more toward PMR.

The committee is developing a stepwise approach to the diagnosis of PMR. Fully establishing the diagnosis in this way takes 4-6 weeks.

▸ Step 1 of the diagnostic algorithm requires that a patient meet all of the core inclusion criteria: age 50 years or more, bilateral shoulder and/or bilateral pelvic girdle ache, morning stiffness lasting more than 45 minutes, duration of symptoms greater than 2 weeks, and an acute phase response in the form of an elevated erythrocyte sedimentation rate and/or C-reactive protein level.

▸ Step 2 involves evaluating the patient who has successfully passed step 1 for the core exclusion criteria, including active infection, neoplasia, and giant cell arteritis.

▸ Step 3 is a brief therapeutic trial of low-dose steroids; that is, 15-20 mg/day of prednisone. A positive result consistent with a diagnosis of PMR is a clinical response within 1 week marked by at least 70% global improvement, plus laboratory resolution of the acute phase response in 3-4 weeks.

The proposed algorithm calls for a series of lab tests to be done prior to giving low-dose steroids. These include dipstick urinalysis, a full blood count, rheumatoid factor, liver function tests, a bone profile, and measurements of thyroid-stimulating hormone, anti-cyclic citrullinated peptide antibody, and creatine kinase. Selectively ordering a chest x-ray in those patients with systemic symptoms is deemed appropriate, but use of chest computed tomography to screen for malignancies is not, Dr. Dasgupta said.

▸ Step 4, the final stage in the diagnostic process, is follow-up at 4-6 weeks to make sure no alternative diagnoses have come to the fore.

When it comes to distinguishing PMR from seronegative arthropathies, there are two useful clues. First, keep in mind that synovitis of more than 6 weeks' duration is more likely to be an inflammatory arthropathy. Second, a patient who has both bilateral shoulder pain and bilateral hip pain is more likely to have PMR, Dr. Dasgupta said in response to a question from the audience.

But when it's really tough to make the distinction, the most practical issue is simply whether the patient in question responds to low-dose steroids.

“If a patient like this hasn't responded to 5 or 6 weeks of prednisone at 15-20 mg/day, you—d probably want to consider starting a DMARD,” he said.

Disclosures: Dr. Dasgupta's study is funded by grants from both the ACR and EULAR.

'We have a group of patients …who are currently unclassifiable. So we need to do more work.'

Source DR. DASGUPTA

A warning about the risks of suicide associated with use of the opioid analgesic tramadol in certain patients has been added to the drug's prescribing information, the Food and Drug Administration has announced.

The warnings section advises clinicians against prescribing tramadol to patients who are suicidal or prone to addictions, emphasizing that patients who are addiction-prone or taking tranquilizers or antidepressant drugs are at risk of suicide if they are taking tramadol.

Tramadol-related deaths have been reported in patients with histories of emotional disturbances or suicidal ideation or attempts, and histories of misuse of tranquilizers, alcohol, and other CNS-active drugs, according to the FDA statement.

Tramadol, a centrally acting synthetic opioid analgesic approved for the management of moderate to moderately severe chronic pain, is marketed as Ultram and Ultracet (tramadol with acetaminophen).

The revised warnings are summarized in “Dear Healthcare Professional” letters for Ultram and Ultracet, dated in April, from PriCara, a division of Ortho-McNeil-Janssen Pharmaceuticals Inc. that markets tramadol.

The Ultracet warning letter also points out the risks for acetaminophen overdoses.

The revised label also advises that tramadol tablets be prescribed “with caution” to patients who are treated with tranquilizers or antidepressant drugs, patients who abuse alcohol, and those who have emotional disturbances or depression.

The FDA statement and letters can be found at www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213264.htmwww.fda.gov/medwatch

A warning about the risks of suicide associated with use of the opioid analgesic tramadol in certain patients has been added to the drug's prescribing information, the Food and Drug Administration has announced.

The warnings section advises clinicians against prescribing tramadol to patients who are suicidal or prone to addictions, emphasizing that patients who are addiction-prone or taking tranquilizers or antidepressant drugs are at risk of suicide if they are taking tramadol.

Tramadol-related deaths have been reported in patients with histories of emotional disturbances or suicidal ideation or attempts, and histories of misuse of tranquilizers, alcohol, and other CNS-active drugs, according to the FDA statement.

Tramadol, a centrally acting synthetic opioid analgesic approved for the management of moderate to moderately severe chronic pain, is marketed as Ultram and Ultracet (tramadol with acetaminophen).

The revised warnings are summarized in “Dear Healthcare Professional” letters for Ultram and Ultracet, dated in April, from PriCara, a division of Ortho-McNeil-Janssen Pharmaceuticals Inc. that markets tramadol.

The Ultracet warning letter also points out the risks for acetaminophen overdoses.

The revised label also advises that tramadol tablets be prescribed “with caution” to patients who are treated with tranquilizers or antidepressant drugs, patients who abuse alcohol, and those who have emotional disturbances or depression.

The FDA statement and letters can be found at www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213264.htmwww.fda.gov/medwatch

A warning about the risks of suicide associated with use of the opioid analgesic tramadol in certain patients has been added to the drug's prescribing information, the Food and Drug Administration has announced.

The warnings section advises clinicians against prescribing tramadol to patients who are suicidal or prone to addictions, emphasizing that patients who are addiction-prone or taking tranquilizers or antidepressant drugs are at risk of suicide if they are taking tramadol.

Tramadol-related deaths have been reported in patients with histories of emotional disturbances or suicidal ideation or attempts, and histories of misuse of tranquilizers, alcohol, and other CNS-active drugs, according to the FDA statement.

Tramadol, a centrally acting synthetic opioid analgesic approved for the management of moderate to moderately severe chronic pain, is marketed as Ultram and Ultracet (tramadol with acetaminophen).

The revised warnings are summarized in “Dear Healthcare Professional” letters for Ultram and Ultracet, dated in April, from PriCara, a division of Ortho-McNeil-Janssen Pharmaceuticals Inc. that markets tramadol.

The Ultracet warning letter also points out the risks for acetaminophen overdoses.

The revised label also advises that tramadol tablets be prescribed “with caution” to patients who are treated with tranquilizers or antidepressant drugs, patients who abuse alcohol, and those who have emotional disturbances or depression.

The FDA statement and letters can be found at www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213264.htmwww.fda.gov/medwatch

CHICAGO — Redefining the upper limit of serum urate for a diagnosis of gout from 9-10 mg/dL to 6.8-7 mg/dL would better serve patients, said Dr. John S. Sundy of Duke Clinical Research Institute, Chapel Hill, N.C.

Although there is no indication for urate-lowering therapy in patients with asymptomatic uricemia, practice patterns need to be changed and include earlier use of diet to reduce urate levels, he said.

Many patients currently classified as normal are in fact slowly depositing urate crystals in soft tissue, he said, and are therefore at risk for developing gout. Proper diet that limits alcohol and fructose consumption is a key intervention.

Alcohol drinkers who consume more than five drinks daily have a 2.5-fold increased risk for developing gout. A weight gain of 30 pounds since high school doubles the relative risk of developing gout, whereas a weight loss of only 10 pounds actually cuts the risk almost in half, he said.

One can of fructose-sweetened soft drink per day represents a 1.4 increase in relative risk of developing gout, and two or more represent a 1.8 relative risk (BMJ 2008;336:309-12). Fruit juice and high-fructose fruits such as oranges and apples are also significantly associated with gout. “There are clearly metabolic pathways where fructose consumption actually leads to marked elevations in serum urate values, leading to acceleration of deposition of urate crystals in soft tissues. I've really begun to counsel my patients about this and counsel them to reduce their intake of fructose,” said Dr. Sundy.

To manage flares or symptoms, the low-dose colchicine regimen of 1.2 mg at onset of flare followed by 0.6 mg within 1 hour was as effective as high-dose therapy (4.8 mg), but better tolerated, he said. “It shows we can do much lower doses to achieve the same outcome, with far fewer side effects.”

The most important urate-lowering drugs remain allopurinol, febuxostat, and probenecid, said Dr. Sundy, although probenecid is rarely used. He expects the approval of enzyme replacement therapy with polyethylene glycol–modified uricase (PEG-uricase) and expects this to be an IV drug, administered every 2 weeks, for the severe, end-of-spectrum, treatment-failure gout population. “This will be a rheumatologist's drug, maybe a nephrologist's drug, for certain populations.”

At least two new uricosuric agents are on the horizon, he said. The drugs are RDEA594, which he described as “totally experimental,” and Tranilast, a drug already approved in Asia for anti-inflammation.

Moderator Dr. Herbert Baraf, a rheumatologist in private practice in Silver Spring, Md., questioned interleukin-1 inhibition. “Do you think that's realistic, or is that the elephant gun on the mouse?”

“For certain applications, it's realistic,” said Dr. Sundy. “For example for patients who don't respond well and require large doses of corticosteroids to manage a gout flare. For patients in whom there are contraindications to using the nonsteroidal. For example, the brittle diabetic with moderate or severe chronic disease. This is the strategy for the short term. For people with severe disease it could be a corticoteroid-sparing drug.”

Disclosures: Dr. Sundy disclosed research support from Savient Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and Ardea Biosciences; consulting to Ardea, Anadys Pharmceuticals, Regeneron, and Savient; and speakers bureau with Takeda Pharmaceuticals. Duke University and Mountain View Pharmaceuticals hold patent rights in pegylated urate oxidase and its use which have been licensed to Savient Pharmaceuticals. He disclosed off-label use of allopurinol and anakinra, and experimental use of pegloticase, rilonacept, canakinumab, and RDEA594. Dr. Baraf disclosed no financial relationships.

CHICAGO — Redefining the upper limit of serum urate for a diagnosis of gout from 9-10 mg/dL to 6.8-7 mg/dL would better serve patients, said Dr. John S. Sundy of Duke Clinical Research Institute, Chapel Hill, N.C.

Although there is no indication for urate-lowering therapy in patients with asymptomatic uricemia, practice patterns need to be changed and include earlier use of diet to reduce urate levels, he said.

Many patients currently classified as normal are in fact slowly depositing urate crystals in soft tissue, he said, and are therefore at risk for developing gout. Proper diet that limits alcohol and fructose consumption is a key intervention.

Alcohol drinkers who consume more than five drinks daily have a 2.5-fold increased risk for developing gout. A weight gain of 30 pounds since high school doubles the relative risk of developing gout, whereas a weight loss of only 10 pounds actually cuts the risk almost in half, he said.

One can of fructose-sweetened soft drink per day represents a 1.4 increase in relative risk of developing gout, and two or more represent a 1.8 relative risk (BMJ 2008;336:309-12). Fruit juice and high-fructose fruits such as oranges and apples are also significantly associated with gout. “There are clearly metabolic pathways where fructose consumption actually leads to marked elevations in serum urate values, leading to acceleration of deposition of urate crystals in soft tissues. I've really begun to counsel my patients about this and counsel them to reduce their intake of fructose,” said Dr. Sundy.

To manage flares or symptoms, the low-dose colchicine regimen of 1.2 mg at onset of flare followed by 0.6 mg within 1 hour was as effective as high-dose therapy (4.8 mg), but better tolerated, he said. “It shows we can do much lower doses to achieve the same outcome, with far fewer side effects.”

The most important urate-lowering drugs remain allopurinol, febuxostat, and probenecid, said Dr. Sundy, although probenecid is rarely used. He expects the approval of enzyme replacement therapy with polyethylene glycol–modified uricase (PEG-uricase) and expects this to be an IV drug, administered every 2 weeks, for the severe, end-of-spectrum, treatment-failure gout population. “This will be a rheumatologist's drug, maybe a nephrologist's drug, for certain populations.”

At least two new uricosuric agents are on the horizon, he said. The drugs are RDEA594, which he described as “totally experimental,” and Tranilast, a drug already approved in Asia for anti-inflammation.

Moderator Dr. Herbert Baraf, a rheumatologist in private practice in Silver Spring, Md., questioned interleukin-1 inhibition. “Do you think that's realistic, or is that the elephant gun on the mouse?”

“For certain applications, it's realistic,” said Dr. Sundy. “For example for patients who don't respond well and require large doses of corticosteroids to manage a gout flare. For patients in whom there are contraindications to using the nonsteroidal. For example, the brittle diabetic with moderate or severe chronic disease. This is the strategy for the short term. For people with severe disease it could be a corticoteroid-sparing drug.”

Disclosures: Dr. Sundy disclosed research support from Savient Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and Ardea Biosciences; consulting to Ardea, Anadys Pharmceuticals, Regeneron, and Savient; and speakers bureau with Takeda Pharmaceuticals. Duke University and Mountain View Pharmaceuticals hold patent rights in pegylated urate oxidase and its use which have been licensed to Savient Pharmaceuticals. He disclosed off-label use of allopurinol and anakinra, and experimental use of pegloticase, rilonacept, canakinumab, and RDEA594. Dr. Baraf disclosed no financial relationships.

CHICAGO — Redefining the upper limit of serum urate for a diagnosis of gout from 9-10 mg/dL to 6.8-7 mg/dL would better serve patients, said Dr. John S. Sundy of Duke Clinical Research Institute, Chapel Hill, N.C.

Although there is no indication for urate-lowering therapy in patients with asymptomatic uricemia, practice patterns need to be changed and include earlier use of diet to reduce urate levels, he said.

Many patients currently classified as normal are in fact slowly depositing urate crystals in soft tissue, he said, and are therefore at risk for developing gout. Proper diet that limits alcohol and fructose consumption is a key intervention.

Alcohol drinkers who consume more than five drinks daily have a 2.5-fold increased risk for developing gout. A weight gain of 30 pounds since high school doubles the relative risk of developing gout, whereas a weight loss of only 10 pounds actually cuts the risk almost in half, he said.

One can of fructose-sweetened soft drink per day represents a 1.4 increase in relative risk of developing gout, and two or more represent a 1.8 relative risk (BMJ 2008;336:309-12). Fruit juice and high-fructose fruits such as oranges and apples are also significantly associated with gout. “There are clearly metabolic pathways where fructose consumption actually leads to marked elevations in serum urate values, leading to acceleration of deposition of urate crystals in soft tissues. I've really begun to counsel my patients about this and counsel them to reduce their intake of fructose,” said Dr. Sundy.

To manage flares or symptoms, the low-dose colchicine regimen of 1.2 mg at onset of flare followed by 0.6 mg within 1 hour was as effective as high-dose therapy (4.8 mg), but better tolerated, he said. “It shows we can do much lower doses to achieve the same outcome, with far fewer side effects.”

The most important urate-lowering drugs remain allopurinol, febuxostat, and probenecid, said Dr. Sundy, although probenecid is rarely used. He expects the approval of enzyme replacement therapy with polyethylene glycol–modified uricase (PEG-uricase) and expects this to be an IV drug, administered every 2 weeks, for the severe, end-of-spectrum, treatment-failure gout population. “This will be a rheumatologist's drug, maybe a nephrologist's drug, for certain populations.”

At least two new uricosuric agents are on the horizon, he said. The drugs are RDEA594, which he described as “totally experimental,” and Tranilast, a drug already approved in Asia for anti-inflammation.

Moderator Dr. Herbert Baraf, a rheumatologist in private practice in Silver Spring, Md., questioned interleukin-1 inhibition. “Do you think that's realistic, or is that the elephant gun on the mouse?”

“For certain applications, it's realistic,” said Dr. Sundy. “For example for patients who don't respond well and require large doses of corticosteroids to manage a gout flare. For patients in whom there are contraindications to using the nonsteroidal. For example, the brittle diabetic with moderate or severe chronic disease. This is the strategy for the short term. For people with severe disease it could be a corticoteroid-sparing drug.”

Disclosures: Dr. Sundy disclosed research support from Savient Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and Ardea Biosciences; consulting to Ardea, Anadys Pharmceuticals, Regeneron, and Savient; and speakers bureau with Takeda Pharmaceuticals. Duke University and Mountain View Pharmaceuticals hold patent rights in pegylated urate oxidase and its use which have been licensed to Savient Pharmaceuticals. He disclosed off-label use of allopurinol and anakinra, and experimental use of pegloticase, rilonacept, canakinumab, and RDEA594. Dr. Baraf disclosed no financial relationships.

ROME — A strontium-chloride–based topical agent showed favorable efficacy and safety for the relief of moderate to severe osteoarthritic knee pain in a phase II study.

Known as 2PX for research purposes, this low-viscosity liquid contains 10% strontium chloride hexahydrate as its active ingredient.

It proved significantly more effective than placebo in the 8-week, double-blind, randomized, crossover trial involving 78 patients with moderate to severe knee pain from osteoarthritis that was not controlled by NSAIDs or weak opioids, Dr. Stuart H.R. Ratcliffe reported.

The primary efficacy end point was change from baseline through week 4 in the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index pain subscale score. The mean 3.9-point drop in the 2PX group was significantly greater than the 2.2-point reduction with placebo.

After 4 weeks, patients were crossed to the other study arm. At 8 weeks, patients on 2PX did better on several secondary end points as well.

They had a mean 2.61-point greater decrease in WOMAC total score and a 1.87-point greater reduction in the physical function subscale, as well as a 0.23-point greater decline in the stiffness subscale, which was of borderline statistical significance.

In addition, the 2PX group demonstrated significantly greater reductions in self-reported pain intensity and greater pain relief, noted Dr. Ratcliffe, director of pain research at MAC (U.K.) Neuroscience Ltd. of Blackpool, England, which conducted the study.

Strontium chloride hexahydrate has an excellent, well-established safety profile. It is used in toothpastes for people with sensitive teeth, he said in an interview.

Indeed, 2PX was very well tolerated in the study. Mild erythema was the only side effect more common with the agent than with saline placebo.

The need for effective pain relief with a low risk of side effects for patients with osteoarthritis has become more pressing in light of the safety concerns surrounding NSAIDs, reported to be the direct cause of 100,000 hospitalizations annually in the United States. Weak opioids are sometimes ineffective, so many osteoarthritis patients rely on strong opioids for symptom relief, with their attendant increased nausea, vomiting, dizziness, and constipation, Dr. Ratcliffe said.

It is a topical with almost no systemic absorption, so “clearly you can add it to any oral medication because there will be no drug-drug interactions. It probably will be a very good add-on therapy, but also safe and efficacious to use by itself in an acceptable proportion of people with osteoarthritis—knee or hand,” he said.

Strontium's mechanism of benefit stems from its antagonistic effect on calcium-driven pathways that are involved in pain and inflammation.

In preliminary studies, 2PX has shown efficacy in neuropathic as well as nociceptive pain conditions. An ongoing, multicenter, phase III clinical trial of topical 2PX in patients with osteoarthritis of the knee is underway, as well as a phase III trial of 2PX for chronic postamputation pain. The agent is applied twice daily with a roll-on applicator.

Disclosures: Dr. Ratcliffe is employed by a company funded to conduct the phase II clinical trial by SantoSolve AS of Oslo, which is developing 2PX.

The mean 3.9-point drop in the 2PX group was significantly greater than the reduction with placebo.

Source DR. RATCLIFFE

ROME — A strontium-chloride–based topical agent showed favorable efficacy and safety for the relief of moderate to severe osteoarthritic knee pain in a phase II study.

Known as 2PX for research purposes, this low-viscosity liquid contains 10% strontium chloride hexahydrate as its active ingredient.

It proved significantly more effective than placebo in the 8-week, double-blind, randomized, crossover trial involving 78 patients with moderate to severe knee pain from osteoarthritis that was not controlled by NSAIDs or weak opioids, Dr. Stuart H.R. Ratcliffe reported.

The primary efficacy end point was change from baseline through week 4 in the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index pain subscale score. The mean 3.9-point drop in the 2PX group was significantly greater than the 2.2-point reduction with placebo.

After 4 weeks, patients were crossed to the other study arm. At 8 weeks, patients on 2PX did better on several secondary end points as well.

They had a mean 2.61-point greater decrease in WOMAC total score and a 1.87-point greater reduction in the physical function subscale, as well as a 0.23-point greater decline in the stiffness subscale, which was of borderline statistical significance.

In addition, the 2PX group demonstrated significantly greater reductions in self-reported pain intensity and greater pain relief, noted Dr. Ratcliffe, director of pain research at MAC (U.K.) Neuroscience Ltd. of Blackpool, England, which conducted the study.

Strontium chloride hexahydrate has an excellent, well-established safety profile. It is used in toothpastes for people with sensitive teeth, he said in an interview.

Indeed, 2PX was very well tolerated in the study. Mild erythema was the only side effect more common with the agent than with saline placebo.

The need for effective pain relief with a low risk of side effects for patients with osteoarthritis has become more pressing in light of the safety concerns surrounding NSAIDs, reported to be the direct cause of 100,000 hospitalizations annually in the United States. Weak opioids are sometimes ineffective, so many osteoarthritis patients rely on strong opioids for symptom relief, with their attendant increased nausea, vomiting, dizziness, and constipation, Dr. Ratcliffe said.

It is a topical with almost no systemic absorption, so “clearly you can add it to any oral medication because there will be no drug-drug interactions. It probably will be a very good add-on therapy, but also safe and efficacious to use by itself in an acceptable proportion of people with osteoarthritis—knee or hand,” he said.

Strontium's mechanism of benefit stems from its antagonistic effect on calcium-driven pathways that are involved in pain and inflammation.

In preliminary studies, 2PX has shown efficacy in neuropathic as well as nociceptive pain conditions. An ongoing, multicenter, phase III clinical trial of topical 2PX in patients with osteoarthritis of the knee is underway, as well as a phase III trial of 2PX for chronic postamputation pain. The agent is applied twice daily with a roll-on applicator.

Disclosures: Dr. Ratcliffe is employed by a company funded to conduct the phase II clinical trial by SantoSolve AS of Oslo, which is developing 2PX.

The mean 3.9-point drop in the 2PX group was significantly greater than the reduction with placebo.

Source DR. RATCLIFFE

ROME — A strontium-chloride–based topical agent showed favorable efficacy and safety for the relief of moderate to severe osteoarthritic knee pain in a phase II study.

Known as 2PX for research purposes, this low-viscosity liquid contains 10% strontium chloride hexahydrate as its active ingredient.

It proved significantly more effective than placebo in the 8-week, double-blind, randomized, crossover trial involving 78 patients with moderate to severe knee pain from osteoarthritis that was not controlled by NSAIDs or weak opioids, Dr. Stuart H.R. Ratcliffe reported.

The primary efficacy end point was change from baseline through week 4 in the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index pain subscale score. The mean 3.9-point drop in the 2PX group was significantly greater than the 2.2-point reduction with placebo.

After 4 weeks, patients were crossed to the other study arm. At 8 weeks, patients on 2PX did better on several secondary end points as well.

They had a mean 2.61-point greater decrease in WOMAC total score and a 1.87-point greater reduction in the physical function subscale, as well as a 0.23-point greater decline in the stiffness subscale, which was of borderline statistical significance.

In addition, the 2PX group demonstrated significantly greater reductions in self-reported pain intensity and greater pain relief, noted Dr. Ratcliffe, director of pain research at MAC (U.K.) Neuroscience Ltd. of Blackpool, England, which conducted the study.

Strontium chloride hexahydrate has an excellent, well-established safety profile. It is used in toothpastes for people with sensitive teeth, he said in an interview.

Indeed, 2PX was very well tolerated in the study. Mild erythema was the only side effect more common with the agent than with saline placebo.

The need for effective pain relief with a low risk of side effects for patients with osteoarthritis has become more pressing in light of the safety concerns surrounding NSAIDs, reported to be the direct cause of 100,000 hospitalizations annually in the United States. Weak opioids are sometimes ineffective, so many osteoarthritis patients rely on strong opioids for symptom relief, with their attendant increased nausea, vomiting, dizziness, and constipation, Dr. Ratcliffe said.

It is a topical with almost no systemic absorption, so “clearly you can add it to any oral medication because there will be no drug-drug interactions. It probably will be a very good add-on therapy, but also safe and efficacious to use by itself in an acceptable proportion of people with osteoarthritis—knee or hand,” he said.

Strontium's mechanism of benefit stems from its antagonistic effect on calcium-driven pathways that are involved in pain and inflammation.

In preliminary studies, 2PX has shown efficacy in neuropathic as well as nociceptive pain conditions. An ongoing, multicenter, phase III clinical trial of topical 2PX in patients with osteoarthritis of the knee is underway, as well as a phase III trial of 2PX for chronic postamputation pain. The agent is applied twice daily with a roll-on applicator.

Disclosures: Dr. Ratcliffe is employed by a company funded to conduct the phase II clinical trial by SantoSolve AS of Oslo, which is developing 2PX.

The mean 3.9-point drop in the 2PX group was significantly greater than the reduction with placebo.

Source DR. RATCLIFFE

Major Finding: Among 875 patients with osteoarthritis, those who took 200 mg of celecoxib every day had significantly fewer flares than those who took the drug only during a flare.

Data Source: A three-phase randomized, placebo-controlled trial.

Disclosures: Pfizer Inc. sponsored the study; the data were reported by Pfizer employee Dr. Sands.

CANCUN, MEXICO — Osteoarthritis flares were reduced by 42% in patients who took 200 mg of celecoxib daily, compared with those who took the medication only when they experienced a disease flare, judging from findings from a randomized, placebo-controlled trial.

Osteoarthritis patients who took the drug daily were no more likely than intermittent users to have either new-onset hypertension or an aggravation of existing hypertension, Dr. George Sands reported.

“Over the 22-week treatment period, continuous daily celecoxib was more effective in terms of fewer osteoarthritis flares, less pain, and less stiffness than intermittent celecoxib, with no difference in overall adverse effects or in hypertension,” said Dr. Sands, senior medical director at Pfizer Inc., which sponsored the study.

The study group comprised 875 patients with hip or knee osteoarthritis. All patients had to be taking a daily NSAID to control their disease. The study had three phases: In phase I, patients stopped their NSAID until they had a flare at their index joint. In phase II, patients with flares received open-label celecoxib until the flare resolved. Phase III consisted of the 22-week randomized, placebo-controlled study. Patients had two study medications, one for daily use and one for use during a flare. Half of the patients (440) received celecoxib every day and a placebo during the flare. The rest of the group (435) received daily placebo and celecoxib during the flare. Treatment continued for 22 weeks.

“Only patients who had resolved flares could be entered into the trial,” Dr. Sands said. “This is different from the usual arthritis studies, where they stop their NSAID, get worse, and are treated. In this study, patients were randomized after a successful treatment of a flare.”

The patients' mean age was 58 years; 30% were 65 or older. Their mean weight was 83 kg. Most (80%) had knee osteoarthritis; the hip was the affected joint in the remaining 20%. The baseline WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index score was 25 in both groups. Hypertension was present in 45%. Most of the continuous-use patients (80%) and 74% of the intermittent-use patients completed the trial.

The primary end point was the number of flares occurring during the randomized portion of the study. The median time to first flare was significantly longer in the continuous-use group than in the intermittent-use group (16 days vs. 8 days, respectively). “This is not surprising, since in this part of the study, before anyone had a flare, you were testing celecoxib against placebo,” noted Dr. Sands.

By the end of the 22-week treatment period, continuous users had a mean of 0.54 flares per month, significantly fewer than the mean 0.93 flares experienced by the intermittent users. This translates into 42% fewer flares per month, or about two fewer flares per month, Dr. Sands said.

At the end of the treatment period, WOMAC scores were significantly better in the continuous-use group. The change in total WOMAC score was 1.6 in the continuous users vs. 4.99 in the intermittent users.

At the final visit, 23% of the continuous-use group and 11% of the intermittent-use group had been flare free—a significant difference. Adverse events occurred in 57% of the continuous users and 59% of the intermittent users.

The continuous users of celecoxib had a mean of 0.54 flares per month, vs. 0.93 flares for the intermittent users.

Source DR. SANDS

Major Finding: Among 875 patients with osteoarthritis, those who took 200 mg of celecoxib every day had significantly fewer flares than those who took the drug only during a flare.

Data Source: A three-phase randomized, placebo-controlled trial.

Disclosures: Pfizer Inc. sponsored the study; the data were reported by Pfizer employee Dr. Sands.

CANCUN, MEXICO — Osteoarthritis flares were reduced by 42% in patients who took 200 mg of celecoxib daily, compared with those who took the medication only when they experienced a disease flare, judging from findings from a randomized, placebo-controlled trial.

Osteoarthritis patients who took the drug daily were no more likely than intermittent users to have either new-onset hypertension or an aggravation of existing hypertension, Dr. George Sands reported.

“Over the 22-week treatment period, continuous daily celecoxib was more effective in terms of fewer osteoarthritis flares, less pain, and less stiffness than intermittent celecoxib, with no difference in overall adverse effects or in hypertension,” said Dr. Sands, senior medical director at Pfizer Inc., which sponsored the study.

The study group comprised 875 patients with hip or knee osteoarthritis. All patients had to be taking a daily NSAID to control their disease. The study had three phases: In phase I, patients stopped their NSAID until they had a flare at their index joint. In phase II, patients with flares received open-label celecoxib until the flare resolved. Phase III consisted of the 22-week randomized, placebo-controlled study. Patients had two study medications, one for daily use and one for use during a flare. Half of the patients (440) received celecoxib every day and a placebo during the flare. The rest of the group (435) received daily placebo and celecoxib during the flare. Treatment continued for 22 weeks.

“Only patients who had resolved flares could be entered into the trial,” Dr. Sands said. “This is different from the usual arthritis studies, where they stop their NSAID, get worse, and are treated. In this study, patients were randomized after a successful treatment of a flare.”

The patients' mean age was 58 years; 30% were 65 or older. Their mean weight was 83 kg. Most (80%) had knee osteoarthritis; the hip was the affected joint in the remaining 20%. The baseline WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index score was 25 in both groups. Hypertension was present in 45%. Most of the continuous-use patients (80%) and 74% of the intermittent-use patients completed the trial.

The primary end point was the number of flares occurring during the randomized portion of the study. The median time to first flare was significantly longer in the continuous-use group than in the intermittent-use group (16 days vs. 8 days, respectively). “This is not surprising, since in this part of the study, before anyone had a flare, you were testing celecoxib against placebo,” noted Dr. Sands.

By the end of the 22-week treatment period, continuous users had a mean of 0.54 flares per month, significantly fewer than the mean 0.93 flares experienced by the intermittent users. This translates into 42% fewer flares per month, or about two fewer flares per month, Dr. Sands said.

At the end of the treatment period, WOMAC scores were significantly better in the continuous-use group. The change in total WOMAC score was 1.6 in the continuous users vs. 4.99 in the intermittent users.

At the final visit, 23% of the continuous-use group and 11% of the intermittent-use group had been flare free—a significant difference. Adverse events occurred in 57% of the continuous users and 59% of the intermittent users.

The continuous users of celecoxib had a mean of 0.54 flares per month, vs. 0.93 flares for the intermittent users.

Source DR. SANDS

Major Finding: Among 875 patients with osteoarthritis, those who took 200 mg of celecoxib every day had significantly fewer flares than those who took the drug only during a flare.

Data Source: A three-phase randomized, placebo-controlled trial.

Disclosures: Pfizer Inc. sponsored the study; the data were reported by Pfizer employee Dr. Sands.

CANCUN, MEXICO — Osteoarthritis flares were reduced by 42% in patients who took 200 mg of celecoxib daily, compared with those who took the medication only when they experienced a disease flare, judging from findings from a randomized, placebo-controlled trial.

Osteoarthritis patients who took the drug daily were no more likely than intermittent users to have either new-onset hypertension or an aggravation of existing hypertension, Dr. George Sands reported.

“Over the 22-week treatment period, continuous daily celecoxib was more effective in terms of fewer osteoarthritis flares, less pain, and less stiffness than intermittent celecoxib, with no difference in overall adverse effects or in hypertension,” said Dr. Sands, senior medical director at Pfizer Inc., which sponsored the study.

The study group comprised 875 patients with hip or knee osteoarthritis. All patients had to be taking a daily NSAID to control their disease. The study had three phases: In phase I, patients stopped their NSAID until they had a flare at their index joint. In phase II, patients with flares received open-label celecoxib until the flare resolved. Phase III consisted of the 22-week randomized, placebo-controlled study. Patients had two study medications, one for daily use and one for use during a flare. Half of the patients (440) received celecoxib every day and a placebo during the flare. The rest of the group (435) received daily placebo and celecoxib during the flare. Treatment continued for 22 weeks.

“Only patients who had resolved flares could be entered into the trial,” Dr. Sands said. “This is different from the usual arthritis studies, where they stop their NSAID, get worse, and are treated. In this study, patients were randomized after a successful treatment of a flare.”

The patients' mean age was 58 years; 30% were 65 or older. Their mean weight was 83 kg. Most (80%) had knee osteoarthritis; the hip was the affected joint in the remaining 20%. The baseline WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index score was 25 in both groups. Hypertension was present in 45%. Most of the continuous-use patients (80%) and 74% of the intermittent-use patients completed the trial.

The primary end point was the number of flares occurring during the randomized portion of the study. The median time to first flare was significantly longer in the continuous-use group than in the intermittent-use group (16 days vs. 8 days, respectively). “This is not surprising, since in this part of the study, before anyone had a flare, you were testing celecoxib against placebo,” noted Dr. Sands.

By the end of the 22-week treatment period, continuous users had a mean of 0.54 flares per month, significantly fewer than the mean 0.93 flares experienced by the intermittent users. This translates into 42% fewer flares per month, or about two fewer flares per month, Dr. Sands said.

At the end of the treatment period, WOMAC scores were significantly better in the continuous-use group. The change in total WOMAC score was 1.6 in the continuous users vs. 4.99 in the intermittent users.

At the final visit, 23% of the continuous-use group and 11% of the intermittent-use group had been flare free—a significant difference. Adverse events occurred in 57% of the continuous users and 59% of the intermittent users.

The continuous users of celecoxib had a mean of 0.54 flares per month, vs. 0.93 flares for the intermittent users.

Source DR. SANDS

Major Finding: In patients with rheumatoid arthritis or osteoarthritis on long-term NSAID treatment, daily celecoxib produced a 0.9% rate of lower gastrointestinal bleeding events, significantly less than the 3.6% rate in patients treated with diclofenac plus omeprazole.

Data Source: Multicenter, randomized trial with 4,484 patients.

Disclosures: The study was sponsored by Pfizer. Dr. Goldstein said that he has received grant support and honoraria from Pfizer. He also disclosed financial relationships with AstraZeneca, TAP, Takeda, Novartis, Pozen, Logical Therapeutics, Procter & Gamble, PLX, Wyeth, Astellas, Amgen, Given, GlaxoSmithKline, and Merck.

ROME — Daily treatment with a selective cyclo-oxygenase-2 inhibitor triggered significantly fewer lower gastrointestinal adverse events than did a nonsteroidal anti-inflammatory drug plus a proton pump inhibitor, in a randomized trial with more than 4,000 patients.

Results from many studies have already shown that small bowel ulcers, obstruction, perforations, and bleeding can all occur during treatment with a non-steroidal anti-inflammatory drug, although at a lower rate than in the upper gastrointestinal tract. The new findings “give us an idea of what is the relative risk up and down the gastrointestinal tract,” Dr. Jay L. Goldstein said while presenting a poster at the meeting.

“Upper GI tract [adverse events] are still more common, but injury in the small bowel is a real phenomenon. This is the first study to systematically address the issue of these events in a prospective, randomized control trial,” said Dr. Goldstein of the University of Illinois at Chicago.

He acknowledged that upper GI bleeds usually have a more acute and dramatic onset, often causing vomiting and even shock, whereas the anemias resulting from the lower GI bleeds in this study had a more insidious course. The lower GI events “are not immediately life threatening, but when you see a drop in hemoglobin, it's a call to action,” Dr. Goldstein said in an interview.

CONDOR (Study of Celecoxib or Diclofenac and Omeprazole for Gastrointestinal Safety in High GI Risk Patients With Arthritis) ran at 196 centers in 32 countries during 2005-2009. The study randomized patients expected to need regular NSAID treatment for at least 6 months to either the cyclo-oxygenase-2 inhibitor (coxib) celecoxib at 200 mg b.i.d, or to a slow-release formulation of the nonselective NSAID diclofenac at 75 mg b.i.d. plus the proton pump inhibitor omeprazole at 20 mg once daily. The study was sponsored by Pfizer, which markets celecoxib (Celebrex).

“It makes sense that a proton pump inhibitor will only protect the upper GI tract. The concept was that we wanted to be sure that the patients [in the control arm] had upper GI protection to find out what goes on beyond the upper GI tract,” Dr. Goldstein said.

The study's primary end point was the composite incidence of clinically significant events occurring throughout the gastrointestinal tract during the first 6 months of treatment. The investigators confirmed 20 primary end points among 2,238 patients on celecoxib (0.9%), and 81 events among 2,246 patients on diclofenac plus omeprazole (3.6%). The difference in event rates between the two treatment arms was statistically significant. The main driver behind this difference was a higher incidence of patients with a hemoglobin decrease of at least 20 g/L: 15 patients in the celecoxib arm and 77 in the control arm.

These primary results from the trial appeared in an article published simultaneously with Dr. Goldstein's poster report at the meeting (Lancet 2010;376:173-9).

A new analysis that he presented in his poster identified risk factors linked with the increased risk for GI events in CONDOR, including age of 65 or older, which boosted the risk by 40% compared with younger patients; a history of gastritis, which boosted the risk by 50% compared with patients without this history; having rheumatoid arthritis, which raised the risk by 90% compared with osteoarthritis; and a C-reactive protein level at baseline of more than 1 mg/dL, which raised the risk by 50% compared with patients with lower C-reactive protein levels.

“We know that age is a risk factor for upper GI events; now we're suggesting that it's also a risk factor for lower events. And patients with prior GI problems may also be at risk,” Dr. Goldstein said. The increased risks linked with RA and elevated C-reactive protein “may be very similar things,” reflecting the effect of a chronic, underlying inflammatory disease. “The evidence is split on a role [for RA] in upper GI events. Here we have a clear signal of lower GI sensitivity that warrants further study.”

The findings suggest that an otherwise healthy 55-year-old patient with no history of gastritis who needs long-term NSAID treatment would face a relatively low risk for GI bleeds on a nonselective NSAID, Dr. Goldstein said. But in a similar, 65-year-old patient, “I—d use a coxib or add a proton pump inhibitor,” he said.

“Our findings show a clear advantage for the coxib, but the question is, is it worth it [the additional cost]? Is it economically feasible?” Dr. Goldstein also stressed that the results from CONDOR do not apply to patients with an elevated cardiovascular risk, including those on a chronic aspirin regimen.

An accompanying editorial agreed that the CONDOR study is “the first large, double-blind, randomized clinical trial to assess upper and lower gastrointestinal events in patients needing chronic NSAID therapy.” The editorial authors, Dr. Elham Rahme and Dr. Sasha Bernatsky of McGill University in Montreal, called the 6-month duration of CONDOR “short” and “a drawback” that “hinders extrapolation to long-term treatment. The editorial also called “premature” the suggestion by Dr. Goldstein and his coauthors to revise existing recommendations for selecting NSAID therapy based on CONDOR's results (Lancet 2010;376:146-8).

Major Finding: In patients with rheumatoid arthritis or osteoarthritis on long-term NSAID treatment, daily celecoxib produced a 0.9% rate of lower gastrointestinal bleeding events, significantly less than the 3.6% rate in patients treated with diclofenac plus omeprazole.

Data Source: Multicenter, randomized trial with 4,484 patients.

Disclosures: The study was sponsored by Pfizer. Dr. Goldstein said that he has received grant support and honoraria from Pfizer. He also disclosed financial relationships with AstraZeneca, TAP, Takeda, Novartis, Pozen, Logical Therapeutics, Procter & Gamble, PLX, Wyeth, Astellas, Amgen, Given, GlaxoSmithKline, and Merck.

ROME — Daily treatment with a selective cyclo-oxygenase-2 inhibitor triggered significantly fewer lower gastrointestinal adverse events than did a nonsteroidal anti-inflammatory drug plus a proton pump inhibitor, in a randomized trial with more than 4,000 patients.

Results from many studies have already shown that small bowel ulcers, obstruction, perforations, and bleeding can all occur during treatment with a non-steroidal anti-inflammatory drug, although at a lower rate than in the upper gastrointestinal tract. The new findings “give us an idea of what is the relative risk up and down the gastrointestinal tract,” Dr. Jay L. Goldstein said while presenting a poster at the meeting.

“Upper GI tract [adverse events] are still more common, but injury in the small bowel is a real phenomenon. This is the first study to systematically address the issue of these events in a prospective, randomized control trial,” said Dr. Goldstein of the University of Illinois at Chicago.

He acknowledged that upper GI bleeds usually have a more acute and dramatic onset, often causing vomiting and even shock, whereas the anemias resulting from the lower GI bleeds in this study had a more insidious course. The lower GI events “are not immediately life threatening, but when you see a drop in hemoglobin, it's a call to action,” Dr. Goldstein said in an interview.

CONDOR (Study of Celecoxib or Diclofenac and Omeprazole for Gastrointestinal Safety in High GI Risk Patients With Arthritis) ran at 196 centers in 32 countries during 2005-2009. The study randomized patients expected to need regular NSAID treatment for at least 6 months to either the cyclo-oxygenase-2 inhibitor (coxib) celecoxib at 200 mg b.i.d, or to a slow-release formulation of the nonselective NSAID diclofenac at 75 mg b.i.d. plus the proton pump inhibitor omeprazole at 20 mg once daily. The study was sponsored by Pfizer, which markets celecoxib (Celebrex).

“It makes sense that a proton pump inhibitor will only protect the upper GI tract. The concept was that we wanted to be sure that the patients [in the control arm] had upper GI protection to find out what goes on beyond the upper GI tract,” Dr. Goldstein said.

The study's primary end point was the composite incidence of clinically significant events occurring throughout the gastrointestinal tract during the first 6 months of treatment. The investigators confirmed 20 primary end points among 2,238 patients on celecoxib (0.9%), and 81 events among 2,246 patients on diclofenac plus omeprazole (3.6%). The difference in event rates between the two treatment arms was statistically significant. The main driver behind this difference was a higher incidence of patients with a hemoglobin decrease of at least 20 g/L: 15 patients in the celecoxib arm and 77 in the control arm.

These primary results from the trial appeared in an article published simultaneously with Dr. Goldstein's poster report at the meeting (Lancet 2010;376:173-9).

A new analysis that he presented in his poster identified risk factors linked with the increased risk for GI events in CONDOR, including age of 65 or older, which boosted the risk by 40% compared with younger patients; a history of gastritis, which boosted the risk by 50% compared with patients without this history; having rheumatoid arthritis, which raised the risk by 90% compared with osteoarthritis; and a C-reactive protein level at baseline of more than 1 mg/dL, which raised the risk by 50% compared with patients with lower C-reactive protein levels.

“We know that age is a risk factor for upper GI events; now we're suggesting that it's also a risk factor for lower events. And patients with prior GI problems may also be at risk,” Dr. Goldstein said. The increased risks linked with RA and elevated C-reactive protein “may be very similar things,” reflecting the effect of a chronic, underlying inflammatory disease. “The evidence is split on a role [for RA] in upper GI events. Here we have a clear signal of lower GI sensitivity that warrants further study.”

The findings suggest that an otherwise healthy 55-year-old patient with no history of gastritis who needs long-term NSAID treatment would face a relatively low risk for GI bleeds on a nonselective NSAID, Dr. Goldstein said. But in a similar, 65-year-old patient, “I—d use a coxib or add a proton pump inhibitor,” he said.

“Our findings show a clear advantage for the coxib, but the question is, is it worth it [the additional cost]? Is it economically feasible?” Dr. Goldstein also stressed that the results from CONDOR do not apply to patients with an elevated cardiovascular risk, including those on a chronic aspirin regimen.

An accompanying editorial agreed that the CONDOR study is “the first large, double-blind, randomized clinical trial to assess upper and lower gastrointestinal events in patients needing chronic NSAID therapy.” The editorial authors, Dr. Elham Rahme and Dr. Sasha Bernatsky of McGill University in Montreal, called the 6-month duration of CONDOR “short” and “a drawback” that “hinders extrapolation to long-term treatment. The editorial also called “premature” the suggestion by Dr. Goldstein and his coauthors to revise existing recommendations for selecting NSAID therapy based on CONDOR's results (Lancet 2010;376:146-8).

Major Finding: In patients with rheumatoid arthritis or osteoarthritis on long-term NSAID treatment, daily celecoxib produced a 0.9% rate of lower gastrointestinal bleeding events, significantly less than the 3.6% rate in patients treated with diclofenac plus omeprazole.

Data Source: Multicenter, randomized trial with 4,484 patients.

Disclosures: The study was sponsored by Pfizer. Dr. Goldstein said that he has received grant support and honoraria from Pfizer. He also disclosed financial relationships with AstraZeneca, TAP, Takeda, Novartis, Pozen, Logical Therapeutics, Procter & Gamble, PLX, Wyeth, Astellas, Amgen, Given, GlaxoSmithKline, and Merck.

ROME — Daily treatment with a selective cyclo-oxygenase-2 inhibitor triggered significantly fewer lower gastrointestinal adverse events than did a nonsteroidal anti-inflammatory drug plus a proton pump inhibitor, in a randomized trial with more than 4,000 patients.

Results from many studies have already shown that small bowel ulcers, obstruction, perforations, and bleeding can all occur during treatment with a non-steroidal anti-inflammatory drug, although at a lower rate than in the upper gastrointestinal tract. The new findings “give us an idea of what is the relative risk up and down the gastrointestinal tract,” Dr. Jay L. Goldstein said while presenting a poster at the meeting.

“Upper GI tract [adverse events] are still more common, but injury in the small bowel is a real phenomenon. This is the first study to systematically address the issue of these events in a prospective, randomized control trial,” said Dr. Goldstein of the University of Illinois at Chicago.

He acknowledged that upper GI bleeds usually have a more acute and dramatic onset, often causing vomiting and even shock, whereas the anemias resulting from the lower GI bleeds in this study had a more insidious course. The lower GI events “are not immediately life threatening, but when you see a drop in hemoglobin, it's a call to action,” Dr. Goldstein said in an interview.

CONDOR (Study of Celecoxib or Diclofenac and Omeprazole for Gastrointestinal Safety in High GI Risk Patients With Arthritis) ran at 196 centers in 32 countries during 2005-2009. The study randomized patients expected to need regular NSAID treatment for at least 6 months to either the cyclo-oxygenase-2 inhibitor (coxib) celecoxib at 200 mg b.i.d, or to a slow-release formulation of the nonselective NSAID diclofenac at 75 mg b.i.d. plus the proton pump inhibitor omeprazole at 20 mg once daily. The study was sponsored by Pfizer, which markets celecoxib (Celebrex).

“It makes sense that a proton pump inhibitor will only protect the upper GI tract. The concept was that we wanted to be sure that the patients [in the control arm] had upper GI protection to find out what goes on beyond the upper GI tract,” Dr. Goldstein said.

The study's primary end point was the composite incidence of clinically significant events occurring throughout the gastrointestinal tract during the first 6 months of treatment. The investigators confirmed 20 primary end points among 2,238 patients on celecoxib (0.9%), and 81 events among 2,246 patients on diclofenac plus omeprazole (3.6%). The difference in event rates between the two treatment arms was statistically significant. The main driver behind this difference was a higher incidence of patients with a hemoglobin decrease of at least 20 g/L: 15 patients in the celecoxib arm and 77 in the control arm.

These primary results from the trial appeared in an article published simultaneously with Dr. Goldstein's poster report at the meeting (Lancet 2010;376:173-9).

A new analysis that he presented in his poster identified risk factors linked with the increased risk for GI events in CONDOR, including age of 65 or older, which boosted the risk by 40% compared with younger patients; a history of gastritis, which boosted the risk by 50% compared with patients without this history; having rheumatoid arthritis, which raised the risk by 90% compared with osteoarthritis; and a C-reactive protein level at baseline of more than 1 mg/dL, which raised the risk by 50% compared with patients with lower C-reactive protein levels.

“We know that age is a risk factor for upper GI events; now we're suggesting that it's also a risk factor for lower events. And patients with prior GI problems may also be at risk,” Dr. Goldstein said. The increased risks linked with RA and elevated C-reactive protein “may be very similar things,” reflecting the effect of a chronic, underlying inflammatory disease. “The evidence is split on a role [for RA] in upper GI events. Here we have a clear signal of lower GI sensitivity that warrants further study.”

The findings suggest that an otherwise healthy 55-year-old patient with no history of gastritis who needs long-term NSAID treatment would face a relatively low risk for GI bleeds on a nonselective NSAID, Dr. Goldstein said. But in a similar, 65-year-old patient, “I—d use a coxib or add a proton pump inhibitor,” he said.

“Our findings show a clear advantage for the coxib, but the question is, is it worth it [the additional cost]? Is it economically feasible?” Dr. Goldstein also stressed that the results from CONDOR do not apply to patients with an elevated cardiovascular risk, including those on a chronic aspirin regimen.

An accompanying editorial agreed that the CONDOR study is “the first large, double-blind, randomized clinical trial to assess upper and lower gastrointestinal events in patients needing chronic NSAID therapy.” The editorial authors, Dr. Elham Rahme and Dr. Sasha Bernatsky of McGill University in Montreal, called the 6-month duration of CONDOR “short” and “a drawback” that “hinders extrapolation to long-term treatment. The editorial also called “premature” the suggestion by Dr. Goldstein and his coauthors to revise existing recommendations for selecting NSAID therapy based on CONDOR's results (Lancet 2010;376:146-8).

Major Finding: More patients achieved a EULAR good response at 6 months and 12 months when treated with leflunomide along with rituximab (and also had a lower incidence of retreatment) than did patients who were treated with methotrexate plus rituximab, or rituximab alone.

Data Source: A population study based on analysis of data from 10 European registries.

Disclosures: Dr. Gabay said he has no conflicts of interest relevant to this study. The CERERRA collaboration (of which the European registries are a part) that was mentioned in the story is described by Dr. Gabay as an investigator-led, industry-supported initiative that was formed to evaluate the clinical aspects of rituximab use for RA. This analysis and study abstract were prepared, “without any influence from the supporting medical industry,” Dr. Gabay said.

Leflunomide is an effective concomitant treatment with rituximab in patients with rheumatoid arthritis, according to findings from a population-based study.

In fact, “a combination of leflunomide and rituximab is probably better than a combination of methotrexate and rituximab,” said Dr. Cem Gabay of the University Hospitals of Geneva in an interview with Rheumatology News.

Ten European registries that are participating in the CERERRA collaboration submitted data sets for patients who were treated with rituximab, and more than 1,900 patients were analyzed for their response to treatment with one of three therapeutic approaches: rituximab with either methotrexate (MTX) or leflunomide (LEF), or rituximab alone. Significantly more patients achieved a EULAR good response at 6 months when treated with rituximab and LEF (33%), compared with rituximab and MTX (21%) or with rituximab alone (20%).

A similar trend was observed at 12 months. Fewer patients, moreover, were retreated during the first 12 months when they received LEF (11% in the rituximab plus LEF group vs. 20% in the rituximab plus MTX group and 19% among those on rituximab monotherapy).

A univariate analysis adjusted for age and sex showed that patients who received LEF in combination with rituximab were 2.6 times more likely to have a good EULAR response at 6 months than were patients who received MTX plus rituximab. They were also three times more likely to have a good EULAR response at 6 months than were patients who received rituximab monotherapy. At 12 months, patients who received LEF as a combination therapy were about twice as likely to have a good EULAR response as were patients in the other groups.

Combination therapy with LEF was still predictive of a good EULAR response in a multivariate analysis that took into account factors like disease duration and the number of previous biologic agents used.

“This is a population-based study, so we need to be cautious about the conclusions we draw from the data,” said Dr. Gabay. Among the study's limitations are the lack of randomization and control. The Food and Drug Administration recently required that the leflunomide label contain a Boxed Warning about severe liver injury.

To see an interview with Dr. Cem Gabay, go to

Source Heidi Splete/Elsevier Global Medical Newswww.youtube.com/elsglobalmedical

Major Finding: More patients achieved a EULAR good response at 6 months and 12 months when treated with leflunomide along with rituximab (and also had a lower incidence of retreatment) than did patients who were treated with methotrexate plus rituximab, or rituximab alone.

Data Source: A population study based on analysis of data from 10 European registries.

Disclosures: Dr. Gabay said he has no conflicts of interest relevant to this study. The CERERRA collaboration (of which the European registries are a part) that was mentioned in the story is described by Dr. Gabay as an investigator-led, industry-supported initiative that was formed to evaluate the clinical aspects of rituximab use for RA. This analysis and study abstract were prepared, “without any influence from the supporting medical industry,” Dr. Gabay said.

Leflunomide is an effective concomitant treatment with rituximab in patients with rheumatoid arthritis, according to findings from a population-based study.

In fact, “a combination of leflunomide and rituximab is probably better than a combination of methotrexate and rituximab,” said Dr. Cem Gabay of the University Hospitals of Geneva in an interview with Rheumatology News.

Ten European registries that are participating in the CERERRA collaboration submitted data sets for patients who were treated with rituximab, and more than 1,900 patients were analyzed for their response to treatment with one of three therapeutic approaches: rituximab with either methotrexate (MTX) or leflunomide (LEF), or rituximab alone. Significantly more patients achieved a EULAR good response at 6 months when treated with rituximab and LEF (33%), compared with rituximab and MTX (21%) or with rituximab alone (20%).

A similar trend was observed at 12 months. Fewer patients, moreover, were retreated during the first 12 months when they received LEF (11% in the rituximab plus LEF group vs. 20% in the rituximab plus MTX group and 19% among those on rituximab monotherapy).

A univariate analysis adjusted for age and sex showed that patients who received LEF in combination with rituximab were 2.6 times more likely to have a good EULAR response at 6 months than were patients who received MTX plus rituximab. They were also three times more likely to have a good EULAR response at 6 months than were patients who received rituximab monotherapy. At 12 months, patients who received LEF as a combination therapy were about twice as likely to have a good EULAR response as were patients in the other groups.

Combination therapy with LEF was still predictive of a good EULAR response in a multivariate analysis that took into account factors like disease duration and the number of previous biologic agents used.

“This is a population-based study, so we need to be cautious about the conclusions we draw from the data,” said Dr. Gabay. Among the study's limitations are the lack of randomization and control. The Food and Drug Administration recently required that the leflunomide label contain a Boxed Warning about severe liver injury.

To see an interview with Dr. Cem Gabay, go to

Source Heidi Splete/Elsevier Global Medical Newswww.youtube.com/elsglobalmedical

Major Finding: More patients achieved a EULAR good response at 6 months and 12 months when treated with leflunomide along with rituximab (and also had a lower incidence of retreatment) than did patients who were treated with methotrexate plus rituximab, or rituximab alone.

Data Source: A population study based on analysis of data from 10 European registries.

Disclosures: Dr. Gabay said he has no conflicts of interest relevant to this study. The CERERRA collaboration (of which the European registries are a part) that was mentioned in the story is described by Dr. Gabay as an investigator-led, industry-supported initiative that was formed to evaluate the clinical aspects of rituximab use for RA. This analysis and study abstract were prepared, “without any influence from the supporting medical industry,” Dr. Gabay said.

Leflunomide is an effective concomitant treatment with rituximab in patients with rheumatoid arthritis, according to findings from a population-based study.

In fact, “a combination of leflunomide and rituximab is probably better than a combination of methotrexate and rituximab,” said Dr. Cem Gabay of the University Hospitals of Geneva in an interview with Rheumatology News.

Ten European registries that are participating in the CERERRA collaboration submitted data sets for patients who were treated with rituximab, and more than 1,900 patients were analyzed for their response to treatment with one of three therapeutic approaches: rituximab with either methotrexate (MTX) or leflunomide (LEF), or rituximab alone. Significantly more patients achieved a EULAR good response at 6 months when treated with rituximab and LEF (33%), compared with rituximab and MTX (21%) or with rituximab alone (20%).

A similar trend was observed at 12 months. Fewer patients, moreover, were retreated during the first 12 months when they received LEF (11% in the rituximab plus LEF group vs. 20% in the rituximab plus MTX group and 19% among those on rituximab monotherapy).

A univariate analysis adjusted for age and sex showed that patients who received LEF in combination with rituximab were 2.6 times more likely to have a good EULAR response at 6 months than were patients who received MTX plus rituximab. They were also three times more likely to have a good EULAR response at 6 months than were patients who received rituximab monotherapy. At 12 months, patients who received LEF as a combination therapy were about twice as likely to have a good EULAR response as were patients in the other groups.

Combination therapy with LEF was still predictive of a good EULAR response in a multivariate analysis that took into account factors like disease duration and the number of previous biologic agents used.

“This is a population-based study, so we need to be cautious about the conclusions we draw from the data,” said Dr. Gabay. Among the study's limitations are the lack of randomization and control. The Food and Drug Administration recently required that the leflunomide label contain a Boxed Warning about severe liver injury.

To see an interview with Dr. Cem Gabay, go to

Source Heidi Splete/Elsevier Global Medical Newswww.youtube.com/elsglobalmedical

Major Finding: Early rheumatoid arthritis patients who had an initial clinical response to methotrexate and had a 72% remission rate after 2 years on treatment continued to develop radiographic progression of joint damage, with an average rise of four points in their van der Heijde-modified Sharp score over 2 years.

Data Source: A total of 114 patients who initially had clinical responses to methotrexate monotherapy and had full radiographic follow-up after 1 and 2 years on treatment enrolled in the SWEFOT trial.

Disclosures: Mr. Rezaei said that he had no disclosures. Dr. van Vollenhoven said that he has been a consultant to Abbott, Bristol-Myers Squibb, Pfizer/Wyeth, Roche, Shering Plough, and UCB, and that he has received grant support from Abbott, Pfizer/Wyeth, Roche, and Schering-Plough. The SWEFOT study was funded in part by Schering-Plough. Dr. Gossec had no disclosures.

ROME — Rheumatoid arthritis patients with a sustained clinical response to methotrexate therapy can still have radio-graphic progression of the disease in the joints of their hands and feet, even when in remission, based on follow-up of 114 patients.

“A good clinical response to methotrexate does not preclude radiographic progression,” Hamed Rezaei said at the annual European Congress of Rheumatology.

“If you choose to use methotrexate [monotherapy] you need to monitor patients both clinically and radiologically. Even when patients are doing well clinically, you can't stop there. You need to also look at their x-rays,” said Dr. Ronald F. van Vollenhoven, senior physician at the Karolinska Institute in Stockholm and senior researcher for the new report.

“A possible driver of radio-graphic progression is synovitis, so aim for a low level or absence of synovitis” with rheumatoid arthritis (RA) treatment, commented Dr. Laure Gossec, a rheumatologist at Cochin Hospital, Paris.

The new analysis reported by Mr. Rezaei focused on 147 of 487 early RA patients enrolled in the Swedish Pharmacotherapy (SWEFOT) trial who had significant clinical responses to methotrexate monotherapy when treatment began at the start of the study, with their disease activity score (DAS)28 falling to 3.2 or less. The main portion of the SWEFOT trial focused on the 340 patients who did not respond adequately to methotrexate monotherapy and then underwent randomization to additional treatment (Lancet 2009;374:459-66).

The report from Mr. Rezaei reviewed the x-ray scans obtained from 114 of the 147 initial methotrexate responders at 1 year and 2 years after initiation of their treatment. During these 2 years of ongoing treatment with methotrexate, at dosages of at least 20 mg/week, 61% of the initial responders were in full remission after 1 year and 72% reached full remission after 2 years of treatment. Also at 2 years, 88% of patients had low disease activity. Despite this good level of clinical response, radiologic assessments showed a different situation. The average van der Heijde-modified Sharp score at baseline was 3.8, which rose to 6.0 after 1 year and 7.9 after 2 years. The percent of the 114 patients followed radiologically who had a 10-point or greater increase in their van der Heijde-modified Sharp score after 2 years on treatment was 15%, with an additional 15% having an increase of 5-9 points. A 10-point or greater rise in the score is clinically significant, the Karolinska researchers said.

The average joint erosion score and joint narrowing score for all 114 patients also showed increases from baseline to year 1 and year 2.

The percent of patients showing no joint damage at all on their x-rays was 48% at baseline, 27% after 1 year, and 20% after 2 years, said Mr. Rezaei, a doctoral student and researcher in the rheumatology unit at the Karolinska Institute.

Additional analysis showed that patients who were positive for rheumatoid factor had a higher average van der Heijde-modified Sharp score after 2 years compared with patients negative for rheumatoid factor, but the link was not statistically significant. Patients who were positive for anti-citrullinated protein antibody (ACPA) had no significant difference in their average score compared with ACPA-negative patients, and gender also did not have a significant link to radiologic progression.

Based on these findings, “we need to have more frequent x-ray examinations over the first 2 years of treatment in patients who clinically respond to methotrexate,” Mr. Rezaei said. He declined to suggest what additional treatment should be added to slow or prevent further joint damage in patients on methotrexate monotherapy.

'Even when patients are doing well … you can't stop there. You need to also look at their x-rays.'

Source DR. VAN VOLLENHOVEN

Major Finding: Early rheumatoid arthritis patients who had an initial clinical response to methotrexate and had a 72% remission rate after 2 years on treatment continued to develop radiographic progression of joint damage, with an average rise of four points in their van der Heijde-modified Sharp score over 2 years.

Data Source: A total of 114 patients who initially had clinical responses to methotrexate monotherapy and had full radiographic follow-up after 1 and 2 years on treatment enrolled in the SWEFOT trial.

Disclosures: Mr. Rezaei said that he had no disclosures. Dr. van Vollenhoven said that he has been a consultant to Abbott, Bristol-Myers Squibb, Pfizer/Wyeth, Roche, Shering Plough, and UCB, and that he has received grant support from Abbott, Pfizer/Wyeth, Roche, and Schering-Plough. The SWEFOT study was funded in part by Schering-Plough. Dr. Gossec had no disclosures.

ROME — Rheumatoid arthritis patients with a sustained clinical response to methotrexate therapy can still have radio-graphic progression of the disease in the joints of their hands and feet, even when in remission, based on follow-up of 114 patients.

“A good clinical response to methotrexate does not preclude radiographic progression,” Hamed Rezaei said at the annual European Congress of Rheumatology.

“If you choose to use methotrexate [monotherapy] you need to monitor patients both clinically and radiologically. Even when patients are doing well clinically, you can't stop there. You need to also look at their x-rays,” said Dr. Ronald F. van Vollenhoven, senior physician at the Karolinska Institute in Stockholm and senior researcher for the new report.

“A possible driver of radio-graphic progression is synovitis, so aim for a low level or absence of synovitis” with rheumatoid arthritis (RA) treatment, commented Dr. Laure Gossec, a rheumatologist at Cochin Hospital, Paris.

The new analysis reported by Mr. Rezaei focused on 147 of 487 early RA patients enrolled in the Swedish Pharmacotherapy (SWEFOT) trial who had significant clinical responses to methotrexate monotherapy when treatment began at the start of the study, with their disease activity score (DAS)28 falling to 3.2 or less. The main portion of the SWEFOT trial focused on the 340 patients who did not respond adequately to methotrexate monotherapy and then underwent randomization to additional treatment (Lancet 2009;374:459-66).

The report from Mr. Rezaei reviewed the x-ray scans obtained from 114 of the 147 initial methotrexate responders at 1 year and 2 years after initiation of their treatment. During these 2 years of ongoing treatment with methotrexate, at dosages of at least 20 mg/week, 61% of the initial responders were in full remission after 1 year and 72% reached full remission after 2 years of treatment. Also at 2 years, 88% of patients had low disease activity. Despite this good level of clinical response, radiologic assessments showed a different situation. The average van der Heijde-modified Sharp score at baseline was 3.8, which rose to 6.0 after 1 year and 7.9 after 2 years. The percent of the 114 patients followed radiologically who had a 10-point or greater increase in their van der Heijde-modified Sharp score after 2 years on treatment was 15%, with an additional 15% having an increase of 5-9 points. A 10-point or greater rise in the score is clinically significant, the Karolinska researchers said.

The average joint erosion score and joint narrowing score for all 114 patients also showed increases from baseline to year 1 and year 2.

The percent of patients showing no joint damage at all on their x-rays was 48% at baseline, 27% after 1 year, and 20% after 2 years, said Mr. Rezaei, a doctoral student and researcher in the rheumatology unit at the Karolinska Institute.

Additional analysis showed that patients who were positive for rheumatoid factor had a higher average van der Heijde-modified Sharp score after 2 years compared with patients negative for rheumatoid factor, but the link was not statistically significant. Patients who were positive for anti-citrullinated protein antibody (ACPA) had no significant difference in their average score compared with ACPA-negative patients, and gender also did not have a significant link to radiologic progression.

Based on these findings, “we need to have more frequent x-ray examinations over the first 2 years of treatment in patients who clinically respond to methotrexate,” Mr. Rezaei said. He declined to suggest what additional treatment should be added to slow or prevent further joint damage in patients on methotrexate monotherapy.

'Even when patients are doing well … you can't stop there. You need to also look at their x-rays.'

Source DR. VAN VOLLENHOVEN

Major Finding: Early rheumatoid arthritis patients who had an initial clinical response to methotrexate and had a 72% remission rate after 2 years on treatment continued to develop radiographic progression of joint damage, with an average rise of four points in their van der Heijde-modified Sharp score over 2 years.

Data Source: A total of 114 patients who initially had clinical responses to methotrexate monotherapy and had full radiographic follow-up after 1 and 2 years on treatment enrolled in the SWEFOT trial.

Disclosures: Mr. Rezaei said that he had no disclosures. Dr. van Vollenhoven said that he has been a consultant to Abbott, Bristol-Myers Squibb, Pfizer/Wyeth, Roche, Shering Plough, and UCB, and that he has received grant support from Abbott, Pfizer/Wyeth, Roche, and Schering-Plough. The SWEFOT study was funded in part by Schering-Plough. Dr. Gossec had no disclosures.

ROME — Rheumatoid arthritis patients with a sustained clinical response to methotrexate therapy can still have radio-graphic progression of the disease in the joints of their hands and feet, even when in remission, based on follow-up of 114 patients.

“A good clinical response to methotrexate does not preclude radiographic progression,” Hamed Rezaei said at the annual European Congress of Rheumatology.

“If you choose to use methotrexate [monotherapy] you need to monitor patients both clinically and radiologically. Even when patients are doing well clinically, you can't stop there. You need to also look at their x-rays,” said Dr. Ronald F. van Vollenhoven, senior physician at the Karolinska Institute in Stockholm and senior researcher for the new report.

“A possible driver of radio-graphic progression is synovitis, so aim for a low level or absence of synovitis” with rheumatoid arthritis (RA) treatment, commented Dr. Laure Gossec, a rheumatologist at Cochin Hospital, Paris.

The new analysis reported by Mr. Rezaei focused on 147 of 487 early RA patients enrolled in the Swedish Pharmacotherapy (SWEFOT) trial who had significant clinical responses to methotrexate monotherapy when treatment began at the start of the study, with their disease activity score (DAS)28 falling to 3.2 or less. The main portion of the SWEFOT trial focused on the 340 patients who did not respond adequately to methotrexate monotherapy and then underwent randomization to additional treatment (Lancet 2009;374:459-66).

The report from Mr. Rezaei reviewed the x-ray scans obtained from 114 of the 147 initial methotrexate responders at 1 year and 2 years after initiation of their treatment. During these 2 years of ongoing treatment with methotrexate, at dosages of at least 20 mg/week, 61% of the initial responders were in full remission after 1 year and 72% reached full remission after 2 years of treatment. Also at 2 years, 88% of patients had low disease activity. Despite this good level of clinical response, radiologic assessments showed a different situation. The average van der Heijde-modified Sharp score at baseline was 3.8, which rose to 6.0 after 1 year and 7.9 after 2 years. The percent of the 114 patients followed radiologically who had a 10-point or greater increase in their van der Heijde-modified Sharp score after 2 years on treatment was 15%, with an additional 15% having an increase of 5-9 points. A 10-point or greater rise in the score is clinically significant, the Karolinska researchers said.

The average joint erosion score and joint narrowing score for all 114 patients also showed increases from baseline to year 1 and year 2.

The percent of patients showing no joint damage at all on their x-rays was 48% at baseline, 27% after 1 year, and 20% after 2 years, said Mr. Rezaei, a doctoral student and researcher in the rheumatology unit at the Karolinska Institute.

Additional analysis showed that patients who were positive for rheumatoid factor had a higher average van der Heijde-modified Sharp score after 2 years compared with patients negative for rheumatoid factor, but the link was not statistically significant. Patients who were positive for anti-citrullinated protein antibody (ACPA) had no significant difference in their average score compared with ACPA-negative patients, and gender also did not have a significant link to radiologic progression.

Based on these findings, “we need to have more frequent x-ray examinations over the first 2 years of treatment in patients who clinically respond to methotrexate,” Mr. Rezaei said. He declined to suggest what additional treatment should be added to slow or prevent further joint damage in patients on methotrexate monotherapy.

'Even when patients are doing well … you can't stop there. You need to also look at their x-rays.'

Source DR. VAN VOLLENHOVEN

ROME — Although the updated classification criteria for rheumatoid arthritis released by the American College of Rheumatology and the European League Against Rheumatism last October marked the start of a new era of identifying patients earlier in the course of their disease, the new criteria do not trump the diagnostic experience and medical judgment of a rheumatologist.

“A clinical diagnosis [of rheumatoid arthritis (RA)] has to be established by the physician. It includes many more aspects than can be included in formal criteria, [which] might be a guide to establish a clinical diagnosis,” Dr. Daniel Aletaha said.

“Rheumatologists are still in charge for making a diagnosis. We are not replaced by the new criteria,” said Dr. Aletaha, a rheumatologist at the Medical University of Vienna and a key member of the joint ACR/EULAR task force that developed the criteria. “The new criteria are not diagnostic, but in clinical practice, they may inform a physician's diagnosis.” His talk in the meeting's opening session formally introduced the new criteria to the EULAR audience, since they have not yet been published. The only other public presentation of the criteria took place last October at the annual meeting of the ACR in Philadelphia.

An important difference between RA classification and diagnosis is that classification is primarily for studies, and generally involves a well-defined and relatively small patient population, while diagnosis is for clinical management and deals with a patient population that is larger and less well defined.

In reviewing the new classification criteria, Dr. Aletaha emphasized several elements of how they should be applied.

First, he dealt with what to do about patients whose score from the criteria falls below 6 (of a possible 10), the threshold for identifying patients with definite RA. He suggested that such patients be followed and might eventually reach a score of 6 or more with time, or their history can be reviewed to identify a time in the past when their score reached at least 6.

It's appropriate for physicians to tally classification criteria points for any patient with at least one joint with definite clinical synovitis, such as a swollen joint, and when the synovitis is not explicable by another disease.

And although the new criteria do not rely on radiologic evidence of joint damage, a patient with radiologically apparent joint damage can be classified as having RA even if their score falls short of 6.

“Radiographs serve as an option for classifying patients with a history but with no documentation of symptoms compatible with RA.” But, he added “the term 'erosions typical for RA' needs yet to be exactly defined.”

Joint involvement means any swollen or tender joint, excluding the distal interphalangeal joints of the hands and feet, the first metatarsophalangeal joint, or the first carpometacarpal joint, the joints that are commonly affected in osteoarthritis. Small joints that fulfill the criteria are the metacarpophalangeal, the proximal interphalangeal, the second-fifth metatarsophalangeal, the thumb interphalangeal, and the wrist.

The maximum score of 55 for joint involvement requires at least 10 affected joints, including at least 1 small joint. Other joints that can count toward the total of 10 include the temporomandibular, the sternoclavicular, and the acromioclavicular, or others that are typically involved in RA. Joints considered large when scoring the criteria include the shoulders, elbows, hips, knees, and neck.

For the serology scoring category, which includes both rheumatoid factor and anticitrullinated protein antibody, a negative finding is a level at or below the upper limit of normal for both these factors. A low positive level is above the upper limit of normal but not more than three times the upper limit for one or both. A high positive is a level more than three times the upper limit of normal for at least one.

Finally, he noted that scoring symptom duration can depend entirely on a patient's self-report of the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment.

Disclosures: Dr. Aletaha reported having no relevant disclosures.

ROME — Although the updated classification criteria for rheumatoid arthritis released by the American College of Rheumatology and the European League Against Rheumatism last October marked the start of a new era of identifying patients earlier in the course of their disease, the new criteria do not trump the diagnostic experience and medical judgment of a rheumatologist.

“A clinical diagnosis [of rheumatoid arthritis (RA)] has to be established by the physician. It includes many more aspects than can be included in formal criteria, [which] might be a guide to establish a clinical diagnosis,” Dr. Daniel Aletaha said.

“Rheumatologists are still in charge for making a diagnosis. We are not replaced by the new criteria,” said Dr. Aletaha, a rheumatologist at the Medical University of Vienna and a key member of the joint ACR/EULAR task force that developed the criteria. “The new criteria are not diagnostic, but in clinical practice, they may inform a physician's diagnosis.” His talk in the meeting's opening session formally introduced the new criteria to the EULAR audience, since they have not yet been published. The only other public presentation of the criteria took place last October at the annual meeting of the ACR in Philadelphia.

An important difference between RA classification and diagnosis is that classification is primarily for studies, and generally involves a well-defined and relatively small patient population, while diagnosis is for clinical management and deals with a patient population that is larger and less well defined.

In reviewing the new classification criteria, Dr. Aletaha emphasized several elements of how they should be applied.

First, he dealt with what to do about patients whose score from the criteria falls below 6 (of a possible 10), the threshold for identifying patients with definite RA. He suggested that such patients be followed and might eventually reach a score of 6 or more with time, or their history can be reviewed to identify a time in the past when their score reached at least 6.

It's appropriate for physicians to tally classification criteria points for any patient with at least one joint with definite clinical synovitis, such as a swollen joint, and when the synovitis is not explicable by another disease.

And although the new criteria do not rely on radiologic evidence of joint damage, a patient with radiologically apparent joint damage can be classified as having RA even if their score falls short of 6.

“Radiographs serve as an option for classifying patients with a history but with no documentation of symptoms compatible with RA.” But, he added “the term 'erosions typical for RA' needs yet to be exactly defined.”

Joint involvement means any swollen or tender joint, excluding the distal interphalangeal joints of the hands and feet, the first metatarsophalangeal joint, or the first carpometacarpal joint, the joints that are commonly affected in osteoarthritis. Small joints that fulfill the criteria are the metacarpophalangeal, the proximal interphalangeal, the second-fifth metatarsophalangeal, the thumb interphalangeal, and the wrist.

The maximum score of 55 for joint involvement requires at least 10 affected joints, including at least 1 small joint. Other joints that can count toward the total of 10 include the temporomandibular, the sternoclavicular, and the acromioclavicular, or others that are typically involved in RA. Joints considered large when scoring the criteria include the shoulders, elbows, hips, knees, and neck.

For the serology scoring category, which includes both rheumatoid factor and anticitrullinated protein antibody, a negative finding is a level at or below the upper limit of normal for both these factors. A low positive level is above the upper limit of normal but not more than three times the upper limit for one or both. A high positive is a level more than three times the upper limit of normal for at least one.

Finally, he noted that scoring symptom duration can depend entirely on a patient's self-report of the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment.

Disclosures: Dr. Aletaha reported having no relevant disclosures.

ROME — Although the updated classification criteria for rheumatoid arthritis released by the American College of Rheumatology and the European League Against Rheumatism last October marked the start of a new era of identifying patients earlier in the course of their disease, the new criteria do not trump the diagnostic experience and medical judgment of a rheumatologist.

“A clinical diagnosis [of rheumatoid arthritis (RA)] has to be established by the physician. It includes many more aspects than can be included in formal criteria, [which] might be a guide to establish a clinical diagnosis,” Dr. Daniel Aletaha said.

“Rheumatologists are still in charge for making a diagnosis. We are not replaced by the new criteria,” said Dr. Aletaha, a rheumatologist at the Medical University of Vienna and a key member of the joint ACR/EULAR task force that developed the criteria. “The new criteria are not diagnostic, but in clinical practice, they may inform a physician's diagnosis.” His talk in the meeting's opening session formally introduced the new criteria to the EULAR audience, since they have not yet been published. The only other public presentation of the criteria took place last October at the annual meeting of the ACR in Philadelphia.

An important difference between RA classification and diagnosis is that classification is primarily for studies, and generally involves a well-defined and relatively small patient population, while diagnosis is for clinical management and deals with a patient population that is larger and less well defined.

In reviewing the new classification criteria, Dr. Aletaha emphasized several elements of how they should be applied.

First, he dealt with what to do about patients whose score from the criteria falls below 6 (of a possible 10), the threshold for identifying patients with definite RA. He suggested that such patients be followed and might eventually reach a score of 6 or more with time, or their history can be reviewed to identify a time in the past when their score reached at least 6.

It's appropriate for physicians to tally classification criteria points for any patient with at least one joint with definite clinical synovitis, such as a swollen joint, and when the synovitis is not explicable by another disease.

And although the new criteria do not rely on radiologic evidence of joint damage, a patient with radiologically apparent joint damage can be classified as having RA even if their score falls short of 6.

“Radiographs serve as an option for classifying patients with a history but with no documentation of symptoms compatible with RA.” But, he added “the term 'erosions typical for RA' needs yet to be exactly defined.”

Joint involvement means any swollen or tender joint, excluding the distal interphalangeal joints of the hands and feet, the first metatarsophalangeal joint, or the first carpometacarpal joint, the joints that are commonly affected in osteoarthritis. Small joints that fulfill the criteria are the metacarpophalangeal, the proximal interphalangeal, the second-fifth metatarsophalangeal, the thumb interphalangeal, and the wrist.

The maximum score of 55 for joint involvement requires at least 10 affected joints, including at least 1 small joint. Other joints that can count toward the total of 10 include the temporomandibular, the sternoclavicular, and the acromioclavicular, or others that are typically involved in RA. Joints considered large when scoring the criteria include the shoulders, elbows, hips, knees, and neck.

For the serology scoring category, which includes both rheumatoid factor and anticitrullinated protein antibody, a negative finding is a level at or below the upper limit of normal for both these factors. A low positive level is above the upper limit of normal but not more than three times the upper limit for one or both. A high positive is a level more than three times the upper limit of normal for at least one.

Finally, he noted that scoring symptom duration can depend entirely on a patient's self-report of the maximum duration of signs and symptoms of any joint that is clinically involved at the time of assessment.

Disclosures: Dr. Aletaha reported having no relevant disclosures.