Diana Mahoney

Major Finding: At 6 months, the mean hemoglobin A_1c of patients in the intervention group decreased from 8.02% to 7.73%, while the mean hemoglobin A_1c of the controls increased from 7.93% to 8.22%.

Data Source: Randomized, controlled trial comparing a peer-support intervention with conventional nurse-led case management in 244 men who had poor glycemic control and were treated in a Veterans Affairs program.

Disclosures: Dr. Heisler had no financial conflicts to disclose.

MINNEAPOLIS — A peer-support intervention was associated with better diabetes control, compared with conventional nurse-led case management, in a 6-month Veterans Affairs study of men with poor glycemic control.

In the randomized prospective study, hemoglobin A_1c (HbA_1c) levels, insulin starts, and self-reported social support significantly improved in the 125 men with diabetes and HbA_1c levels higher than 7.5% who were enrolled in a peer-support intervention. The outcome measures did not improve in 119 matched patients who were randomized to usual care and conventional nurse-led case management, Dr. Michele Heisler reported.

Additionally, peer support was far less time intensive from a staff and resource perspective than other tested programs that have shown similar or less-significant improvements, Dr. Heisler said.

Blood pressure changes during the study were not significantly different for the two groups. Levels of diabetes distress and diabetes social support were assessed based on patient interviews, and new insulin starts were documented from patients' medical records.

For the study, all participants attended an initial session led by a Veterans Affairs (VA) nurse case manager, during which their baseline HbA_1c and blood pressure measures were reviewed and their questions were addressed, explained Dr. Heisler of the University of Michigan in Ann Arbor. After the initial meeting, patients assigned to the intervention arm participated in a group session designed to facilitate communication skills and help them set short-term goals for behavioral changes. Those assigned to usual care received nurse-led case management.

The demographics and baseline patient characteristics were similar in both groups. “The mean age of the predominantly white [82%] male veterans participating in the study was 62 years, and the majority [63%] had an annual income less than $30,000,” Dr. Heisler said. At baseline, the mean HbA_1c levels for the intervention and control groups, respectively, were 8.03% and 7.93%.

Age-matched patients were paired within the same cohort to serve as peer partners, Dr. Heisler said. “Patients were encouraged to call their peer partners at least weekly to provide mutual support and encouragement,” she noted. “We developed a computer platform that enabled them to use their own phones to make calls without exchanging personal phone numbers, and it let us monitor and record the initiation, frequency, and duration of the calls. If patients hadn't made contact with each other within a week, they received reminders.”

Intervention participants also were offered three optional 1.5-hour group sessions at months 1, 3, and 6. “Although these were nurse-led programs, they were completely patient driven and served as a forum for sharing concerns, questions, and strategies and for discussing progress on their action plans,” Dr. Heisler said. In the control arm of the study, patients attended an educational session on nurse-led case management and were offered the services of a nurse case manager.

“At 6 months, the mean A_1c of the intervention patients decreased from 8.02% to 7.73%, while the mean A_1c of the control arm participants increased from 7.93% to 8.22%,” Dr. Heisler reported. “We were especially concerned about patients at high risk, so we did a stratified analysis, looking specifically at the change in A_1c at 6 months for those patients with a baseline A_1c higher than 9.0% and the differences remained significant.” Specifically, in the latter analysis, the mean HbA_1c decrease for intervention arm participants with a baseline HbA_1c higher than 9.0% was 0.88%, compared with a decrease of 0.07% in the control group, she said.

Regarding secondary outcomes, “we did see a 3.4% reduction in blood pressure results for the intervention group, but the differences compared with the control group were not statistically significant,” Dr. Heisler said. “Also, there were eight new insulin starts in the intervention group and only one in the control group, and the diabetes social support outcomes were significantly higher for the intervention group as well.”

An evaluation of intervention participation showed that more than 90% of the peer partners made computer-facilitated weekly calls. Also, 40% of the intervention patients attended all three of the optional group sessions, while 25% attended two sessions and 12% went to one session, she said.

“This model is far less time and resource intensive than other tested programs that have led to similar improvements in A_1c,” Dr. Heisler said.

Major Finding: At 6 months, the mean hemoglobin A_1c of patients in the intervention group decreased from 8.02% to 7.73%, while the mean hemoglobin A_1c of the controls increased from 7.93% to 8.22%.

Data Source: Randomized, controlled trial comparing a peer-support intervention with conventional nurse-led case management in 244 men who had poor glycemic control and were treated in a Veterans Affairs program.

Disclosures: Dr. Heisler had no financial conflicts to disclose.

MINNEAPOLIS — A peer-support intervention was associated with better diabetes control, compared with conventional nurse-led case management, in a 6-month Veterans Affairs study of men with poor glycemic control.

In the randomized prospective study, hemoglobin A_1c (HbA_1c) levels, insulin starts, and self-reported social support significantly improved in the 125 men with diabetes and HbA_1c levels higher than 7.5% who were enrolled in a peer-support intervention. The outcome measures did not improve in 119 matched patients who were randomized to usual care and conventional nurse-led case management, Dr. Michele Heisler reported.

Additionally, peer support was far less time intensive from a staff and resource perspective than other tested programs that have shown similar or less-significant improvements, Dr. Heisler said.

Blood pressure changes during the study were not significantly different for the two groups. Levels of diabetes distress and diabetes social support were assessed based on patient interviews, and new insulin starts were documented from patients' medical records.

For the study, all participants attended an initial session led by a Veterans Affairs (VA) nurse case manager, during which their baseline HbA_1c and blood pressure measures were reviewed and their questions were addressed, explained Dr. Heisler of the University of Michigan in Ann Arbor. After the initial meeting, patients assigned to the intervention arm participated in a group session designed to facilitate communication skills and help them set short-term goals for behavioral changes. Those assigned to usual care received nurse-led case management.

The demographics and baseline patient characteristics were similar in both groups. “The mean age of the predominantly white [82%] male veterans participating in the study was 62 years, and the majority [63%] had an annual income less than $30,000,” Dr. Heisler said. At baseline, the mean HbA_1c levels for the intervention and control groups, respectively, were 8.03% and 7.93%.

Age-matched patients were paired within the same cohort to serve as peer partners, Dr. Heisler said. “Patients were encouraged to call their peer partners at least weekly to provide mutual support and encouragement,” she noted. “We developed a computer platform that enabled them to use their own phones to make calls without exchanging personal phone numbers, and it let us monitor and record the initiation, frequency, and duration of the calls. If patients hadn't made contact with each other within a week, they received reminders.”

Intervention participants also were offered three optional 1.5-hour group sessions at months 1, 3, and 6. “Although these were nurse-led programs, they were completely patient driven and served as a forum for sharing concerns, questions, and strategies and for discussing progress on their action plans,” Dr. Heisler said. In the control arm of the study, patients attended an educational session on nurse-led case management and were offered the services of a nurse case manager.

“At 6 months, the mean A_1c of the intervention patients decreased from 8.02% to 7.73%, while the mean A_1c of the control arm participants increased from 7.93% to 8.22%,” Dr. Heisler reported. “We were especially concerned about patients at high risk, so we did a stratified analysis, looking specifically at the change in A_1c at 6 months for those patients with a baseline A_1c higher than 9.0% and the differences remained significant.” Specifically, in the latter analysis, the mean HbA_1c decrease for intervention arm participants with a baseline HbA_1c higher than 9.0% was 0.88%, compared with a decrease of 0.07% in the control group, she said.

Regarding secondary outcomes, “we did see a 3.4% reduction in blood pressure results for the intervention group, but the differences compared with the control group were not statistically significant,” Dr. Heisler said. “Also, there were eight new insulin starts in the intervention group and only one in the control group, and the diabetes social support outcomes were significantly higher for the intervention group as well.”

An evaluation of intervention participation showed that more than 90% of the peer partners made computer-facilitated weekly calls. Also, 40% of the intervention patients attended all three of the optional group sessions, while 25% attended two sessions and 12% went to one session, she said.

“This model is far less time and resource intensive than other tested programs that have led to similar improvements in A_1c,” Dr. Heisler said.

Major Finding: At 6 months, the mean hemoglobin A_1c of patients in the intervention group decreased from 8.02% to 7.73%, while the mean hemoglobin A_1c of the controls increased from 7.93% to 8.22%.

Data Source: Randomized, controlled trial comparing a peer-support intervention with conventional nurse-led case management in 244 men who had poor glycemic control and were treated in a Veterans Affairs program.

Disclosures: Dr. Heisler had no financial conflicts to disclose.

MINNEAPOLIS — A peer-support intervention was associated with better diabetes control, compared with conventional nurse-led case management, in a 6-month Veterans Affairs study of men with poor glycemic control.

In the randomized prospective study, hemoglobin A_1c (HbA_1c) levels, insulin starts, and self-reported social support significantly improved in the 125 men with diabetes and HbA_1c levels higher than 7.5% who were enrolled in a peer-support intervention. The outcome measures did not improve in 119 matched patients who were randomized to usual care and conventional nurse-led case management, Dr. Michele Heisler reported.

Additionally, peer support was far less time intensive from a staff and resource perspective than other tested programs that have shown similar or less-significant improvements, Dr. Heisler said.

Blood pressure changes during the study were not significantly different for the two groups. Levels of diabetes distress and diabetes social support were assessed based on patient interviews, and new insulin starts were documented from patients' medical records.

For the study, all participants attended an initial session led by a Veterans Affairs (VA) nurse case manager, during which their baseline HbA_1c and blood pressure measures were reviewed and their questions were addressed, explained Dr. Heisler of the University of Michigan in Ann Arbor. After the initial meeting, patients assigned to the intervention arm participated in a group session designed to facilitate communication skills and help them set short-term goals for behavioral changes. Those assigned to usual care received nurse-led case management.

The demographics and baseline patient characteristics were similar in both groups. “The mean age of the predominantly white [82%] male veterans participating in the study was 62 years, and the majority [63%] had an annual income less than $30,000,” Dr. Heisler said. At baseline, the mean HbA_1c levels for the intervention and control groups, respectively, were 8.03% and 7.93%.

Age-matched patients were paired within the same cohort to serve as peer partners, Dr. Heisler said. “Patients were encouraged to call their peer partners at least weekly to provide mutual support and encouragement,” she noted. “We developed a computer platform that enabled them to use their own phones to make calls without exchanging personal phone numbers, and it let us monitor and record the initiation, frequency, and duration of the calls. If patients hadn't made contact with each other within a week, they received reminders.”

Intervention participants also were offered three optional 1.5-hour group sessions at months 1, 3, and 6. “Although these were nurse-led programs, they were completely patient driven and served as a forum for sharing concerns, questions, and strategies and for discussing progress on their action plans,” Dr. Heisler said. In the control arm of the study, patients attended an educational session on nurse-led case management and were offered the services of a nurse case manager.

“At 6 months, the mean A_1c of the intervention patients decreased from 8.02% to 7.73%, while the mean A_1c of the control arm participants increased from 7.93% to 8.22%,” Dr. Heisler reported. “We were especially concerned about patients at high risk, so we did a stratified analysis, looking specifically at the change in A_1c at 6 months for those patients with a baseline A_1c higher than 9.0% and the differences remained significant.” Specifically, in the latter analysis, the mean HbA_1c decrease for intervention arm participants with a baseline HbA_1c higher than 9.0% was 0.88%, compared with a decrease of 0.07% in the control group, she said.

Regarding secondary outcomes, “we did see a 3.4% reduction in blood pressure results for the intervention group, but the differences compared with the control group were not statistically significant,” Dr. Heisler said. “Also, there were eight new insulin starts in the intervention group and only one in the control group, and the diabetes social support outcomes were significantly higher for the intervention group as well.”

An evaluation of intervention participation showed that more than 90% of the peer partners made computer-facilitated weekly calls. Also, 40% of the intervention patients attended all three of the optional group sessions, while 25% attended two sessions and 12% went to one session, she said.

“This model is far less time and resource intensive than other tested programs that have led to similar improvements in A_1c,” Dr. Heisler said.

Major Finding: Office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interacting with the legal system, from 16% to 1%.

Data Source: A secondary analysis of data from a randomized clinical trial of 166 opioid-addicted individuals treated with buprenorphine/naloxone in a primary care clinic.

Disclosures: Dr. Fiellin reported no relevant financial conflicts of interest.

MINNEAPOLIS — Opioid-dependent patients with a history of incarceration do well with office-based buprenorphine/naloxone therapy and have fewer interactions over time with the legal and criminal justice systems, according to a data analysis of a previous randomized, controlled trial.

“Our findings should offer some reassurance for community health care providers about initiating buprenorphine/naloxone treatment in the office setting,” Dr. David Fiellin reported.

Dr. Fiellin, along with lead investigator Dr. Emily Wang and colleagues at Yale University, New Haven, Conn., performed a secondary data analysis of a previous trial of three levels of psychosocial counseling and medication dispensing along with buprenorphine/naloxone maintenance treatment in a primary care clinic (N. Engl. J. Med. 2006;355:365-74). The researchers compared demographics, clinical characteristics, and treatment outcomes for 166 adults receiving primary care–based buprenorphine/naloxone treatment, stratifying by history of incarceration as determined by the legal domain of the Addiction Severity Index.

Of the 166 patients, 52 had previously been incarcerated, Dr. Fiellin reported. Former inmates were more likely than other patients to be older, male, an ethnic minority, and unemployed. Also, they were more likely to have long histories of opioid dependence, have received methadone treatment, and have hepatitis C infection. The mean dose of buprenorphine/naloxone was 18.0 mg.

Among the previously incarcerated patients, the mean consecutive weeks of opioid abstinence was 6.2 based on opioid-negative urine samples. For other patients, it was 5.9 weeks. Mean treatment duration was 17.9 weeks and 17.6 weeks. The percentage of previously incarcerated patients completing treatment was 38%; for other patients, it was 46%.

Among patients who remained in treatment, a subsequent longitudinal analysis of self-reported illegal activity and interactions with the legal and criminal justice systems, conducted at 4-week intervals, showed that “office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interactions with the legal system, from 16% to 1%,” Dr. Fiellin said.

“Approximately 25% of all of those dependent on heroin pass through the criminal justice system each year,” Dr. Fiellin commented. Correctional facilities provide an obvious opportunity to engage opioid-dependent individuals with treatment.

“Unfortunately, less than 0.5% of all opioid-dependent individuals receive treatment while incarcerated, and as such they are more likely to connect with services in office-based programs upon release,” he said.

Major Finding: Office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interacting with the legal system, from 16% to 1%.

Data Source: A secondary analysis of data from a randomized clinical trial of 166 opioid-addicted individuals treated with buprenorphine/naloxone in a primary care clinic.

Disclosures: Dr. Fiellin reported no relevant financial conflicts of interest.

MINNEAPOLIS — Opioid-dependent patients with a history of incarceration do well with office-based buprenorphine/naloxone therapy and have fewer interactions over time with the legal and criminal justice systems, according to a data analysis of a previous randomized, controlled trial.

“Our findings should offer some reassurance for community health care providers about initiating buprenorphine/naloxone treatment in the office setting,” Dr. David Fiellin reported.

Dr. Fiellin, along with lead investigator Dr. Emily Wang and colleagues at Yale University, New Haven, Conn., performed a secondary data analysis of a previous trial of three levels of psychosocial counseling and medication dispensing along with buprenorphine/naloxone maintenance treatment in a primary care clinic (N. Engl. J. Med. 2006;355:365-74). The researchers compared demographics, clinical characteristics, and treatment outcomes for 166 adults receiving primary care–based buprenorphine/naloxone treatment, stratifying by history of incarceration as determined by the legal domain of the Addiction Severity Index.

Of the 166 patients, 52 had previously been incarcerated, Dr. Fiellin reported. Former inmates were more likely than other patients to be older, male, an ethnic minority, and unemployed. Also, they were more likely to have long histories of opioid dependence, have received methadone treatment, and have hepatitis C infection. The mean dose of buprenorphine/naloxone was 18.0 mg.

Among the previously incarcerated patients, the mean consecutive weeks of opioid abstinence was 6.2 based on opioid-negative urine samples. For other patients, it was 5.9 weeks. Mean treatment duration was 17.9 weeks and 17.6 weeks. The percentage of previously incarcerated patients completing treatment was 38%; for other patients, it was 46%.

Among patients who remained in treatment, a subsequent longitudinal analysis of self-reported illegal activity and interactions with the legal and criminal justice systems, conducted at 4-week intervals, showed that “office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interactions with the legal system, from 16% to 1%,” Dr. Fiellin said.

“Approximately 25% of all of those dependent on heroin pass through the criminal justice system each year,” Dr. Fiellin commented. Correctional facilities provide an obvious opportunity to engage opioid-dependent individuals with treatment.

“Unfortunately, less than 0.5% of all opioid-dependent individuals receive treatment while incarcerated, and as such they are more likely to connect with services in office-based programs upon release,” he said.

Major Finding: Office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interacting with the legal system, from 16% to 1%.

Data Source: A secondary analysis of data from a randomized clinical trial of 166 opioid-addicted individuals treated with buprenorphine/naloxone in a primary care clinic.

Disclosures: Dr. Fiellin reported no relevant financial conflicts of interest.

MINNEAPOLIS — Opioid-dependent patients with a history of incarceration do well with office-based buprenorphine/naloxone therapy and have fewer interactions over time with the legal and criminal justice systems, according to a data analysis of a previous randomized, controlled trial.

“Our findings should offer some reassurance for community health care providers about initiating buprenorphine/naloxone treatment in the office setting,” Dr. David Fiellin reported.

Dr. Fiellin, along with lead investigator Dr. Emily Wang and colleagues at Yale University, New Haven, Conn., performed a secondary data analysis of a previous trial of three levels of psychosocial counseling and medication dispensing along with buprenorphine/naloxone maintenance treatment in a primary care clinic (N. Engl. J. Med. 2006;355:365-74). The researchers compared demographics, clinical characteristics, and treatment outcomes for 166 adults receiving primary care–based buprenorphine/naloxone treatment, stratifying by history of incarceration as determined by the legal domain of the Addiction Severity Index.

Of the 166 patients, 52 had previously been incarcerated, Dr. Fiellin reported. Former inmates were more likely than other patients to be older, male, an ethnic minority, and unemployed. Also, they were more likely to have long histories of opioid dependence, have received methadone treatment, and have hepatitis C infection. The mean dose of buprenorphine/naloxone was 18.0 mg.

Among the previously incarcerated patients, the mean consecutive weeks of opioid abstinence was 6.2 based on opioid-negative urine samples. For other patients, it was 5.9 weeks. Mean treatment duration was 17.9 weeks and 17.6 weeks. The percentage of previously incarcerated patients completing treatment was 38%; for other patients, it was 46%.

Among patients who remained in treatment, a subsequent longitudinal analysis of self-reported illegal activity and interactions with the legal and criminal justice systems, conducted at 4-week intervals, showed that “office-based buprenorphine/naloxone treatment was associated with a statistically significant decrease in participants reporting illegal activity, from 19% to 2%, and in interactions with the legal system, from 16% to 1%,” Dr. Fiellin said.

“Approximately 25% of all of those dependent on heroin pass through the criminal justice system each year,” Dr. Fiellin commented. Correctional facilities provide an obvious opportunity to engage opioid-dependent individuals with treatment.

“Unfortunately, less than 0.5% of all opioid-dependent individuals receive treatment while incarcerated, and as such they are more likely to connect with services in office-based programs upon release,” he said.

Major Findings: TNF-alpha blockade decreases circulating levels of a clinically relevant biomarker for heart failure and alters the neurotransmitter pathway linked to depression in RA.

Data Source: Two observational studies.

Disclosures: Dr. McInnes has received research support or honoraria from Schering-Plough, Roche, Bristol-Myers Squibb Co., and Wyeth and has served as a consultant for Schering-Plough and Roche.

DESTIN, FLA. — The benefits of tumor necrosis factor blockade extend beyond the joints to the hearts and minds of rheumatoid arthritis patients, Dr. Iain McInnes reported at the Congress of Clinical Rheumatology.

Findings from two new studies suggest that anti-TNF treatment can inhibit the cytokine-induced chain of events that leads to the increased risk of cardiovascular disease and clinical depression in RA.

Along with lead investigator Dr. Mike J.L. Peters of VU University Medical Center in Amsterdam, Dr. McInnes and colleagues at the University of Glasgow (Scotland) have shown, for the first time, that anti-TNF-alpha therapy decreases circulating levels of the cardiac neurohormone N-terminal prohormone brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) who do not have evident heart failure.

Previously identified as a clinically relevant biomarker for heart failure, NT-proBNP is independently associated with cardiovascular risk in individuals with and without preexisting cardiovascular disease. Thus, the observed reduction in NT-proBNP suggests a “potential beneficial effect of [TNF-alpha] blockers with respect to vascular risk and ventricular function in rheumatoid arthritis,” said Dr. McInnes.

The study measured serum NT-pro-BNP at baseline and after 16 weeks of biweekly adalimumab treatment in 171 consecutive RA patients without heart failure (Ann. Rheum. Dis. 2010 April 7 [doi:10.1136/ard.2009.119412]). After week 16, the investigators observed an approximately 18% reduction in NT-proBNP levels, providing biological evidence that TNF-alpha blockade does not worsen ventricular function in patients with RA who do not have prevalent heart failure, and supporting epidemiologic findings that indicate it may reduce overall cardiovascular risks in these patients, Dr. McInnes explained.

The results also add weight to the accumulating evidence that implicates TNF-alpha in the cardiovascular events associated with RA, and support the beneficial effect that blocking TNF-alpha has on surrogate vascular markers, he said.

In a separate study, Dr. McInnes and colleagues sought to assess the functional effects of anti-TNF-alpha therapy on the brains of depressed patients with RA, and determined that TNF-alpha blockade mediates altered serotonin transporter availability and induces an improvement in depression measures.

“This is critically important,” Dr. McInnes stressed, referring to a 2006 report suggesting that the prevalence of major depressive disorder exceeds 40% and that of suicidal ideation is up to 11% in RA patients (Rheumatology [Oxford] 2006;45:1325-7).

Findings from earlier research have shown that proinflammatory cytokines can increase the density and activity of the serotonin transporter (SERT), a primary target for antidepressant therapy. On that basis, Dr. McInnes and his associates hypothesized that TNF blockade might be associated with altered SERT activity in RA patients, he said. They tested this hypothesis in a clinical, proof-of-concept study by measuring SERT density using SPECT (single-photon emission CT) in six patients with seropositive RA 2 weeks before the initiation of adalimumab therapy and 4 days after the last treatment, Dr. McInnes said.

After anti-TNF-alpha therapy, “there was a significant decrease in the [SERT] density in all of the patients.” Along with that came overall improvements in physical and mental functioning, as measured by the Hamilton Rating Scale for Depression, the Social Functioning 36-item scale, the Hospital Anxiety and Depression Scale, and the composite 28 joint count Disease Activity Score, Dr. McInnes reported.

Major Findings: TNF-alpha blockade decreases circulating levels of a clinically relevant biomarker for heart failure and alters the neurotransmitter pathway linked to depression in RA.

Data Source: Two observational studies.

Disclosures: Dr. McInnes has received research support or honoraria from Schering-Plough, Roche, Bristol-Myers Squibb Co., and Wyeth and has served as a consultant for Schering-Plough and Roche.

DESTIN, FLA. — The benefits of tumor necrosis factor blockade extend beyond the joints to the hearts and minds of rheumatoid arthritis patients, Dr. Iain McInnes reported at the Congress of Clinical Rheumatology.

Findings from two new studies suggest that anti-TNF treatment can inhibit the cytokine-induced chain of events that leads to the increased risk of cardiovascular disease and clinical depression in RA.

Along with lead investigator Dr. Mike J.L. Peters of VU University Medical Center in Amsterdam, Dr. McInnes and colleagues at the University of Glasgow (Scotland) have shown, for the first time, that anti-TNF-alpha therapy decreases circulating levels of the cardiac neurohormone N-terminal prohormone brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) who do not have evident heart failure.

Previously identified as a clinically relevant biomarker for heart failure, NT-proBNP is independently associated with cardiovascular risk in individuals with and without preexisting cardiovascular disease. Thus, the observed reduction in NT-proBNP suggests a “potential beneficial effect of [TNF-alpha] blockers with respect to vascular risk and ventricular function in rheumatoid arthritis,” said Dr. McInnes.

The study measured serum NT-pro-BNP at baseline and after 16 weeks of biweekly adalimumab treatment in 171 consecutive RA patients without heart failure (Ann. Rheum. Dis. 2010 April 7 [doi:10.1136/ard.2009.119412]). After week 16, the investigators observed an approximately 18% reduction in NT-proBNP levels, providing biological evidence that TNF-alpha blockade does not worsen ventricular function in patients with RA who do not have prevalent heart failure, and supporting epidemiologic findings that indicate it may reduce overall cardiovascular risks in these patients, Dr. McInnes explained.

The results also add weight to the accumulating evidence that implicates TNF-alpha in the cardiovascular events associated with RA, and support the beneficial effect that blocking TNF-alpha has on surrogate vascular markers, he said.

In a separate study, Dr. McInnes and colleagues sought to assess the functional effects of anti-TNF-alpha therapy on the brains of depressed patients with RA, and determined that TNF-alpha blockade mediates altered serotonin transporter availability and induces an improvement in depression measures.

“This is critically important,” Dr. McInnes stressed, referring to a 2006 report suggesting that the prevalence of major depressive disorder exceeds 40% and that of suicidal ideation is up to 11% in RA patients (Rheumatology [Oxford] 2006;45:1325-7).

Findings from earlier research have shown that proinflammatory cytokines can increase the density and activity of the serotonin transporter (SERT), a primary target for antidepressant therapy. On that basis, Dr. McInnes and his associates hypothesized that TNF blockade might be associated with altered SERT activity in RA patients, he said. They tested this hypothesis in a clinical, proof-of-concept study by measuring SERT density using SPECT (single-photon emission CT) in six patients with seropositive RA 2 weeks before the initiation of adalimumab therapy and 4 days after the last treatment, Dr. McInnes said.

After anti-TNF-alpha therapy, “there was a significant decrease in the [SERT] density in all of the patients.” Along with that came overall improvements in physical and mental functioning, as measured by the Hamilton Rating Scale for Depression, the Social Functioning 36-item scale, the Hospital Anxiety and Depression Scale, and the composite 28 joint count Disease Activity Score, Dr. McInnes reported.

Major Findings: TNF-alpha blockade decreases circulating levels of a clinically relevant biomarker for heart failure and alters the neurotransmitter pathway linked to depression in RA.

Data Source: Two observational studies.

Disclosures: Dr. McInnes has received research support or honoraria from Schering-Plough, Roche, Bristol-Myers Squibb Co., and Wyeth and has served as a consultant for Schering-Plough and Roche.

DESTIN, FLA. — The benefits of tumor necrosis factor blockade extend beyond the joints to the hearts and minds of rheumatoid arthritis patients, Dr. Iain McInnes reported at the Congress of Clinical Rheumatology.

Findings from two new studies suggest that anti-TNF treatment can inhibit the cytokine-induced chain of events that leads to the increased risk of cardiovascular disease and clinical depression in RA.

Along with lead investigator Dr. Mike J.L. Peters of VU University Medical Center in Amsterdam, Dr. McInnes and colleagues at the University of Glasgow (Scotland) have shown, for the first time, that anti-TNF-alpha therapy decreases circulating levels of the cardiac neurohormone N-terminal prohormone brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) who do not have evident heart failure.

Previously identified as a clinically relevant biomarker for heart failure, NT-proBNP is independently associated with cardiovascular risk in individuals with and without preexisting cardiovascular disease. Thus, the observed reduction in NT-proBNP suggests a “potential beneficial effect of [TNF-alpha] blockers with respect to vascular risk and ventricular function in rheumatoid arthritis,” said Dr. McInnes.

The study measured serum NT-pro-BNP at baseline and after 16 weeks of biweekly adalimumab treatment in 171 consecutive RA patients without heart failure (Ann. Rheum. Dis. 2010 April 7 [doi:10.1136/ard.2009.119412]). After week 16, the investigators observed an approximately 18% reduction in NT-proBNP levels, providing biological evidence that TNF-alpha blockade does not worsen ventricular function in patients with RA who do not have prevalent heart failure, and supporting epidemiologic findings that indicate it may reduce overall cardiovascular risks in these patients, Dr. McInnes explained.

The results also add weight to the accumulating evidence that implicates TNF-alpha in the cardiovascular events associated with RA, and support the beneficial effect that blocking TNF-alpha has on surrogate vascular markers, he said.

In a separate study, Dr. McInnes and colleagues sought to assess the functional effects of anti-TNF-alpha therapy on the brains of depressed patients with RA, and determined that TNF-alpha blockade mediates altered serotonin transporter availability and induces an improvement in depression measures.

“This is critically important,” Dr. McInnes stressed, referring to a 2006 report suggesting that the prevalence of major depressive disorder exceeds 40% and that of suicidal ideation is up to 11% in RA patients (Rheumatology [Oxford] 2006;45:1325-7).

Findings from earlier research have shown that proinflammatory cytokines can increase the density and activity of the serotonin transporter (SERT), a primary target for antidepressant therapy. On that basis, Dr. McInnes and his associates hypothesized that TNF blockade might be associated with altered SERT activity in RA patients, he said. They tested this hypothesis in a clinical, proof-of-concept study by measuring SERT density using SPECT (single-photon emission CT) in six patients with seropositive RA 2 weeks before the initiation of adalimumab therapy and 4 days after the last treatment, Dr. McInnes said.

After anti-TNF-alpha therapy, “there was a significant decrease in the [SERT] density in all of the patients.” Along with that came overall improvements in physical and mental functioning, as measured by the Hamilton Rating Scale for Depression, the Social Functioning 36-item scale, the Hospital Anxiety and Depression Scale, and the composite 28 joint count Disease Activity Score, Dr. McInnes reported.

Major Findings: TNF-alpha blockade resulted in an 18% reduction in levels of NT-proBNP, a biomarker for heart failure, as well as altered serotonin transporter availability, affecting depression.

Data Source: Two studies of 171 and 6 patients.

Disclosures: Dr. McInnes has financial ties with Schering-Plough, Roche, Bristol-Myers Squibb, and Wyeth and has served as a consultant for Schering-Plough and Roche.

DESTIN, FLA. — The benefits of tumor necrosis factor blockade extend beyond the joints to the hearts and minds of rheumatoid arthritis patients, Dr. Iain McInnes reported at the Congress of Clinical Rheumatology.

Findings from two new studies suggest that anti-TNF treatment can inhibit the cytokine-induced chain of events that leads to the increased risk of cardiovascular disease and clinical depression in RA.

Along with lead investigator Dr. Mike J.L. Peters of VU University Medical Center in Amsterdam, Dr. McInnes and colleagues at the University of Glasgow (Scotland) have shown, for the first time, that anti-TNF-alpha therapy decreases circulating levels of the cardiac neurohormone N-terminal prohormone brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) who do not have evident heart failure.

Previously identified as a clinically relevant biomarker for heart failure, NT-proBNP is independently associated with cardiovascular risk. Thus, the observed reduction in NT-proBNP suggests a “potential beneficial effect of [TNF-alpha] blockers with respect to vascular risk and ventricular function in rheumatoid arthritis,” Dr. McInnes said.

The study measured serum NT-proBNP at baseline and after 16 weeks of biweekly adalimumab treatment in 171 consecutive RA patients without heart failure (Ann. Rheum. Dis. 2010 April 7 [doi:10.1136/ard.2009.119412

In a separate study, Dr. McInnes and colleagues sought to assess the functional effects of anti-TNF-alpha therapy on the brains of depressed patients with RA, and determined that TNF-alpha blockade mediates altered serotonin transporter availability and induces an improvement in depression measures.

“This is critically important,” Dr. McInnes stressed, referring to a 2006 report suggesting that the prevalence of major depressive disorder exceeds 40% in RA patients (Rheumatology [Oxford] 2006;45:1325–7).

Findings from earlier research have shown that proinflammatory cytokines can increase the density and activity of the serotonin transporter (SERT), a primary target for antidepressant therapy. On that basis, Dr. McInnes and his associates hypothesized that TNF blockade might be associated with altered SERT activity in RA patients, he said. They tested this hypothesis in a clinical, proof-of-concept study by measuring SERT density using SPECT (single-photon emission CT) in six patients with seropositive RA 2 weeks before the initiation of adalimumab therapy and 4 days after the last treatment, he said.

After anti-TNF-alpha therapy, “there was a significant decrease in the [SERT] density in all of the patients,” as well as overall improvements in physical and mental functioning, Dr. McInnes said.

Although it is yet unclear whether the observed SERT alterations are specific to RA or are related to cytokine action in general, “the findings provide important insight into the biology linking clinical depression and rheumatoid arthritis.” If confirmed in larger studies, the findings may offer guidance for developing treatment strategies, he said.

Major Findings: TNF-alpha blockade resulted in an 18% reduction in levels of NT-proBNP, a biomarker for heart failure, as well as altered serotonin transporter availability, affecting depression.

Data Source: Two studies of 171 and 6 patients.

Disclosures: Dr. McInnes has financial ties with Schering-Plough, Roche, Bristol-Myers Squibb, and Wyeth and has served as a consultant for Schering-Plough and Roche.

DESTIN, FLA. — The benefits of tumor necrosis factor blockade extend beyond the joints to the hearts and minds of rheumatoid arthritis patients, Dr. Iain McInnes reported at the Congress of Clinical Rheumatology.

Findings from two new studies suggest that anti-TNF treatment can inhibit the cytokine-induced chain of events that leads to the increased risk of cardiovascular disease and clinical depression in RA.

Along with lead investigator Dr. Mike J.L. Peters of VU University Medical Center in Amsterdam, Dr. McInnes and colleagues at the University of Glasgow (Scotland) have shown, for the first time, that anti-TNF-alpha therapy decreases circulating levels of the cardiac neurohormone N-terminal prohormone brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) who do not have evident heart failure.

Previously identified as a clinically relevant biomarker for heart failure, NT-proBNP is independently associated with cardiovascular risk. Thus, the observed reduction in NT-proBNP suggests a “potential beneficial effect of [TNF-alpha] blockers with respect to vascular risk and ventricular function in rheumatoid arthritis,” Dr. McInnes said.

The study measured serum NT-proBNP at baseline and after 16 weeks of biweekly adalimumab treatment in 171 consecutive RA patients without heart failure (Ann. Rheum. Dis. 2010 April 7 [doi:10.1136/ard.2009.119412

In a separate study, Dr. McInnes and colleagues sought to assess the functional effects of anti-TNF-alpha therapy on the brains of depressed patients with RA, and determined that TNF-alpha blockade mediates altered serotonin transporter availability and induces an improvement in depression measures.

“This is critically important,” Dr. McInnes stressed, referring to a 2006 report suggesting that the prevalence of major depressive disorder exceeds 40% in RA patients (Rheumatology [Oxford] 2006;45:1325–7).

Findings from earlier research have shown that proinflammatory cytokines can increase the density and activity of the serotonin transporter (SERT), a primary target for antidepressant therapy. On that basis, Dr. McInnes and his associates hypothesized that TNF blockade might be associated with altered SERT activity in RA patients, he said. They tested this hypothesis in a clinical, proof-of-concept study by measuring SERT density using SPECT (single-photon emission CT) in six patients with seropositive RA 2 weeks before the initiation of adalimumab therapy and 4 days after the last treatment, he said.

After anti-TNF-alpha therapy, “there was a significant decrease in the [SERT] density in all of the patients,” as well as overall improvements in physical and mental functioning, Dr. McInnes said.

Although it is yet unclear whether the observed SERT alterations are specific to RA or are related to cytokine action in general, “the findings provide important insight into the biology linking clinical depression and rheumatoid arthritis.” If confirmed in larger studies, the findings may offer guidance for developing treatment strategies, he said.

Major Findings: TNF-alpha blockade resulted in an 18% reduction in levels of NT-proBNP, a biomarker for heart failure, as well as altered serotonin transporter availability, affecting depression.

Data Source: Two studies of 171 and 6 patients.

Disclosures: Dr. McInnes has financial ties with Schering-Plough, Roche, Bristol-Myers Squibb, and Wyeth and has served as a consultant for Schering-Plough and Roche.

DESTIN, FLA. — The benefits of tumor necrosis factor blockade extend beyond the joints to the hearts and minds of rheumatoid arthritis patients, Dr. Iain McInnes reported at the Congress of Clinical Rheumatology.

Findings from two new studies suggest that anti-TNF treatment can inhibit the cytokine-induced chain of events that leads to the increased risk of cardiovascular disease and clinical depression in RA.

Along with lead investigator Dr. Mike J.L. Peters of VU University Medical Center in Amsterdam, Dr. McInnes and colleagues at the University of Glasgow (Scotland) have shown, for the first time, that anti-TNF-alpha therapy decreases circulating levels of the cardiac neurohormone N-terminal prohormone brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) who do not have evident heart failure.

Previously identified as a clinically relevant biomarker for heart failure, NT-proBNP is independently associated with cardiovascular risk. Thus, the observed reduction in NT-proBNP suggests a “potential beneficial effect of [TNF-alpha] blockers with respect to vascular risk and ventricular function in rheumatoid arthritis,” Dr. McInnes said.

The study measured serum NT-proBNP at baseline and after 16 weeks of biweekly adalimumab treatment in 171 consecutive RA patients without heart failure (Ann. Rheum. Dis. 2010 April 7 [doi:10.1136/ard.2009.119412

In a separate study, Dr. McInnes and colleagues sought to assess the functional effects of anti-TNF-alpha therapy on the brains of depressed patients with RA, and determined that TNF-alpha blockade mediates altered serotonin transporter availability and induces an improvement in depression measures.

“This is critically important,” Dr. McInnes stressed, referring to a 2006 report suggesting that the prevalence of major depressive disorder exceeds 40% in RA patients (Rheumatology [Oxford] 2006;45:1325–7).

Findings from earlier research have shown that proinflammatory cytokines can increase the density and activity of the serotonin transporter (SERT), a primary target for antidepressant therapy. On that basis, Dr. McInnes and his associates hypothesized that TNF blockade might be associated with altered SERT activity in RA patients, he said. They tested this hypothesis in a clinical, proof-of-concept study by measuring SERT density using SPECT (single-photon emission CT) in six patients with seropositive RA 2 weeks before the initiation of adalimumab therapy and 4 days after the last treatment, he said.

After anti-TNF-alpha therapy, “there was a significant decrease in the [SERT] density in all of the patients,” as well as overall improvements in physical and mental functioning, Dr. McInnes said.

Although it is yet unclear whether the observed SERT alterations are specific to RA or are related to cytokine action in general, “the findings provide important insight into the biology linking clinical depression and rheumatoid arthritis.” If confirmed in larger studies, the findings may offer guidance for developing treatment strategies, he said.

Major Finding: Hypertensive patients in a medical home model of care were more likely to reach their blood pressure goal than were those in a traditional internal medicine clinic (OR 1.26).

Data Source: A retrospective cohort study of 2,611 patients with hypertension at two internal medicine clinics within the same health care organization.

Disclosures: Dr. Beran had no financial conflicts of interest to disclose.

MINNEAPOLIS — Hypertensive patients in a medical home intervention were significantly more likely to reach their blood pressure goals by the third year of a 4-year pilot intervention, compared with matched patients seen at a traditional internal medicine clinic.

Based on the findings, Dr. Mary Sue Beran of Park Nicollet Health Services in Minneapolis and her colleagues speculated that the availability of chronic care nurses to manage patient registries and provide regular feedback to providers, and the establishment of a care team to help manage medically complex patients, may have contributed to the results obtained in the medical home setting.

In 2006, one internal medicine clinic within the Park Nicollet organization began reorganizing as a medical home in order to improve the quality of care of patients with complex medical conditions, Dr. Beran said at the annual meeting of the Society of General Internal Medicine.

“This was a phased intervention over time, beginning in 2006 with the addition of one chronic care nurse. By mid-2007, the clinic had four full-time nurses devoted to chronic disease management.”

In a 2008 care-team redesign, the clinic formed teams comprising three or four physicians, a department assistant, a medical information nurse, call staff, and a chronic disease nurse who facilitated such things as visit planning to make sure patients' lab appointments were scheduled at the time of their visits. “They also developed an electronic care plan, and had care coordinators available on-site to identify and remove barriers to care,” Dr. Beran reported. In early 2009, the phone system was redesigned to improve phone access.

To evaluate whether the medical home intervention improved the quality of care in these patients, compared with a control group of patients from another internal medicine clinic within the Park Nicollet organization, “we used a retrospective cohort study design, analyzing the data that had been collected by electronic medical record over a 5-year period, beginning in 2005, before the intervention and yearly through 2009,” Dr. Beran said. Patients in the study were 18 years or older and had at least one chronic health condition: hypertension, type 2 diabetes, coronary artery disease (including peripheral artery disease), or heart failure. Patients had to have been seen at least once annually at one of the sites during the study period.

“The first outcome we looked at was hypertension, and our main outcome measure was whether patients, on their last blood pressure result for a given calendar year, met their outcome goal, which differed depending on medical complexity,” Dr. Beran said. For patients with hypertension only, the outcome goal was a blood pressure below 140/90 mm Hg; for patients with concomitant heart failure, coronary artery disease, or type 2 diabetes the goal was below 130/80 mm Hg.

Of the 2,611 patients who met the study criteria, 1,119 were in the intervention group and 692 were in the control group. “The difference in size reflects the difference in the sizes of the clinics,” Dr. Beran explained. “There were 14 physicians at the intervention site and 5 at the control site.”

At baseline, blood pressures were not significantly different between the intervention and control sites, although adjusted clinical group score, which measures the burden of illness, was slightly higher among the intervention patients.

Most patients were white, the payer group was primarily Medicare or commercial insurance at both sites, and patient age was slightly higher in the intervention group.

In the unadjusted model, “the percentage of patients meeting their blood pressure goals by site over time improved in both groups,” Dr. Beran reported. In the adjusted model, which looked at the population overall, women were less likely than men to reach their blood pressure goal, and the likelihood of meeting the goal decreased with increasing age. Patients with hypertension only were significantly more likely to reach the blood pressure goal, she said.

No significant differences in the likelihood of achieving blood pressure goals were observed between the intervention and control sites for 2006, but moderate increases were observed in 2007, Dr. Beran said. “In 2008, there was a statistically significant increase in the likelihood of achieving blood pressure goals in the intervention group, compared with the control group, with an odds ratio of 1.64,” she reported.

In 2009, “the differences in the likelihood of reaching the blood pressure goal between the intervention and control patients diminished, although it was still statistically significant, with an odds ratio of 1.26,” Dr. Beran said. This trend coincided with significant effort within the organization overall to improve the quality of care and to increase transparency, and with the adoption of care components—such as the use of multiple blood pressure measurements to assess hypertension in at-risk patients—already in place in the medical home model.

“In many ways, the medical home intervention, in effect, raised the bar for quality in the organization,” she said, although more research is needed.

Major Finding: Hypertensive patients in a medical home model of care were more likely to reach their blood pressure goal than were those in a traditional internal medicine clinic (OR 1.26).

Data Source: A retrospective cohort study of 2,611 patients with hypertension at two internal medicine clinics within the same health care organization.

Disclosures: Dr. Beran had no financial conflicts of interest to disclose.

MINNEAPOLIS — Hypertensive patients in a medical home intervention were significantly more likely to reach their blood pressure goals by the third year of a 4-year pilot intervention, compared with matched patients seen at a traditional internal medicine clinic.

Based on the findings, Dr. Mary Sue Beran of Park Nicollet Health Services in Minneapolis and her colleagues speculated that the availability of chronic care nurses to manage patient registries and provide regular feedback to providers, and the establishment of a care team to help manage medically complex patients, may have contributed to the results obtained in the medical home setting.

In 2006, one internal medicine clinic within the Park Nicollet organization began reorganizing as a medical home in order to improve the quality of care of patients with complex medical conditions, Dr. Beran said at the annual meeting of the Society of General Internal Medicine.

“This was a phased intervention over time, beginning in 2006 with the addition of one chronic care nurse. By mid-2007, the clinic had four full-time nurses devoted to chronic disease management.”

In a 2008 care-team redesign, the clinic formed teams comprising three or four physicians, a department assistant, a medical information nurse, call staff, and a chronic disease nurse who facilitated such things as visit planning to make sure patients' lab appointments were scheduled at the time of their visits. “They also developed an electronic care plan, and had care coordinators available on-site to identify and remove barriers to care,” Dr. Beran reported. In early 2009, the phone system was redesigned to improve phone access.

To evaluate whether the medical home intervention improved the quality of care in these patients, compared with a control group of patients from another internal medicine clinic within the Park Nicollet organization, “we used a retrospective cohort study design, analyzing the data that had been collected by electronic medical record over a 5-year period, beginning in 2005, before the intervention and yearly through 2009,” Dr. Beran said. Patients in the study were 18 years or older and had at least one chronic health condition: hypertension, type 2 diabetes, coronary artery disease (including peripheral artery disease), or heart failure. Patients had to have been seen at least once annually at one of the sites during the study period.

“The first outcome we looked at was hypertension, and our main outcome measure was whether patients, on their last blood pressure result for a given calendar year, met their outcome goal, which differed depending on medical complexity,” Dr. Beran said. For patients with hypertension only, the outcome goal was a blood pressure below 140/90 mm Hg; for patients with concomitant heart failure, coronary artery disease, or type 2 diabetes the goal was below 130/80 mm Hg.

Of the 2,611 patients who met the study criteria, 1,119 were in the intervention group and 692 were in the control group. “The difference in size reflects the difference in the sizes of the clinics,” Dr. Beran explained. “There were 14 physicians at the intervention site and 5 at the control site.”

At baseline, blood pressures were not significantly different between the intervention and control sites, although adjusted clinical group score, which measures the burden of illness, was slightly higher among the intervention patients.

Most patients were white, the payer group was primarily Medicare or commercial insurance at both sites, and patient age was slightly higher in the intervention group.

In the unadjusted model, “the percentage of patients meeting their blood pressure goals by site over time improved in both groups,” Dr. Beran reported. In the adjusted model, which looked at the population overall, women were less likely than men to reach their blood pressure goal, and the likelihood of meeting the goal decreased with increasing age. Patients with hypertension only were significantly more likely to reach the blood pressure goal, she said.

No significant differences in the likelihood of achieving blood pressure goals were observed between the intervention and control sites for 2006, but moderate increases were observed in 2007, Dr. Beran said. “In 2008, there was a statistically significant increase in the likelihood of achieving blood pressure goals in the intervention group, compared with the control group, with an odds ratio of 1.64,” she reported.

In 2009, “the differences in the likelihood of reaching the blood pressure goal between the intervention and control patients diminished, although it was still statistically significant, with an odds ratio of 1.26,” Dr. Beran said. This trend coincided with significant effort within the organization overall to improve the quality of care and to increase transparency, and with the adoption of care components—such as the use of multiple blood pressure measurements to assess hypertension in at-risk patients—already in place in the medical home model.

“In many ways, the medical home intervention, in effect, raised the bar for quality in the organization,” she said, although more research is needed.

Major Finding: Hypertensive patients in a medical home model of care were more likely to reach their blood pressure goal than were those in a traditional internal medicine clinic (OR 1.26).

Data Source: A retrospective cohort study of 2,611 patients with hypertension at two internal medicine clinics within the same health care organization.

Disclosures: Dr. Beran had no financial conflicts of interest to disclose.

MINNEAPOLIS — Hypertensive patients in a medical home intervention were significantly more likely to reach their blood pressure goals by the third year of a 4-year pilot intervention, compared with matched patients seen at a traditional internal medicine clinic.

Based on the findings, Dr. Mary Sue Beran of Park Nicollet Health Services in Minneapolis and her colleagues speculated that the availability of chronic care nurses to manage patient registries and provide regular feedback to providers, and the establishment of a care team to help manage medically complex patients, may have contributed to the results obtained in the medical home setting.

In 2006, one internal medicine clinic within the Park Nicollet organization began reorganizing as a medical home in order to improve the quality of care of patients with complex medical conditions, Dr. Beran said at the annual meeting of the Society of General Internal Medicine.

“This was a phased intervention over time, beginning in 2006 with the addition of one chronic care nurse. By mid-2007, the clinic had four full-time nurses devoted to chronic disease management.”

In a 2008 care-team redesign, the clinic formed teams comprising three or four physicians, a department assistant, a medical information nurse, call staff, and a chronic disease nurse who facilitated such things as visit planning to make sure patients' lab appointments were scheduled at the time of their visits. “They also developed an electronic care plan, and had care coordinators available on-site to identify and remove barriers to care,” Dr. Beran reported. In early 2009, the phone system was redesigned to improve phone access.

To evaluate whether the medical home intervention improved the quality of care in these patients, compared with a control group of patients from another internal medicine clinic within the Park Nicollet organization, “we used a retrospective cohort study design, analyzing the data that had been collected by electronic medical record over a 5-year period, beginning in 2005, before the intervention and yearly through 2009,” Dr. Beran said. Patients in the study were 18 years or older and had at least one chronic health condition: hypertension, type 2 diabetes, coronary artery disease (including peripheral artery disease), or heart failure. Patients had to have been seen at least once annually at one of the sites during the study period.

“The first outcome we looked at was hypertension, and our main outcome measure was whether patients, on their last blood pressure result for a given calendar year, met their outcome goal, which differed depending on medical complexity,” Dr. Beran said. For patients with hypertension only, the outcome goal was a blood pressure below 140/90 mm Hg; for patients with concomitant heart failure, coronary artery disease, or type 2 diabetes the goal was below 130/80 mm Hg.

Of the 2,611 patients who met the study criteria, 1,119 were in the intervention group and 692 were in the control group. “The difference in size reflects the difference in the sizes of the clinics,” Dr. Beran explained. “There were 14 physicians at the intervention site and 5 at the control site.”

At baseline, blood pressures were not significantly different between the intervention and control sites, although adjusted clinical group score, which measures the burden of illness, was slightly higher among the intervention patients.

Most patients were white, the payer group was primarily Medicare or commercial insurance at both sites, and patient age was slightly higher in the intervention group.

In the unadjusted model, “the percentage of patients meeting their blood pressure goals by site over time improved in both groups,” Dr. Beran reported. In the adjusted model, which looked at the population overall, women were less likely than men to reach their blood pressure goal, and the likelihood of meeting the goal decreased with increasing age. Patients with hypertension only were significantly more likely to reach the blood pressure goal, she said.

No significant differences in the likelihood of achieving blood pressure goals were observed between the intervention and control sites for 2006, but moderate increases were observed in 2007, Dr. Beran said. “In 2008, there was a statistically significant increase in the likelihood of achieving blood pressure goals in the intervention group, compared with the control group, with an odds ratio of 1.64,” she reported.

In 2009, “the differences in the likelihood of reaching the blood pressure goal between the intervention and control patients diminished, although it was still statistically significant, with an odds ratio of 1.26,” Dr. Beran said. This trend coincided with significant effort within the organization overall to improve the quality of care and to increase transparency, and with the adoption of care components—such as the use of multiple blood pressure measurements to assess hypertension in at-risk patients—already in place in the medical home model.

“In many ways, the medical home intervention, in effect, raised the bar for quality in the organization,” she said, although more research is needed.

Major Finding: ALS patients experienced similar numbers of events (a decline of six or more points on the ALSFRS-R or death) during treatment with lithium plus riluzole or placebo plus riluzole (22 of 40 patients vs. 20 of 44 patients, respectively).

Data Source: Double-blind, randomized, placebo-controlled trial of 84 patients.

Disclosures: The trial was funded by the National Institute for Neurological Disorders and Stroke and the ALS Society of Canada. Mr. Swash and the investigators reported no relevant conflicts of interest.

The addition of lithium to riluzole for the treatment of amyotrophic lateral sclerosis does not substantially slow disease progression compared with riluzole alone, according to data from a double-blind, randomized, phase II study.

The findings contradict those of a small pilot study that was published in 2008 suggesting that the addition of lithium to standard riluzole therapy led to a slower decline in disease-related disability compared with riluzole therapy alone, according to the lead investigator Dr. Swati P. Aggarwal of Massachusetts General Hospital, Boston, and her colleagues.

The investigators stopped the trial on the recommendation of the data and safety monitoring board and the National Institute of Neurological Disorders and Stroke after the first planned interim analysis showed that lithium in combination with riluzole provided no added benefit over placebo plus riluzole (Lancet Neurol. 2010 April 6 [doi:10.1016/S1474-4422(10)70068-5

Although the findings of the phase II study provide “no convincing evidence for the use of lithium as a treatment for patients with ALS,” Dr. Aggarwal and her associates wrote that future studies should assess the possibility of smaller beneficial effects of lithium in ALS and the therapeutic potential of compounds that target the induction of autophagy.

The phase II trial of 84 patients with ALS from the United States and Canada used a time-to-event design to try to validate the promising results of the earlier study (Proc. Natl. Acad. Sci. U.S.A. 2008;105:2052–7).

This design allowed the investigators to compare the distributions of how long it took patients to show a decrease of at least six points on the ALS functional rating scale–revised (ALSFRS-R) or to die. The study was designed to have greater than 80% power to detect a 40% decrease in the rate of ALSFRS-R decline if all of the originally planned 250 patients had completed the study, they noted.

In an accompanying editorial, Michael Swash from Barts and the London School of Medicine and Dentistry, London, praised the novelty of the study's time-to-event design, which was powered specifically to detect a major effect of lithium, because of the potential for a rapid result and the possibility of crossover from placebo to treatment (Lancet Neurol. 2010 April 6 [doi:10.1016/S1474-4422(10)70085-5

“Use of this study design in trials of ALS represents an important advance,” he wrote.

“Now all that is required is a drug that has plausible pharmacology and pharmacokinetics, and has a favorable side effect profile, which has been studied in rigorous experiments using SOD1 mice.” This tall order, he noted, is “worth striving for.”

Of the 40 patients in the lithium group, 1 patient died and 21 had a decrease of at least six points on the ALSFRS-R. In the placebo group, 3 of 44 patients died and 17 had a decrease of six points or more on the ALSFRS-R. In addition to the reported deaths, 18 patients experienced 29 serious events after randomization, with no difference in the rate of occurrence between the two groups, Dr. Aggarwal and her coauthors reported.

The lithium doses in the study ranged from 150 mg to 1,050 mg per day to achieve a serum concentration of 0.4–0.8 mEq/L, which matches the range used in the pilot study, the authors wrote.

Although the investigators could not rule out the possibility of a small positive effect associated with lithium or that other serum concentration ranges could be beneficial, “the lower limit of the 95% CI around the difference in rates of decline of the ALSFRS-R total score was −0.43, suggesting that although a modest benefit of lithium was not ruled out by this study, an effect of 43% or more could be eliminated,” they wrote.

Major Finding: ALS patients experienced similar numbers of events (a decline of six or more points on the ALSFRS-R or death) during treatment with lithium plus riluzole or placebo plus riluzole (22 of 40 patients vs. 20 of 44 patients, respectively).

Data Source: Double-blind, randomized, placebo-controlled trial of 84 patients.

Disclosures: The trial was funded by the National Institute for Neurological Disorders and Stroke and the ALS Society of Canada. Mr. Swash and the investigators reported no relevant conflicts of interest.

The addition of lithium to riluzole for the treatment of amyotrophic lateral sclerosis does not substantially slow disease progression compared with riluzole alone, according to data from a double-blind, randomized, phase II study.

The findings contradict those of a small pilot study that was published in 2008 suggesting that the addition of lithium to standard riluzole therapy led to a slower decline in disease-related disability compared with riluzole therapy alone, according to the lead investigator Dr. Swati P. Aggarwal of Massachusetts General Hospital, Boston, and her colleagues.

The investigators stopped the trial on the recommendation of the data and safety monitoring board and the National Institute of Neurological Disorders and Stroke after the first planned interim analysis showed that lithium in combination with riluzole provided no added benefit over placebo plus riluzole (Lancet Neurol. 2010 April 6 [doi:10.1016/S1474-4422(10)70068-5

Although the findings of the phase II study provide “no convincing evidence for the use of lithium as a treatment for patients with ALS,” Dr. Aggarwal and her associates wrote that future studies should assess the possibility of smaller beneficial effects of lithium in ALS and the therapeutic potential of compounds that target the induction of autophagy.

The phase II trial of 84 patients with ALS from the United States and Canada used a time-to-event design to try to validate the promising results of the earlier study (Proc. Natl. Acad. Sci. U.S.A. 2008;105:2052–7).

This design allowed the investigators to compare the distributions of how long it took patients to show a decrease of at least six points on the ALS functional rating scale–revised (ALSFRS-R) or to die. The study was designed to have greater than 80% power to detect a 40% decrease in the rate of ALSFRS-R decline if all of the originally planned 250 patients had completed the study, they noted.

In an accompanying editorial, Michael Swash from Barts and the London School of Medicine and Dentistry, London, praised the novelty of the study's time-to-event design, which was powered specifically to detect a major effect of lithium, because of the potential for a rapid result and the possibility of crossover from placebo to treatment (Lancet Neurol. 2010 April 6 [doi:10.1016/S1474-4422(10)70085-5

“Use of this study design in trials of ALS represents an important advance,” he wrote.

“Now all that is required is a drug that has plausible pharmacology and pharmacokinetics, and has a favorable side effect profile, which has been studied in rigorous experiments using SOD1 mice.” This tall order, he noted, is “worth striving for.”

Of the 40 patients in the lithium group, 1 patient died and 21 had a decrease of at least six points on the ALSFRS-R. In the placebo group, 3 of 44 patients died and 17 had a decrease of six points or more on the ALSFRS-R. In addition to the reported deaths, 18 patients experienced 29 serious events after randomization, with no difference in the rate of occurrence between the two groups, Dr. Aggarwal and her coauthors reported.

The lithium doses in the study ranged from 150 mg to 1,050 mg per day to achieve a serum concentration of 0.4–0.8 mEq/L, which matches the range used in the pilot study, the authors wrote.

Although the investigators could not rule out the possibility of a small positive effect associated with lithium or that other serum concentration ranges could be beneficial, “the lower limit of the 95% CI around the difference in rates of decline of the ALSFRS-R total score was −0.43, suggesting that although a modest benefit of lithium was not ruled out by this study, an effect of 43% or more could be eliminated,” they wrote.

Major Finding: ALS patients experienced similar numbers of events (a decline of six or more points on the ALSFRS-R or death) during treatment with lithium plus riluzole or placebo plus riluzole (22 of 40 patients vs. 20 of 44 patients, respectively).

Data Source: Double-blind, randomized, placebo-controlled trial of 84 patients.

Disclosures: The trial was funded by the National Institute for Neurological Disorders and Stroke and the ALS Society of Canada. Mr. Swash and the investigators reported no relevant conflicts of interest.

The addition of lithium to riluzole for the treatment of amyotrophic lateral sclerosis does not substantially slow disease progression compared with riluzole alone, according to data from a double-blind, randomized, phase II study.

The findings contradict those of a small pilot study that was published in 2008 suggesting that the addition of lithium to standard riluzole therapy led to a slower decline in disease-related disability compared with riluzole therapy alone, according to the lead investigator Dr. Swati P. Aggarwal of Massachusetts General Hospital, Boston, and her colleagues.

The investigators stopped the trial on the recommendation of the data and safety monitoring board and the National Institute of Neurological Disorders and Stroke after the first planned interim analysis showed that lithium in combination with riluzole provided no added benefit over placebo plus riluzole (Lancet Neurol. 2010 April 6 [doi:10.1016/S1474-4422(10)70068-5

Although the findings of the phase II study provide “no convincing evidence for the use of lithium as a treatment for patients with ALS,” Dr. Aggarwal and her associates wrote that future studies should assess the possibility of smaller beneficial effects of lithium in ALS and the therapeutic potential of compounds that target the induction of autophagy.

The phase II trial of 84 patients with ALS from the United States and Canada used a time-to-event design to try to validate the promising results of the earlier study (Proc. Natl. Acad. Sci. U.S.A. 2008;105:2052–7).

This design allowed the investigators to compare the distributions of how long it took patients to show a decrease of at least six points on the ALS functional rating scale–revised (ALSFRS-R) or to die. The study was designed to have greater than 80% power to detect a 40% decrease in the rate of ALSFRS-R decline if all of the originally planned 250 patients had completed the study, they noted.

In an accompanying editorial, Michael Swash from Barts and the London School of Medicine and Dentistry, London, praised the novelty of the study's time-to-event design, which was powered specifically to detect a major effect of lithium, because of the potential for a rapid result and the possibility of crossover from placebo to treatment (Lancet Neurol. 2010 April 6 [doi:10.1016/S1474-4422(10)70085-5

“Use of this study design in trials of ALS represents an important advance,” he wrote.

“Now all that is required is a drug that has plausible pharmacology and pharmacokinetics, and has a favorable side effect profile, which has been studied in rigorous experiments using SOD1 mice.” This tall order, he noted, is “worth striving for.”

Of the 40 patients in the lithium group, 1 patient died and 21 had a decrease of at least six points on the ALSFRS-R. In the placebo group, 3 of 44 patients died and 17 had a decrease of six points or more on the ALSFRS-R. In addition to the reported deaths, 18 patients experienced 29 serious events after randomization, with no difference in the rate of occurrence between the two groups, Dr. Aggarwal and her coauthors reported.

The lithium doses in the study ranged from 150 mg to 1,050 mg per day to achieve a serum concentration of 0.4–0.8 mEq/L, which matches the range used in the pilot study, the authors wrote.

Although the investigators could not rule out the possibility of a small positive effect associated with lithium or that other serum concentration ranges could be beneficial, “the lower limit of the 95% CI around the difference in rates of decline of the ALSFRS-R total score was −0.43, suggesting that although a modest benefit of lithium was not ruled out by this study, an effect of 43% or more could be eliminated,” they wrote.

DESTIN, FLA. — “The problem with drug development in lupus is lupus,” Dr. Joan T. Merrill said at the Congress of Clinical Rheumatology.

“Lupus is an incredibly heterogeneous disease. We know from the results of clinical trials that no one drug can be expected to work for more than 60% of patients with lupus. But we can't yet pick out in advance the subgroup of patients who will respond to a given drug,” she said.

The heterogeneity of the disease across patients and the absence of scientific evidence to explain the biological mechanisms underlying the variations have been impediments to fruitful clinical experimentation, and have led to a series of disappointing clinical trial outcomes, said Dr. Merrill, of the University of Oklahoma in Oklahoma City.

“Targeted therapies can only work if you know what you're targeting, in whom, and why,” she noted. “We have the technology to be able to identify those subsets of patients that we ought to be targeting with each treatment, but we don't have the will.

Additional complications include the inconsistent clinical course of the disease, which is characterized by flares and remissions that make it difficult to assess the impact of investigational therapies and also complicate the selection of meaningful clinical end points, and the need (according to the Food and Drug Administration) to show clinical superiority of the investigational agents over standard treatment, said Dr. Merrill. “The irony, of course, is that the standard of care in lupus is off-label therapy, because there hasn't been a new drug approved for the disease in more than 50 years,” she said.

Because the standard treatments are off label, their therapeutic effect has not been established in clinical trials. “Many clinical trials in lupus have to be carried out for a whole year, and they can't really be performed unless patients are on these background medications, but we don't know what these background medications are doing biologically to patients, or how they are interfering with our assessment of a study agent,” Dr. Merrill said.

Arguably, the potentially promising agents that have failed to achieve intended levels of improvement in patient outcomes in lupus trials—including mycophenolate mofetil (CellCept), abatacept (Orencia), prasterone (Prestara), abetimus sodium (Riquent), and rituximab (Rituxan)—might have demonstrated treatment effects if patient selection had been optimized based on patient-specific biology, if investigators had a better understanding of the impact that background medications have on patient response and adverse events, and if more specific responder indices were available to assess treatment effect, according to Dr. Merrill.

In fact, it is the attention paid to some of these factors that likely contributed to the recent success of two separate phase III trials of belimumab (Benlysta), the monoclonal antibody that targets B-lymphocyte stimulator (BLyS), she said.

In the initial phase II, double-blind, placebo-controlled trial of belimumab in patients with active lupus, the drug failed to improve disease activity as measured by the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), and did not decrease time to first SLE flare (Arthritis Rheum. 2009;61:1168–78).

In a post hoc exploratory analysis of the data, however, the investigators “noticed that if they looked just at the subset of patients who had been either ANA [antinuclear antibody] positive or [anti–double-stranded DNA] positive at study entry, they actually could see more patients with a 4-point reduction in the SLEDAI over time at each visit” than in the placebo group, said Dr. Merrill.

Based on this observation, the investigators used the phase II trial data to develop a new SLE Responder Index (SRI) that incorporated components of the SLEDAI, the BILAG (British Isles Lupus Assessment Group) disease activity instrument, and the PGA (Physician Global Assessment).

They used the new instrument as the primary efficacy end point at week 52 in the BLISS-52 (Belimumab in Subjects With Systemic Lupus Erythematosus–52) and BLISS-76 phase III trials, said Dr. Merrill.

In both BLISS trials, belimumab met the efficacy end point, which was defined as a reduction from baseline of at least 4 points on the SLEDAI disease activity scale, no worsening of disease as measured by the PGA, no new BILAG grade A organ domain score, and no more than one new BILAG grade B organ domain score, Dr. Merrill noted.

The differences between the treatment and control groups that were observed in both trials were small but statistically significant, and they were historically meaningful because they put the drug on the pathway for FDA approval, she said.

“This is a major development, not because [belimumab] is expected to be a cure-all or the best treatment for every lupus patient, because it is not,” said Dr. Merrill. Rather, FDA approval of belimumab, if it happens, will break ground for other studies to follow and, after 50 years, “there will finally be an approved therapy that we can hold other [experimental] therapies up against.”

Disclosures: Dr. Merrill has served as a consultant and clinical trialist for Genentech/Roche, Bristol-Myers Squibb Co., MedImmune Inc., and Human Genome Sciences; she has been a consultant for Amgen Inc., UCB Pharma Inc., and Serono Inc.; and she has received grants from Aspreva/Vifor and Wyeth/Pfizer for investigator-initiated studies.

In lupus, 'targeted therapies can only work if you know what you're targeting, in whom, and why.'

Source DR. MERRILL

DESTIN, FLA. — “The problem with drug development in lupus is lupus,” Dr. Joan T. Merrill said at the Congress of Clinical Rheumatology.

“Lupus is an incredibly heterogeneous disease. We know from the results of clinical trials that no one drug can be expected to work for more than 60% of patients with lupus. But we can't yet pick out in advance the subgroup of patients who will respond to a given drug,” she said.

The heterogeneity of the disease across patients and the absence of scientific evidence to explain the biological mechanisms underlying the variations have been impediments to fruitful clinical experimentation, and have led to a series of disappointing clinical trial outcomes, said Dr. Merrill, of the University of Oklahoma in Oklahoma City.

“Targeted therapies can only work if you know what you're targeting, in whom, and why,” she noted. “We have the technology to be able to identify those subsets of patients that we ought to be targeting with each treatment, but we don't have the will.

Additional complications include the inconsistent clinical course of the disease, which is characterized by flares and remissions that make it difficult to assess the impact of investigational therapies and also complicate the selection of meaningful clinical end points, and the need (according to the Food and Drug Administration) to show clinical superiority of the investigational agents over standard treatment, said Dr. Merrill. “The irony, of course, is that the standard of care in lupus is off-label therapy, because there hasn't been a new drug approved for the disease in more than 50 years,” she said.

Because the standard treatments are off label, their therapeutic effect has not been established in clinical trials. “Many clinical trials in lupus have to be carried out for a whole year, and they can't really be performed unless patients are on these background medications, but we don't know what these background medications are doing biologically to patients, or how they are interfering with our assessment of a study agent,” Dr. Merrill said.

Arguably, the potentially promising agents that have failed to achieve intended levels of improvement in patient outcomes in lupus trials—including mycophenolate mofetil (CellCept), abatacept (Orencia), prasterone (Prestara), abetimus sodium (Riquent), and rituximab (Rituxan)—might have demonstrated treatment effects if patient selection had been optimized based on patient-specific biology, if investigators had a better understanding of the impact that background medications have on patient response and adverse events, and if more specific responder indices were available to assess treatment effect, according to Dr. Merrill.

In fact, it is the attention paid to some of these factors that likely contributed to the recent success of two separate phase III trials of belimumab (Benlysta), the monoclonal antibody that targets B-lymphocyte stimulator (BLyS), she said.

In the initial phase II, double-blind, placebo-controlled trial of belimumab in patients with active lupus, the drug failed to improve disease activity as measured by the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), and did not decrease time to first SLE flare (Arthritis Rheum. 2009;61:1168–78).

In a post hoc exploratory analysis of the data, however, the investigators “noticed that if they looked just at the subset of patients who had been either ANA [antinuclear antibody] positive or [anti–double-stranded DNA] positive at study entry, they actually could see more patients with a 4-point reduction in the SLEDAI over time at each visit” than in the placebo group, said Dr. Merrill.

Based on this observation, the investigators used the phase II trial data to develop a new SLE Responder Index (SRI) that incorporated components of the SLEDAI, the BILAG (British Isles Lupus Assessment Group) disease activity instrument, and the PGA (Physician Global Assessment).

They used the new instrument as the primary efficacy end point at week 52 in the BLISS-52 (Belimumab in Subjects With Systemic Lupus Erythematosus–52) and BLISS-76 phase III trials, said Dr. Merrill.

In both BLISS trials, belimumab met the efficacy end point, which was defined as a reduction from baseline of at least 4 points on the SLEDAI disease activity scale, no worsening of disease as measured by the PGA, no new BILAG grade A organ domain score, and no more than one new BILAG grade B organ domain score, Dr. Merrill noted.

The differences between the treatment and control groups that were observed in both trials were small but statistically significant, and they were historically meaningful because they put the drug on the pathway for FDA approval, she said.

“This is a major development, not because [belimumab] is expected to be a cure-all or the best treatment for every lupus patient, because it is not,” said Dr. Merrill. Rather, FDA approval of belimumab, if it happens, will break ground for other studies to follow and, after 50 years, “there will finally be an approved therapy that we can hold other [experimental] therapies up against.”

Disclosures: Dr. Merrill has served as a consultant and clinical trialist for Genentech/Roche, Bristol-Myers Squibb Co., MedImmune Inc., and Human Genome Sciences; she has been a consultant for Amgen Inc., UCB Pharma Inc., and Serono Inc.; and she has received grants from Aspreva/Vifor and Wyeth/Pfizer for investigator-initiated studies.

In lupus, 'targeted therapies can only work if you know what you're targeting, in whom, and why.'

Source DR. MERRILL

DESTIN, FLA. — “The problem with drug development in lupus is lupus,” Dr. Joan T. Merrill said at the Congress of Clinical Rheumatology.

“Lupus is an incredibly heterogeneous disease. We know from the results of clinical trials that no one drug can be expected to work for more than 60% of patients with lupus. But we can't yet pick out in advance the subgroup of patients who will respond to a given drug,” she said.

The heterogeneity of the disease across patients and the absence of scientific evidence to explain the biological mechanisms underlying the variations have been impediments to fruitful clinical experimentation, and have led to a series of disappointing clinical trial outcomes, said Dr. Merrill, of the University of Oklahoma in Oklahoma City.

“Targeted therapies can only work if you know what you're targeting, in whom, and why,” she noted. “We have the technology to be able to identify those subsets of patients that we ought to be targeting with each treatment, but we don't have the will.

Additional complications include the inconsistent clinical course of the disease, which is characterized by flares and remissions that make it difficult to assess the impact of investigational therapies and also complicate the selection of meaningful clinical end points, and the need (according to the Food and Drug Administration) to show clinical superiority of the investigational agents over standard treatment, said Dr. Merrill. “The irony, of course, is that the standard of care in lupus is off-label therapy, because there hasn't been a new drug approved for the disease in more than 50 years,” she said.

Because the standard treatments are off label, their therapeutic effect has not been established in clinical trials. “Many clinical trials in lupus have to be carried out for a whole year, and they can't really be performed unless patients are on these background medications, but we don't know what these background medications are doing biologically to patients, or how they are interfering with our assessment of a study agent,” Dr. Merrill said.

Arguably, the potentially promising agents that have failed to achieve intended levels of improvement in patient outcomes in lupus trials—including mycophenolate mofetil (CellCept), abatacept (Orencia), prasterone (Prestara), abetimus sodium (Riquent), and rituximab (Rituxan)—might have demonstrated treatment effects if patient selection had been optimized based on patient-specific biology, if investigators had a better understanding of the impact that background medications have on patient response and adverse events, and if more specific responder indices were available to assess treatment effect, according to Dr. Merrill.

In fact, it is the attention paid to some of these factors that likely contributed to the recent success of two separate phase III trials of belimumab (Benlysta), the monoclonal antibody that targets B-lymphocyte stimulator (BLyS), she said.

In the initial phase II, double-blind, placebo-controlled trial of belimumab in patients with active lupus, the drug failed to improve disease activity as measured by the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), and did not decrease time to first SLE flare (Arthritis Rheum. 2009;61:1168–78).

In a post hoc exploratory analysis of the data, however, the investigators “noticed that if they looked just at the subset of patients who had been either ANA [antinuclear antibody] positive or [anti–double-stranded DNA] positive at study entry, they actually could see more patients with a 4-point reduction in the SLEDAI over time at each visit” than in the placebo group, said Dr. Merrill.

Based on this observation, the investigators used the phase II trial data to develop a new SLE Responder Index (SRI) that incorporated components of the SLEDAI, the BILAG (British Isles Lupus Assessment Group) disease activity instrument, and the PGA (Physician Global Assessment).

They used the new instrument as the primary efficacy end point at week 52 in the BLISS-52 (Belimumab in Subjects With Systemic Lupus Erythematosus–52) and BLISS-76 phase III trials, said Dr. Merrill.

In both BLISS trials, belimumab met the efficacy end point, which was defined as a reduction from baseline of at least 4 points on the SLEDAI disease activity scale, no worsening of disease as measured by the PGA, no new BILAG grade A organ domain score, and no more than one new BILAG grade B organ domain score, Dr. Merrill noted.

The differences between the treatment and control groups that were observed in both trials were small but statistically significant, and they were historically meaningful because they put the drug on the pathway for FDA approval, she said.

“This is a major development, not because [belimumab] is expected to be a cure-all or the best treatment for every lupus patient, because it is not,” said Dr. Merrill. Rather, FDA approval of belimumab, if it happens, will break ground for other studies to follow and, after 50 years, “there will finally be an approved therapy that we can hold other [experimental] therapies up against.”

Disclosures: Dr. Merrill has served as a consultant and clinical trialist for Genentech/Roche, Bristol-Myers Squibb Co., MedImmune Inc., and Human Genome Sciences; she has been a consultant for Amgen Inc., UCB Pharma Inc., and Serono Inc.; and she has received grants from Aspreva/Vifor and Wyeth/Pfizer for investigator-initiated studies.

In lupus, 'targeted therapies can only work if you know what you're targeting, in whom, and why.'

Source DR. MERRILL

The teen birth rate in the United States dropped by 2% in 2008, following 2 consecutive years of increase, a government report has shown.

There was also a significant decline between 2007 and 2008 in the percentage of babies born prematurely, according to a provisional report released by the Centers for Disease Control's National Center for Health Statistics.

The birth rate for U.S. teenagers (aged 15–19 years) fell from 42.5 per 1,000 teenagers in 2007 to 41.5 per 1,000 in 2008, according to the report, which is based on analysis of 99.9% of registered vital records occurring in calendar year 2008, said lead author Brady E. Hamilton, Ph.D., and colleagues at the center.

“The decline reverses 2 consecutive years of increase that interrupted the 34% decline in teenage childbearing from 1991 to 2005,” the authors wrote (Natl. Vital Stat. Rep. 2010;58:1–17).

The birth rate among older teenagers (18–19 years) decreased 4% to 70.7 per 1,000, and the birth rate among Hispanic teenagers dropped to 77.4 per 1,000—the lowest rate reported for this group in the 2 decades that the rates have been available.

Although the birth rate among younger teenagers aged 10–14 years (0.6 births per 1,000) did not change, “the number of births to this age group fell 7% from 2007 to 2008, to 5,775, the fewest reported since 1954,” the authors noted.

The preliminary estimate of all U.S. births for 2008 was 4,251,095, nearly 2% less than the 4,317,119 reported for 2007.

Among unmarried women, the birth rate among those aged 15–44 years declined nearly 2%, from 52.9 per 1,000 women in 2007 to 52 per 1,000 in 2008—the first reported decline since 2001–2002.

The total number of births to unmarried women increased about 1% to 1,727,950 in 2008, which is about 27% higher than in 2002, “when the recent steady increases began,” the authors wrote.

The number of births to unmarried women increased for all age groups, including women 25 years old and older, but declined for unmarried teenagers and women in their early 20s.

With respect to preterm births, the rate of infants delivered at less than 37 weeks of gestation per 100 births decreased by 3% in 2008 to 12.3% of all births.

“This fairly sizable decrease follows a small decline in the preterm rate between 2006 and 2007 [12.8% to 12.7%],” the authors wrote.

Before that, they noted that “the rate of preterm births had risen by more than 20% between 1990 and 2006.”

The teen birth rate in the United States dropped by 2% in 2008, following 2 consecutive years of increase, a government report has shown.

There was also a significant decline between 2007 and 2008 in the percentage of babies born prematurely, according to a provisional report released by the Centers for Disease Control's National Center for Health Statistics.

The birth rate for U.S. teenagers (aged 15–19 years) fell from 42.5 per 1,000 teenagers in 2007 to 41.5 per 1,000 in 2008, according to the report, which is based on analysis of 99.9% of registered vital records occurring in calendar year 2008, said lead author Brady E. Hamilton, Ph.D., and colleagues at the center.

“The decline reverses 2 consecutive years of increase that interrupted the 34% decline in teenage childbearing from 1991 to 2005,” the authors wrote (Natl. Vital Stat. Rep. 2010;58:1–17).

The birth rate among older teenagers (18–19 years) decreased 4% to 70.7 per 1,000, and the birth rate among Hispanic teenagers dropped to 77.4 per 1,000—the lowest rate reported for this group in the 2 decades that the rates have been available.

Although the birth rate among younger teenagers aged 10–14 years (0.6 births per 1,000) did not change, “the number of births to this age group fell 7% from 2007 to 2008, to 5,775, the fewest reported since 1954,” the authors noted.

The preliminary estimate of all U.S. births for 2008 was 4,251,095, nearly 2% less than the 4,317,119 reported for 2007.

Among unmarried women, the birth rate among those aged 15–44 years declined nearly 2%, from 52.9 per 1,000 women in 2007 to 52 per 1,000 in 2008—the first reported decline since 2001–2002.

The total number of births to unmarried women increased about 1% to 1,727,950 in 2008, which is about 27% higher than in 2002, “when the recent steady increases began,” the authors wrote.

The number of births to unmarried women increased for all age groups, including women 25 years old and older, but declined for unmarried teenagers and women in their early 20s.

With respect to preterm births, the rate of infants delivered at less than 37 weeks of gestation per 100 births decreased by 3% in 2008 to 12.3% of all births.

“This fairly sizable decrease follows a small decline in the preterm rate between 2006 and 2007 [12.8% to 12.7%],” the authors wrote.

Before that, they noted that “the rate of preterm births had risen by more than 20% between 1990 and 2006.”

The teen birth rate in the United States dropped by 2% in 2008, following 2 consecutive years of increase, a government report has shown.

There was also a significant decline between 2007 and 2008 in the percentage of babies born prematurely, according to a provisional report released by the Centers for Disease Control's National Center for Health Statistics.

The birth rate for U.S. teenagers (aged 15–19 years) fell from 42.5 per 1,000 teenagers in 2007 to 41.5 per 1,000 in 2008, according to the report, which is based on analysis of 99.9% of registered vital records occurring in calendar year 2008, said lead author Brady E. Hamilton, Ph.D., and colleagues at the center.

“The decline reverses 2 consecutive years of increase that interrupted the 34% decline in teenage childbearing from 1991 to 2005,” the authors wrote (Natl. Vital Stat. Rep. 2010;58:1–17).

The birth rate among older teenagers (18–19 years) decreased 4% to 70.7 per 1,000, and the birth rate among Hispanic teenagers dropped to 77.4 per 1,000—the lowest rate reported for this group in the 2 decades that the rates have been available.

Although the birth rate among younger teenagers aged 10–14 years (0.6 births per 1,000) did not change, “the number of births to this age group fell 7% from 2007 to 2008, to 5,775, the fewest reported since 1954,” the authors noted.

The preliminary estimate of all U.S. births for 2008 was 4,251,095, nearly 2% less than the 4,317,119 reported for 2007.

Among unmarried women, the birth rate among those aged 15–44 years declined nearly 2%, from 52.9 per 1,000 women in 2007 to 52 per 1,000 in 2008—the first reported decline since 2001–2002.

The total number of births to unmarried women increased about 1% to 1,727,950 in 2008, which is about 27% higher than in 2002, “when the recent steady increases began,” the authors wrote.

The number of births to unmarried women increased for all age groups, including women 25 years old and older, but declined for unmarried teenagers and women in their early 20s.

With respect to preterm births, the rate of infants delivered at less than 37 weeks of gestation per 100 births decreased by 3% in 2008 to 12.3% of all births.

“This fairly sizable decrease follows a small decline in the preterm rate between 2006 and 2007 [12.8% to 12.7%],” the authors wrote.

Before that, they noted that “the rate of preterm births had risen by more than 20% between 1990 and 2006.”

Hormone therapy to treat menopause-related symptoms or to reduce the risk of certain disorders in postmenopausal women is associated with a favorable benefit-risk ratio when initiated around the time of menopause, but the benefits diminish as the duration of time since menopause increases and among older women, according to the 2010 position statement published by the North American Menopause Society.

The new document updates the organization's 2008 position statement on the role of estrogen and progestogen hormone therapy (HT) by including consensus recommendations derived from key data published since the earlier statement, the authors wrote, noting that the revised statement includes new sections on ovarian and lung cancer, as well as updates to the sections on breast cancer, cognitive aging and decline, dementia, coronary heart disease, stroke, and discontinuance (Menopause 2010;17:242–55)

“Recent data support the initiation of hormone therapy around the time of menopause” to treat menopause-related vasomotor symptoms, sleep disturbance, vaginal atrophy, dyspareunia, or diminished libido and to reduce the risk of osteoporosis and fractures in some women, the authors wrote.

Specifically, findings from the Women's Health Initiative (WHI) trial of estrogen therapy showed that 0.625 mg/day of oral conjugated estrogen effectively treats menopause-related symptoms with low absolute risks. Similarly, in the WHI trial of combined estrogen-progestogen therapy, most risks were deemed rare—except for stroke, which was above the rare category—based on the criteria of the Council for International Organizations of Medical Sciences, the authors wrote.

They noted, however, that “there is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects.” As such, more research is needed before the risks and benefits of HT can be generalized, and “it cannot be assumed that benefits and risks of [HT] apply to all age ranges and durations of therapy,” they wrote.

The most notable changes in the NAMS 2010 position statement on postmenopausal HT are the two new sections on ovarian cancer and lung cancer, which were not included in the 2008 position statement, as well as the assertion that HT is not recommended in women with a history of endometrial cancer, Dr. Margery L.S. Gass, executive director of NAMS, commented in an interview.

The new statement also reflects the latest research on the effect of age on the benefit/risk ratio of postmenopausal HT. The current understanding that the benefit/risk ratio is greatest among women who start HT close to the time of menopause and decreases with time since menopause should make clinicians and women more comfortable using HT right at the time of menopause and more cautious about using it later in life for the prevention of osteoporosis. Most of the side effects associated with HT become more common with aging, even without the use of HT. Adding the HT just compounds the problem. Therefore, rather than recommending oral or transdermal estrogen for such problems as vaginal dryness and painful intercourse, we place emphasis on using local/topical estrogen, said Dr. Gass, also a consultant to the Cleveland Clinic Center for Specialized Women's Health, Mayfield Heights, Ohio.

Regarding the association between hormone therapy and cancer, the data are conflicting, according to the NAMS statement authors. “Unopposed systemic estrogen therapy in postmenopausal women with an intact uterus is associated with increased endometrial cancer risk related to the [estrogen therapy] dose and duration,” they wrote. Thus, concomitant progestogen is recommended in those who use systemic estrogen therapy, and HT is not recommended for women with a history of endometrial cancer.

With respect to ovarian cancer, most epidemiologic studies show no association or a modest association with HT, but observational trial data suggest an increased ovarian cancer risk, the authors wrote. Based on the available data, “the association between ovarian cancer and hormone therapy beyond 5 years, if any, would fall into the rare or very rare category,” they stated, noting that women with a positive family history or other risk factors for ovarian cancer “should be counseled about this rare association.”

The link between HT and breast cancer also is uncertain. Studies have demonstrated that diagnosis of breast cancer increases with estrogen-progestogen use beyond 3–5 years. However, a reanalysis of WHI data suggested that women who started estrogen-progestogen shortly after menopause experienced an increased breast cancer risk over the next 5 years, while those with a gap of more than 5 years between menopause and treatment did not, the authors explained.

Among breast cancer survivors, estrogen-progestogen therapy has not been proven safe and may be associated with an increased risk of recurrence, as indicated in a one randomized controlled trial, which “showed a statistically significant 2.4 fold increase in new breast cancer events,” the authors wrote.

The data on lung cancer are particularly contradictory in that, overall, it appears that starting estrogen-progestogen therapy in older women with a history of smoking may promote the growth of existing lung cancers, while “evidence from the WHI and some case-control and cohort studies of hormone therapy in a younger population [less than 60 years] shows some protection against lung cancer,” the authors stated. Although confusing, the findings “reinforce the need to encourage prevention or cessation of smoking and possibly to increase surveillance in older smokers who are current or past users of hormone therapy,” they wrote.

The revised statement also addresses the issues of cognitive impairment and coronary heart disease. It recommends against the use of HT at any age “for the sole or primary indication of preventing cognitive aging or dementia,” noting that it may increase the incidence of dementia when initiated in women who are 65 years or older.

Additionally, HT is not recommended as a sole or main indication for coronary protection in women of any age. When HT is started in recently menopausal women for the treatment of menopause symptoms, there does not appear to be an increased risk for coronary heart disease; however, women who initiate HT more than 10 years beyond menopause are at increased CHD risk, the authors noted.

In all cases, because each woman is unique with her own risk profile and preferences, “individualization of [hormone] therapy is key to providing health benefits with minimal risks, thereby enhancing quality of life,” the authors wrote. Women should be informed of known risks, with the understanding that “a woman's willingness to accept risks of [HT] will vary depending on her individual situation.” okOverall, “NAMS continues

Overall, “NAMS continues to refine our recommendations and approach to hormone therapy as data from the WHI and other studies continue to emerge,” NAMS president Cynthia A. Stuenkel said in an interview. “While we support the use of hormone therapy for symptomatic women [younger than age 60 years], close to the time of menopause, we remind our readers that there are some risks, though small, and there are some uncertainties remaining regarding short-term and long-term effects of hormone therapy.”

In general, “we strongly advocate for the lowest dose for the shortest time for the individual woman who has been carefully counseled about risks and benefits,” said Dr. Stuenkel, clinical professor of medicine at the University of California, San Diego.

The advisory panel members' financial disclosures are listed on the position statement, which can be found at www.menopause.org/PSht10.pdf

There are new sections on ovarian cancer and lung cancer, Dr. Margery L.S. Gass said.

My Take

Hormone Therapy Still Plays a Role

In general, the 2010 NAMS position statement on postmenopausal hormone therapy is in line with clinical practice; however, many doctors are not prescribing hormones, even when supported by the science, because of bad publicity and a lack of interest combined with fear of litigation.

It is pretty clear that hormone therapy should be used for patients with a clear indication, and the statement outlines what the relevant indications are. The data coming from the Women's Health Initiative] seem to be a reversal on the cardiovascular issue. Some of the subanalyses suggest that hormone therapy is associated with a cardiovascular benefit in women close to the age of menopause, while other studies from the same group suggest that this isn't so. Obviously, the science is evolving, and we are only beginning to understand the mechanism of cardiovascular risks and benefits. Overall, however, the statement is pretty clear that we should not use hormones to prevent cardiovascular disease.

In all cases, the decision to initiate hormone therapy has to be individualized to each patient. There is not a one-size-fits-all solution. The main issue is determining what is the safest drug for a woman at a particular time in her life.

MICHELLE P. WARREN, M.D., is director of the Center for Menopause, Hormonal Disorders, and Women's Health at Columbia University Medical Center in New York.

Hormone therapy to treat menopause-related symptoms or to reduce the risk of certain disorders in postmenopausal women is associated with a favorable benefit-risk ratio when initiated around the time of menopause, but the benefits diminish as the duration of time since menopause increases and among older women, according to the 2010 position statement published by the North American Menopause Society.

The new document updates the organization's 2008 position statement on the role of estrogen and progestogen hormone therapy (HT) by including consensus recommendations derived from key data published since the earlier statement, the authors wrote, noting that the revised statement includes new sections on ovarian and lung cancer, as well as updates to the sections on breast cancer, cognitive aging and decline, dementia, coronary heart disease, stroke, and discontinuance (Menopause 2010;17:242–55)

“Recent data support the initiation of hormone therapy around the time of menopause” to treat menopause-related vasomotor symptoms, sleep disturbance, vaginal atrophy, dyspareunia, or diminished libido and to reduce the risk of osteoporosis and fractures in some women, the authors wrote.

Specifically, findings from the Women's Health Initiative (WHI) trial of estrogen therapy showed that 0.625 mg/day of oral conjugated estrogen effectively treats menopause-related symptoms with low absolute risks. Similarly, in the WHI trial of combined estrogen-progestogen therapy, most risks were deemed rare—except for stroke, which was above the rare category—based on the criteria of the Council for International Organizations of Medical Sciences, the authors wrote.

They noted, however, that “there is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects.” As such, more research is needed before the risks and benefits of HT can be generalized, and “it cannot be assumed that benefits and risks of [HT] apply to all age ranges and durations of therapy,” they wrote.

The most notable changes in the NAMS 2010 position statement on postmenopausal HT are the two new sections on ovarian cancer and lung cancer, which were not included in the 2008 position statement, as well as the assertion that HT is not recommended in women with a history of endometrial cancer, Dr. Margery L.S. Gass, executive director of NAMS, commented in an interview.

The new statement also reflects the latest research on the effect of age on the benefit/risk ratio of postmenopausal HT. The current understanding that the benefit/risk ratio is greatest among women who start HT close to the time of menopause and decreases with time since menopause should make clinicians and women more comfortable using HT right at the time of menopause and more cautious about using it later in life for the prevention of osteoporosis. Most of the side effects associated with HT become more common with aging, even without the use of HT. Adding the HT just compounds the problem. Therefore, rather than recommending oral or transdermal estrogen for such problems as vaginal dryness and painful intercourse, we place emphasis on using local/topical estrogen, said Dr. Gass, also a consultant to the Cleveland Clinic Center for Specialized Women's Health, Mayfield Heights, Ohio.

Regarding the association between hormone therapy and cancer, the data are conflicting, according to the NAMS statement authors. “Unopposed systemic estrogen therapy in postmenopausal women with an intact uterus is associated with increased endometrial cancer risk related to the [estrogen therapy] dose and duration,” they wrote. Thus, concomitant progestogen is recommended in those who use systemic estrogen therapy, and HT is not recommended for women with a history of endometrial cancer.

With respect to ovarian cancer, most epidemiologic studies show no association or a modest association with HT, but observational trial data suggest an increased ovarian cancer risk, the authors wrote. Based on the available data, “the association between ovarian cancer and hormone therapy beyond 5 years, if any, would fall into the rare or very rare category,” they stated, noting that women with a positive family history or other risk factors for ovarian cancer “should be counseled about this rare association.”

The link between HT and breast cancer also is uncertain. Studies have demonstrated that diagnosis of breast cancer increases with estrogen-progestogen use beyond 3–5 years. However, a reanalysis of WHI data suggested that women who started estrogen-progestogen shortly after menopause experienced an increased breast cancer risk over the next 5 years, while those with a gap of more than 5 years between menopause and treatment did not, the authors explained.

Among breast cancer survivors, estrogen-progestogen therapy has not been proven safe and may be associated with an increased risk of recurrence, as indicated in a one randomized controlled trial, which “showed a statistically significant 2.4 fold increase in new breast cancer events,” the authors wrote.

The data on lung cancer are particularly contradictory in that, overall, it appears that starting estrogen-progestogen therapy in older women with a history of smoking may promote the growth of existing lung cancers, while “evidence from the WHI and some case-control and cohort studies of hormone therapy in a younger population [less than 60 years] shows some protection against lung cancer,” the authors stated. Although confusing, the findings “reinforce the need to encourage prevention or cessation of smoking and possibly to increase surveillance in older smokers who are current or past users of hormone therapy,” they wrote.

The revised statement also addresses the issues of cognitive impairment and coronary heart disease. It recommends against the use of HT at any age “for the sole or primary indication of preventing cognitive aging or dementia,” noting that it may increase the incidence of dementia when initiated in women who are 65 years or older.

Additionally, HT is not recommended as a sole or main indication for coronary protection in women of any age. When HT is started in recently menopausal women for the treatment of menopause symptoms, there does not appear to be an increased risk for coronary heart disease; however, women who initiate HT more than 10 years beyond menopause are at increased CHD risk, the authors noted.

In all cases, because each woman is unique with her own risk profile and preferences, “individualization of [hormone] therapy is key to providing health benefits with minimal risks, thereby enhancing quality of life,” the authors wrote. Women should be informed of known risks, with the understanding that “a woman's willingness to accept risks of [HT] will vary depending on her individual situation.” okOverall, “NAMS continues

Overall, “NAMS continues to refine our recommendations and approach to hormone therapy as data from the WHI and other studies continue to emerge,” NAMS president Cynthia A. Stuenkel said in an interview. “While we support the use of hormone therapy for symptomatic women [younger than age 60 years], close to the time of menopause, we remind our readers that there are some risks, though small, and there are some uncertainties remaining regarding short-term and long-term effects of hormone therapy.”

In general, “we strongly advocate for the lowest dose for the shortest time for the individual woman who has been carefully counseled about risks and benefits,” said Dr. Stuenkel, clinical professor of medicine at the University of California, San Diego.

The advisory panel members' financial disclosures are listed on the position statement, which can be found at www.menopause.org/PSht10.pdf

There are new sections on ovarian cancer and lung cancer, Dr. Margery L.S. Gass said.

My Take

Hormone Therapy Still Plays a Role

In general, the 2010 NAMS position statement on postmenopausal hormone therapy is in line with clinical practice; however, many doctors are not prescribing hormones, even when supported by the science, because of bad publicity and a lack of interest combined with fear of litigation.

It is pretty clear that hormone therapy should be used for patients with a clear indication, and the statement outlines what the relevant indications are. The data coming from the Women's Health Initiative] seem to be a reversal on the cardiovascular issue. Some of the subanalyses suggest that hormone therapy is associated with a cardiovascular benefit in women close to the age of menopause, while other studies from the same group suggest that this isn't so. Obviously, the science is evolving, and we are only beginning to understand the mechanism of cardiovascular risks and benefits. Overall, however, the statement is pretty clear that we should not use hormones to prevent cardiovascular disease.

In all cases, the decision to initiate hormone therapy has to be individualized to each patient. There is not a one-size-fits-all solution. The main issue is determining what is the safest drug for a woman at a particular time in her life.

MICHELLE P. WARREN, M.D., is director of the Center for Menopause, Hormonal Disorders, and Women's Health at Columbia University Medical Center in New York.

Hormone therapy to treat menopause-related symptoms or to reduce the risk of certain disorders in postmenopausal women is associated with a favorable benefit-risk ratio when initiated around the time of menopause, but the benefits diminish as the duration of time since menopause increases and among older women, according to the 2010 position statement published by the North American Menopause Society.

The new document updates the organization's 2008 position statement on the role of estrogen and progestogen hormone therapy (HT) by including consensus recommendations derived from key data published since the earlier statement, the authors wrote, noting that the revised statement includes new sections on ovarian and lung cancer, as well as updates to the sections on breast cancer, cognitive aging and decline, dementia, coronary heart disease, stroke, and discontinuance (Menopause 2010;17:242–55)

“Recent data support the initiation of hormone therapy around the time of menopause” to treat menopause-related vasomotor symptoms, sleep disturbance, vaginal atrophy, dyspareunia, or diminished libido and to reduce the risk of osteoporosis and fractures in some women, the authors wrote.

Specifically, findings from the Women's Health Initiative (WHI) trial of estrogen therapy showed that 0.625 mg/day of oral conjugated estrogen effectively treats menopause-related symptoms with low absolute risks. Similarly, in the WHI trial of combined estrogen-progestogen therapy, most risks were deemed rare—except for stroke, which was above the rare category—based on the criteria of the Council for International Organizations of Medical Sciences, the authors wrote.

They noted, however, that “there is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects.” As such, more research is needed before the risks and benefits of HT can be generalized, and “it cannot be assumed that benefits and risks of [HT] apply to all age ranges and durations of therapy,” they wrote.

The most notable changes in the NAMS 2010 position statement on postmenopausal HT are the two new sections on ovarian cancer and lung cancer, which were not included in the 2008 position statement, as well as the assertion that HT is not recommended in women with a history of endometrial cancer, Dr. Margery L.S. Gass, executive director of NAMS, commented in an interview.

The new statement also reflects the latest research on the effect of age on the benefit/risk ratio of postmenopausal HT. The current understanding that the benefit/risk ratio is greatest among women who start HT close to the time of menopause and decreases with time since menopause should make clinicians and women more comfortable using HT right at the time of menopause and more cautious about using it later in life for the prevention of osteoporosis. Most of the side effects associated with HT become more common with aging, even without the use of HT. Adding the HT just compounds the problem. Therefore, rather than recommending oral or transdermal estrogen for such problems as vaginal dryness and painful intercourse, we place emphasis on using local/topical estrogen, said Dr. Gass, also a consultant to the Cleveland Clinic Center for Specialized Women's Health, Mayfield Heights, Ohio.

Regarding the association between hormone therapy and cancer, the data are conflicting, according to the NAMS statement authors. “Unopposed systemic estrogen therapy in postmenopausal women with an intact uterus is associated with increased endometrial cancer risk related to the [estrogen therapy] dose and duration,” they wrote. Thus, concomitant progestogen is recommended in those who use systemic estrogen therapy, and HT is not recommended for women with a history of endometrial cancer.

With respect to ovarian cancer, most epidemiologic studies show no association or a modest association with HT, but observational trial data suggest an increased ovarian cancer risk, the authors wrote. Based on the available data, “the association between ovarian cancer and hormone therapy beyond 5 years, if any, would fall into the rare or very rare category,” they stated, noting that women with a positive family history or other risk factors for ovarian cancer “should be counseled about this rare association.”

The link between HT and breast cancer also is uncertain. Studies have demonstrated that diagnosis of breast cancer increases with estrogen-progestogen use beyond 3–5 years. However, a reanalysis of WHI data suggested that women who started estrogen-progestogen shortly after menopause experienced an increased breast cancer risk over the next 5 years, while those with a gap of more than 5 years between menopause and treatment did not, the authors explained.

Among breast cancer survivors, estrogen-progestogen therapy has not been proven safe and may be associated with an increased risk of recurrence, as indicated in a one randomized controlled trial, which “showed a statistically significant 2.4 fold increase in new breast cancer events,” the authors wrote.

The data on lung cancer are particularly contradictory in that, overall, it appears that starting estrogen-progestogen therapy in older women with a history of smoking may promote the growth of existing lung cancers, while “evidence from the WHI and some case-control and cohort studies of hormone therapy in a younger population [less than 60 years] shows some protection against lung cancer,” the authors stated. Although confusing, the findings “reinforce the need to encourage prevention or cessation of smoking and possibly to increase surveillance in older smokers who are current or past users of hormone therapy,” they wrote.

The revised statement also addresses the issues of cognitive impairment and coronary heart disease. It recommends against the use of HT at any age “for the sole or primary indication of preventing cognitive aging or dementia,” noting that it may increase the incidence of dementia when initiated in women who are 65 years or older.

Additionally, HT is not recommended as a sole or main indication for coronary protection in women of any age. When HT is started in recently menopausal women for the treatment of menopause symptoms, there does not appear to be an increased risk for coronary heart disease; however, women who initiate HT more than 10 years beyond menopause are at increased CHD risk, the authors noted.

In all cases, because each woman is unique with her own risk profile and preferences, “individualization of [hormone] therapy is key to providing health benefits with minimal risks, thereby enhancing quality of life,” the authors wrote. Women should be informed of known risks, with the understanding that “a woman's willingness to accept risks of [HT] will vary depending on her individual situation.” okOverall, “NAMS continues

Overall, “NAMS continues to refine our recommendations and approach to hormone therapy as data from the WHI and other studies continue to emerge,” NAMS president Cynthia A. Stuenkel said in an interview. “While we support the use of hormone therapy for symptomatic women [younger than age 60 years], close to the time of menopause, we remind our readers that there are some risks, though small, and there are some uncertainties remaining regarding short-term and long-term effects of hormone therapy.”

In general, “we strongly advocate for the lowest dose for the shortest time for the individual woman who has been carefully counseled about risks and benefits,” said Dr. Stuenkel, clinical professor of medicine at the University of California, San Diego.

The advisory panel members' financial disclosures are listed on the position statement, which can be found at www.menopause.org/PSht10.pdf

There are new sections on ovarian cancer and lung cancer, Dr. Margery L.S. Gass said.

My Take

Hormone Therapy Still Plays a Role

In general, the 2010 NAMS position statement on postmenopausal hormone therapy is in line with clinical practice; however, many doctors are not prescribing hormones, even when supported by the science, because of bad publicity and a lack of interest combined with fear of litigation.

It is pretty clear that hormone therapy should be used for patients with a clear indication, and the statement outlines what the relevant indications are. The data coming from the Women's Health Initiative] seem to be a reversal on the cardiovascular issue. Some of the subanalyses suggest that hormone therapy is associated with a cardiovascular benefit in women close to the age of menopause, while other studies from the same group suggest that this isn't so. Obviously, the science is evolving, and we are only beginning to understand the mechanism of cardiovascular risks and benefits. Overall, however, the statement is pretty clear that we should not use hormones to prevent cardiovascular disease.

In all cases, the decision to initiate hormone therapy has to be individualized to each patient. There is not a one-size-fits-all solution. The main issue is determining what is the safest drug for a woman at a particular time in her life.

MICHELLE P. WARREN, M.D., is director of the Center for Menopause, Hormonal Disorders, and Women's Health at Columbia University Medical Center in New York.

Major Finding: Prior vaccination for 2008 seasonal influenza was associated with a 68%- to 123%-increased risk for pandemic H1N1 infection. In two additional studies, prior 2008 seasonal influenza vaccine was tied to a 1.5 to 2 times higher risk for H1N1 infection.

Data Source: Four epidemiologic studies by a network of Canadian researchers comparing occurrence of H1N1 infection in participants who were received prior seasonal influenza vaccination and those not previously vaccinated.

Disclosures: Dr. Skowronski and coauthors received research grant funding from GlaxoSmithKline and Sanofi-Pasteur for separate studies. One coauthor also received speaking honoraria from GlaxoSmithKline and Sanofi-Pasteur.

Vaccination for the seasonal flu may have rendered people more susceptible to pandemic H1N1 infection, according to results from four observational studies.

In the four epidemiologic studies, conducted by Canadian investigators, prior receipt of the 2008–2009 trivalent inactivated influenza vaccine (TIV) was associated with an increased risk of pH1N1 illness in the spring and summer of 2009, wrote Dr. Danuta M. Skowronski of the British Columbia Centre for Disease Control, Vancouver, and colleagues.

The observational findings raise the possibility of a real biologic effect that warrants further investigation, the authors wrote (PLoS Med. 2010 April 6 [doi:10.1371/journal.pmed.1000258

The investigations, which involved a total of 2,700 people with and without pH1N1, were undertaken following an outbreak of pH1N1 in a rural British Columbia school the spring of 2009 in which fever and cough illness occurred more often among individuals previously vaccinated for the seasonal flu.

The first study compared the frequency of prior vaccination with the 2008 TIV between individuals with influenza-like illness who tested positive for seasonal or pH1N1 influenza and those who tested negative for both. An analysis of the data showed that prior vaccination with TIV significantly reduced the risk of reported seasonal influenza but was associated with a 68% increased risk for pH1N1 infection, and a 123% increased risk among participants younger than age 50 years, the authors wrote.

Similar case-control studies conducted in Quebec- and Ontario-based populations found that those who had received prior TIV were, respectively, 1.5 and 2 times more likely to experience pH1N1 illness than controls who had not received prior vaccination.

Prior TIV administration among participants in a third study involving a prospectively studied cohort found that household transmission study was associated with a significantly increased risk of laboratory-confirmed pH1N1, they said.

Among the possible biologic mechanisms to explain the association, the authors hypothesized that repeat immunization may effectively block “the more robust, complex, and cross-protective immunity afforded by prior infection,” which has been suggested by previous studies. Additionally, the possibility of a direct immune mechanism might explain the results, though they stressed that the various proposed mechanisms “must each be viewed as speculative since our epidemiologic studies were not designed to assess them.”

In an accompanying editorial, Cecile Viboud, Ph.D., of the National Institutes of Health, Bethesda, Md., and Lone Simonsen, Ph.D., of George Washington University in Washington, warn that “it would be premature to conclude that TIV increased the risk of 2009 pandemic illness,” considering the fact that contemporaneous observational studies have produced conflicting results. The “perplexing experience,” they wrote, “should teach us how to best react to disparate and conflicting studies and prepare us for the next public health crisis, so that we can better manage future alerts of unexpected risk factors” (PLoS Med. 2010 April 6 [doi: 10.1371/journal.pmed.1000259

Major Finding: Prior vaccination for 2008 seasonal influenza was associated with a 68%- to 123%-increased risk for pandemic H1N1 infection. In two additional studies, prior 2008 seasonal influenza vaccine was tied to a 1.5 to 2 times higher risk for H1N1 infection.

Data Source: Four epidemiologic studies by a network of Canadian researchers comparing occurrence of H1N1 infection in participants who were received prior seasonal influenza vaccination and those not previously vaccinated.

Disclosures: Dr. Skowronski and coauthors received research grant funding from GlaxoSmithKline and Sanofi-Pasteur for separate studies. One coauthor also received speaking honoraria from GlaxoSmithKline and Sanofi-Pasteur.

Vaccination for the seasonal flu may have rendered people more susceptible to pandemic H1N1 infection, according to results from four observational studies.

In the four epidemiologic studies, conducted by Canadian investigators, prior receipt of the 2008–2009 trivalent inactivated influenza vaccine (TIV) was associated with an increased risk of pH1N1 illness in the spring and summer of 2009, wrote Dr. Danuta M. Skowronski of the British Columbia Centre for Disease Control, Vancouver, and colleagues.

The observational findings raise the possibility of a real biologic effect that warrants further investigation, the authors wrote (PLoS Med. 2010 April 6 [doi:10.1371/journal.pmed.1000258

The investigations, which involved a total of 2,700 people with and without pH1N1, were undertaken following an outbreak of pH1N1 in a rural British Columbia school the spring of 2009 in which fever and cough illness occurred more often among individuals previously vaccinated for the seasonal flu.

The first study compared the frequency of prior vaccination with the 2008 TIV between individuals with influenza-like illness who tested positive for seasonal or pH1N1 influenza and those who tested negative for both. An analysis of the data showed that prior vaccination with TIV significantly reduced the risk of reported seasonal influenza but was associated with a 68% increased risk for pH1N1 infection, and a 123% increased risk among participants younger than age 50 years, the authors wrote.

Similar case-control studies conducted in Quebec- and Ontario-based populations found that those who had received prior TIV were, respectively, 1.5 and 2 times more likely to experience pH1N1 illness than controls who had not received prior vaccination.

Prior TIV administration among participants in a third study involving a prospectively studied cohort found that household transmission study was associated with a significantly increased risk of laboratory-confirmed pH1N1, they said.

Among the possible biologic mechanisms to explain the association, the authors hypothesized that repeat immunization may effectively block “the more robust, complex, and cross-protective immunity afforded by prior infection,” which has been suggested by previous studies. Additionally, the possibility of a direct immune mechanism might explain the results, though they stressed that the various proposed mechanisms “must each be viewed as speculative since our epidemiologic studies were not designed to assess them.”

In an accompanying editorial, Cecile Viboud, Ph.D., of the National Institutes of Health, Bethesda, Md., and Lone Simonsen, Ph.D., of George Washington University in Washington, warn that “it would be premature to conclude that TIV increased the risk of 2009 pandemic illness,” considering the fact that contemporaneous observational studies have produced conflicting results. The “perplexing experience,” they wrote, “should teach us how to best react to disparate and conflicting studies and prepare us for the next public health crisis, so that we can better manage future alerts of unexpected risk factors” (PLoS Med. 2010 April 6 [doi: 10.1371/journal.pmed.1000259

Major Finding: Prior vaccination for 2008 seasonal influenza was associated with a 68%- to 123%-increased risk for pandemic H1N1 infection. In two additional studies, prior 2008 seasonal influenza vaccine was tied to a 1.5 to 2 times higher risk for H1N1 infection.

Data Source: Four epidemiologic studies by a network of Canadian researchers comparing occurrence of H1N1 infection in participants who were received prior seasonal influenza vaccination and those not previously vaccinated.

Disclosures: Dr. Skowronski and coauthors received research grant funding from GlaxoSmithKline and Sanofi-Pasteur for separate studies. One coauthor also received speaking honoraria from GlaxoSmithKline and Sanofi-Pasteur.

Vaccination for the seasonal flu may have rendered people more susceptible to pandemic H1N1 infection, according to results from four observational studies.

In the four epidemiologic studies, conducted by Canadian investigators, prior receipt of the 2008–2009 trivalent inactivated influenza vaccine (TIV) was associated with an increased risk of pH1N1 illness in the spring and summer of 2009, wrote Dr. Danuta M. Skowronski of the British Columbia Centre for Disease Control, Vancouver, and colleagues.

The observational findings raise the possibility of a real biologic effect that warrants further investigation, the authors wrote (PLoS Med. 2010 April 6 [doi:10.1371/journal.pmed.1000258

The investigations, which involved a total of 2,700 people with and without pH1N1, were undertaken following an outbreak of pH1N1 in a rural British Columbia school the spring of 2009 in which fever and cough illness occurred more often among individuals previously vaccinated for the seasonal flu.

The first study compared the frequency of prior vaccination with the 2008 TIV between individuals with influenza-like illness who tested positive for seasonal or pH1N1 influenza and those who tested negative for both. An analysis of the data showed that prior vaccination with TIV significantly reduced the risk of reported seasonal influenza but was associated with a 68% increased risk for pH1N1 infection, and a 123% increased risk among participants younger than age 50 years, the authors wrote.

Similar case-control studies conducted in Quebec- and Ontario-based populations found that those who had received prior TIV were, respectively, 1.5 and 2 times more likely to experience pH1N1 illness than controls who had not received prior vaccination.

Prior TIV administration among participants in a third study involving a prospectively studied cohort found that household transmission study was associated with a significantly increased risk of laboratory-confirmed pH1N1, they said.

Among the possible biologic mechanisms to explain the association, the authors hypothesized that repeat immunization may effectively block “the more robust, complex, and cross-protective immunity afforded by prior infection,” which has been suggested by previous studies. Additionally, the possibility of a direct immune mechanism might explain the results, though they stressed that the various proposed mechanisms “must each be viewed as speculative since our epidemiologic studies were not designed to assess them.”

In an accompanying editorial, Cecile Viboud, Ph.D., of the National Institutes of Health, Bethesda, Md., and Lone Simonsen, Ph.D., of George Washington University in Washington, warn that “it would be premature to conclude that TIV increased the risk of 2009 pandemic illness,” considering the fact that contemporaneous observational studies have produced conflicting results. The “perplexing experience,” they wrote, “should teach us how to best react to disparate and conflicting studies and prepare us for the next public health crisis, so that we can better manage future alerts of unexpected risk factors” (PLoS Med. 2010 April 6 [doi: 10.1371/journal.pmed.1000259