Rheumatoid Arthritis

PHILADELPHIA — Drinking water or skim milk can improve gout control, according to findings from two studies that highlight the important contribution of lifestyle factors on gout prevention and management.

“Our results show that drinking water is a simple, safe, and effective means of trying to reduce recurrent gout attacks,” Dr. Tuhina Neogi said at the annual meeting of the American College of Rheumatology.

The study included 535 people who had had a gout attack within the past year (78% male; mean age, 53 years) and who provided information via the Internet about food, drink, medications, physical activity, and other possible gout risk factors during periods preceding the attack and during attack-free periods. By using a case crossover study design, the participants acted as their own controls. Medical records were accessed to verify gout diagnosis, explained Dr. Neogi of Boston University.

The findings showed that increasing water intake was associated with decreased risk for recurrent gout attacks. Compared with those who drank no or one 8-ounce glass of water per day, those who drank five to eight glasses had a 40% lower chance of a gout attack and those who drank more than eight glasses had a 46% lower chance.

In the second study, researchers from New Zealand measured the acute effects of skim milk consumption on serum urate concentrations in 16 healthy male volunteers, in light of reports that skim milk was beneficial in gout prevention. The randomized controlled crossover study was designed to assess the effects of skim milk that was from the early season and the late season, as well as MPC85, a milk protein concentrate that contains 85% protein. The effects of soy milk consumption also were assessed, and it was considered the control.

“Late-season” skim milk, primarily available from countries where milking is seasonal and cows are grass fed, is high in orotic acid, a substance known to promote uric acid removal by the kidneys, explained Dr. Nicola Dalbeth, a senior lecturer in clinical medicine at the University of Auckland (New Zealand). MPC85 skim milk is ultrafiltered and contains very low concentrations of orotic acid, purines, and lactose.

Each participant received a single dose of each product in a random order, with each study visit separated by a week. The amount consumed was equal to about 3.5 8-ounce glasses of milk in one sitting (80 g of protein in 800 mL). Serum and urine were obtained immediately before ingestion and then hourly over the next 3 hours.

Drinking soy milk led to a 10% increase in serum urate. In contrast, all skim milks decreased serum urate by about 10% (P less than .0001). All products, including soy, led to an increase in the fractional excretion of uric acid (FEUA).

Interestingly, there were differences among the types of skim milk, which may shed light on the underlying mechanism. Late-season skim milk led to a greater increase in FEUA, compared with either ultrafiltered skim milk or early-season skim milk, suggesting that the acute urate-lowering effect of orotic acid may explain these effects.

“We cannot necessarily extrapolate these results from [healthy individuals] to those with gout,” Dr. Dalbeth acknowledged. “Furthermore, I am not saying drinking milk should replace allopurinol. But one of the key things we do is spend a lot of time telling people with gout what not to do, such as do not eat red meat. It is very useful to have some positive information.”

“Even though gout has been known since antiquity, and we have had treatments around for decades, it is not a well-managed disease. Medical management is still the cornerstone. Still, there are a lot of lifestyle and behavioral aspects that people with gout can do for themselves to reduce their risk,” Dr. M. Elaine Husni, vice chair of rheumatology and director of the arthritis and musculoskeletal center at the Cleveland Clinic, said when she was asked to comment on the results of both studies.

Dr. Neogi reported having no conflicts of interest. Dr. Dalbeth said that her study was funded in part by the Fonterra Dairy Cooperative, and that one of the study authors was an employee of Fonterra.

Elsevier Global Medical News

PHILADELPHIA — Drinking water or skim milk can improve gout control, according to findings from two studies that highlight the important contribution of lifestyle factors on gout prevention and management.

“Our results show that drinking water is a simple, safe, and effective means of trying to reduce recurrent gout attacks,” Dr. Tuhina Neogi said at the annual meeting of the American College of Rheumatology.

The study included 535 people who had had a gout attack within the past year (78% male; mean age, 53 years) and who provided information via the Internet about food, drink, medications, physical activity, and other possible gout risk factors during periods preceding the attack and during attack-free periods. By using a case crossover study design, the participants acted as their own controls. Medical records were accessed to verify gout diagnosis, explained Dr. Neogi of Boston University.

The findings showed that increasing water intake was associated with decreased risk for recurrent gout attacks. Compared with those who drank no or one 8-ounce glass of water per day, those who drank five to eight glasses had a 40% lower chance of a gout attack and those who drank more than eight glasses had a 46% lower chance.

In the second study, researchers from New Zealand measured the acute effects of skim milk consumption on serum urate concentrations in 16 healthy male volunteers, in light of reports that skim milk was beneficial in gout prevention. The randomized controlled crossover study was designed to assess the effects of skim milk that was from the early season and the late season, as well as MPC85, a milk protein concentrate that contains 85% protein. The effects of soy milk consumption also were assessed, and it was considered the control.

“Late-season” skim milk, primarily available from countries where milking is seasonal and cows are grass fed, is high in orotic acid, a substance known to promote uric acid removal by the kidneys, explained Dr. Nicola Dalbeth, a senior lecturer in clinical medicine at the University of Auckland (New Zealand). MPC85 skim milk is ultrafiltered and contains very low concentrations of orotic acid, purines, and lactose.

Each participant received a single dose of each product in a random order, with each study visit separated by a week. The amount consumed was equal to about 3.5 8-ounce glasses of milk in one sitting (80 g of protein in 800 mL). Serum and urine were obtained immediately before ingestion and then hourly over the next 3 hours.

Drinking soy milk led to a 10% increase in serum urate. In contrast, all skim milks decreased serum urate by about 10% (P less than .0001). All products, including soy, led to an increase in the fractional excretion of uric acid (FEUA).

Interestingly, there were differences among the types of skim milk, which may shed light on the underlying mechanism. Late-season skim milk led to a greater increase in FEUA, compared with either ultrafiltered skim milk or early-season skim milk, suggesting that the acute urate-lowering effect of orotic acid may explain these effects.

“We cannot necessarily extrapolate these results from [healthy individuals] to those with gout,” Dr. Dalbeth acknowledged. “Furthermore, I am not saying drinking milk should replace allopurinol. But one of the key things we do is spend a lot of time telling people with gout what not to do, such as do not eat red meat. It is very useful to have some positive information.”

“Even though gout has been known since antiquity, and we have had treatments around for decades, it is not a well-managed disease. Medical management is still the cornerstone. Still, there are a lot of lifestyle and behavioral aspects that people with gout can do for themselves to reduce their risk,” Dr. M. Elaine Husni, vice chair of rheumatology and director of the arthritis and musculoskeletal center at the Cleveland Clinic, said when she was asked to comment on the results of both studies.

Dr. Neogi reported having no conflicts of interest. Dr. Dalbeth said that her study was funded in part by the Fonterra Dairy Cooperative, and that one of the study authors was an employee of Fonterra.

Elsevier Global Medical News

PHILADELPHIA — Drinking water or skim milk can improve gout control, according to findings from two studies that highlight the important contribution of lifestyle factors on gout prevention and management.

“Our results show that drinking water is a simple, safe, and effective means of trying to reduce recurrent gout attacks,” Dr. Tuhina Neogi said at the annual meeting of the American College of Rheumatology.

The study included 535 people who had had a gout attack within the past year (78% male; mean age, 53 years) and who provided information via the Internet about food, drink, medications, physical activity, and other possible gout risk factors during periods preceding the attack and during attack-free periods. By using a case crossover study design, the participants acted as their own controls. Medical records were accessed to verify gout diagnosis, explained Dr. Neogi of Boston University.

The findings showed that increasing water intake was associated with decreased risk for recurrent gout attacks. Compared with those who drank no or one 8-ounce glass of water per day, those who drank five to eight glasses had a 40% lower chance of a gout attack and those who drank more than eight glasses had a 46% lower chance.

In the second study, researchers from New Zealand measured the acute effects of skim milk consumption on serum urate concentrations in 16 healthy male volunteers, in light of reports that skim milk was beneficial in gout prevention. The randomized controlled crossover study was designed to assess the effects of skim milk that was from the early season and the late season, as well as MPC85, a milk protein concentrate that contains 85% protein. The effects of soy milk consumption also were assessed, and it was considered the control.

“Late-season” skim milk, primarily available from countries where milking is seasonal and cows are grass fed, is high in orotic acid, a substance known to promote uric acid removal by the kidneys, explained Dr. Nicola Dalbeth, a senior lecturer in clinical medicine at the University of Auckland (New Zealand). MPC85 skim milk is ultrafiltered and contains very low concentrations of orotic acid, purines, and lactose.

Each participant received a single dose of each product in a random order, with each study visit separated by a week. The amount consumed was equal to about 3.5 8-ounce glasses of milk in one sitting (80 g of protein in 800 mL). Serum and urine were obtained immediately before ingestion and then hourly over the next 3 hours.

Drinking soy milk led to a 10% increase in serum urate. In contrast, all skim milks decreased serum urate by about 10% (P less than .0001). All products, including soy, led to an increase in the fractional excretion of uric acid (FEUA).

Interestingly, there were differences among the types of skim milk, which may shed light on the underlying mechanism. Late-season skim milk led to a greater increase in FEUA, compared with either ultrafiltered skim milk or early-season skim milk, suggesting that the acute urate-lowering effect of orotic acid may explain these effects.

“We cannot necessarily extrapolate these results from [healthy individuals] to those with gout,” Dr. Dalbeth acknowledged. “Furthermore, I am not saying drinking milk should replace allopurinol. But one of the key things we do is spend a lot of time telling people with gout what not to do, such as do not eat red meat. It is very useful to have some positive information.”

“Even though gout has been known since antiquity, and we have had treatments around for decades, it is not a well-managed disease. Medical management is still the cornerstone. Still, there are a lot of lifestyle and behavioral aspects that people with gout can do for themselves to reduce their risk,” Dr. M. Elaine Husni, vice chair of rheumatology and director of the arthritis and musculoskeletal center at the Cleveland Clinic, said when she was asked to comment on the results of both studies.

Dr. Neogi reported having no conflicts of interest. Dr. Dalbeth said that her study was funded in part by the Fonterra Dairy Cooperative, and that one of the study authors was an employee of Fonterra.

Elsevier Global Medical News

PHILADELPHIA — Women's risk factors for developing gout are similar to those in men, and baseline serum levels of uric acid may be the most powerful predictor, findings from the Framingham Heart Study show.

Women with no clinical indication of gout but a serum uric acid level of 8.0 mg/dL or greater at baseline had a subsequent 2.7% rate of gout during an average 28 years of follow-up—a 46-fold higher rate than women with a serum uric acid level of less than 5 mg/dL at baseline, Dr. Vidula Bhole said at the annual meeting of the American College of Rheumatology.

Serum uric acid likewise posed a powerful risk in men. Those with a level of 8 mg/dL or more at baseline had a 3.3% incidence rate during follow-up, 61-fold higher than men who entered the study with a serum level below 5.0 mg/dL.

Even a baseline uric acid level of 5-5.9 mg/dL conferred a greater than threefold higher risk for developing gout in women and a greater than fourfold higher risk in men, compared with those whose level was under 5 mg/dL, said Dr. Bhole, an epidemiologist in the Arthritis Research Centre of Canada at the University of British Columbia in Vancouver. (See table.)

Dr. Bhole and her associates used prospectively collected data from the more than 5,000 residents of Framingham, Mass., who entered the Heart Study in 1948, at a baseline age of 29-62 years. Among the enrollees, 4,427 had no history of gout at entry and formed the focus for the new analysis.

The group included 2,476 women, with an average age of 47 years and an average serum uric acid level of 4.0 mg/dL. The group also included 1,967 men who entered at an average age of 46 years and a mean serum uric acid level of 5.1 mg/dL.

Average body mass index was 25 kg/m

The subjects developed 304 cases of gout during an average 28 years of follow-up, with an incidence rate of 1.4 cases/1,000 person-years of follow-up in the women and 4.0 cases/1,000 person years follow-up in the men.

An analysis of gout incidence rates relative to baseline serum uric acid showed that, for any baseline level, women developed less gout than men. For example, among people who entered the study with a serum level of 7.0-7.9 mg/dL, the subsequent incidence was 1.3% in women and 1.8% in men.

A multivariate analysis identified several baseline factors linked to a significantly higher rate of incident gout in both genders: age, obesity, heavy alcohol use, hypertension, and diuretic use.

Dr. Bhole said she had no relevant financial relationships. Two of her study colleagues received grant support from and served as consultants to Takeda. One of Dr. Bhole's associates also serves on the advisory board for Savient, a company developing a uric acid–lowering drug.

Age, obesity, and heavy alcohol and diuretic use were linked to a higher rate of incident gout in both genders.

Source DR. BHOLE

Elsevier Global Medical News

PHILADELPHIA — Women's risk factors for developing gout are similar to those in men, and baseline serum levels of uric acid may be the most powerful predictor, findings from the Framingham Heart Study show.

Women with no clinical indication of gout but a serum uric acid level of 8.0 mg/dL or greater at baseline had a subsequent 2.7% rate of gout during an average 28 years of follow-up—a 46-fold higher rate than women with a serum uric acid level of less than 5 mg/dL at baseline, Dr. Vidula Bhole said at the annual meeting of the American College of Rheumatology.

Serum uric acid likewise posed a powerful risk in men. Those with a level of 8 mg/dL or more at baseline had a 3.3% incidence rate during follow-up, 61-fold higher than men who entered the study with a serum level below 5.0 mg/dL.

Even a baseline uric acid level of 5-5.9 mg/dL conferred a greater than threefold higher risk for developing gout in women and a greater than fourfold higher risk in men, compared with those whose level was under 5 mg/dL, said Dr. Bhole, an epidemiologist in the Arthritis Research Centre of Canada at the University of British Columbia in Vancouver. (See table.)

Dr. Bhole and her associates used prospectively collected data from the more than 5,000 residents of Framingham, Mass., who entered the Heart Study in 1948, at a baseline age of 29-62 years. Among the enrollees, 4,427 had no history of gout at entry and formed the focus for the new analysis.

The group included 2,476 women, with an average age of 47 years and an average serum uric acid level of 4.0 mg/dL. The group also included 1,967 men who entered at an average age of 46 years and a mean serum uric acid level of 5.1 mg/dL.

Average body mass index was 25 kg/m

The subjects developed 304 cases of gout during an average 28 years of follow-up, with an incidence rate of 1.4 cases/1,000 person-years of follow-up in the women and 4.0 cases/1,000 person years follow-up in the men.

An analysis of gout incidence rates relative to baseline serum uric acid showed that, for any baseline level, women developed less gout than men. For example, among people who entered the study with a serum level of 7.0-7.9 mg/dL, the subsequent incidence was 1.3% in women and 1.8% in men.

A multivariate analysis identified several baseline factors linked to a significantly higher rate of incident gout in both genders: age, obesity, heavy alcohol use, hypertension, and diuretic use.

Dr. Bhole said she had no relevant financial relationships. Two of her study colleagues received grant support from and served as consultants to Takeda. One of Dr. Bhole's associates also serves on the advisory board for Savient, a company developing a uric acid–lowering drug.

Age, obesity, and heavy alcohol and diuretic use were linked to a higher rate of incident gout in both genders.

Source DR. BHOLE

Elsevier Global Medical News

PHILADELPHIA — Women's risk factors for developing gout are similar to those in men, and baseline serum levels of uric acid may be the most powerful predictor, findings from the Framingham Heart Study show.

Women with no clinical indication of gout but a serum uric acid level of 8.0 mg/dL or greater at baseline had a subsequent 2.7% rate of gout during an average 28 years of follow-up—a 46-fold higher rate than women with a serum uric acid level of less than 5 mg/dL at baseline, Dr. Vidula Bhole said at the annual meeting of the American College of Rheumatology.

Serum uric acid likewise posed a powerful risk in men. Those with a level of 8 mg/dL or more at baseline had a 3.3% incidence rate during follow-up, 61-fold higher than men who entered the study with a serum level below 5.0 mg/dL.

Even a baseline uric acid level of 5-5.9 mg/dL conferred a greater than threefold higher risk for developing gout in women and a greater than fourfold higher risk in men, compared with those whose level was under 5 mg/dL, said Dr. Bhole, an epidemiologist in the Arthritis Research Centre of Canada at the University of British Columbia in Vancouver. (See table.)

Dr. Bhole and her associates used prospectively collected data from the more than 5,000 residents of Framingham, Mass., who entered the Heart Study in 1948, at a baseline age of 29-62 years. Among the enrollees, 4,427 had no history of gout at entry and formed the focus for the new analysis.

The group included 2,476 women, with an average age of 47 years and an average serum uric acid level of 4.0 mg/dL. The group also included 1,967 men who entered at an average age of 46 years and a mean serum uric acid level of 5.1 mg/dL.

Average body mass index was 25 kg/m

The subjects developed 304 cases of gout during an average 28 years of follow-up, with an incidence rate of 1.4 cases/1,000 person-years of follow-up in the women and 4.0 cases/1,000 person years follow-up in the men.

An analysis of gout incidence rates relative to baseline serum uric acid showed that, for any baseline level, women developed less gout than men. For example, among people who entered the study with a serum level of 7.0-7.9 mg/dL, the subsequent incidence was 1.3% in women and 1.8% in men.

A multivariate analysis identified several baseline factors linked to a significantly higher rate of incident gout in both genders: age, obesity, heavy alcohol use, hypertension, and diuretic use.

Dr. Bhole said she had no relevant financial relationships. Two of her study colleagues received grant support from and served as consultants to Takeda. One of Dr. Bhole's associates also serves on the advisory board for Savient, a company developing a uric acid–lowering drug.

Age, obesity, and heavy alcohol and diuretic use were linked to a higher rate of incident gout in both genders.

Source DR. BHOLE

Elsevier Global Medical News

PHILADELPHIA —Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than was a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

“Although outcomes were presented for these pregnancies, I always caution health care providers and patients that these are ongoing studies with a target sample size that is intended to have sufficient power to answer our research questions. For that reason, we have not performed any formal interim statistical analysis nor have we adjusted for differences between groups, such as maternal smoking or folic acid use, that may affect pregnancy outcomes,” said Dr. Chambers of the department of pediatrics and family and preventive medicine at the University of California, San Diego.

OTIS is a prospective observational cohort study with the purpose of evaluating the effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment began in 2000 and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500.

Pregnant women are typically enrolled in the study before they reach 20 weeks of gestation. To be enrolled, the women must have current diagnoses of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease. Many participants are referred by their rheumatologists to the OTIS coordinating center, where they undergo multiple interviews and review of their symptom management. After birth, the infants are followed for up to a year, during which time they are assessed by their pediatricians, undergo blinded dysmorphological examination by OTIS physicians, and are photographed.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized controlled trial for obvious ethical reasons,” said Dr. Chambers. Although the literature contains case reports, the OTIS project is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared with 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls. The percentage of live births was higher in those treated with etanercept, compared with those with similar rheumatic diseases (92% vs. 85%), and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). There were no ectopic pregnancies in either group. One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%).

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls.

The defects included displaced stomach with epispa-dias and congenital eye defect; ventricular septal defect with peripheral pulmonic stenosis; pyloric stenosis; hypospadias; ventricular septal defect with patent foramen ovale and patent ductus arteriosus; volvulus; patent foramen ovale; atrial septal defect with patent ductus arteriosus; microcephaly; congenital hypothyroidism; and an unspecified heart defect. Three abnormalities—Noonan syndrome, Turner syndrome, and Down syndrome—were genetic or chromosomal. No cases of the malformation patterns VATER or VACTERL were found.

“Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” Dr. Chambers said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%) compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy (1%) cohorts. There were no ectopic pregnancies or stillbirths in the drug-treated group.

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups, compared with healthy controls (4%). Mean birth weight was approximately 300 g less in term infants whose mothers had received adalimumab, compared with healthy controls, but similar to term infants in the disease-matched comparison group. Rates of major malformations were similar (4% to 5%) in all groups and within the range of expected numbers in the general population, said Dr. Chambers.

“Firm conclusions await the accumulation of target sample size for adalimumab and etanercept and multivariate analysis.

“It is important to recognize that many differences between medication-exposed and comparison groups can be accounted for by other maternal risk factors, and so until these are addressed in multivariate analysis, we are dealing with very preliminary results. We also will be evaluating minor anomalies, 1-year growth, and developmental screening data,” Dr. Chambers said.

'Firm conclusions await the accumulation of target sample size' needed for multivariate analysis.

Source DR. CHAMBERS

PHILADELPHIA —Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than was a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

“Although outcomes were presented for these pregnancies, I always caution health care providers and patients that these are ongoing studies with a target sample size that is intended to have sufficient power to answer our research questions. For that reason, we have not performed any formal interim statistical analysis nor have we adjusted for differences between groups, such as maternal smoking or folic acid use, that may affect pregnancy outcomes,” said Dr. Chambers of the department of pediatrics and family and preventive medicine at the University of California, San Diego.

OTIS is a prospective observational cohort study with the purpose of evaluating the effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment began in 2000 and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500.

Pregnant women are typically enrolled in the study before they reach 20 weeks of gestation. To be enrolled, the women must have current diagnoses of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease. Many participants are referred by their rheumatologists to the OTIS coordinating center, where they undergo multiple interviews and review of their symptom management. After birth, the infants are followed for up to a year, during which time they are assessed by their pediatricians, undergo blinded dysmorphological examination by OTIS physicians, and are photographed.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized controlled trial for obvious ethical reasons,” said Dr. Chambers. Although the literature contains case reports, the OTIS project is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared with 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls. The percentage of live births was higher in those treated with etanercept, compared with those with similar rheumatic diseases (92% vs. 85%), and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). There were no ectopic pregnancies in either group. One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%).

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls.

The defects included displaced stomach with epispa-dias and congenital eye defect; ventricular septal defect with peripheral pulmonic stenosis; pyloric stenosis; hypospadias; ventricular septal defect with patent foramen ovale and patent ductus arteriosus; volvulus; patent foramen ovale; atrial septal defect with patent ductus arteriosus; microcephaly; congenital hypothyroidism; and an unspecified heart defect. Three abnormalities—Noonan syndrome, Turner syndrome, and Down syndrome—were genetic or chromosomal. No cases of the malformation patterns VATER or VACTERL were found.

“Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” Dr. Chambers said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%) compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy (1%) cohorts. There were no ectopic pregnancies or stillbirths in the drug-treated group.

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups, compared with healthy controls (4%). Mean birth weight was approximately 300 g less in term infants whose mothers had received adalimumab, compared with healthy controls, but similar to term infants in the disease-matched comparison group. Rates of major malformations were similar (4% to 5%) in all groups and within the range of expected numbers in the general population, said Dr. Chambers.

“Firm conclusions await the accumulation of target sample size for adalimumab and etanercept and multivariate analysis.

“It is important to recognize that many differences between medication-exposed and comparison groups can be accounted for by other maternal risk factors, and so until these are addressed in multivariate analysis, we are dealing with very preliminary results. We also will be evaluating minor anomalies, 1-year growth, and developmental screening data,” Dr. Chambers said.

'Firm conclusions await the accumulation of target sample size' needed for multivariate analysis.

Source DR. CHAMBERS

PHILADELPHIA —Women with rheumatic disease who took etanercept during pregnancy were three times more likely to have a child with a major malformation than was a disease-matched comparison group, judging from interim results from a small sample.

Most of the malformations were isolated, and no patterns of birth defect were apparent, according to Christina Chambers, Ph.D., who presented the findings from the Autoimmune Diseases in Pregnancy Project being conducted by the Organization of Teratology Information Specialists (OTIS) at the annual meeting of the American College of Rheumatology.

“Although outcomes were presented for these pregnancies, I always caution health care providers and patients that these are ongoing studies with a target sample size that is intended to have sufficient power to answer our research questions. For that reason, we have not performed any formal interim statistical analysis nor have we adjusted for differences between groups, such as maternal smoking or folic acid use, that may affect pregnancy outcomes,” said Dr. Chambers of the department of pediatrics and family and preventive medicine at the University of California, San Diego.

OTIS is a prospective observational cohort study with the purpose of evaluating the effects of autoimmune diseases and their treatment on pregnancy outcomes and fetal development. Recruitment began in 2000 and is projected to continue through 2015. Current recruitment stands at 944, with a goal of 1,500.

Pregnant women are typically enrolled in the study before they reach 20 weeks of gestation. To be enrolled, the women must have current diagnoses of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, or Crohn's disease. Many participants are referred by their rheumatologists to the OTIS coordinating center, where they undergo multiple interviews and review of their symptom management. After birth, the infants are followed for up to a year, during which time they are assessed by their pediatricians, undergo blinded dysmorphological examination by OTIS physicians, and are photographed.

“Evaluating pregnancy outcomes following medication exposure is a not a situation that lends itself to conducting a randomized controlled trial for obvious ethical reasons,” said Dr. Chambers. Although the literature contains case reports, the OTIS project is designed to give clinicians the evidence-based information they need to counsel patients who are pregnant or considering becoming pregnant.

At the time of this progress report, outcome was available for 115 women with RA who had been exposed to etanercept, compared with 55 disease-comparison controls. Outcome was available for 42 women with RA who were exposed to adalimumab, compared with 58 disease-matched women and 84 healthy controls. The percentage of live births was higher in those treated with etanercept, compared with those with similar rheumatic diseases (92% vs. 85%), and fewer spontaneous abortions occurred in the etanercept-treated group (4% vs. 11%). There were no ectopic pregnancies in either group. One stillbirth was reported in the etanercept cohort and none in the controls. Preterm deliveries were more common in women who were taking etanercept (23% vs. 13%).

Of the major malformations among all pregnancies enrolled in OTIS, 12% (14 of 114) were reported in the etanercept group, compared with 3.8% (2 of 53) in the disease-matched controls.

The defects included displaced stomach with epispa-dias and congenital eye defect; ventricular septal defect with peripheral pulmonic stenosis; pyloric stenosis; hypospadias; ventricular septal defect with patent foramen ovale and patent ductus arteriosus; volvulus; patent foramen ovale; atrial septal defect with patent ductus arteriosus; microcephaly; congenital hypothyroidism; and an unspecified heart defect. Three abnormalities—Noonan syndrome, Turner syndrome, and Down syndrome—were genetic or chromosomal. No cases of the malformation patterns VATER or VACTERL were found.

“Typically we would see a specific pattern of malformation with a medication that truly causes defects, but our results indicate that most of the defects were isolated with no apparent patterns,” Dr. Chambers said.

For those exposed to adalimumab, the percentage of live births was lower in those receiving the drug (88%) compared with those with similar autoimmune illnesses (93%) and healthy controls (92%). The rate of spontaneous abortions also was higher in the adalimumab-treated cohort (12%) compared with the disease-matched (5%) and healthy (1%) cohorts. There were no ectopic pregnancies or stillbirths in the drug-treated group.

Preterm delivery was higher in both the adalimumab-treated (14%) and disease-matched comparison (17%) groups, compared with healthy controls (4%). Mean birth weight was approximately 300 g less in term infants whose mothers had received adalimumab, compared with healthy controls, but similar to term infants in the disease-matched comparison group. Rates of major malformations were similar (4% to 5%) in all groups and within the range of expected numbers in the general population, said Dr. Chambers.

“Firm conclusions await the accumulation of target sample size for adalimumab and etanercept and multivariate analysis.

“It is important to recognize that many differences between medication-exposed and comparison groups can be accounted for by other maternal risk factors, and so until these are addressed in multivariate analysis, we are dealing with very preliminary results. We also will be evaluating minor anomalies, 1-year growth, and developmental screening data,” Dr. Chambers said.

'Firm conclusions await the accumulation of target sample size' needed for multivariate analysis.

Source DR. CHAMBERS

Epidemiology was the word of the day in a sampling of posters presented at the annual meeting of the American College of Rheumatology. Below are three posters that received a lot of attention at this year's meeting. The report on heart failure risk in rheumatoid arthritis was one of this year's blue ribbon–winning posters.

RA Severity Predicts Heart Failure

The risk for new-onset heart failure in patients with RA is greatest in patients with the most severe disease, Dr. Soko Setoguchi of Brigham and Women's Hospital in Boston and her associates reported. The research involves 8,483 patients whose RA was diagnosed by a rheumatologist and who were enrolled in the CORRONA (Consortium of Rheumatology Researchers of North America) registry. Patients were followed from the time of registry enrollment until Dec. 15, 2006, or death, whichever happened sooner. Patients' mean age was 59 years, 75% were female, 93% were white, 15% were current smokers, and their mean body mass index was 29 kg/m

Women's RA Risk Is Twice Men's

The lifetime risk for RA has remained “remarkably stable” during 1945-1995, according to Cynthia S. Crowson and her associates from the Mayo Clinic in Olmsted, Minn. For men, the lifetime risk is 1.8%; for women, it ranges from 3.4% to 3.7%. This stability occurred despite a gradual decrease in the incidence of RA from 1955 to the mid-1980s. More recently, women are experiencing an increased incidence, whereas that of men remains steady. The investigators used participants in the population-based incident cohort of Olmsted County who fulfilled the 1987 ACR criteria for RA between 1995 and 2005. These findings come from Poisson regression analyses performed to calculate the observed incidence rate in each sex. Calling the lifetime risk “significant” and women's higher lifetime risk “substantial,” the investigators noted an additional worry in their poster: The lifetime risk may be even higher in some subgroups with high-risk genotypes. This research was funded by the National Institutes of Health.

Uveitis Incidence Established in AS

Noninfectious uveitis is more than 20 times more common in patients with ankylosing spondylitis than in the general population, judging from findings presented by Shelagh M. Szabo of Oxford Outcomes in Vancouver, B.C., and colleagues. Using longitudinal physician billing data from Quebec province, the investigators calculated that 7,663 people were diagnosed with AS between 1998 and 2006 (the AS 1 group); another 3,006 people were diagnosed with AS during that time period and were seen for a related visit at least once during the next year (AS 2). The AS 1 group was designed to maximize sensitivity and the AS 2 group to maximize specificity. The AS 1 patients may have had milder disease. The investigators used a 1% random sample of unaffected individuals from Quebec (the population of which was 7.6 million in 2006) as the control group. The crude 10-year incidence of noninfectious uveitis in the AS 1 patients was 368 cases per 10,000 persons; for the AS 2 group, it was 482 cases per 10,000 persons; in the control group, the incidence was 21 cases per 10,000 persons. The standardized incidence ratio (SIR) for uveitis development during the study period was 18.04 for those in AS 1 vs. the controls. The SIR was 23.88 for those in the AS 2 group vs. controls. Age played a significant factor in incidence, with those in the 20- to 39-year-old age group having the largest risk. In the AS 1 group, the uveitis incidence was 53 cases per 1,000 persons in those aged 20-39 years vs. 33 per 1,000 for those aged 40-59 years, and 8 per 1,000 for those aged 60 years or older. In the AS 2 group, the uveitis incidence was 69 per 1,000 persons in those aged 20-39 years vs. 40 per 1,000 persons for those aged 40-59 years, and 13 per 1,000 for those aged 60 years or older. Several of the researchers were employed by Abbott Laboratories.

Epidemiology was the word of the day in a sampling of posters presented at the annual meeting of the American College of Rheumatology. Below are three posters that received a lot of attention at this year's meeting. The report on heart failure risk in rheumatoid arthritis was one of this year's blue ribbon–winning posters.

RA Severity Predicts Heart Failure

The risk for new-onset heart failure in patients with RA is greatest in patients with the most severe disease, Dr. Soko Setoguchi of Brigham and Women's Hospital in Boston and her associates reported. The research involves 8,483 patients whose RA was diagnosed by a rheumatologist and who were enrolled in the CORRONA (Consortium of Rheumatology Researchers of North America) registry. Patients were followed from the time of registry enrollment until Dec. 15, 2006, or death, whichever happened sooner. Patients' mean age was 59 years, 75% were female, 93% were white, 15% were current smokers, and their mean body mass index was 29 kg/m

Women's RA Risk Is Twice Men's

The lifetime risk for RA has remained “remarkably stable” during 1945-1995, according to Cynthia S. Crowson and her associates from the Mayo Clinic in Olmsted, Minn. For men, the lifetime risk is 1.8%; for women, it ranges from 3.4% to 3.7%. This stability occurred despite a gradual decrease in the incidence of RA from 1955 to the mid-1980s. More recently, women are experiencing an increased incidence, whereas that of men remains steady. The investigators used participants in the population-based incident cohort of Olmsted County who fulfilled the 1987 ACR criteria for RA between 1995 and 2005. These findings come from Poisson regression analyses performed to calculate the observed incidence rate in each sex. Calling the lifetime risk “significant” and women's higher lifetime risk “substantial,” the investigators noted an additional worry in their poster: The lifetime risk may be even higher in some subgroups with high-risk genotypes. This research was funded by the National Institutes of Health.

Uveitis Incidence Established in AS

Noninfectious uveitis is more than 20 times more common in patients with ankylosing spondylitis than in the general population, judging from findings presented by Shelagh M. Szabo of Oxford Outcomes in Vancouver, B.C., and colleagues. Using longitudinal physician billing data from Quebec province, the investigators calculated that 7,663 people were diagnosed with AS between 1998 and 2006 (the AS 1 group); another 3,006 people were diagnosed with AS during that time period and were seen for a related visit at least once during the next year (AS 2). The AS 1 group was designed to maximize sensitivity and the AS 2 group to maximize specificity. The AS 1 patients may have had milder disease. The investigators used a 1% random sample of unaffected individuals from Quebec (the population of which was 7.6 million in 2006) as the control group. The crude 10-year incidence of noninfectious uveitis in the AS 1 patients was 368 cases per 10,000 persons; for the AS 2 group, it was 482 cases per 10,000 persons; in the control group, the incidence was 21 cases per 10,000 persons. The standardized incidence ratio (SIR) for uveitis development during the study period was 18.04 for those in AS 1 vs. the controls. The SIR was 23.88 for those in the AS 2 group vs. controls. Age played a significant factor in incidence, with those in the 20- to 39-year-old age group having the largest risk. In the AS 1 group, the uveitis incidence was 53 cases per 1,000 persons in those aged 20-39 years vs. 33 per 1,000 for those aged 40-59 years, and 8 per 1,000 for those aged 60 years or older. In the AS 2 group, the uveitis incidence was 69 per 1,000 persons in those aged 20-39 years vs. 40 per 1,000 persons for those aged 40-59 years, and 13 per 1,000 for those aged 60 years or older. Several of the researchers were employed by Abbott Laboratories.

Epidemiology was the word of the day in a sampling of posters presented at the annual meeting of the American College of Rheumatology. Below are three posters that received a lot of attention at this year's meeting. The report on heart failure risk in rheumatoid arthritis was one of this year's blue ribbon–winning posters.

RA Severity Predicts Heart Failure

The risk for new-onset heart failure in patients with RA is greatest in patients with the most severe disease, Dr. Soko Setoguchi of Brigham and Women's Hospital in Boston and her associates reported. The research involves 8,483 patients whose RA was diagnosed by a rheumatologist and who were enrolled in the CORRONA (Consortium of Rheumatology Researchers of North America) registry. Patients were followed from the time of registry enrollment until Dec. 15, 2006, or death, whichever happened sooner. Patients' mean age was 59 years, 75% were female, 93% were white, 15% were current smokers, and their mean body mass index was 29 kg/m

Women's RA Risk Is Twice Men's

The lifetime risk for RA has remained “remarkably stable” during 1945-1995, according to Cynthia S. Crowson and her associates from the Mayo Clinic in Olmsted, Minn. For men, the lifetime risk is 1.8%; for women, it ranges from 3.4% to 3.7%. This stability occurred despite a gradual decrease in the incidence of RA from 1955 to the mid-1980s. More recently, women are experiencing an increased incidence, whereas that of men remains steady. The investigators used participants in the population-based incident cohort of Olmsted County who fulfilled the 1987 ACR criteria for RA between 1995 and 2005. These findings come from Poisson regression analyses performed to calculate the observed incidence rate in each sex. Calling the lifetime risk “significant” and women's higher lifetime risk “substantial,” the investigators noted an additional worry in their poster: The lifetime risk may be even higher in some subgroups with high-risk genotypes. This research was funded by the National Institutes of Health.

Uveitis Incidence Established in AS

Noninfectious uveitis is more than 20 times more common in patients with ankylosing spondylitis than in the general population, judging from findings presented by Shelagh M. Szabo of Oxford Outcomes in Vancouver, B.C., and colleagues. Using longitudinal physician billing data from Quebec province, the investigators calculated that 7,663 people were diagnosed with AS between 1998 and 2006 (the AS 1 group); another 3,006 people were diagnosed with AS during that time period and were seen for a related visit at least once during the next year (AS 2). The AS 1 group was designed to maximize sensitivity and the AS 2 group to maximize specificity. The AS 1 patients may have had milder disease. The investigators used a 1% random sample of unaffected individuals from Quebec (the population of which was 7.6 million in 2006) as the control group. The crude 10-year incidence of noninfectious uveitis in the AS 1 patients was 368 cases per 10,000 persons; for the AS 2 group, it was 482 cases per 10,000 persons; in the control group, the incidence was 21 cases per 10,000 persons. The standardized incidence ratio (SIR) for uveitis development during the study period was 18.04 for those in AS 1 vs. the controls. The SIR was 23.88 for those in the AS 2 group vs. controls. Age played a significant factor in incidence, with those in the 20- to 39-year-old age group having the largest risk. In the AS 1 group, the uveitis incidence was 53 cases per 1,000 persons in those aged 20-39 years vs. 33 per 1,000 for those aged 40-59 years, and 8 per 1,000 for those aged 60 years or older. In the AS 2 group, the uveitis incidence was 69 per 1,000 persons in those aged 20-39 years vs. 40 per 1,000 persons for those aged 40-59 years, and 13 per 1,000 for those aged 60 years or older. Several of the researchers were employed by Abbott Laboratories.

The cardiovascular risks associated with rofecoxib (Vioxx) would have been apparent in 2001, more than 3 years before the drug was withdrawn from the market, had data from unpublished trials been disclosed, according to a report.

The data “have only now become available through litigation” against Merck & Co., the manufacturer of Vioxx, said Dr. Joseph S. Ross of Mount Sinai School of Medicine, New York, and his associates.

“These findings are particularly compelling because as early as the late 1990s there were concerns about cardiovascular risk that emerged in the drug development process,” the investigators noted (Arch. Intern. Med. 2009;169:1976-85).

Merck & Co. disavowed the research. “We believe the analysis published in Archives used flawed methods and reached incorrect conclusions,” Merck spokesman Ron Rogers said in an interview. The study notes that all of the study authors are or were consultants for plaintiffs in litigation against Merck regarding rofecoxib.

The researchers analyzed data from 30 randomized clinical trials that had already been completed by September 2004, when the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial was terminated and rofecoxib was voluntarily withdrawn from the market, in response to reports of adverse cardiovascular effects.

Dr. Ross and his colleagues assessed only studies that compared a daily dose of 12.5 mg or more of rofecoxib with placebo in adults who were treated for at least 4 weeks. A total of 17,256 subjects were included.

Six of these trials were unpublished and came to light only as a result of litigation. “Therefore, data representing 36% of patients studied in placebo-controlled trials prior to APPROVe” had never been disclosed or included in safety analyses, the investigators said.

If all these data had been analyzed, the use of rofecoxib would have been seen to be associated with a 43% increase in risk of a cardiovascular thromboembolic event or death, according to the investigators.

The cardiovascular risks associated with rofecoxib (Vioxx) would have been apparent in 2001, more than 3 years before the drug was withdrawn from the market, had data from unpublished trials been disclosed, according to a report.

The data “have only now become available through litigation” against Merck & Co., the manufacturer of Vioxx, said Dr. Joseph S. Ross of Mount Sinai School of Medicine, New York, and his associates.

“These findings are particularly compelling because as early as the late 1990s there were concerns about cardiovascular risk that emerged in the drug development process,” the investigators noted (Arch. Intern. Med. 2009;169:1976-85).

Merck & Co. disavowed the research. “We believe the analysis published in Archives used flawed methods and reached incorrect conclusions,” Merck spokesman Ron Rogers said in an interview. The study notes that all of the study authors are or were consultants for plaintiffs in litigation against Merck regarding rofecoxib.

The researchers analyzed data from 30 randomized clinical trials that had already been completed by September 2004, when the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial was terminated and rofecoxib was voluntarily withdrawn from the market, in response to reports of adverse cardiovascular effects.

Dr. Ross and his colleagues assessed only studies that compared a daily dose of 12.5 mg or more of rofecoxib with placebo in adults who were treated for at least 4 weeks. A total of 17,256 subjects were included.

Six of these trials were unpublished and came to light only as a result of litigation. “Therefore, data representing 36% of patients studied in placebo-controlled trials prior to APPROVe” had never been disclosed or included in safety analyses, the investigators said.

If all these data had been analyzed, the use of rofecoxib would have been seen to be associated with a 43% increase in risk of a cardiovascular thromboembolic event or death, according to the investigators.

The cardiovascular risks associated with rofecoxib (Vioxx) would have been apparent in 2001, more than 3 years before the drug was withdrawn from the market, had data from unpublished trials been disclosed, according to a report.

The data “have only now become available through litigation” against Merck & Co., the manufacturer of Vioxx, said Dr. Joseph S. Ross of Mount Sinai School of Medicine, New York, and his associates.

“These findings are particularly compelling because as early as the late 1990s there were concerns about cardiovascular risk that emerged in the drug development process,” the investigators noted (Arch. Intern. Med. 2009;169:1976-85).

Merck & Co. disavowed the research. “We believe the analysis published in Archives used flawed methods and reached incorrect conclusions,” Merck spokesman Ron Rogers said in an interview. The study notes that all of the study authors are or were consultants for plaintiffs in litigation against Merck regarding rofecoxib.

The researchers analyzed data from 30 randomized clinical trials that had already been completed by September 2004, when the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial was terminated and rofecoxib was voluntarily withdrawn from the market, in response to reports of adverse cardiovascular effects.

Dr. Ross and his colleagues assessed only studies that compared a daily dose of 12.5 mg or more of rofecoxib with placebo in adults who were treated for at least 4 weeks. A total of 17,256 subjects were included.

Six of these trials were unpublished and came to light only as a result of litigation. “Therefore, data representing 36% of patients studied in placebo-controlled trials prior to APPROVe” had never been disclosed or included in safety analyses, the investigators said.

If all these data had been analyzed, the use of rofecoxib would have been seen to be associated with a 43% increase in risk of a cardiovascular thromboembolic event or death, according to the investigators.

PHILADELPHIA — Treatment with golimumab reversed structural joint damage in patients with psoriatic arthritis in a placebo-controlled, phase III study with about 400 patients.

The structural joint benefit from golimumab in this analysis complemented clinical improvements previously reported from the same study. Those benefits led the Food and Drug Administration to give marketing approval to golimumab for psoriatic arthritis (PsA) last April.

The results showed structural improvement with golimumab after 24 weeks of treatment (the primary end point of the radiographic assessment), independent of methotrexate co-treatment. The benefit continued through 52 weeks of follow-up, Dr. Arthur F. Kavanaugh said at the annual meeting of the American College of Rheumatology.

The GO-REVEAL (Golimumab—A Randomized Evaluation of Safety and Efficacy in Subjects With Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody) study enrolled patients at 58 sites in the United States, Canada, and Europe. It was the largest completed study of its kind (405 patients) with a biologic agent in patients with PsA. Subjects had active disease despite treatment with DMARDs or NSAIDs. Their average age was 47 years, their average duration of PsA was 8 years, 60% were men, 97% were white, and 48% were on methotrexate treatment.

Patients received subcutaneous injections of 50 mg golimumab (146 patients), 100 mg golimumab (146 patients), or placebo (113 patients) at week 0, and then every 4 weeks through week 20. Starting at week 24, all patients received golimumab.

The clinical outcomes published last April showed that treatment with golimumab led to an ACR 20 response in 51% of patients on the 50-mg dose and in 45% of those receiving a 100-mg dose at week 14, compared with 9% of placebo patients, which were statistically significant differences for the primary end point (Arthritis Rheum. 2009;60:976-86).

Golimumab treatment also produced significant improvements, compared with placebo, on a psoriatic index and other measures of clinical response.

The new analysis used total Sharp/van der Heijde scores to measure structural joint damage. At baseline, average scores were 18 in placebo patients, 24 in the 50-mg group, and 23 in the 100-mg group. After 24 weeks, the scores changed by an average of +0.27 in the placebo patients (a worsening), −0.16 in patients getting 50-mg doses, and −0.02 in those on 100-mg doses. The difference between the 50-mg group and placebo patients was statistically significant.

The difference between the 100-mg and placebo group did not reach statistical significance, said Dr. Kavanaugh, a rheumatologist and professor of clinical medicine at the University of California, San Diego.

The difference in average Sharp/van der Heijde scores between the placebo patients and those in both golimumab groups continued through 52 weeks of treatment, even though the placebo patients switched to golimumab treatment after the first 24 weeks of the study.

Another radiographic outcome—the percentage of patients with clear progression on their Sharp/van der Heijde scores—tallied 8% in the placebo group and 2% in the 50-mg group, a statistically significant difference.

Centocor Ortho Biotech Products LP, the company that developed and markets golimumab (Simponi), sponsored the study. Dr. Kavanaugh said that he and five of his associates on the study were researcher investigators for Centocor. Another five associates are Centocor employees.

The results showed structural improvement with golimumab after 24 weeks of treatment, the primary end point.

Source DR. KAVANAUGH

PHILADELPHIA — Treatment with golimumab reversed structural joint damage in patients with psoriatic arthritis in a placebo-controlled, phase III study with about 400 patients.

The structural joint benefit from golimumab in this analysis complemented clinical improvements previously reported from the same study. Those benefits led the Food and Drug Administration to give marketing approval to golimumab for psoriatic arthritis (PsA) last April.

The results showed structural improvement with golimumab after 24 weeks of treatment (the primary end point of the radiographic assessment), independent of methotrexate co-treatment. The benefit continued through 52 weeks of follow-up, Dr. Arthur F. Kavanaugh said at the annual meeting of the American College of Rheumatology.

The GO-REVEAL (Golimumab—A Randomized Evaluation of Safety and Efficacy in Subjects With Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody) study enrolled patients at 58 sites in the United States, Canada, and Europe. It was the largest completed study of its kind (405 patients) with a biologic agent in patients with PsA. Subjects had active disease despite treatment with DMARDs or NSAIDs. Their average age was 47 years, their average duration of PsA was 8 years, 60% were men, 97% were white, and 48% were on methotrexate treatment.

Patients received subcutaneous injections of 50 mg golimumab (146 patients), 100 mg golimumab (146 patients), or placebo (113 patients) at week 0, and then every 4 weeks through week 20. Starting at week 24, all patients received golimumab.

The clinical outcomes published last April showed that treatment with golimumab led to an ACR 20 response in 51% of patients on the 50-mg dose and in 45% of those receiving a 100-mg dose at week 14, compared with 9% of placebo patients, which were statistically significant differences for the primary end point (Arthritis Rheum. 2009;60:976-86).

Golimumab treatment also produced significant improvements, compared with placebo, on a psoriatic index and other measures of clinical response.

The new analysis used total Sharp/van der Heijde scores to measure structural joint damage. At baseline, average scores were 18 in placebo patients, 24 in the 50-mg group, and 23 in the 100-mg group. After 24 weeks, the scores changed by an average of +0.27 in the placebo patients (a worsening), −0.16 in patients getting 50-mg doses, and −0.02 in those on 100-mg doses. The difference between the 50-mg group and placebo patients was statistically significant.

The difference between the 100-mg and placebo group did not reach statistical significance, said Dr. Kavanaugh, a rheumatologist and professor of clinical medicine at the University of California, San Diego.

The difference in average Sharp/van der Heijde scores between the placebo patients and those in both golimumab groups continued through 52 weeks of treatment, even though the placebo patients switched to golimumab treatment after the first 24 weeks of the study.

Another radiographic outcome—the percentage of patients with clear progression on their Sharp/van der Heijde scores—tallied 8% in the placebo group and 2% in the 50-mg group, a statistically significant difference.

Centocor Ortho Biotech Products LP, the company that developed and markets golimumab (Simponi), sponsored the study. Dr. Kavanaugh said that he and five of his associates on the study were researcher investigators for Centocor. Another five associates are Centocor employees.

The results showed structural improvement with golimumab after 24 weeks of treatment, the primary end point.

Source DR. KAVANAUGH

PHILADELPHIA — Treatment with golimumab reversed structural joint damage in patients with psoriatic arthritis in a placebo-controlled, phase III study with about 400 patients.

The structural joint benefit from golimumab in this analysis complemented clinical improvements previously reported from the same study. Those benefits led the Food and Drug Administration to give marketing approval to golimumab for psoriatic arthritis (PsA) last April.

The results showed structural improvement with golimumab after 24 weeks of treatment (the primary end point of the radiographic assessment), independent of methotrexate co-treatment. The benefit continued through 52 weeks of follow-up, Dr. Arthur F. Kavanaugh said at the annual meeting of the American College of Rheumatology.

The GO-REVEAL (Golimumab—A Randomized Evaluation of Safety and Efficacy in Subjects With Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody) study enrolled patients at 58 sites in the United States, Canada, and Europe. It was the largest completed study of its kind (405 patients) with a biologic agent in patients with PsA. Subjects had active disease despite treatment with DMARDs or NSAIDs. Their average age was 47 years, their average duration of PsA was 8 years, 60% were men, 97% were white, and 48% were on methotrexate treatment.

Patients received subcutaneous injections of 50 mg golimumab (146 patients), 100 mg golimumab (146 patients), or placebo (113 patients) at week 0, and then every 4 weeks through week 20. Starting at week 24, all patients received golimumab.

The clinical outcomes published last April showed that treatment with golimumab led to an ACR 20 response in 51% of patients on the 50-mg dose and in 45% of those receiving a 100-mg dose at week 14, compared with 9% of placebo patients, which were statistically significant differences for the primary end point (Arthritis Rheum. 2009;60:976-86).

Golimumab treatment also produced significant improvements, compared with placebo, on a psoriatic index and other measures of clinical response.

The new analysis used total Sharp/van der Heijde scores to measure structural joint damage. At baseline, average scores were 18 in placebo patients, 24 in the 50-mg group, and 23 in the 100-mg group. After 24 weeks, the scores changed by an average of +0.27 in the placebo patients (a worsening), −0.16 in patients getting 50-mg doses, and −0.02 in those on 100-mg doses. The difference between the 50-mg group and placebo patients was statistically significant.

The difference between the 100-mg and placebo group did not reach statistical significance, said Dr. Kavanaugh, a rheumatologist and professor of clinical medicine at the University of California, San Diego.

The difference in average Sharp/van der Heijde scores between the placebo patients and those in both golimumab groups continued through 52 weeks of treatment, even though the placebo patients switched to golimumab treatment after the first 24 weeks of the study.

Another radiographic outcome—the percentage of patients with clear progression on their Sharp/van der Heijde scores—tallied 8% in the placebo group and 2% in the 50-mg group, a statistically significant difference.

Centocor Ortho Biotech Products LP, the company that developed and markets golimumab (Simponi), sponsored the study. Dr. Kavanaugh said that he and five of his associates on the study were researcher investigators for Centocor. Another five associates are Centocor employees.

The results showed structural improvement with golimumab after 24 weeks of treatment, the primary end point.

Source DR. KAVANAUGH

PHILADELPHIA — The increased atherosclerotic disease that generally accompanies rheumatoid arthritis may not consistently involve carotid artery stenosis, according to two reports at the annual meeting of the American College of Rheumatology.

In a study with 195 RA patients and a nearly equal number of controls, carotid atherosclerosis was not clearly linked with coronary atherosclerosis in RA patients, although the link existed in controls, said Dr. Jon T. Giles, a rheumatologist at Johns Hopkins Medical Center in Baltimore.

Results from a second study, a meta-analysis of 22 prior reports in a total of 1,384 RA patients, showed that the average extent of carotid intima-media thickness was “far less than expected.” Patients' average carotid stenosis corresponded to about a 10%–15% increase in cardiovascular risk, compared with similar people without RA, said Dr. Michael T. Nurmohamed, a rheumatologist at the Free University Medical Center in Amsterdam.

But the relationship between RA and carotid disease is more complex, according to a second set of results reported by Dr. Nurmohamed. Preliminary results from measurement of carotid intima-media thickness in 100 patients with RA showed a mean thickness of 0.83 mm, which is “comparable” to the carotid thickness in patients with type 2 diabetes—and enough stenosis to produce “a significantly increased cardiovascular risk,” Dr. Nurmohamed said.

“For now, there is no recommendation on how to measure” subclinical cardiovascular disease, Dr. Giles said in an interview. No one can say whether measuring coronary disease is better or worse than measuring carotid atherosclerosis. If an RA patient “does not have carotid atherosclerosis, you can't be comfortable that nothing is going on,” he said.

The study he reported included 195 RA patients who were seen at the arthritis center at Johns Hopkins during October 2004–May 2008 and were enrolled in the ESCAPE-RA (Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis) study. Patients were 45–84 years old at enrollment and met the 1987 ACR classification criteria for RA.

Enrollment excluded patients with clinically apparent cardiovascular disease, including those with a history of MI, heart failure, stroke, and peripheral vascular disease. For this analysis, RA patients were matched by age, sex, and ethnicity with 198 controls who did not have RA and who had been enrolled in the Baltimore cohort of MESA (Multi-Ethnic Study of Atherosclerosis). Carotid intima-media thickness was measured by B-mode ultrasound, and coronary calcium was measured by multidetector row CT. The results showed that carotid stenosis was linked to a high level of coronary calcium in both RA patients and controls. But many RA patients without carotid atherosclerosis nonetheless had an increased prevalence of coronary calcium, an incongruous combination that was not seen in the controls.

“The absence of carotid atherosclerosis cannot rule out coronary atherosclerosis in RA patients in the same way that it does in the general population,” Dr. Giles said. The implication is that “using subclinical carotid atherosclerosis as a surrogate for coronary atherosclerosis in studies of RA patients may be inaccurate.”

The meta-analysis of 22 studies by Dr. Nurmohamed and his associates involved a total of 1,147 controls and more than 1,300 RA patients. In 17 of the studies, the carotid intima-media thickness was greater in the RA patients than in the controls. But the average intima-media thickness in the RA patients was 0.71 mm, an average of 0.09 mm larger than in the controls, a difference that corresponds to a modest 10%–15% higher rate of cardiovascular risk. The low risk level may have occurred because the studies excluded people with cardiovascular disease or risk factors at baseline, a step that may have led to an underestimate of the difference in carotid intima-media thickness between the RA patients and controls.

The carotid data collected directly by Dr. Nurmohamed and his associates came from the CARRÉ (Cardiovascular Research and Rheumatoid Arthritis) study. A report from CARRÉ showed the substantially higher level of cardiovascular disease events in 294 patients with RA (13%), compared with 258 controls (5%) (Ann. Rheum. Dis. 2009;68:1395–400). So far, Dr. Nurmohamed and his associates have measured the carotid intima-media thickness in 100 of these RA patients. In this preliminary assessment, the average intima-media thickness in RA patients was 0.83 mm, a level high enough to produce a significant risk for cardiovascular events. The carotid atherosclerosis in RA patients showed no link with inflammatory parameters or with disease duration, Dr. Nurmohamed said. Additional prospective, controlled studies are needed to further define the cardiovascular disease risk in RA patients, he added.

Neither Dr. Giles nor Dr. Nurmohamed has any disclosures relevant to their research to report.

RA patients' carotid stenosis corresponded with 'a significantly increased cardiovascular risk.'

Source DR. NURMOHAMED

PHILADELPHIA — The increased atherosclerotic disease that generally accompanies rheumatoid arthritis may not consistently involve carotid artery stenosis, according to two reports at the annual meeting of the American College of Rheumatology.

In a study with 195 RA patients and a nearly equal number of controls, carotid atherosclerosis was not clearly linked with coronary atherosclerosis in RA patients, although the link existed in controls, said Dr. Jon T. Giles, a rheumatologist at Johns Hopkins Medical Center in Baltimore.

Results from a second study, a meta-analysis of 22 prior reports in a total of 1,384 RA patients, showed that the average extent of carotid intima-media thickness was “far less than expected.” Patients' average carotid stenosis corresponded to about a 10%–15% increase in cardiovascular risk, compared with similar people without RA, said Dr. Michael T. Nurmohamed, a rheumatologist at the Free University Medical Center in Amsterdam.

But the relationship between RA and carotid disease is more complex, according to a second set of results reported by Dr. Nurmohamed. Preliminary results from measurement of carotid intima-media thickness in 100 patients with RA showed a mean thickness of 0.83 mm, which is “comparable” to the carotid thickness in patients with type 2 diabetes—and enough stenosis to produce “a significantly increased cardiovascular risk,” Dr. Nurmohamed said.

“For now, there is no recommendation on how to measure” subclinical cardiovascular disease, Dr. Giles said in an interview. No one can say whether measuring coronary disease is better or worse than measuring carotid atherosclerosis. If an RA patient “does not have carotid atherosclerosis, you can't be comfortable that nothing is going on,” he said.

The study he reported included 195 RA patients who were seen at the arthritis center at Johns Hopkins during October 2004–May 2008 and were enrolled in the ESCAPE-RA (Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis) study. Patients were 45–84 years old at enrollment and met the 1987 ACR classification criteria for RA.

Enrollment excluded patients with clinically apparent cardiovascular disease, including those with a history of MI, heart failure, stroke, and peripheral vascular disease. For this analysis, RA patients were matched by age, sex, and ethnicity with 198 controls who did not have RA and who had been enrolled in the Baltimore cohort of MESA (Multi-Ethnic Study of Atherosclerosis). Carotid intima-media thickness was measured by B-mode ultrasound, and coronary calcium was measured by multidetector row CT. The results showed that carotid stenosis was linked to a high level of coronary calcium in both RA patients and controls. But many RA patients without carotid atherosclerosis nonetheless had an increased prevalence of coronary calcium, an incongruous combination that was not seen in the controls.

“The absence of carotid atherosclerosis cannot rule out coronary atherosclerosis in RA patients in the same way that it does in the general population,” Dr. Giles said. The implication is that “using subclinical carotid atherosclerosis as a surrogate for coronary atherosclerosis in studies of RA patients may be inaccurate.”

The meta-analysis of 22 studies by Dr. Nurmohamed and his associates involved a total of 1,147 controls and more than 1,300 RA patients. In 17 of the studies, the carotid intima-media thickness was greater in the RA patients than in the controls. But the average intima-media thickness in the RA patients was 0.71 mm, an average of 0.09 mm larger than in the controls, a difference that corresponds to a modest 10%–15% higher rate of cardiovascular risk. The low risk level may have occurred because the studies excluded people with cardiovascular disease or risk factors at baseline, a step that may have led to an underestimate of the difference in carotid intima-media thickness between the RA patients and controls.

The carotid data collected directly by Dr. Nurmohamed and his associates came from the CARRÉ (Cardiovascular Research and Rheumatoid Arthritis) study. A report from CARRÉ showed the substantially higher level of cardiovascular disease events in 294 patients with RA (13%), compared with 258 controls (5%) (Ann. Rheum. Dis. 2009;68:1395–400). So far, Dr. Nurmohamed and his associates have measured the carotid intima-media thickness in 100 of these RA patients. In this preliminary assessment, the average intima-media thickness in RA patients was 0.83 mm, a level high enough to produce a significant risk for cardiovascular events. The carotid atherosclerosis in RA patients showed no link with inflammatory parameters or with disease duration, Dr. Nurmohamed said. Additional prospective, controlled studies are needed to further define the cardiovascular disease risk in RA patients, he added.

Neither Dr. Giles nor Dr. Nurmohamed has any disclosures relevant to their research to report.

RA patients' carotid stenosis corresponded with 'a significantly increased cardiovascular risk.'

Source DR. NURMOHAMED

PHILADELPHIA — The increased atherosclerotic disease that generally accompanies rheumatoid arthritis may not consistently involve carotid artery stenosis, according to two reports at the annual meeting of the American College of Rheumatology.

In a study with 195 RA patients and a nearly equal number of controls, carotid atherosclerosis was not clearly linked with coronary atherosclerosis in RA patients, although the link existed in controls, said Dr. Jon T. Giles, a rheumatologist at Johns Hopkins Medical Center in Baltimore.

Results from a second study, a meta-analysis of 22 prior reports in a total of 1,384 RA patients, showed that the average extent of carotid intima-media thickness was “far less than expected.” Patients' average carotid stenosis corresponded to about a 10%–15% increase in cardiovascular risk, compared with similar people without RA, said Dr. Michael T. Nurmohamed, a rheumatologist at the Free University Medical Center in Amsterdam.

But the relationship between RA and carotid disease is more complex, according to a second set of results reported by Dr. Nurmohamed. Preliminary results from measurement of carotid intima-media thickness in 100 patients with RA showed a mean thickness of 0.83 mm, which is “comparable” to the carotid thickness in patients with type 2 diabetes—and enough stenosis to produce “a significantly increased cardiovascular risk,” Dr. Nurmohamed said.

“For now, there is no recommendation on how to measure” subclinical cardiovascular disease, Dr. Giles said in an interview. No one can say whether measuring coronary disease is better or worse than measuring carotid atherosclerosis. If an RA patient “does not have carotid atherosclerosis, you can't be comfortable that nothing is going on,” he said.

The study he reported included 195 RA patients who were seen at the arthritis center at Johns Hopkins during October 2004–May 2008 and were enrolled in the ESCAPE-RA (Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis) study. Patients were 45–84 years old at enrollment and met the 1987 ACR classification criteria for RA.

Enrollment excluded patients with clinically apparent cardiovascular disease, including those with a history of MI, heart failure, stroke, and peripheral vascular disease. For this analysis, RA patients were matched by age, sex, and ethnicity with 198 controls who did not have RA and who had been enrolled in the Baltimore cohort of MESA (Multi-Ethnic Study of Atherosclerosis). Carotid intima-media thickness was measured by B-mode ultrasound, and coronary calcium was measured by multidetector row CT. The results showed that carotid stenosis was linked to a high level of coronary calcium in both RA patients and controls. But many RA patients without carotid atherosclerosis nonetheless had an increased prevalence of coronary calcium, an incongruous combination that was not seen in the controls.

“The absence of carotid atherosclerosis cannot rule out coronary atherosclerosis in RA patients in the same way that it does in the general population,” Dr. Giles said. The implication is that “using subclinical carotid atherosclerosis as a surrogate for coronary atherosclerosis in studies of RA patients may be inaccurate.”

The meta-analysis of 22 studies by Dr. Nurmohamed and his associates involved a total of 1,147 controls and more than 1,300 RA patients. In 17 of the studies, the carotid intima-media thickness was greater in the RA patients than in the controls. But the average intima-media thickness in the RA patients was 0.71 mm, an average of 0.09 mm larger than in the controls, a difference that corresponds to a modest 10%–15% higher rate of cardiovascular risk. The low risk level may have occurred because the studies excluded people with cardiovascular disease or risk factors at baseline, a step that may have led to an underestimate of the difference in carotid intima-media thickness between the RA patients and controls.

The carotid data collected directly by Dr. Nurmohamed and his associates came from the CARRÉ (Cardiovascular Research and Rheumatoid Arthritis) study. A report from CARRÉ showed the substantially higher level of cardiovascular disease events in 294 patients with RA (13%), compared with 258 controls (5%) (Ann. Rheum. Dis. 2009;68:1395–400). So far, Dr. Nurmohamed and his associates have measured the carotid intima-media thickness in 100 of these RA patients. In this preliminary assessment, the average intima-media thickness in RA patients was 0.83 mm, a level high enough to produce a significant risk for cardiovascular events. The carotid atherosclerosis in RA patients showed no link with inflammatory parameters or with disease duration, Dr. Nurmohamed said. Additional prospective, controlled studies are needed to further define the cardiovascular disease risk in RA patients, he added.

Neither Dr. Giles nor Dr. Nurmohamed has any disclosures relevant to their research to report.

RA patients' carotid stenosis corresponded with 'a significantly increased cardiovascular risk.'

Source DR. NURMOHAMED

Rituximab seems to be the most effective biologic disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis, according to a Cochrane systematic review of the literature. Anakinra appeared to be the least effective of the agents evaluated.

All six biologics studied provided clinically important improvement in pain and disability. However, the degree of relief differed among the agents, which also included abatacept, adalimumab, etanercept, and infliximab.

Absolute improvement (defined as ACR 50) was reported in 51% more people on rituximab than on placebo. Compared with those taking placebo, 42% more people taking adalimumab achieved that level of improvement, as did 40% more people taking etanercept, 26% more people taking abatacept, 24% more people taking infliximab, and 6% more people on anakinra, according to the report's authors, who are all members of the Cochrane Musculoskeletal Group and were led by Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

People on abatacept, etanercept, or rituximab were no more likely than those on placebo to drop out of the trial because of side effects. For infliximab, the absolute difference of people who dropped out of the trial, compared with placebo, was 6%; for anakinra, that difference was 4%; and for adalimumab, that difference was 3%.

The researchers searched the Cochrane Database of Systematic Reviews for literature reviews with the term “rheumatoid” in the title that had concluded by May 20, 2009; included at least one randomized, controlled trial; had clinically relevant outcomes; and included clear inclusion and exclusion criteria for studies. Only trials of adults were considered. The review was limited to studies of standard rheumatoid arthritis dosing regimens of the six agents, used either alone or in combination with another biologic or conventional DMARD, compared with either placebo alone or placebo plus a biologic or conventional DMARD.

Primary outcomes were ACR 50 and withdrawal because of any adverse event. Six reviews were included in this overview. The biologic DMARDs included in this review were abatacept (seven studies), adalimumab (eight studies), anakinra (five studies), etanercept (four studies), infliximab (three studies), and rituximab (three studies) (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007848.pub2])

The six biologic DMARDs in this overview had similar efficacy for primary outcomes with three exceptions: Anakinra was less effective than etanercept (relative risk, 0.44) and less effective than rituximab (RR, 0.45), and adalimumab was more efficacious than anakinra (RR, 2.34).

In terms of safety, adalimumab was more likely to lead to withdrawal, compared with etanercept (odds ratio, 1.89); anakinra was more likely than etanercept (OR, 2.05), and etanercept was less likely to lead to withdrawal for side effects than was infliximab (OR, 0.37).

Dr. Singh reported receiving speaker honoraria from Abbott Laboratories; research grants from Amgen Inc., Allergan Inc., Takeda Pharmaceutical Co., and Savient Pharmaceuticals Inc.; and a consultant fee from Savient.

Rituximab seems to be the most effective biologic disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis, according to a Cochrane systematic review of the literature. Anakinra appeared to be the least effective of the agents evaluated.

All six biologics studied provided clinically important improvement in pain and disability. However, the degree of relief differed among the agents, which also included abatacept, adalimumab, etanercept, and infliximab.

Absolute improvement (defined as ACR 50) was reported in 51% more people on rituximab than on placebo. Compared with those taking placebo, 42% more people taking adalimumab achieved that level of improvement, as did 40% more people taking etanercept, 26% more people taking abatacept, 24% more people taking infliximab, and 6% more people on anakinra, according to the report's authors, who are all members of the Cochrane Musculoskeletal Group and were led by Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

People on abatacept, etanercept, or rituximab were no more likely than those on placebo to drop out of the trial because of side effects. For infliximab, the absolute difference of people who dropped out of the trial, compared with placebo, was 6%; for anakinra, that difference was 4%; and for adalimumab, that difference was 3%.

The researchers searched the Cochrane Database of Systematic Reviews for literature reviews with the term “rheumatoid” in the title that had concluded by May 20, 2009; included at least one randomized, controlled trial; had clinically relevant outcomes; and included clear inclusion and exclusion criteria for studies. Only trials of adults were considered. The review was limited to studies of standard rheumatoid arthritis dosing regimens of the six agents, used either alone or in combination with another biologic or conventional DMARD, compared with either placebo alone or placebo plus a biologic or conventional DMARD.

Primary outcomes were ACR 50 and withdrawal because of any adverse event. Six reviews were included in this overview. The biologic DMARDs included in this review were abatacept (seven studies), adalimumab (eight studies), anakinra (five studies), etanercept (four studies), infliximab (three studies), and rituximab (three studies) (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007848.pub2])

The six biologic DMARDs in this overview had similar efficacy for primary outcomes with three exceptions: Anakinra was less effective than etanercept (relative risk, 0.44) and less effective than rituximab (RR, 0.45), and adalimumab was more efficacious than anakinra (RR, 2.34).

In terms of safety, adalimumab was more likely to lead to withdrawal, compared with etanercept (odds ratio, 1.89); anakinra was more likely than etanercept (OR, 2.05), and etanercept was less likely to lead to withdrawal for side effects than was infliximab (OR, 0.37).

Dr. Singh reported receiving speaker honoraria from Abbott Laboratories; research grants from Amgen Inc., Allergan Inc., Takeda Pharmaceutical Co., and Savient Pharmaceuticals Inc.; and a consultant fee from Savient.

Rituximab seems to be the most effective biologic disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis, according to a Cochrane systematic review of the literature. Anakinra appeared to be the least effective of the agents evaluated.

All six biologics studied provided clinically important improvement in pain and disability. However, the degree of relief differed among the agents, which also included abatacept, adalimumab, etanercept, and infliximab.

Absolute improvement (defined as ACR 50) was reported in 51% more people on rituximab than on placebo. Compared with those taking placebo, 42% more people taking adalimumab achieved that level of improvement, as did 40% more people taking etanercept, 26% more people taking abatacept, 24% more people taking infliximab, and 6% more people on anakinra, according to the report's authors, who are all members of the Cochrane Musculoskeletal Group and were led by Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

People on abatacept, etanercept, or rituximab were no more likely than those on placebo to drop out of the trial because of side effects. For infliximab, the absolute difference of people who dropped out of the trial, compared with placebo, was 6%; for anakinra, that difference was 4%; and for adalimumab, that difference was 3%.

The researchers searched the Cochrane Database of Systematic Reviews for literature reviews with the term “rheumatoid” in the title that had concluded by May 20, 2009; included at least one randomized, controlled trial; had clinically relevant outcomes; and included clear inclusion and exclusion criteria for studies. Only trials of adults were considered. The review was limited to studies of standard rheumatoid arthritis dosing regimens of the six agents, used either alone or in combination with another biologic or conventional DMARD, compared with either placebo alone or placebo plus a biologic or conventional DMARD.

Primary outcomes were ACR 50 and withdrawal because of any adverse event. Six reviews were included in this overview. The biologic DMARDs included in this review were abatacept (seven studies), adalimumab (eight studies), anakinra (five studies), etanercept (four studies), infliximab (three studies), and rituximab (three studies) (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007848.pub2])

The six biologic DMARDs in this overview had similar efficacy for primary outcomes with three exceptions: Anakinra was less effective than etanercept (relative risk, 0.44) and less effective than rituximab (RR, 0.45), and adalimumab was more efficacious than anakinra (RR, 2.34).

In terms of safety, adalimumab was more likely to lead to withdrawal, compared with etanercept (odds ratio, 1.89); anakinra was more likely than etanercept (OR, 2.05), and etanercept was less likely to lead to withdrawal for side effects than was infliximab (OR, 0.37).

Dr. Singh reported receiving speaker honoraria from Abbott Laboratories; research grants from Amgen Inc., Allergan Inc., Takeda Pharmaceutical Co., and Savient Pharmaceuticals Inc.; and a consultant fee from Savient.

PHILADELPHIA — Septic arthritis was twice as common in patients taking anti–tumor necrosis factor drugs for rheumatoid arthritis as in patients with the disease who did not take anti-TNFs.

However, the results may not be fully translatable to a U.S. population of RA patients, according to Dr. Deborah P. Symmons, who presented the findings during a press briefing at the annual meeting of the American College of Rheumatology.

In the United Kingdom, she explained, patients must have failed two disease-modifying antirheumatic drugs and have a high disease activity score in order to be eligible for treatment with TNF blockers. “Those people may have more serious disease” than do those in the United States, said Dr. Symmons, professor of rheumatology and musculoskeletal epidemiology at the University of Manchester (England).

Dr. Symmons and her associates studied the records of 11,757 RA patients from the British Society for Rheumatology Biologics Register who received anti-TNF drugs from October 2001 through May 2008. Patients were followed for 6 months or until death. Septic arthritis was counted in all patients who received that diagnosis either while taking anti-TNFs or within 90 days of their last dose. The control group was 3,515 patients with active RA who were taking only DMARDs.

According to Dr. Symmons, 179 cases of septic arthritis that met study criteria occurred during the study period, for an incident rate of 1 per 200 patients (5 cases per 1,000 patient-years). In contrast, among the DMARD-only control group, there were 17 cases of septic arthritis, for an incidence of 1.9 cases per 1,000 patient-years.

That amounted to a hazard ratio for contracting septic arthritis of 2.0 for the anti-TNF patients, compared with controls (95% confidence interval, 1.1–3.5) after adjustment for age, sex, disease severity, prior joint replacement, comorbidity, and steroid use.

Additionally, the investigators reported that 51% of septic arthritis cases occurred in patients' “native” joints (that is, not prosthetic joints), which are generally considered to have a higher risk of septic arthritis. However, “in both groups, having a replaced joint increased the patient's risk for an infection, but that risk was not further increased by use of an anti-TNF drug,” said Dr. Symmons.

The risk was highest with the use of etanercept, compared with infliximab and adalimumab. Staphylococcus bacteria made up 50% of infection in the DMARD group, and fully 75% of infections in the anti-TNF group.

Dr. Symmons reported affiliation with the British Society for Rheumatology. The researchers wrote that they had no other conflicts to disclose.

Use of an anti-TNF agent did not increase the risk of septic arthritis more than did having a prosthetic knee.

Source DR. SYMMONS

PHILADELPHIA — Septic arthritis was twice as common in patients taking anti–tumor necrosis factor drugs for rheumatoid arthritis as in patients with the disease who did not take anti-TNFs.

However, the results may not be fully translatable to a U.S. population of RA patients, according to Dr. Deborah P. Symmons, who presented the findings during a press briefing at the annual meeting of the American College of Rheumatology.

In the United Kingdom, she explained, patients must have failed two disease-modifying antirheumatic drugs and have a high disease activity score in order to be eligible for treatment with TNF blockers. “Those people may have more serious disease” than do those in the United States, said Dr. Symmons, professor of rheumatology and musculoskeletal epidemiology at the University of Manchester (England).

Dr. Symmons and her associates studied the records of 11,757 RA patients from the British Society for Rheumatology Biologics Register who received anti-TNF drugs from October 2001 through May 2008. Patients were followed for 6 months or until death. Septic arthritis was counted in all patients who received that diagnosis either while taking anti-TNFs or within 90 days of their last dose. The control group was 3,515 patients with active RA who were taking only DMARDs.

According to Dr. Symmons, 179 cases of septic arthritis that met study criteria occurred during the study period, for an incident rate of 1 per 200 patients (5 cases per 1,000 patient-years). In contrast, among the DMARD-only control group, there were 17 cases of septic arthritis, for an incidence of 1.9 cases per 1,000 patient-years.

That amounted to a hazard ratio for contracting septic arthritis of 2.0 for the anti-TNF patients, compared with controls (95% confidence interval, 1.1–3.5) after adjustment for age, sex, disease severity, prior joint replacement, comorbidity, and steroid use.

Additionally, the investigators reported that 51% of septic arthritis cases occurred in patients' “native” joints (that is, not prosthetic joints), which are generally considered to have a higher risk of septic arthritis. However, “in both groups, having a replaced joint increased the patient's risk for an infection, but that risk was not further increased by use of an anti-TNF drug,” said Dr. Symmons.

The risk was highest with the use of etanercept, compared with infliximab and adalimumab. Staphylococcus bacteria made up 50% of infection in the DMARD group, and fully 75% of infections in the anti-TNF group.

Dr. Symmons reported affiliation with the British Society for Rheumatology. The researchers wrote that they had no other conflicts to disclose.

Use of an anti-TNF agent did not increase the risk of septic arthritis more than did having a prosthetic knee.

Source DR. SYMMONS

PHILADELPHIA — Septic arthritis was twice as common in patients taking anti–tumor necrosis factor drugs for rheumatoid arthritis as in patients with the disease who did not take anti-TNFs.

However, the results may not be fully translatable to a U.S. population of RA patients, according to Dr. Deborah P. Symmons, who presented the findings during a press briefing at the annual meeting of the American College of Rheumatology.

In the United Kingdom, she explained, patients must have failed two disease-modifying antirheumatic drugs and have a high disease activity score in order to be eligible for treatment with TNF blockers. “Those people may have more serious disease” than do those in the United States, said Dr. Symmons, professor of rheumatology and musculoskeletal epidemiology at the University of Manchester (England).

Dr. Symmons and her associates studied the records of 11,757 RA patients from the British Society for Rheumatology Biologics Register who received anti-TNF drugs from October 2001 through May 2008. Patients were followed for 6 months or until death. Septic arthritis was counted in all patients who received that diagnosis either while taking anti-TNFs or within 90 days of their last dose. The control group was 3,515 patients with active RA who were taking only DMARDs.

According to Dr. Symmons, 179 cases of septic arthritis that met study criteria occurred during the study period, for an incident rate of 1 per 200 patients (5 cases per 1,000 patient-years). In contrast, among the DMARD-only control group, there were 17 cases of septic arthritis, for an incidence of 1.9 cases per 1,000 patient-years.

That amounted to a hazard ratio for contracting septic arthritis of 2.0 for the anti-TNF patients, compared with controls (95% confidence interval, 1.1–3.5) after adjustment for age, sex, disease severity, prior joint replacement, comorbidity, and steroid use.

Additionally, the investigators reported that 51% of septic arthritis cases occurred in patients' “native” joints (that is, not prosthetic joints), which are generally considered to have a higher risk of septic arthritis. However, “in both groups, having a replaced joint increased the patient's risk for an infection, but that risk was not further increased by use of an anti-TNF drug,” said Dr. Symmons.

The risk was highest with the use of etanercept, compared with infliximab and adalimumab. Staphylococcus bacteria made up 50% of infection in the DMARD group, and fully 75% of infections in the anti-TNF group.

Dr. Symmons reported affiliation with the British Society for Rheumatology. The researchers wrote that they had no other conflicts to disclose.

Use of an anti-TNF agent did not increase the risk of septic arthritis more than did having a prosthetic knee.

Source DR. SYMMONS

Abatacept has been shown to be an effective biologic agent for use in the treatment of rheumatoid arthritis, according to findings of a Cochrane review of seven studies involving almost 3,000 patients.

Of the 2,908 patients in this review, 1,863 were randomized to abatacept and 1,045 to placebo. Most were white women, and their average age was 48–56 years, depending on the trial. Most trials used a dose of 10 mg/kg of abatacept, and patients continued to use a disease-modifying antirheumatic drug in addition to abatacept for the duration of the study, according to the review's authors, Lara Maxwell of the University of Ottawa and Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

Patients treated with abatacept were 2.2 times more likely than those on placebo to have an ACR 50 response (the primary end point) at the end of year 1 (relative risk, 2.21). There was a 21% absolute risk difference between the two groups. The number needed to achieve an ACR 50 was five patients.

Physical function significantly improved and both disease activity and pain lessened in patients who were treated with abatacept, compared with placebo.

Findings from one of the seven randomized, controlled trials in the review showed that abatacept significantly slowed radiographic progression of joint damage at 12 months, compared with placebo. However, it is unclear whether that finding had any clinical relevance. The other six studies did not assess ra-diographic progression.

The rate of adverse events was greater in abatacept-treated patients than in those on placebo (RR, 1.05). The number of infections after 12 months was significantly greater in the abatacept group vs. the placebo group (Peto odds ratio, 1.91). Serious adverse events were increased when abatacept was used in combination with other biologics (RR, 2.3), an observation that led the authors to recommend that abatacept should not be used in combination with other biologics to treat RA.

Of the seven studies included in the review, only two were free of any risk of bias arising from flawed methodology. Four of the seven did not address incomplete efficacy outcome data; two of those four also did not address incomplete safety outcome data; and a fifth study provided unclear information on both adequate sequence generation and allocation concealment. In addition, because all the included trials were funded by abatacept's manufacturer, it is possible that the findings overestimated the treatment benefit, according to Ms. Maxwell and Dr. Singh (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858. D007277.pub2]).

The studies that were included in this Cochrane review were identified through an extensive literature search. The selected trials were all randomized, controlled studies evaluating the effectiveness and safety of abatacept either alone or in combination with a DMARD or another biologic, vs. placebo alone or a DMARD or biologic, in patients with moderate to severe RA.

The cost of 1 year of abatacept therapy is estimated to be approximately $22,000. The prevalence of RA among white adults aged older than 18 years in the United States is 0.6%.

Abatacept is the first biologic agent to work by disrupting T-cell activation. The drug is a selective costimulation modulator, inhibiting T-lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28.

All the trials included in this review were funded by Bristol-Myers Squibb Co., the manufacturer of abatacept.

The authors declared that they received financial support from the University of Ottawa and the Minneapolis VA Medical Center.

Abatacept has been shown to be an effective biologic agent for use in the treatment of rheumatoid arthritis, according to findings of a Cochrane review of seven studies involving almost 3,000 patients.

Of the 2,908 patients in this review, 1,863 were randomized to abatacept and 1,045 to placebo. Most were white women, and their average age was 48–56 years, depending on the trial. Most trials used a dose of 10 mg/kg of abatacept, and patients continued to use a disease-modifying antirheumatic drug in addition to abatacept for the duration of the study, according to the review's authors, Lara Maxwell of the University of Ottawa and Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

Patients treated with abatacept were 2.2 times more likely than those on placebo to have an ACR 50 response (the primary end point) at the end of year 1 (relative risk, 2.21). There was a 21% absolute risk difference between the two groups. The number needed to achieve an ACR 50 was five patients.

Physical function significantly improved and both disease activity and pain lessened in patients who were treated with abatacept, compared with placebo.

Findings from one of the seven randomized, controlled trials in the review showed that abatacept significantly slowed radiographic progression of joint damage at 12 months, compared with placebo. However, it is unclear whether that finding had any clinical relevance. The other six studies did not assess ra-diographic progression.

The rate of adverse events was greater in abatacept-treated patients than in those on placebo (RR, 1.05). The number of infections after 12 months was significantly greater in the abatacept group vs. the placebo group (Peto odds ratio, 1.91). Serious adverse events were increased when abatacept was used in combination with other biologics (RR, 2.3), an observation that led the authors to recommend that abatacept should not be used in combination with other biologics to treat RA.

Of the seven studies included in the review, only two were free of any risk of bias arising from flawed methodology. Four of the seven did not address incomplete efficacy outcome data; two of those four also did not address incomplete safety outcome data; and a fifth study provided unclear information on both adequate sequence generation and allocation concealment. In addition, because all the included trials were funded by abatacept's manufacturer, it is possible that the findings overestimated the treatment benefit, according to Ms. Maxwell and Dr. Singh (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858. D007277.pub2]).

The studies that were included in this Cochrane review were identified through an extensive literature search. The selected trials were all randomized, controlled studies evaluating the effectiveness and safety of abatacept either alone or in combination with a DMARD or another biologic, vs. placebo alone or a DMARD or biologic, in patients with moderate to severe RA.

The cost of 1 year of abatacept therapy is estimated to be approximately $22,000. The prevalence of RA among white adults aged older than 18 years in the United States is 0.6%.

Abatacept is the first biologic agent to work by disrupting T-cell activation. The drug is a selective costimulation modulator, inhibiting T-lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28.

All the trials included in this review were funded by Bristol-Myers Squibb Co., the manufacturer of abatacept.

The authors declared that they received financial support from the University of Ottawa and the Minneapolis VA Medical Center.

Abatacept has been shown to be an effective biologic agent for use in the treatment of rheumatoid arthritis, according to findings of a Cochrane review of seven studies involving almost 3,000 patients.

Of the 2,908 patients in this review, 1,863 were randomized to abatacept and 1,045 to placebo. Most were white women, and their average age was 48–56 years, depending on the trial. Most trials used a dose of 10 mg/kg of abatacept, and patients continued to use a disease-modifying antirheumatic drug in addition to abatacept for the duration of the study, according to the review's authors, Lara Maxwell of the University of Ottawa and Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

Patients treated with abatacept were 2.2 times more likely than those on placebo to have an ACR 50 response (the primary end point) at the end of year 1 (relative risk, 2.21). There was a 21% absolute risk difference between the two groups. The number needed to achieve an ACR 50 was five patients.

Physical function significantly improved and both disease activity and pain lessened in patients who were treated with abatacept, compared with placebo.

Findings from one of the seven randomized, controlled trials in the review showed that abatacept significantly slowed radiographic progression of joint damage at 12 months, compared with placebo. However, it is unclear whether that finding had any clinical relevance. The other six studies did not assess ra-diographic progression.

The rate of adverse events was greater in abatacept-treated patients than in those on placebo (RR, 1.05). The number of infections after 12 months was significantly greater in the abatacept group vs. the placebo group (Peto odds ratio, 1.91). Serious adverse events were increased when abatacept was used in combination with other biologics (RR, 2.3), an observation that led the authors to recommend that abatacept should not be used in combination with other biologics to treat RA.

Of the seven studies included in the review, only two were free of any risk of bias arising from flawed methodology. Four of the seven did not address incomplete efficacy outcome data; two of those four also did not address incomplete safety outcome data; and a fifth study provided unclear information on both adequate sequence generation and allocation concealment. In addition, because all the included trials were funded by abatacept's manufacturer, it is possible that the findings overestimated the treatment benefit, according to Ms. Maxwell and Dr. Singh (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858. D007277.pub2]).

The studies that were included in this Cochrane review were identified through an extensive literature search. The selected trials were all randomized, controlled studies evaluating the effectiveness and safety of abatacept either alone or in combination with a DMARD or another biologic, vs. placebo alone or a DMARD or biologic, in patients with moderate to severe RA.

The cost of 1 year of abatacept therapy is estimated to be approximately $22,000. The prevalence of RA among white adults aged older than 18 years in the United States is 0.6%.

Abatacept is the first biologic agent to work by disrupting T-cell activation. The drug is a selective costimulation modulator, inhibiting T-lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28.

All the trials included in this review were funded by Bristol-Myers Squibb Co., the manufacturer of abatacept.

The authors declared that they received financial support from the University of Ottawa and the Minneapolis VA Medical Center.