Rheumatoid Arthritis

Most patients with psoriatic arthritis fare better when remaining on a single tumor necrosis factor inhibitor than when switching to a second medication, Norwegian researchers have found.

Karen Fagerli, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital in Oslo, and her colleagues found that patients who switched tumor necrosis factor inhibitor (TNFi) medications had significantly poorer responses in factors like American College of Rheumatology-50 (ACR 50) response and Disease Activity Score-28 (DAS28) remission, compared with those who stayed on one TNFi. Drug-survival rates at 3 years also were lower among patients who changed medications (Ann. Rheum. Dis. 2013 April 5 [doi: 10.1136/annrheumdis-2012-203018]).

Because some (20%-40%) patients showed a response to a second TNFi at 3 months, "our results do not imply that a second TNFi should not be attempted in those who fail their first TNFi, but rather highlight the need for treatments with other mechanisms of action for patients with psoriatic arthritis," Dr. Fagerli and her colleagues wrote.

The investigators studied patient data from the observational NOR-DMARD study, a registry at five centers in Norway of all patients with inflammatory arthropathies starting disease-modifying antirheumatic drugs (DMARDs). Patients in the registry were assessed at baseline and 3, 6, and 12 months after starting treatment. They had annual follow-up visits thereafter.

The researchers included 439 patients with psoriatic arthritis who started their first TNFi between February 2001 and October 2011. They labeled the 95 patients who started a second TNFi as the "switchers," and the remaining 344 patients who stayed on one TNFi as the "nonswitchers." Researchers compared 3-month responses and 3-year drug-survival between switchers and nonswitchers, and within switchers. Among switchers, etanercept (Enbrel) was the most commonly prescribed first TNFi, and adalimumab (Humira) the most commonly prescribed second TNFi.

The switchers receiving their second TNFi had significantly poorer responses by 3 months than the nonswitchers: The ACR 50 response was 22.5% in switchers taking a second TNFi, versus 40% in nonswitchers, and DAS28 remission rates were 28% in switchers taking a second TNFi, versus 54% in nonswitchers.

Researchers also found a trend among the switchers toward poorer responses to the second TNFi, compared with the first. "The estimated 3-year drug-survival was 36% for the second TNFi, compared with 57% for the first TNFi overall," they wrote.

The investigators noted that the comparisons between switchers and nonswitchers could be biased by "some patients still having residual effects of their first TNFi when starting the second, ... but the pattern of poorer response to the second TNFi was consistent for both analytic approaches."

Even though the approach to evaluating effectiveness through the assessment of treatment completers "likely overestimates effectiveness due to discontinuations prior to assessment in poor responders," there was only a small difference in the rate of discontinuation prior to the 3-month assessment between the switchers, who had the poorest response, and the nonswitchers, the investigators said.

The study was supported by the Norwegian South Eastern Health Board. The NOR-DMARD study received funding from Abbott, Amgen, and other companies. Dr. Fagerli reported having received speaker’s honoraria from Abbott and Pfizer. Other authors reported financial ties to manufacturers of TNF inhibitors and other biologics.

Most patients with psoriatic arthritis fare better when remaining on a single tumor necrosis factor inhibitor than when switching to a second medication, Norwegian researchers have found.

Karen Fagerli, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital in Oslo, and her colleagues found that patients who switched tumor necrosis factor inhibitor (TNFi) medications had significantly poorer responses in factors like American College of Rheumatology-50 (ACR 50) response and Disease Activity Score-28 (DAS28) remission, compared with those who stayed on one TNFi. Drug-survival rates at 3 years also were lower among patients who changed medications (Ann. Rheum. Dis. 2013 April 5 [doi: 10.1136/annrheumdis-2012-203018]).

Because some (20%-40%) patients showed a response to a second TNFi at 3 months, "our results do not imply that a second TNFi should not be attempted in those who fail their first TNFi, but rather highlight the need for treatments with other mechanisms of action for patients with psoriatic arthritis," Dr. Fagerli and her colleagues wrote.

The investigators studied patient data from the observational NOR-DMARD study, a registry at five centers in Norway of all patients with inflammatory arthropathies starting disease-modifying antirheumatic drugs (DMARDs). Patients in the registry were assessed at baseline and 3, 6, and 12 months after starting treatment. They had annual follow-up visits thereafter.

The researchers included 439 patients with psoriatic arthritis who started their first TNFi between February 2001 and October 2011. They labeled the 95 patients who started a second TNFi as the "switchers," and the remaining 344 patients who stayed on one TNFi as the "nonswitchers." Researchers compared 3-month responses and 3-year drug-survival between switchers and nonswitchers, and within switchers. Among switchers, etanercept (Enbrel) was the most commonly prescribed first TNFi, and adalimumab (Humira) the most commonly prescribed second TNFi.

The switchers receiving their second TNFi had significantly poorer responses by 3 months than the nonswitchers: The ACR 50 response was 22.5% in switchers taking a second TNFi, versus 40% in nonswitchers, and DAS28 remission rates were 28% in switchers taking a second TNFi, versus 54% in nonswitchers.

Researchers also found a trend among the switchers toward poorer responses to the second TNFi, compared with the first. "The estimated 3-year drug-survival was 36% for the second TNFi, compared with 57% for the first TNFi overall," they wrote.

The investigators noted that the comparisons between switchers and nonswitchers could be biased by "some patients still having residual effects of their first TNFi when starting the second, ... but the pattern of poorer response to the second TNFi was consistent for both analytic approaches."

Even though the approach to evaluating effectiveness through the assessment of treatment completers "likely overestimates effectiveness due to discontinuations prior to assessment in poor responders," there was only a small difference in the rate of discontinuation prior to the 3-month assessment between the switchers, who had the poorest response, and the nonswitchers, the investigators said.

The study was supported by the Norwegian South Eastern Health Board. The NOR-DMARD study received funding from Abbott, Amgen, and other companies. Dr. Fagerli reported having received speaker’s honoraria from Abbott and Pfizer. Other authors reported financial ties to manufacturers of TNF inhibitors and other biologics.

Most patients with psoriatic arthritis fare better when remaining on a single tumor necrosis factor inhibitor than when switching to a second medication, Norwegian researchers have found.

Karen Fagerli, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital in Oslo, and her colleagues found that patients who switched tumor necrosis factor inhibitor (TNFi) medications had significantly poorer responses in factors like American College of Rheumatology-50 (ACR 50) response and Disease Activity Score-28 (DAS28) remission, compared with those who stayed on one TNFi. Drug-survival rates at 3 years also were lower among patients who changed medications (Ann. Rheum. Dis. 2013 April 5 [doi: 10.1136/annrheumdis-2012-203018]).

Because some (20%-40%) patients showed a response to a second TNFi at 3 months, "our results do not imply that a second TNFi should not be attempted in those who fail their first TNFi, but rather highlight the need for treatments with other mechanisms of action for patients with psoriatic arthritis," Dr. Fagerli and her colleagues wrote.

The investigators studied patient data from the observational NOR-DMARD study, a registry at five centers in Norway of all patients with inflammatory arthropathies starting disease-modifying antirheumatic drugs (DMARDs). Patients in the registry were assessed at baseline and 3, 6, and 12 months after starting treatment. They had annual follow-up visits thereafter.

The researchers included 439 patients with psoriatic arthritis who started their first TNFi between February 2001 and October 2011. They labeled the 95 patients who started a second TNFi as the "switchers," and the remaining 344 patients who stayed on one TNFi as the "nonswitchers." Researchers compared 3-month responses and 3-year drug-survival between switchers and nonswitchers, and within switchers. Among switchers, etanercept (Enbrel) was the most commonly prescribed first TNFi, and adalimumab (Humira) the most commonly prescribed second TNFi.

The switchers receiving their second TNFi had significantly poorer responses by 3 months than the nonswitchers: The ACR 50 response was 22.5% in switchers taking a second TNFi, versus 40% in nonswitchers, and DAS28 remission rates were 28% in switchers taking a second TNFi, versus 54% in nonswitchers.

Researchers also found a trend among the switchers toward poorer responses to the second TNFi, compared with the first. "The estimated 3-year drug-survival was 36% for the second TNFi, compared with 57% for the first TNFi overall," they wrote.

The investigators noted that the comparisons between switchers and nonswitchers could be biased by "some patients still having residual effects of their first TNFi when starting the second, ... but the pattern of poorer response to the second TNFi was consistent for both analytic approaches."

Even though the approach to evaluating effectiveness through the assessment of treatment completers "likely overestimates effectiveness due to discontinuations prior to assessment in poor responders," there was only a small difference in the rate of discontinuation prior to the 3-month assessment between the switchers, who had the poorest response, and the nonswitchers, the investigators said.

The study was supported by the Norwegian South Eastern Health Board. The NOR-DMARD study received funding from Abbott, Amgen, and other companies. Dr. Fagerli reported having received speaker’s honoraria from Abbott and Pfizer. Other authors reported financial ties to manufacturers of TNF inhibitors and other biologics.

NEW YORK – Patients with rheumatoid arthritis had significantly greater aortic wall inflammation than did control patients with coronary artery disease but without autoimmune disease in an 18- fluorodeoxyglucose PET imaging study. No differences in carotid artery wall inflammation were found between the groups.

"These results suggest that part of the risk of cardiovascular disease in rheumatoid arthritis patients may not only be from systemic inflammation but truly localized inflammation that is causing plaques to become more vulnerable, less stable, and more likely to rupture," said Dr. Jeffrey D. Greenberg, who presented the results of the cross-sectional comparison at the NYU Seminar in Advanced Rheumatology, sponsored by New York University.

It has been known for some time that rheumatoid arthritis (RA) patients have systemic inflammation as well as vascular inflammation and have an increased risk of cardiovascular-related death, according to Dr. Greenberg, associate director of clinical translational sciences in the division of rheumatology at New York University Langone Medical Center and the NYU Hospital for Joint Diseases. He cited multifactorial mechanisms by which RA patients may incur heightened cardiovascular risk, including traditional cardiovascular risk factors (altered lipid balance, impaired insulin sensitivity), abnormal endothelial function, and increased plaque vulnerability. He said that the results of this study demonstrate another factor – localized inflammation causing subclinical vasculitis in the aorta and perhaps coronary vessels.

Dr. Greenberg and his associates used a 10 mCi injection of 18-fluorodeoxyglucose (18-FDG) and PET imaging in two separate cohorts of patients, one consisting of 27 RA patients (aged 35-64 years) and another of 70 controls with coronary artery disease but without autoimmune disease (aged 41-76 years). The investigators determined vascular 18-FDG uptake by calculating target to background ratios (TBRs) that served as proxies for macrophage activity and inflammation in the vessel walls.

RA patients had significantly higher TBR scores than did controls for the aorta mean TBR (1.46 vs. 1.25; P less than .0001), aorta maximum TBR (2.08 vs. 1.75; P less than .0001) and the TBR of the most diseased segment of aorta (2.23 vs. 1.87; P = .0004). These values were adjusted for differences in age, gender, and body mass index between the groups in multivariate regression models. RA patients had mean disease duration of about 11 years and mean DAS28 of 4.6, with no history of coronary artery disease, myocardial infarction, or stroke.

The results of the study were presented previously at the 2012 ACR Annual Meeting.

Dr. Greenberg serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA) and Pfizer and holds an ownership interest in CORRONA. He also receives grant support from the American College of Rheumatology, the Arthritis National Research Foundation, the Agency for Healthcare Research and Quality, the National Institute for Arthritis, and Musculoskeletal and Skin Diseases, and the NYU Clinical and Translational Science Institute.

NEW YORK – Patients with rheumatoid arthritis had significantly greater aortic wall inflammation than did control patients with coronary artery disease but without autoimmune disease in an 18- fluorodeoxyglucose PET imaging study. No differences in carotid artery wall inflammation were found between the groups.

"These results suggest that part of the risk of cardiovascular disease in rheumatoid arthritis patients may not only be from systemic inflammation but truly localized inflammation that is causing plaques to become more vulnerable, less stable, and more likely to rupture," said Dr. Jeffrey D. Greenberg, who presented the results of the cross-sectional comparison at the NYU Seminar in Advanced Rheumatology, sponsored by New York University.

It has been known for some time that rheumatoid arthritis (RA) patients have systemic inflammation as well as vascular inflammation and have an increased risk of cardiovascular-related death, according to Dr. Greenberg, associate director of clinical translational sciences in the division of rheumatology at New York University Langone Medical Center and the NYU Hospital for Joint Diseases. He cited multifactorial mechanisms by which RA patients may incur heightened cardiovascular risk, including traditional cardiovascular risk factors (altered lipid balance, impaired insulin sensitivity), abnormal endothelial function, and increased plaque vulnerability. He said that the results of this study demonstrate another factor – localized inflammation causing subclinical vasculitis in the aorta and perhaps coronary vessels.

Dr. Greenberg and his associates used a 10 mCi injection of 18-fluorodeoxyglucose (18-FDG) and PET imaging in two separate cohorts of patients, one consisting of 27 RA patients (aged 35-64 years) and another of 70 controls with coronary artery disease but without autoimmune disease (aged 41-76 years). The investigators determined vascular 18-FDG uptake by calculating target to background ratios (TBRs) that served as proxies for macrophage activity and inflammation in the vessel walls.

RA patients had significantly higher TBR scores than did controls for the aorta mean TBR (1.46 vs. 1.25; P less than .0001), aorta maximum TBR (2.08 vs. 1.75; P less than .0001) and the TBR of the most diseased segment of aorta (2.23 vs. 1.87; P = .0004). These values were adjusted for differences in age, gender, and body mass index between the groups in multivariate regression models. RA patients had mean disease duration of about 11 years and mean DAS28 of 4.6, with no history of coronary artery disease, myocardial infarction, or stroke.

The results of the study were presented previously at the 2012 ACR Annual Meeting.

Dr. Greenberg serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA) and Pfizer and holds an ownership interest in CORRONA. He also receives grant support from the American College of Rheumatology, the Arthritis National Research Foundation, the Agency for Healthcare Research and Quality, the National Institute for Arthritis, and Musculoskeletal and Skin Diseases, and the NYU Clinical and Translational Science Institute.

NEW YORK – Patients with rheumatoid arthritis had significantly greater aortic wall inflammation than did control patients with coronary artery disease but without autoimmune disease in an 18- fluorodeoxyglucose PET imaging study. No differences in carotid artery wall inflammation were found between the groups.

"These results suggest that part of the risk of cardiovascular disease in rheumatoid arthritis patients may not only be from systemic inflammation but truly localized inflammation that is causing plaques to become more vulnerable, less stable, and more likely to rupture," said Dr. Jeffrey D. Greenberg, who presented the results of the cross-sectional comparison at the NYU Seminar in Advanced Rheumatology, sponsored by New York University.

It has been known for some time that rheumatoid arthritis (RA) patients have systemic inflammation as well as vascular inflammation and have an increased risk of cardiovascular-related death, according to Dr. Greenberg, associate director of clinical translational sciences in the division of rheumatology at New York University Langone Medical Center and the NYU Hospital for Joint Diseases. He cited multifactorial mechanisms by which RA patients may incur heightened cardiovascular risk, including traditional cardiovascular risk factors (altered lipid balance, impaired insulin sensitivity), abnormal endothelial function, and increased plaque vulnerability. He said that the results of this study demonstrate another factor – localized inflammation causing subclinical vasculitis in the aorta and perhaps coronary vessels.

Dr. Greenberg and his associates used a 10 mCi injection of 18-fluorodeoxyglucose (18-FDG) and PET imaging in two separate cohorts of patients, one consisting of 27 RA patients (aged 35-64 years) and another of 70 controls with coronary artery disease but without autoimmune disease (aged 41-76 years). The investigators determined vascular 18-FDG uptake by calculating target to background ratios (TBRs) that served as proxies for macrophage activity and inflammation in the vessel walls.

RA patients had significantly higher TBR scores than did controls for the aorta mean TBR (1.46 vs. 1.25; P less than .0001), aorta maximum TBR (2.08 vs. 1.75; P less than .0001) and the TBR of the most diseased segment of aorta (2.23 vs. 1.87; P = .0004). These values were adjusted for differences in age, gender, and body mass index between the groups in multivariate regression models. RA patients had mean disease duration of about 11 years and mean DAS28 of 4.6, with no history of coronary artery disease, myocardial infarction, or stroke.

The results of the study were presented previously at the 2012 ACR Annual Meeting.

Dr. Greenberg serves as a consultant to the Consortium of Rheumatology Researchers of North America Inc. (CORRONA) and Pfizer and holds an ownership interest in CORRONA. He also receives grant support from the American College of Rheumatology, the Arthritis National Research Foundation, the Agency for Healthcare Research and Quality, the National Institute for Arthritis, and Musculoskeletal and Skin Diseases, and the NYU Clinical and Translational Science Institute.

Use of all glucocorticoids is associated with a two- to threefold increased risk of venous thromboembolism, depending on the type of glucocorticoid, the route of administration, and other factors, according to a report published online April 1 in JAMA Internal Medicine.

Systemic glucocorticoids, as compared with inhaled ones or glucocorticoids that act on the intestines, were associated with the highest risk of VTE. New use was linked to higher risk than continuing or past use, and the VTE risk increased as the dose of glucocorticoids increased, said Sigrun A. Johannesdottir of the department of clinical epidemiology, Aarhus (the Netherlands) University Hospital, and her associates.

These findings are from a population-based case-control study, which cannot prove a cause-and-effect relationship. Moreover, it is difficult to statistically account for all the confounding effects of patients’ underlying disease – the reason they were taking glucocorticoids in the first place – because such disorders raise the risk of VTE directly or cause immobility that in turn can lead to VTE.

However, the timing of this adverse effect, the strength of the association across all types of glucocorticoids, and the fact that the association persisted after the data were adjusted to account for multiple confounders all "increase our confidence that the results reflect a true biological effect," the investigators said.

"Clinicians should be aware of this association," they noted.

Ms. Johannesdottir and her colleagues used data from several Danish national medical registries to identify all adults who were diagnosed with VTE in Denmark in 2005-2012, all patients who filled prescriptions for glucocorticoids during the study period, and all indications for the drugs as well as all relevant comorbidities. They matched 10 control subjects for age and sex from the general population to each study subject.

A total of 38,765 VTE cases and 387,650 controls were included in this study. The median age was 67 years, and slightly more than half of those studied were women.

All glucocorticoid users were found to be at increased risk for VTE, particularly for pulmonary embolism, compared with nonusers, the researchers said.

Systemic glucocorticoids, including betamethasone, methylprednisolone, prednisolone, prednisone, triamcinolone, and hydrocortisone, raised VTE risk to the highest degree. (No patients filled prescriptions for dexamethasone in this study.)

Inhaled corticosteroids and corticosteroids that act on the intestines also raised VTE risk significantly. Among the systemic glucocorticoids, prednisolone and prednisone raised VTE risk the most.

New use of glucocorticoids was associated with the highest risk of VTE, but current use, continuing use, and former use also raised the risk significantly. Oral formulations were associated with the highest risk of VTE, but injectable formulations also raised the risk significantly, Ms. Johannesdottir and her associates reported (JAMA Intern. Med. 2013 April 1 [doi:10.1001/jamainternmed.2013.122]).

In particular, new use of systemic glucocorticoids was associated with the highest risk for VTE, with an estimated incidence rate ratio of 3.06, compared with nonuse of glucocorticoids.

The risk of VTE also rose with increasing cumulative doses of all glucocorticoids.

In further analyses, elevated risk for VTE persisted across all the subgroups that were examined.

The findings did not change appreciably in a sensitivity analysis that included only subjects who took glucocorticoids for at least 5 years.

"The temporality of the association (i.e., the strongest effect at initiation of therapy and the absence of an effect after discontinuation) is in line with an effect on coagulation," Ms. Johannesdottir and her associates said.

This study was supported by the Clinical Epidemiological Research Foundation at Aarhus University Hospital. No relevant conflicts of interest were reported.

Use of all glucocorticoids is associated with a two- to threefold increased risk of venous thromboembolism, depending on the type of glucocorticoid, the route of administration, and other factors, according to a report published online April 1 in JAMA Internal Medicine.

Systemic glucocorticoids, as compared with inhaled ones or glucocorticoids that act on the intestines, were associated with the highest risk of VTE. New use was linked to higher risk than continuing or past use, and the VTE risk increased as the dose of glucocorticoids increased, said Sigrun A. Johannesdottir of the department of clinical epidemiology, Aarhus (the Netherlands) University Hospital, and her associates.

These findings are from a population-based case-control study, which cannot prove a cause-and-effect relationship. Moreover, it is difficult to statistically account for all the confounding effects of patients’ underlying disease – the reason they were taking glucocorticoids in the first place – because such disorders raise the risk of VTE directly or cause immobility that in turn can lead to VTE.

However, the timing of this adverse effect, the strength of the association across all types of glucocorticoids, and the fact that the association persisted after the data were adjusted to account for multiple confounders all "increase our confidence that the results reflect a true biological effect," the investigators said.

"Clinicians should be aware of this association," they noted.

Ms. Johannesdottir and her colleagues used data from several Danish national medical registries to identify all adults who were diagnosed with VTE in Denmark in 2005-2012, all patients who filled prescriptions for glucocorticoids during the study period, and all indications for the drugs as well as all relevant comorbidities. They matched 10 control subjects for age and sex from the general population to each study subject.

A total of 38,765 VTE cases and 387,650 controls were included in this study. The median age was 67 years, and slightly more than half of those studied were women.

All glucocorticoid users were found to be at increased risk for VTE, particularly for pulmonary embolism, compared with nonusers, the researchers said.

Systemic glucocorticoids, including betamethasone, methylprednisolone, prednisolone, prednisone, triamcinolone, and hydrocortisone, raised VTE risk to the highest degree. (No patients filled prescriptions for dexamethasone in this study.)

Inhaled corticosteroids and corticosteroids that act on the intestines also raised VTE risk significantly. Among the systemic glucocorticoids, prednisolone and prednisone raised VTE risk the most.

New use of glucocorticoids was associated with the highest risk of VTE, but current use, continuing use, and former use also raised the risk significantly. Oral formulations were associated with the highest risk of VTE, but injectable formulations also raised the risk significantly, Ms. Johannesdottir and her associates reported (JAMA Intern. Med. 2013 April 1 [doi:10.1001/jamainternmed.2013.122]).

In particular, new use of systemic glucocorticoids was associated with the highest risk for VTE, with an estimated incidence rate ratio of 3.06, compared with nonuse of glucocorticoids.

The risk of VTE also rose with increasing cumulative doses of all glucocorticoids.

In further analyses, elevated risk for VTE persisted across all the subgroups that were examined.

The findings did not change appreciably in a sensitivity analysis that included only subjects who took glucocorticoids for at least 5 years.

"The temporality of the association (i.e., the strongest effect at initiation of therapy and the absence of an effect after discontinuation) is in line with an effect on coagulation," Ms. Johannesdottir and her associates said.

This study was supported by the Clinical Epidemiological Research Foundation at Aarhus University Hospital. No relevant conflicts of interest were reported.

Use of all glucocorticoids is associated with a two- to threefold increased risk of venous thromboembolism, depending on the type of glucocorticoid, the route of administration, and other factors, according to a report published online April 1 in JAMA Internal Medicine.

Systemic glucocorticoids, as compared with inhaled ones or glucocorticoids that act on the intestines, were associated with the highest risk of VTE. New use was linked to higher risk than continuing or past use, and the VTE risk increased as the dose of glucocorticoids increased, said Sigrun A. Johannesdottir of the department of clinical epidemiology, Aarhus (the Netherlands) University Hospital, and her associates.

These findings are from a population-based case-control study, which cannot prove a cause-and-effect relationship. Moreover, it is difficult to statistically account for all the confounding effects of patients’ underlying disease – the reason they were taking glucocorticoids in the first place – because such disorders raise the risk of VTE directly or cause immobility that in turn can lead to VTE.

However, the timing of this adverse effect, the strength of the association across all types of glucocorticoids, and the fact that the association persisted after the data were adjusted to account for multiple confounders all "increase our confidence that the results reflect a true biological effect," the investigators said.

"Clinicians should be aware of this association," they noted.

Ms. Johannesdottir and her colleagues used data from several Danish national medical registries to identify all adults who were diagnosed with VTE in Denmark in 2005-2012, all patients who filled prescriptions for glucocorticoids during the study period, and all indications for the drugs as well as all relevant comorbidities. They matched 10 control subjects for age and sex from the general population to each study subject.

A total of 38,765 VTE cases and 387,650 controls were included in this study. The median age was 67 years, and slightly more than half of those studied were women.

All glucocorticoid users were found to be at increased risk for VTE, particularly for pulmonary embolism, compared with nonusers, the researchers said.

Systemic glucocorticoids, including betamethasone, methylprednisolone, prednisolone, prednisone, triamcinolone, and hydrocortisone, raised VTE risk to the highest degree. (No patients filled prescriptions for dexamethasone in this study.)

Inhaled corticosteroids and corticosteroids that act on the intestines also raised VTE risk significantly. Among the systemic glucocorticoids, prednisolone and prednisone raised VTE risk the most.

New use of glucocorticoids was associated with the highest risk of VTE, but current use, continuing use, and former use also raised the risk significantly. Oral formulations were associated with the highest risk of VTE, but injectable formulations also raised the risk significantly, Ms. Johannesdottir and her associates reported (JAMA Intern. Med. 2013 April 1 [doi:10.1001/jamainternmed.2013.122]).

In particular, new use of systemic glucocorticoids was associated with the highest risk for VTE, with an estimated incidence rate ratio of 3.06, compared with nonuse of glucocorticoids.

The risk of VTE also rose with increasing cumulative doses of all glucocorticoids.

In further analyses, elevated risk for VTE persisted across all the subgroups that were examined.

The findings did not change appreciably in a sensitivity analysis that included only subjects who took glucocorticoids for at least 5 years.

"The temporality of the association (i.e., the strongest effect at initiation of therapy and the absence of an effect after discontinuation) is in line with an effect on coagulation," Ms. Johannesdottir and her associates said.

This study was supported by the Clinical Epidemiological Research Foundation at Aarhus University Hospital. No relevant conflicts of interest were reported.

Rheumatoid arthritis patients had significantly higher long-term mortality after myocardial infarction than did matched MI patients without RA in a review of a population-based cohort of patients.

RA patients also exhibited an increased risk of recurrent ischemia, compared with patients who did not have RA, reported Dr. Sara S. McCoy of the Mayo Clinic, Rochester, Minn., and her colleagues (J. Rheumatol. 2013 Feb. 15 [doi:10.3899/jrheum.120941]).

Dr. McCoy and her coinvestigators analyzed data from the Rochester Epidemiology Project, which includes records from all health care providers for the population of Olmsted County, Minn. They targeted 77 RA patients and 154 age- and sex-matched patients without RA who had an MI between Jan. 1, 1979, and Jan. 1, 2010.

Overall, 55% of patients in both cohorts were female; the mean age at MI was 72.4 years. There were no significant differences between cohorts regarding MI risk factors such as hypertension, dyslipidemia, diabetes, smoking status, and obesity. MI characteristics, severity, and electrocardiogram findings were also similar between groups.

Additionally, RA patients and their unaffected counterparts had no differences in treatment during and after MI and in-hospital mortality (5% of RA patients vs. 8% of controls, P = .37). Mortality at 30 days post MI and at 1 year post MI was also similar.

The similarities ended for long-term mortality. Dr. McCoy and her associates found that during a median follow-up of 2.6 years among the RA cohort, 55 patients died, compared with 85 patients over a median 2.7 years in the control cohort, for a hazard ratio of mortality among RA patients of 1.47, compared with their counterparts (95% confidence interval, 1.04-2.08).

The finding held when extended out to 5 years, with the mortality rate among RA patients at 57%, compared with 36% among controls (log rank P = .036).

"Cardiovascular causes [of death] were found in 28 deaths among patients with RA and in 40 deaths among patients without RA," added the authors, although "there was no apparent difference between groups in the proportion of deaths due to CV causes."

Recurrent ischemia also was more pronounced among the RA patients. At 5 years, 80% of RA patients and 50% of controls had experienced ischemia (log rank P = .043).

The conclusions that can be drawn from the study are limited by its retrospective design, as well as the fact that very few data were collected on RA disease activity at the time of MI.

"Erythrocyte sedimentation rate was documented in less than half the cohort in the months prior to MI, and no other measure of disease activity was consistently used or documented over the study time period," the investigators wrote.

The study also was underpowered to assess any associations between mortality and RA characteristics.

"If RA disease characteristics do indeed play a role in determining long-term survival after MI in persons with RA, this would argue for a more personalized, disease-specific approach to post-MI management for patients with RA, similar to post-MI management in patients with diabetes mellitus," they wrote.

"More research is needed to understand the determinants of long-term outcomes after MI in patients with RA, in particular, the role of RA disease characteristics."

Dr. McCoy and her colleagues disclosed no relevant conflicts of interest. They disclosed funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Heart, Lung, and Blood Institute. The Rochester Epidemiology Project is funded by the National Institute on Aging.

Rheumatoid arthritis patients had significantly higher long-term mortality after myocardial infarction than did matched MI patients without RA in a review of a population-based cohort of patients.

RA patients also exhibited an increased risk of recurrent ischemia, compared with patients who did not have RA, reported Dr. Sara S. McCoy of the Mayo Clinic, Rochester, Minn., and her colleagues (J. Rheumatol. 2013 Feb. 15 [doi:10.3899/jrheum.120941]).

Dr. McCoy and her coinvestigators analyzed data from the Rochester Epidemiology Project, which includes records from all health care providers for the population of Olmsted County, Minn. They targeted 77 RA patients and 154 age- and sex-matched patients without RA who had an MI between Jan. 1, 1979, and Jan. 1, 2010.

Overall, 55% of patients in both cohorts were female; the mean age at MI was 72.4 years. There were no significant differences between cohorts regarding MI risk factors such as hypertension, dyslipidemia, diabetes, smoking status, and obesity. MI characteristics, severity, and electrocardiogram findings were also similar between groups.

Additionally, RA patients and their unaffected counterparts had no differences in treatment during and after MI and in-hospital mortality (5% of RA patients vs. 8% of controls, P = .37). Mortality at 30 days post MI and at 1 year post MI was also similar.

The similarities ended for long-term mortality. Dr. McCoy and her associates found that during a median follow-up of 2.6 years among the RA cohort, 55 patients died, compared with 85 patients over a median 2.7 years in the control cohort, for a hazard ratio of mortality among RA patients of 1.47, compared with their counterparts (95% confidence interval, 1.04-2.08).

The finding held when extended out to 5 years, with the mortality rate among RA patients at 57%, compared with 36% among controls (log rank P = .036).

"Cardiovascular causes [of death] were found in 28 deaths among patients with RA and in 40 deaths among patients without RA," added the authors, although "there was no apparent difference between groups in the proportion of deaths due to CV causes."

Recurrent ischemia also was more pronounced among the RA patients. At 5 years, 80% of RA patients and 50% of controls had experienced ischemia (log rank P = .043).

The conclusions that can be drawn from the study are limited by its retrospective design, as well as the fact that very few data were collected on RA disease activity at the time of MI.

"Erythrocyte sedimentation rate was documented in less than half the cohort in the months prior to MI, and no other measure of disease activity was consistently used or documented over the study time period," the investigators wrote.

The study also was underpowered to assess any associations between mortality and RA characteristics.

"If RA disease characteristics do indeed play a role in determining long-term survival after MI in persons with RA, this would argue for a more personalized, disease-specific approach to post-MI management for patients with RA, similar to post-MI management in patients with diabetes mellitus," they wrote.

"More research is needed to understand the determinants of long-term outcomes after MI in patients with RA, in particular, the role of RA disease characteristics."

Dr. McCoy and her colleagues disclosed no relevant conflicts of interest. They disclosed funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Heart, Lung, and Blood Institute. The Rochester Epidemiology Project is funded by the National Institute on Aging.

Rheumatoid arthritis patients had significantly higher long-term mortality after myocardial infarction than did matched MI patients without RA in a review of a population-based cohort of patients.

RA patients also exhibited an increased risk of recurrent ischemia, compared with patients who did not have RA, reported Dr. Sara S. McCoy of the Mayo Clinic, Rochester, Minn., and her colleagues (J. Rheumatol. 2013 Feb. 15 [doi:10.3899/jrheum.120941]).

Dr. McCoy and her coinvestigators analyzed data from the Rochester Epidemiology Project, which includes records from all health care providers for the population of Olmsted County, Minn. They targeted 77 RA patients and 154 age- and sex-matched patients without RA who had an MI between Jan. 1, 1979, and Jan. 1, 2010.

Overall, 55% of patients in both cohorts were female; the mean age at MI was 72.4 years. There were no significant differences between cohorts regarding MI risk factors such as hypertension, dyslipidemia, diabetes, smoking status, and obesity. MI characteristics, severity, and electrocardiogram findings were also similar between groups.

Additionally, RA patients and their unaffected counterparts had no differences in treatment during and after MI and in-hospital mortality (5% of RA patients vs. 8% of controls, P = .37). Mortality at 30 days post MI and at 1 year post MI was also similar.

The similarities ended for long-term mortality. Dr. McCoy and her associates found that during a median follow-up of 2.6 years among the RA cohort, 55 patients died, compared with 85 patients over a median 2.7 years in the control cohort, for a hazard ratio of mortality among RA patients of 1.47, compared with their counterparts (95% confidence interval, 1.04-2.08).

The finding held when extended out to 5 years, with the mortality rate among RA patients at 57%, compared with 36% among controls (log rank P = .036).

"Cardiovascular causes [of death] were found in 28 deaths among patients with RA and in 40 deaths among patients without RA," added the authors, although "there was no apparent difference between groups in the proportion of deaths due to CV causes."

Recurrent ischemia also was more pronounced among the RA patients. At 5 years, 80% of RA patients and 50% of controls had experienced ischemia (log rank P = .043).

The conclusions that can be drawn from the study are limited by its retrospective design, as well as the fact that very few data were collected on RA disease activity at the time of MI.

"Erythrocyte sedimentation rate was documented in less than half the cohort in the months prior to MI, and no other measure of disease activity was consistently used or documented over the study time period," the investigators wrote.

The study also was underpowered to assess any associations between mortality and RA characteristics.

"If RA disease characteristics do indeed play a role in determining long-term survival after MI in persons with RA, this would argue for a more personalized, disease-specific approach to post-MI management for patients with RA, similar to post-MI management in patients with diabetes mellitus," they wrote.

"More research is needed to understand the determinants of long-term outcomes after MI in patients with RA, in particular, the role of RA disease characteristics."

Dr. McCoy and her colleagues disclosed no relevant conflicts of interest. They disclosed funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Heart, Lung, and Blood Institute. The Rochester Epidemiology Project is funded by the National Institute on Aging.

Patients who initiated anti-TNF therapy for inflammatory diseases had no higher risk of developing herpes zoster than did those who took other disease-modifying antirheumatic drugs.

However, a large database review did find a doubling of risk among those taking at least 10 mg/day of corticosteroids, according to Dr. Kevin Winthrop and colleagues. The report is in the March 6 issue of the JAMA.

These findings shed important light on the current mixed-results in literature on the topic, wrote Dr. Winthrop of Oregon Health and Science University, Portland, and his coauthors. The study is more than twice as large as any other on the subject and looked at a large number of patients with elevated herpes zoster risk (JAMA 2013;309:887-95).

It comprised more than 61,000 patients: 33,324 with newly initiated anti-TNF alpha treatment for rheumatoid arthritis and 25,742 who took other nonbiologic disease modifying anti-rheumatic medications. It was a subanalysis of the ongoing Safety Assessment of Biologic Therapy, a U.S. multi-institutional project evaluating the safety of biologic therapies.

Patients were drawn from five large databases spanning 1998-2008: the National Medicaid and Medicare database; Tennessee Medicaid; New Jersey’s Pharmaceutical Assistance to the Aged and Disabled, Pennsylvania’s Pharmaceutical Assistance for the Elderly; and Kaiser Permanente of Northern California. Database selection was important in this study, the investigators said, "Because it contained a large number of Medicare and Medicaid recipients who might have had higher baseline herpes zoster risk due to comorbidities and other unknown factors."

The regression analysis was based on a propensity matching score that took into account a number of baseline factors, including demographics, markers of comorbidity and disease severity, and other potential risk factors for herpes including cancer or diabetes.

Patients were grouped according to disease: rheumatoid arthritis (36,212), inflammatory bowel disease. (10,717) and psoriasis, psoriatic arthritis, or ankylosing spondylitis (12,137). Across all of the groups, there were 470 cases of herpes zoster; 310 among those taking anti-TNF drugs (crude incidence rate of 10/1,000) and 160 among those taking other DMARDs (crude incidence rate of 11/1,000).

After the investigators adjusted for baseline corticosteroid use and the propensity matching score, they found no significant between-group differences in the risk of herpes zoster (hazard ratio of 11 for anti-TNFs; HR, 10 for DMARDs).

Daily use of at least 10 mg corticosteroids was associated with a significantly increased risk of the disease in all of the patient groups (HR, 2).

Most herpes cases (356) occurred in the rheumatoid arthritis group; the investigators analyzed this group separately. These patients were a median of 60 years old; 266 were taking the anti-TNF drugs and 90 other DMARDs. The median follow-up was almost 1 year (294 days). Herpes caused hospitalization in 16 (6%) of those using the medications and in five of the DMARD group (5.5%) – not a significant difference.

Limiting follow-up to 3-6 months did not change the results. When the researchers extended follow-up in the Medicaid/Medicare groups until the end of 2008, they found similar herpes crude incidence rates in the anti-TNF and DMARD groups, and similar disease risk (HR, 12.6 and HR, 12.4, respectively).

When the authors looked at risk in anti-TNF subgroups, they found the highest crude incidence rate among infliximab users (14/1,000) and the lowest for adalimumab users (10/1,000). However, this significant between-group difference disappeared when examined with the propensity matching score. "Furthermore," they noted, "A higher proportion of infliximab users used concomitant methotrexate at baseline and after [the] index date compared with those using etanercept or adalimumab."

The high herpes rate among patients with rheumatoid arthritis supports widespread use of the live attenuated herpes zoster vaccine in those aged 50 years and older, the authors contended.

"Currently, vaccination during active use of anti-TNF therapy is contraindicated due to theoretical safety concerns of using a live vaccine during such therapy; however, it is unclear if such concerns are valid. Our data suggest that patients who develop herpes zoster while taking anti-TNF therapy are no more likely to be hospitalized than persons with herpes zoster using nonbiologic DMARDs ... Given these findings, the potential importance of this vaccine within the rheumatoid arthritis setting and the difficulty in vaccinating patients given the widespread use of anti-TNF therapy, we believe that a trial to evaluate the safety of this live virus vaccine among current anti-TNF users is warranted."

Dr. Winthrop has consulted for Genentec, Abbott Pfizer, UCB Pharma, and Amgen, and received research grants from Pfizer. Other authors reported relationships with numerous pharmaceutical companies.

michele.sullivan@elsevier.com

Patients who initiated anti-TNF therapy for inflammatory diseases had no higher risk of developing herpes zoster than did those who took other disease-modifying antirheumatic drugs.

However, a large database review did find a doubling of risk among those taking at least 10 mg/day of corticosteroids, according to Dr. Kevin Winthrop and colleagues. The report is in the March 6 issue of the JAMA.

These findings shed important light on the current mixed-results in literature on the topic, wrote Dr. Winthrop of Oregon Health and Science University, Portland, and his coauthors. The study is more than twice as large as any other on the subject and looked at a large number of patients with elevated herpes zoster risk (JAMA 2013;309:887-95).

It comprised more than 61,000 patients: 33,324 with newly initiated anti-TNF alpha treatment for rheumatoid arthritis and 25,742 who took other nonbiologic disease modifying anti-rheumatic medications. It was a subanalysis of the ongoing Safety Assessment of Biologic Therapy, a U.S. multi-institutional project evaluating the safety of biologic therapies.

Patients were drawn from five large databases spanning 1998-2008: the National Medicaid and Medicare database; Tennessee Medicaid; New Jersey’s Pharmaceutical Assistance to the Aged and Disabled, Pennsylvania’s Pharmaceutical Assistance for the Elderly; and Kaiser Permanente of Northern California. Database selection was important in this study, the investigators said, "Because it contained a large number of Medicare and Medicaid recipients who might have had higher baseline herpes zoster risk due to comorbidities and other unknown factors."

The regression analysis was based on a propensity matching score that took into account a number of baseline factors, including demographics, markers of comorbidity and disease severity, and other potential risk factors for herpes including cancer or diabetes.

Patients were grouped according to disease: rheumatoid arthritis (36,212), inflammatory bowel disease. (10,717) and psoriasis, psoriatic arthritis, or ankylosing spondylitis (12,137). Across all of the groups, there were 470 cases of herpes zoster; 310 among those taking anti-TNF drugs (crude incidence rate of 10/1,000) and 160 among those taking other DMARDs (crude incidence rate of 11/1,000).

After the investigators adjusted for baseline corticosteroid use and the propensity matching score, they found no significant between-group differences in the risk of herpes zoster (hazard ratio of 11 for anti-TNFs; HR, 10 for DMARDs).

Daily use of at least 10 mg corticosteroids was associated with a significantly increased risk of the disease in all of the patient groups (HR, 2).

Most herpes cases (356) occurred in the rheumatoid arthritis group; the investigators analyzed this group separately. These patients were a median of 60 years old; 266 were taking the anti-TNF drugs and 90 other DMARDs. The median follow-up was almost 1 year (294 days). Herpes caused hospitalization in 16 (6%) of those using the medications and in five of the DMARD group (5.5%) – not a significant difference.

Limiting follow-up to 3-6 months did not change the results. When the researchers extended follow-up in the Medicaid/Medicare groups until the end of 2008, they found similar herpes crude incidence rates in the anti-TNF and DMARD groups, and similar disease risk (HR, 12.6 and HR, 12.4, respectively).

When the authors looked at risk in anti-TNF subgroups, they found the highest crude incidence rate among infliximab users (14/1,000) and the lowest for adalimumab users (10/1,000). However, this significant between-group difference disappeared when examined with the propensity matching score. "Furthermore," they noted, "A higher proportion of infliximab users used concomitant methotrexate at baseline and after [the] index date compared with those using etanercept or adalimumab."

The high herpes rate among patients with rheumatoid arthritis supports widespread use of the live attenuated herpes zoster vaccine in those aged 50 years and older, the authors contended.

"Currently, vaccination during active use of anti-TNF therapy is contraindicated due to theoretical safety concerns of using a live vaccine during such therapy; however, it is unclear if such concerns are valid. Our data suggest that patients who develop herpes zoster while taking anti-TNF therapy are no more likely to be hospitalized than persons with herpes zoster using nonbiologic DMARDs ... Given these findings, the potential importance of this vaccine within the rheumatoid arthritis setting and the difficulty in vaccinating patients given the widespread use of anti-TNF therapy, we believe that a trial to evaluate the safety of this live virus vaccine among current anti-TNF users is warranted."

Dr. Winthrop has consulted for Genentec, Abbott Pfizer, UCB Pharma, and Amgen, and received research grants from Pfizer. Other authors reported relationships with numerous pharmaceutical companies.

michele.sullivan@elsevier.com

Patients who initiated anti-TNF therapy for inflammatory diseases had no higher risk of developing herpes zoster than did those who took other disease-modifying antirheumatic drugs.

However, a large database review did find a doubling of risk among those taking at least 10 mg/day of corticosteroids, according to Dr. Kevin Winthrop and colleagues. The report is in the March 6 issue of the JAMA.

These findings shed important light on the current mixed-results in literature on the topic, wrote Dr. Winthrop of Oregon Health and Science University, Portland, and his coauthors. The study is more than twice as large as any other on the subject and looked at a large number of patients with elevated herpes zoster risk (JAMA 2013;309:887-95).

It comprised more than 61,000 patients: 33,324 with newly initiated anti-TNF alpha treatment for rheumatoid arthritis and 25,742 who took other nonbiologic disease modifying anti-rheumatic medications. It was a subanalysis of the ongoing Safety Assessment of Biologic Therapy, a U.S. multi-institutional project evaluating the safety of biologic therapies.

Patients were drawn from five large databases spanning 1998-2008: the National Medicaid and Medicare database; Tennessee Medicaid; New Jersey’s Pharmaceutical Assistance to the Aged and Disabled, Pennsylvania’s Pharmaceutical Assistance for the Elderly; and Kaiser Permanente of Northern California. Database selection was important in this study, the investigators said, "Because it contained a large number of Medicare and Medicaid recipients who might have had higher baseline herpes zoster risk due to comorbidities and other unknown factors."

The regression analysis was based on a propensity matching score that took into account a number of baseline factors, including demographics, markers of comorbidity and disease severity, and other potential risk factors for herpes including cancer or diabetes.

Patients were grouped according to disease: rheumatoid arthritis (36,212), inflammatory bowel disease. (10,717) and psoriasis, psoriatic arthritis, or ankylosing spondylitis (12,137). Across all of the groups, there were 470 cases of herpes zoster; 310 among those taking anti-TNF drugs (crude incidence rate of 10/1,000) and 160 among those taking other DMARDs (crude incidence rate of 11/1,000).

After the investigators adjusted for baseline corticosteroid use and the propensity matching score, they found no significant between-group differences in the risk of herpes zoster (hazard ratio of 11 for anti-TNFs; HR, 10 for DMARDs).

Daily use of at least 10 mg corticosteroids was associated with a significantly increased risk of the disease in all of the patient groups (HR, 2).

Most herpes cases (356) occurred in the rheumatoid arthritis group; the investigators analyzed this group separately. These patients were a median of 60 years old; 266 were taking the anti-TNF drugs and 90 other DMARDs. The median follow-up was almost 1 year (294 days). Herpes caused hospitalization in 16 (6%) of those using the medications and in five of the DMARD group (5.5%) – not a significant difference.

Limiting follow-up to 3-6 months did not change the results. When the researchers extended follow-up in the Medicaid/Medicare groups until the end of 2008, they found similar herpes crude incidence rates in the anti-TNF and DMARD groups, and similar disease risk (HR, 12.6 and HR, 12.4, respectively).

When the authors looked at risk in anti-TNF subgroups, they found the highest crude incidence rate among infliximab users (14/1,000) and the lowest for adalimumab users (10/1,000). However, this significant between-group difference disappeared when examined with the propensity matching score. "Furthermore," they noted, "A higher proportion of infliximab users used concomitant methotrexate at baseline and after [the] index date compared with those using etanercept or adalimumab."

The high herpes rate among patients with rheumatoid arthritis supports widespread use of the live attenuated herpes zoster vaccine in those aged 50 years and older, the authors contended.

"Currently, vaccination during active use of anti-TNF therapy is contraindicated due to theoretical safety concerns of using a live vaccine during such therapy; however, it is unclear if such concerns are valid. Our data suggest that patients who develop herpes zoster while taking anti-TNF therapy are no more likely to be hospitalized than persons with herpes zoster using nonbiologic DMARDs ... Given these findings, the potential importance of this vaccine within the rheumatoid arthritis setting and the difficulty in vaccinating patients given the widespread use of anti-TNF therapy, we believe that a trial to evaluate the safety of this live virus vaccine among current anti-TNF users is warranted."

Dr. Winthrop has consulted for Genentec, Abbott Pfizer, UCB Pharma, and Amgen, and received research grants from Pfizer. Other authors reported relationships with numerous pharmaceutical companies.

michele.sullivan@elsevier.com

A small group of Republicans and Democrats in the House has introduced federal legislation to limit patients’ out-of-pocket costs for biologics and other specialty medications often used to treat rheumatoid arthritis, psoriasis, lupus, multiple sclerosis, and some cancers.

The Patients’ Access to Treatments Act (H.R. 460), which was introduced on Feb. 4, would require health plans to charge the same copayments for biologics and specialty drugs that they do for other off-formulary brand-name medications.

Typically, health plans use a three-tier system with set copays for generic drugs (tier 1), brand-name drugs (tier 2), and off-formulary brand-name drugs (tier 3). But some insurers have moved biologics and other high-cost medications into a fourth tier, where patients pay a percentage of the cost of the drug. The costs of the affected medications range from $12,000 to $48,000 a year or more, and the copays can range from 25% to 33%, according to the American College of Rheumatology.

"Over the past 2 years, hearing the stories of patients struggling to pay for medications that would dramatically improve their lives has been heartbreaking," Rep. David McKinley (R-W.Va.), the sponsor of the bill, said in a statement. "After talking with a number of people in these situations, it was clear action was needed."

Rep. McKinley introduced this legislation in the last session of Congress, but the bill stalled in committee.

m.schneider@elsevier.com

A small group of Republicans and Democrats in the House has introduced federal legislation to limit patients’ out-of-pocket costs for biologics and other specialty medications often used to treat rheumatoid arthritis, psoriasis, lupus, multiple sclerosis, and some cancers.

The Patients’ Access to Treatments Act (H.R. 460), which was introduced on Feb. 4, would require health plans to charge the same copayments for biologics and specialty drugs that they do for other off-formulary brand-name medications.

Typically, health plans use a three-tier system with set copays for generic drugs (tier 1), brand-name drugs (tier 2), and off-formulary brand-name drugs (tier 3). But some insurers have moved biologics and other high-cost medications into a fourth tier, where patients pay a percentage of the cost of the drug. The costs of the affected medications range from $12,000 to $48,000 a year or more, and the copays can range from 25% to 33%, according to the American College of Rheumatology.

"Over the past 2 years, hearing the stories of patients struggling to pay for medications that would dramatically improve their lives has been heartbreaking," Rep. David McKinley (R-W.Va.), the sponsor of the bill, said in a statement. "After talking with a number of people in these situations, it was clear action was needed."

Rep. McKinley introduced this legislation in the last session of Congress, but the bill stalled in committee.

m.schneider@elsevier.com

A small group of Republicans and Democrats in the House has introduced federal legislation to limit patients’ out-of-pocket costs for biologics and other specialty medications often used to treat rheumatoid arthritis, psoriasis, lupus, multiple sclerosis, and some cancers.

The Patients’ Access to Treatments Act (H.R. 460), which was introduced on Feb. 4, would require health plans to charge the same copayments for biologics and specialty drugs that they do for other off-formulary brand-name medications.

Typically, health plans use a three-tier system with set copays for generic drugs (tier 1), brand-name drugs (tier 2), and off-formulary brand-name drugs (tier 3). But some insurers have moved biologics and other high-cost medications into a fourth tier, where patients pay a percentage of the cost of the drug. The costs of the affected medications range from $12,000 to $48,000 a year or more, and the copays can range from 25% to 33%, according to the American College of Rheumatology.

"Over the past 2 years, hearing the stories of patients struggling to pay for medications that would dramatically improve their lives has been heartbreaking," Rep. David McKinley (R-W.Va.), the sponsor of the bill, said in a statement. "After talking with a number of people in these situations, it was clear action was needed."

Rep. McKinley introduced this legislation in the last session of Congress, but the bill stalled in committee.

m.schneider@elsevier.com

WASHINGTON – What variables predict the course of an individual patient’s rheumatoid arthritis? It’s a question two research groups are beginning to answer by mining data from a large patient database.

Using data from CORRONA (the Consortium of Rheumatology Researchers of North America), a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients, George W. Reed, Ph.D., of the University of Massachusetts in Worcester, and his colleagues have constructed a Markov model as a framework for analyzing the probabilities of transition between disease states in RA.

It’s a way to "talk about the probability of what’s next [in the course of a patient’s disease], and what’s associated with what’s next," Dr. Reed reported in a poster presentation at the annual meeting of the American College of Rheumatology.

Dr. Reed and his colleagues began by defining disease activity states: Low disease activity was defined as a clinical disease activity index (CDAI) score of 10 or less, moderate disease activity as a CDAI score between 11 and 22, and severe disease activity as a CDAI score of 23 or greater. Then states were determined at each visit, and variables were measured to see if they correlated with any changes. Covariates included initiation of disease-modifying antirheumatic drugs (DMARDs), duration of RA, patient age, and insurance status.

The covariates are just examples of "some possible variables that could be plugged in" to future models, he said.

Overall, the investigators examined 160,262 visits from 24,136 RA patients in the CORRONA database who had CDAI measures at the current and the prior visit.

The data imply that RA management, in general, is improving. Transition from any disease state to a low disease state improved from 2001-2005 to 2009-2012, said Dr. Reed.

If a DMARD was not initiated at the prior visit, "a patient in a prior state of moderate disease had a relative risk ratio of 7.6 (95% confidence interval, 7.08-8.21) to still have moderate disease at the current visit." However, if a DMARD was initiated, CDAI declined, and the relative risk of remaining in a moderate disease state was cut to 4.1 (95% CI, 3.59-4.63).

A longer duration of RA affected transitions in disease states, but patient age and insurance status did not.

In a separate CORRONA-based study, patients with moderate disease were found to transition frequently in and out of severe and low disease states.

In that study, led by Sameer V. Kotak of Pfizer in New York, 60% of 4,118 RA patients who exhibited moderate disease activity at baseline had transitioned to a low CDAI by 6 months. About 31% continued to have a moderate CDAI, and 9% transitioned to a severe CDAI.

At 12 months, about 75% of the patients with a low CDAI at the 6-month benchmark remained in that category, with 20% transitioning back to a moderate CDAI and the remaining 5% transitioning to severe disease.

Similarly, 46% of patients with a moderate CDAI at baseline remained at that level at 6 months and transitioned to a low CDAI by 12 months, while 11% of these patients transitioned to a severe CDAI.

The data show transition potential and disease instability in an understated population, "even within a short follow-up window of 6 months," Mr. Kotak said.

Dr. Reed disclosed that he is supported by a research contract with CORRONA through the University of Massachusetts. Mr. Kotak, along with another coinvestigator, is an employee of Pfizer. Employment with, and other financial relationships to, additional pharmaceutical companies were disclosed by multiple investigators in the studies.

WASHINGTON – What variables predict the course of an individual patient’s rheumatoid arthritis? It’s a question two research groups are beginning to answer by mining data from a large patient database.

Using data from CORRONA (the Consortium of Rheumatology Researchers of North America), a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients, George W. Reed, Ph.D., of the University of Massachusetts in Worcester, and his colleagues have constructed a Markov model as a framework for analyzing the probabilities of transition between disease states in RA.

It’s a way to "talk about the probability of what’s next [in the course of a patient’s disease], and what’s associated with what’s next," Dr. Reed reported in a poster presentation at the annual meeting of the American College of Rheumatology.

Dr. Reed and his colleagues began by defining disease activity states: Low disease activity was defined as a clinical disease activity index (CDAI) score of 10 or less, moderate disease activity as a CDAI score between 11 and 22, and severe disease activity as a CDAI score of 23 or greater. Then states were determined at each visit, and variables were measured to see if they correlated with any changes. Covariates included initiation of disease-modifying antirheumatic drugs (DMARDs), duration of RA, patient age, and insurance status.

The covariates are just examples of "some possible variables that could be plugged in" to future models, he said.

Overall, the investigators examined 160,262 visits from 24,136 RA patients in the CORRONA database who had CDAI measures at the current and the prior visit.

The data imply that RA management, in general, is improving. Transition from any disease state to a low disease state improved from 2001-2005 to 2009-2012, said Dr. Reed.

If a DMARD was not initiated at the prior visit, "a patient in a prior state of moderate disease had a relative risk ratio of 7.6 (95% confidence interval, 7.08-8.21) to still have moderate disease at the current visit." However, if a DMARD was initiated, CDAI declined, and the relative risk of remaining in a moderate disease state was cut to 4.1 (95% CI, 3.59-4.63).

A longer duration of RA affected transitions in disease states, but patient age and insurance status did not.

In a separate CORRONA-based study, patients with moderate disease were found to transition frequently in and out of severe and low disease states.

In that study, led by Sameer V. Kotak of Pfizer in New York, 60% of 4,118 RA patients who exhibited moderate disease activity at baseline had transitioned to a low CDAI by 6 months. About 31% continued to have a moderate CDAI, and 9% transitioned to a severe CDAI.

At 12 months, about 75% of the patients with a low CDAI at the 6-month benchmark remained in that category, with 20% transitioning back to a moderate CDAI and the remaining 5% transitioning to severe disease.

Similarly, 46% of patients with a moderate CDAI at baseline remained at that level at 6 months and transitioned to a low CDAI by 12 months, while 11% of these patients transitioned to a severe CDAI.

The data show transition potential and disease instability in an understated population, "even within a short follow-up window of 6 months," Mr. Kotak said.

Dr. Reed disclosed that he is supported by a research contract with CORRONA through the University of Massachusetts. Mr. Kotak, along with another coinvestigator, is an employee of Pfizer. Employment with, and other financial relationships to, additional pharmaceutical companies were disclosed by multiple investigators in the studies.

WASHINGTON – What variables predict the course of an individual patient’s rheumatoid arthritis? It’s a question two research groups are beginning to answer by mining data from a large patient database.

Using data from CORRONA (the Consortium of Rheumatology Researchers of North America), a multicenter, longitudinal, prospective database in the United States with more than 30,000 patients, George W. Reed, Ph.D., of the University of Massachusetts in Worcester, and his colleagues have constructed a Markov model as a framework for analyzing the probabilities of transition between disease states in RA.

It’s a way to "talk about the probability of what’s next [in the course of a patient’s disease], and what’s associated with what’s next," Dr. Reed reported in a poster presentation at the annual meeting of the American College of Rheumatology.

Dr. Reed and his colleagues began by defining disease activity states: Low disease activity was defined as a clinical disease activity index (CDAI) score of 10 or less, moderate disease activity as a CDAI score between 11 and 22, and severe disease activity as a CDAI score of 23 or greater. Then states were determined at each visit, and variables were measured to see if they correlated with any changes. Covariates included initiation of disease-modifying antirheumatic drugs (DMARDs), duration of RA, patient age, and insurance status.

The covariates are just examples of "some possible variables that could be plugged in" to future models, he said.

Overall, the investigators examined 160,262 visits from 24,136 RA patients in the CORRONA database who had CDAI measures at the current and the prior visit.

The data imply that RA management, in general, is improving. Transition from any disease state to a low disease state improved from 2001-2005 to 2009-2012, said Dr. Reed.

If a DMARD was not initiated at the prior visit, "a patient in a prior state of moderate disease had a relative risk ratio of 7.6 (95% confidence interval, 7.08-8.21) to still have moderate disease at the current visit." However, if a DMARD was initiated, CDAI declined, and the relative risk of remaining in a moderate disease state was cut to 4.1 (95% CI, 3.59-4.63).

A longer duration of RA affected transitions in disease states, but patient age and insurance status did not.

In a separate CORRONA-based study, patients with moderate disease were found to transition frequently in and out of severe and low disease states.

In that study, led by Sameer V. Kotak of Pfizer in New York, 60% of 4,118 RA patients who exhibited moderate disease activity at baseline had transitioned to a low CDAI by 6 months. About 31% continued to have a moderate CDAI, and 9% transitioned to a severe CDAI.

At 12 months, about 75% of the patients with a low CDAI at the 6-month benchmark remained in that category, with 20% transitioning back to a moderate CDAI and the remaining 5% transitioning to severe disease.

Similarly, 46% of patients with a moderate CDAI at baseline remained at that level at 6 months and transitioned to a low CDAI by 12 months, while 11% of these patients transitioned to a severe CDAI.

The data show transition potential and disease instability in an understated population, "even within a short follow-up window of 6 months," Mr. Kotak said.

Dr. Reed disclosed that he is supported by a research contract with CORRONA through the University of Massachusetts. Mr. Kotak, along with another coinvestigator, is an employee of Pfizer. Employment with, and other financial relationships to, additional pharmaceutical companies were disclosed by multiple investigators in the studies.

Abatacept achieved an efficacy similar to that of adalimumab in the treatment of rheumatoid arthritis with a comparable safety profile in a 2-year, head-to-head randomized trial.

The multinational phase IIIb study established the noninferiority of abatacept as compared with the commonly used adalimumab. Both agents are targeted biologic disease-modifying antirheumatic drugs (bDMARDs), but with different mechanisms of action: Adalimumab is a tumor necrosis factor inhibitor, whereas abatacept is a T-cell costimulation modulator.

Dr. Michael E. Weinblatt of Brigham and Women’s Hospital in Boston and his associates conducted a intent-to-treat analysis of the two drugs, administered along with a stable dosage of methotrexate (MTX), in 646 patients who had confirmed diagnoses of rheumatoid arthritis for less than 2 years and had an inadequate response to MTX alone (Arthritis Rheum. 2013;65:28-38 [doi: 10.1002/art.37711]).

The patients had not received previous bDMARD therapy; and all had active disease with a score of at least 3.2 on the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). They were stratified according to whether they had moderate disease (a DAS28-CRP score of 3.2-5.1) or severe disease (greater than 5.1), with approximately equal distribution of disease severity levels in both treatment groups.

A total of 318 patients received 125 mg of subcutaneous abatacept once a week, and 328 patients received 40 mg of subcutaneous adalimumab once every other week. Both groups received stable doses of MTX at 15-25 mg per week (except for those who received 7.5 mg or more if they had a documented intolerance to higher dosages). Patients could not take any other DMARDs during the trial but could receive either hydroxychloroquine or sulfasalazine, as well as low-dose oral corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and up to two courses of high-dose corticosteroids.

Patients could not be blinded to the treatments for logistical reasons, but clinical assessors of their treatment, adverse events, and disease severity were blinded. The 13.8% of abatacept patients and 18% of adalimumab patients who discontinued therapy were considered nonresponders at all visits after they discontinued the study.

The researchers used the American College of Rheumatology 20% improvement response (ACR20) at 1 year as the primary outcome. ACR20 improvement criteria include at least a 20% reduction in the number of tender joints (out of 68) and swollen joints (out of 66), as well as three of five other attributes related to the patient’s pain, the patient’s or doctor’s disease assessment, or the C-reactive protein levels.

At 1 year, 64.8% of patients in the abatacept group (95% confidence interval, 59.5%-70.0%) and 63.4% of patients in the adalimumab group (95% CI, 58.2%-68.6%) achieved an ACR20 response. The researchers estimated the difference between the two groups’ ACR20 response rates to be 1.8% (95% CI, –5.6% to 9.2%).

Secondary outcomes of ACR50 and ACR70 were also reported at 1 year: 46.2% of abatacept patients and 46% of adalimumab patients achieved an ACR50 response. Meanwhile, 29.2% of abatacept patients and 26.2% of adalimumab patients achieved an ACR70 response. The adjusted mean improvement in the DAS28-CRP score at 1 year was –2.30 for the abatacept patients and –2.27 for the adalimumab patients. Using an ACR/European League Against Rheumatism definition, the remission rate among abatacept patients was 13.5%, compared with 15.7% among adalimumab patients.

Safety profiles were similar in both groups, except that more adalimumab patients reported local injection site reactions (9.1%) and injection pain (2.4%) than did abatacept patients (3.8% and 0%, respectively). Overall, the serious adverse event (SAE) rate was 10.1% in the abatacept group and 9.1% in the adalimumab group; related SAEs were 2.5% in the abatacept group and 3.4% in the adalimumab group.

Small percentages of participants discontinued the study because of adverse events: 1.3% of patients taking abatacept and 3% of patients taking adalimumab, while 3.5% of the patients on abatacept and 6.1% of patients on adalimumab discontinued because of non-SAEs.

The researchers concluded that both drugs are of "comparable clinical benefit, suggesting that these two agents should be considered equally for the treatment of rheumatoid arthritis patients who have an inadequate response to MTX."

The study was funded by Bristol-Myers Squibb, which manufactures abatacept. All eight authors have past or present financial relationships, including research grants, consulting fees, and/or stock ownership (two authors) in Bristol-Myers Squibb. Most have financial relationships with Abbott and multiple other pharmaceutical companies.

Abatacept achieved an efficacy similar to that of adalimumab in the treatment of rheumatoid arthritis with a comparable safety profile in a 2-year, head-to-head randomized trial.

The multinational phase IIIb study established the noninferiority of abatacept as compared with the commonly used adalimumab. Both agents are targeted biologic disease-modifying antirheumatic drugs (bDMARDs), but with different mechanisms of action: Adalimumab is a tumor necrosis factor inhibitor, whereas abatacept is a T-cell costimulation modulator.

Dr. Michael E. Weinblatt of Brigham and Women’s Hospital in Boston and his associates conducted a intent-to-treat analysis of the two drugs, administered along with a stable dosage of methotrexate (MTX), in 646 patients who had confirmed diagnoses of rheumatoid arthritis for less than 2 years and had an inadequate response to MTX alone (Arthritis Rheum. 2013;65:28-38 [doi: 10.1002/art.37711]).

The patients had not received previous bDMARD therapy; and all had active disease with a score of at least 3.2 on the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). They were stratified according to whether they had moderate disease (a DAS28-CRP score of 3.2-5.1) or severe disease (greater than 5.1), with approximately equal distribution of disease severity levels in both treatment groups.

A total of 318 patients received 125 mg of subcutaneous abatacept once a week, and 328 patients received 40 mg of subcutaneous adalimumab once every other week. Both groups received stable doses of MTX at 15-25 mg per week (except for those who received 7.5 mg or more if they had a documented intolerance to higher dosages). Patients could not take any other DMARDs during the trial but could receive either hydroxychloroquine or sulfasalazine, as well as low-dose oral corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and up to two courses of high-dose corticosteroids.

Patients could not be blinded to the treatments for logistical reasons, but clinical assessors of their treatment, adverse events, and disease severity were blinded. The 13.8% of abatacept patients and 18% of adalimumab patients who discontinued therapy were considered nonresponders at all visits after they discontinued the study.

The researchers used the American College of Rheumatology 20% improvement response (ACR20) at 1 year as the primary outcome. ACR20 improvement criteria include at least a 20% reduction in the number of tender joints (out of 68) and swollen joints (out of 66), as well as three of five other attributes related to the patient’s pain, the patient’s or doctor’s disease assessment, or the C-reactive protein levels.

At 1 year, 64.8% of patients in the abatacept group (95% confidence interval, 59.5%-70.0%) and 63.4% of patients in the adalimumab group (95% CI, 58.2%-68.6%) achieved an ACR20 response. The researchers estimated the difference between the two groups’ ACR20 response rates to be 1.8% (95% CI, –5.6% to 9.2%).

Secondary outcomes of ACR50 and ACR70 were also reported at 1 year: 46.2% of abatacept patients and 46% of adalimumab patients achieved an ACR50 response. Meanwhile, 29.2% of abatacept patients and 26.2% of adalimumab patients achieved an ACR70 response. The adjusted mean improvement in the DAS28-CRP score at 1 year was –2.30 for the abatacept patients and –2.27 for the adalimumab patients. Using an ACR/European League Against Rheumatism definition, the remission rate among abatacept patients was 13.5%, compared with 15.7% among adalimumab patients.

Safety profiles were similar in both groups, except that more adalimumab patients reported local injection site reactions (9.1%) and injection pain (2.4%) than did abatacept patients (3.8% and 0%, respectively). Overall, the serious adverse event (SAE) rate was 10.1% in the abatacept group and 9.1% in the adalimumab group; related SAEs were 2.5% in the abatacept group and 3.4% in the adalimumab group.

Small percentages of participants discontinued the study because of adverse events: 1.3% of patients taking abatacept and 3% of patients taking adalimumab, while 3.5% of the patients on abatacept and 6.1% of patients on adalimumab discontinued because of non-SAEs.

The researchers concluded that both drugs are of "comparable clinical benefit, suggesting that these two agents should be considered equally for the treatment of rheumatoid arthritis patients who have an inadequate response to MTX."

The study was funded by Bristol-Myers Squibb, which manufactures abatacept. All eight authors have past or present financial relationships, including research grants, consulting fees, and/or stock ownership (two authors) in Bristol-Myers Squibb. Most have financial relationships with Abbott and multiple other pharmaceutical companies.

Abatacept achieved an efficacy similar to that of adalimumab in the treatment of rheumatoid arthritis with a comparable safety profile in a 2-year, head-to-head randomized trial.

The multinational phase IIIb study established the noninferiority of abatacept as compared with the commonly used adalimumab. Both agents are targeted biologic disease-modifying antirheumatic drugs (bDMARDs), but with different mechanisms of action: Adalimumab is a tumor necrosis factor inhibitor, whereas abatacept is a T-cell costimulation modulator.

Dr. Michael E. Weinblatt of Brigham and Women’s Hospital in Boston and his associates conducted a intent-to-treat analysis of the two drugs, administered along with a stable dosage of methotrexate (MTX), in 646 patients who had confirmed diagnoses of rheumatoid arthritis for less than 2 years and had an inadequate response to MTX alone (Arthritis Rheum. 2013;65:28-38 [doi: 10.1002/art.37711]).

The patients had not received previous bDMARD therapy; and all had active disease with a score of at least 3.2 on the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). They were stratified according to whether they had moderate disease (a DAS28-CRP score of 3.2-5.1) or severe disease (greater than 5.1), with approximately equal distribution of disease severity levels in both treatment groups.

A total of 318 patients received 125 mg of subcutaneous abatacept once a week, and 328 patients received 40 mg of subcutaneous adalimumab once every other week. Both groups received stable doses of MTX at 15-25 mg per week (except for those who received 7.5 mg or more if they had a documented intolerance to higher dosages). Patients could not take any other DMARDs during the trial but could receive either hydroxychloroquine or sulfasalazine, as well as low-dose oral corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and up to two courses of high-dose corticosteroids.

Patients could not be blinded to the treatments for logistical reasons, but clinical assessors of their treatment, adverse events, and disease severity were blinded. The 13.8% of abatacept patients and 18% of adalimumab patients who discontinued therapy were considered nonresponders at all visits after they discontinued the study.

The researchers used the American College of Rheumatology 20% improvement response (ACR20) at 1 year as the primary outcome. ACR20 improvement criteria include at least a 20% reduction in the number of tender joints (out of 68) and swollen joints (out of 66), as well as three of five other attributes related to the patient’s pain, the patient’s or doctor’s disease assessment, or the C-reactive protein levels.

At 1 year, 64.8% of patients in the abatacept group (95% confidence interval, 59.5%-70.0%) and 63.4% of patients in the adalimumab group (95% CI, 58.2%-68.6%) achieved an ACR20 response. The researchers estimated the difference between the two groups’ ACR20 response rates to be 1.8% (95% CI, –5.6% to 9.2%).

Secondary outcomes of ACR50 and ACR70 were also reported at 1 year: 46.2% of abatacept patients and 46% of adalimumab patients achieved an ACR50 response. Meanwhile, 29.2% of abatacept patients and 26.2% of adalimumab patients achieved an ACR70 response. The adjusted mean improvement in the DAS28-CRP score at 1 year was –2.30 for the abatacept patients and –2.27 for the adalimumab patients. Using an ACR/European League Against Rheumatism definition, the remission rate among abatacept patients was 13.5%, compared with 15.7% among adalimumab patients.

Safety profiles were similar in both groups, except that more adalimumab patients reported local injection site reactions (9.1%) and injection pain (2.4%) than did abatacept patients (3.8% and 0%, respectively). Overall, the serious adverse event (SAE) rate was 10.1% in the abatacept group and 9.1% in the adalimumab group; related SAEs were 2.5% in the abatacept group and 3.4% in the adalimumab group.

Small percentages of participants discontinued the study because of adverse events: 1.3% of patients taking abatacept and 3% of patients taking adalimumab, while 3.5% of the patients on abatacept and 6.1% of patients on adalimumab discontinued because of non-SAEs.

The researchers concluded that both drugs are of "comparable clinical benefit, suggesting that these two agents should be considered equally for the treatment of rheumatoid arthritis patients who have an inadequate response to MTX."

The study was funded by Bristol-Myers Squibb, which manufactures abatacept. All eight authors have past or present financial relationships, including research grants, consulting fees, and/or stock ownership (two authors) in Bristol-Myers Squibb. Most have financial relationships with Abbott and multiple other pharmaceutical companies.

A majority of studies of patients with rheumatoid arthritis that have collected data on rheumatoid factor status and response to treatment indicate that positivity for the autoantibody predicts response to rituximab and tocilizumab but not abatacept, according to a systematic review and meta-analysis.

The association of rheumatoid factor (RF) and response to certain biologics is disputed, and the findings have been contradictory. Meanwhile, there’s considerable heterogeneity in patient response to biologics: While some don’t benefit from a certain biologic, they do well on a different one, Dr. Jose Ramon Maneiro of Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain, and his colleagues wrote in their report.

The investigators set out to summarize the available evidence for how well RF positivity predicts response to rituximab, tocilizumab, and abatacept. They searched Medline, Embase, and the Cochrane Library for studies published between 2000 and 2011 in English, Spanish, French, Italian, or Portuguese, as well as online abstracts from the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) congresses from the same time period. The search resulted in more than 3,600 references and abstracts, from which they carefully selected 23 studies representing data from more than 5,800 patients (Semin. Arthritis Rheum. 2013 Jan. 3 [doi: 10.1016/j.semarthrit.2012.11.007]).

The researchers identified 14 studies on rituximab involving about 2,100 patients. In 11 studies that analyzed IgM RF status, 6 reported a significant association between IgM RF positivity and clinical response, including 1 that found a significant association with a titer greater than 30 IU/L but not greater than 20 IU/L. IgA RF status was significantly associated with clinical response in one study, while two other studies reported that IgG RF and IgA RF titers were significantly associated with clinical response. In six studies that used EULAR response criteria, patients with IgM RF positivity had significantly greater odds for meeting the response criteria than did those who were IgM RF negative (odds ratio, 3.52). Assessments of ACR response criteria found that RF positivity resulted in greater odds for an ACR20 response to rituximab in three studies (OR, 1.95) and an ACR50 response in three studies (OR, 5.38).

In four studies on tocilizumab, two indicated no relationship between RF status and response to the drug, whereas one report that analyzed data from three clinical trials found a significant association between RF status and ACR20 response. Another study found that the titer of IgM RF could predict Clinical Disease Activity Index. Overall, a meta-analysis of three studies found that RF positivity was significantly associated with greater odds for an ACR20 response (OR, 1.51).

A post hoc analysis of efficacy data from three clinical trials of abatacept showed no association between RF positivity and response to the drug. However, one observational study reported an association.

The review had several limitations, the authors noted. The meta-analysis aggregated results from clinical trials and observational studies, but none of the clinical trials was designed to test the studied association. Also, in observational studies there is a potential for bias from unmeasured confounding factors. In addition, the quality of the studies was low, the authors reported.

The study was partially supported by the Instituto de Salud Carlos III. The currently available version of the report, a corrected proof, did not note any financial disclosures for the authors.

n.miller@elsevier.com

On Twitter @NaseemSMiller

A majority of studies of patients with rheumatoid arthritis that have collected data on rheumatoid factor status and response to treatment indicate that positivity for the autoantibody predicts response to rituximab and tocilizumab but not abatacept, according to a systematic review and meta-analysis.

The association of rheumatoid factor (RF) and response to certain biologics is disputed, and the findings have been contradictory. Meanwhile, there’s considerable heterogeneity in patient response to biologics: While some don’t benefit from a certain biologic, they do well on a different one, Dr. Jose Ramon Maneiro of Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain, and his colleagues wrote in their report.

The investigators set out to summarize the available evidence for how well RF positivity predicts response to rituximab, tocilizumab, and abatacept. They searched Medline, Embase, and the Cochrane Library for studies published between 2000 and 2011 in English, Spanish, French, Italian, or Portuguese, as well as online abstracts from the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) congresses from the same time period. The search resulted in more than 3,600 references and abstracts, from which they carefully selected 23 studies representing data from more than 5,800 patients (Semin. Arthritis Rheum. 2013 Jan. 3 [doi: 10.1016/j.semarthrit.2012.11.007]).

The researchers identified 14 studies on rituximab involving about 2,100 patients. In 11 studies that analyzed IgM RF status, 6 reported a significant association between IgM RF positivity and clinical response, including 1 that found a significant association with a titer greater than 30 IU/L but not greater than 20 IU/L. IgA RF status was significantly associated with clinical response in one study, while two other studies reported that IgG RF and IgA RF titers were significantly associated with clinical response. In six studies that used EULAR response criteria, patients with IgM RF positivity had significantly greater odds for meeting the response criteria than did those who were IgM RF negative (odds ratio, 3.52). Assessments of ACR response criteria found that RF positivity resulted in greater odds for an ACR20 response to rituximab in three studies (OR, 1.95) and an ACR50 response in three studies (OR, 5.38).

In four studies on tocilizumab, two indicated no relationship between RF status and response to the drug, whereas one report that analyzed data from three clinical trials found a significant association between RF status and ACR20 response. Another study found that the titer of IgM RF could predict Clinical Disease Activity Index. Overall, a meta-analysis of three studies found that RF positivity was significantly associated with greater odds for an ACR20 response (OR, 1.51).

A post hoc analysis of efficacy data from three clinical trials of abatacept showed no association between RF positivity and response to the drug. However, one observational study reported an association.

The review had several limitations, the authors noted. The meta-analysis aggregated results from clinical trials and observational studies, but none of the clinical trials was designed to test the studied association. Also, in observational studies there is a potential for bias from unmeasured confounding factors. In addition, the quality of the studies was low, the authors reported.

The study was partially supported by the Instituto de Salud Carlos III. The currently available version of the report, a corrected proof, did not note any financial disclosures for the authors.

n.miller@elsevier.com

On Twitter @NaseemSMiller

A majority of studies of patients with rheumatoid arthritis that have collected data on rheumatoid factor status and response to treatment indicate that positivity for the autoantibody predicts response to rituximab and tocilizumab but not abatacept, according to a systematic review and meta-analysis.

The association of rheumatoid factor (RF) and response to certain biologics is disputed, and the findings have been contradictory. Meanwhile, there’s considerable heterogeneity in patient response to biologics: While some don’t benefit from a certain biologic, they do well on a different one, Dr. Jose Ramon Maneiro of Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain, and his colleagues wrote in their report.

The investigators set out to summarize the available evidence for how well RF positivity predicts response to rituximab, tocilizumab, and abatacept. They searched Medline, Embase, and the Cochrane Library for studies published between 2000 and 2011 in English, Spanish, French, Italian, or Portuguese, as well as online abstracts from the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) congresses from the same time period. The search resulted in more than 3,600 references and abstracts, from which they carefully selected 23 studies representing data from more than 5,800 patients (Semin. Arthritis Rheum. 2013 Jan. 3 [doi: 10.1016/j.semarthrit.2012.11.007]).

The researchers identified 14 studies on rituximab involving about 2,100 patients. In 11 studies that analyzed IgM RF status, 6 reported a significant association between IgM RF positivity and clinical response, including 1 that found a significant association with a titer greater than 30 IU/L but not greater than 20 IU/L. IgA RF status was significantly associated with clinical response in one study, while two other studies reported that IgG RF and IgA RF titers were significantly associated with clinical response. In six studies that used EULAR response criteria, patients with IgM RF positivity had significantly greater odds for meeting the response criteria than did those who were IgM RF negative (odds ratio, 3.52). Assessments of ACR response criteria found that RF positivity resulted in greater odds for an ACR20 response to rituximab in three studies (OR, 1.95) and an ACR50 response in three studies (OR, 5.38).

In four studies on tocilizumab, two indicated no relationship between RF status and response to the drug, whereas one report that analyzed data from three clinical trials found a significant association between RF status and ACR20 response. Another study found that the titer of IgM RF could predict Clinical Disease Activity Index. Overall, a meta-analysis of three studies found that RF positivity was significantly associated with greater odds for an ACR20 response (OR, 1.51).

A post hoc analysis of efficacy data from three clinical trials of abatacept showed no association between RF positivity and response to the drug. However, one observational study reported an association.

The review had several limitations, the authors noted. The meta-analysis aggregated results from clinical trials and observational studies, but none of the clinical trials was designed to test the studied association. Also, in observational studies there is a potential for bias from unmeasured confounding factors. In addition, the quality of the studies was low, the authors reported.

The study was partially supported by the Instituto de Salud Carlos III. The currently available version of the report, a corrected proof, did not note any financial disclosures for the authors.

n.miller@elsevier.com

On Twitter @NaseemSMiller

Among adults with treatment-refractory rheumatoid arthritis, the investigative oral Janus kinase inhibitor tofacitinib taken at doses of 5 and 10 mg twice a day in combination with methotrexate produced rapid and clinically meaningful improvements in signs and symptoms of the disease as well as in physical function at 6 months, results from a large multicenter phase III trial showed.

In the study, funded by Pfizer, makers of tofacitinib, and published online Jan. 5, 2013, in The Lancet, investigators at 82 centers in 13 countries evaluated 399 adult patients with moderate to severe arthritis who were unresponsive to tumor necrosis factor inhibitors. The patients were randomly assigned in a 2:2:1:1 ratio to tofacitinib 5 mg twice a day (133 patients); tofacitinib 10 mg twice a day (134 patients); placebo (132) for 3 months then advanced to 5 mg tofacitinib twice a day; or placebo for 3 months then advanced to 10 mg tofacitinib twice a day, all with stable doses of methotrexate (Lancet 2013 Jan. 5 [doi:10.1016/S0140-6736(12)61424-X]). The three primary endpoints were the American College of Rheumatology–20 (ACR20) response rate, the mean change from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI), and Disease Activity Score of less than 2.6 in 28 joints (DAS28 less than 2.6).

After 3 months, ACR20 response rates were 41.7% in the 5-mg tofacitinib twice-a-day group and 48.1% in the 10-mg tofacitinib twice-a-day group compared with 24.4% in the placebo group. Improvements from baseline in the HAQ-DI were -0.43 in the 5-mg tofacitinib twice-a-day group and -0.46 in the 10-mg tofacitinib twice-a-day group compared with -0.18 in the placebo group. At the same time, DA28 less than 2.6 rates were 6.7% in the 5-mg tofacitinib twice-a-day group and 8.8% in the 10-mg tofacitinib twice-a-day group compared with 1.7% in the placebo group.

The researchers, who were led by Dr. Gerd R. Burmester, a rheumatologist and professor of medicine at Charité Hospital in Berlin, also observed changes in laboratory parameters for both dosing levels compared with placebo, including decreases in mean neutrophil counts and increases in mean HDL and LDL concentration. "Whether changes in lipid levels associated with immune modulatory therapy are necessarily associated with increased cardiovascular risk is unclear," they wrote. Further studies are warranted "to achieve better understanding of the mechanism underlying the lipid changes seen with tofacitinib in patients with rheumatoid arthritis," they added.

The most common safety events observed across all tofacitinib groups during the first 3 months were diarrhea (4.9%), nasopharyngitis (4.1%), headache (4.1%), and urinary tract infection (3%). Nausea was the most common adverse event seen in the placebo group (6.8%).

Dr. Burmester and his associates acknowledged certain limitations of the study, including the fact that most of the patients were white (83%) and from North America or Europe (88%). "Because these patients had severe treatment-refractory rheumatoid arthritis, placebo treatment duration was limited to 3 months; therefore, definitive conclusions about the long-term efficacy and safety of tofacitinib can only be made after additional data are available for longer treatment durations," they wrote.

Pfizer funded the study. Dr. Gerd R. Burmester of Charité in Berlin has a financial relationship with Pfizer as do many of the coauthors.

d.brunk@elsevier.com

Among adults with treatment-refractory rheumatoid arthritis, the investigative oral Janus kinase inhibitor tofacitinib taken at doses of 5 and 10 mg twice a day in combination with methotrexate produced rapid and clinically meaningful improvements in signs and symptoms of the disease as well as in physical function at 6 months, results from a large multicenter phase III trial showed.

In the study, funded by Pfizer, makers of tofacitinib, and published online Jan. 5, 2013, in The Lancet, investigators at 82 centers in 13 countries evaluated 399 adult patients with moderate to severe arthritis who were unresponsive to tumor necrosis factor inhibitors. The patients were randomly assigned in a 2:2:1:1 ratio to tofacitinib 5 mg twice a day (133 patients); tofacitinib 10 mg twice a day (134 patients); placebo (132) for 3 months then advanced to 5 mg tofacitinib twice a day; or placebo for 3 months then advanced to 10 mg tofacitinib twice a day, all with stable doses of methotrexate (Lancet 2013 Jan. 5 [doi:10.1016/S0140-6736(12)61424-X]). The three primary endpoints were the American College of Rheumatology–20 (ACR20) response rate, the mean change from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI), and Disease Activity Score of less than 2.6 in 28 joints (DAS28 less than 2.6).

After 3 months, ACR20 response rates were 41.7% in the 5-mg tofacitinib twice-a-day group and 48.1% in the 10-mg tofacitinib twice-a-day group compared with 24.4% in the placebo group. Improvements from baseline in the HAQ-DI were -0.43 in the 5-mg tofacitinib twice-a-day group and -0.46 in the 10-mg tofacitinib twice-a-day group compared with -0.18 in the placebo group. At the same time, DA28 less than 2.6 rates were 6.7% in the 5-mg tofacitinib twice-a-day group and 8.8% in the 10-mg tofacitinib twice-a-day group compared with 1.7% in the placebo group.

The researchers, who were led by Dr. Gerd R. Burmester, a rheumatologist and professor of medicine at Charité Hospital in Berlin, also observed changes in laboratory parameters for both dosing levels compared with placebo, including decreases in mean neutrophil counts and increases in mean HDL and LDL concentration. "Whether changes in lipid levels associated with immune modulatory therapy are necessarily associated with increased cardiovascular risk is unclear," they wrote. Further studies are warranted "to achieve better understanding of the mechanism underlying the lipid changes seen with tofacitinib in patients with rheumatoid arthritis," they added.

The most common safety events observed across all tofacitinib groups during the first 3 months were diarrhea (4.9%), nasopharyngitis (4.1%), headache (4.1%), and urinary tract infection (3%). Nausea was the most common adverse event seen in the placebo group (6.8%).

Dr. Burmester and his associates acknowledged certain limitations of the study, including the fact that most of the patients were white (83%) and from North America or Europe (88%). "Because these patients had severe treatment-refractory rheumatoid arthritis, placebo treatment duration was limited to 3 months; therefore, definitive conclusions about the long-term efficacy and safety of tofacitinib can only be made after additional data are available for longer treatment durations," they wrote.

Pfizer funded the study. Dr. Gerd R. Burmester of Charité in Berlin has a financial relationship with Pfizer as do many of the coauthors.

d.brunk@elsevier.com

Among adults with treatment-refractory rheumatoid arthritis, the investigative oral Janus kinase inhibitor tofacitinib taken at doses of 5 and 10 mg twice a day in combination with methotrexate produced rapid and clinically meaningful improvements in signs and symptoms of the disease as well as in physical function at 6 months, results from a large multicenter phase III trial showed.

In the study, funded by Pfizer, makers of tofacitinib, and published online Jan. 5, 2013, in The Lancet, investigators at 82 centers in 13 countries evaluated 399 adult patients with moderate to severe arthritis who were unresponsive to tumor necrosis factor inhibitors. The patients were randomly assigned in a 2:2:1:1 ratio to tofacitinib 5 mg twice a day (133 patients); tofacitinib 10 mg twice a day (134 patients); placebo (132) for 3 months then advanced to 5 mg tofacitinib twice a day; or placebo for 3 months then advanced to 10 mg tofacitinib twice a day, all with stable doses of methotrexate (Lancet 2013 Jan. 5 [doi:10.1016/S0140-6736(12)61424-X]). The three primary endpoints were the American College of Rheumatology–20 (ACR20) response rate, the mean change from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI), and Disease Activity Score of less than 2.6 in 28 joints (DAS28 less than 2.6).

After 3 months, ACR20 response rates were 41.7% in the 5-mg tofacitinib twice-a-day group and 48.1% in the 10-mg tofacitinib twice-a-day group compared with 24.4% in the placebo group. Improvements from baseline in the HAQ-DI were -0.43 in the 5-mg tofacitinib twice-a-day group and -0.46 in the 10-mg tofacitinib twice-a-day group compared with -0.18 in the placebo group. At the same time, DA28 less than 2.6 rates were 6.7% in the 5-mg tofacitinib twice-a-day group and 8.8% in the 10-mg tofacitinib twice-a-day group compared with 1.7% in the placebo group.

The researchers, who were led by Dr. Gerd R. Burmester, a rheumatologist and professor of medicine at Charité Hospital in Berlin, also observed changes in laboratory parameters for both dosing levels compared with placebo, including decreases in mean neutrophil counts and increases in mean HDL and LDL concentration. "Whether changes in lipid levels associated with immune modulatory therapy are necessarily associated with increased cardiovascular risk is unclear," they wrote. Further studies are warranted "to achieve better understanding of the mechanism underlying the lipid changes seen with tofacitinib in patients with rheumatoid arthritis," they added.

The most common safety events observed across all tofacitinib groups during the first 3 months were diarrhea (4.9%), nasopharyngitis (4.1%), headache (4.1%), and urinary tract infection (3%). Nausea was the most common adverse event seen in the placebo group (6.8%).

Dr. Burmester and his associates acknowledged certain limitations of the study, including the fact that most of the patients were white (83%) and from North America or Europe (88%). "Because these patients had severe treatment-refractory rheumatoid arthritis, placebo treatment duration was limited to 3 months; therefore, definitive conclusions about the long-term efficacy and safety of tofacitinib can only be made after additional data are available for longer treatment durations," they wrote.

Pfizer funded the study. Dr. Gerd R. Burmester of Charité in Berlin has a financial relationship with Pfizer as do many of the coauthors.

d.brunk@elsevier.com