Elizabeth Mechcatie

Major Finding: Adding neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy was tied to a significantly higher 3-year event-free survival rate, compared with neoadjuvant chemotherapy alone.

Data Source: The open-label, phase III NOAH study of 235 women with HER2-positive locally advanced or inflammatory breast cancer.

Disclosures: The study was funded and the drug was provided by Hoffmann-La Roche, the manufacturer of trastuzumab. The 20 authors included a current and a past employee of Roche, and two others who disclosed having served as adviser and/or consultant to several pharmaceutical companies, including Roche. The rest had no disclosures.

Event-free survival at 3 years was significantly greater among women with HER2-positive locally advanced or inflammatory breast cancer who received trastuzumab as neoadjuvant and adjuvant therapy in the international, open-label, phase III NOAH trial, investigators reported.

“Our results suggest that neoadjuvant trastuzumab should be offered to patients with HER2-positive locally advanced or inflammatory breast cancer alongside neoadjuvant chemotherapy, in addition to the established use of adjuvant trastuzumab” post surgery, concluded Dr. Luca Gianni of the Fondazione IRCCS Instituto Nazionale Tumori in Milan and his coauthors.

The 235-patient study appeared in the Lancet (2010;375:377-84).

A monoclonal antibody, trastuzumab (Herceptin) targets HER2—which is overexpressed in about 22% of early breast cancers—in 35% of locally advanced and metastatic tumors, and in 40% of inflammatory breast cancers, according to the authors.

It is widely approved as a monotherapy and a combination therapy for HER2-positive breast cancer, both in its early operable stages and when it has metastasized.

But the authors noted that it has not been “specifically indicated” for patients with locally advanced or inflammatory breast cancer that is positive for HER2.

Patients in the NOAH (Neoadjuvant Herceptin) trial received either neoadjuvant trastuzumab plus a neoadjuvant chemotherapy regimen (doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil) followed by adjuvant trastuzumab, or neoadjuvant chemotherapy alone.

The primary end point was event-free survival, which was defined as the time from randomization to disease recurrence or progression (local, regional, distant, or contralateral), or death from any cause.

After a median follow-up of 3.2 years, 71% of 117 women who received trastuzumab were event free, compared with 56% of 118 women in the chemotherapy-only group—a significant difference that represented a 41% reduction in the risk of recurrence, progression, or death (hazard ratio, 0.59; P = .013).

Pathological complete response, a secondary end point, was also significantly higher among those in the trastuzumab group, compared with the chemotherapy-only group (38.5% vs. 19.5%).

The 3-year overall survival rate was not significantly different at the time of the report (87% with trastuzumab vs. 79% with chemotherapy alone).

These results indicate that in patients with HER2-positive locally advanced or inflammatory breast cancer, adding 1 year of trastuzumab—starting as neoadjuvant and continuing as adjuvant therapy—to neoadjuvant chemotherapy “improved response rates, almost doubled rates of pathological complete response, and reduced risk of relapse, progression, or death compared with patients who did not receive trastuzumab,” the authors wrote.

Trastuzumab showed benefit in all the subgroups tested, including those with inflammatory disease, “who benefited substantially from trastuzumab,” they added.

Adverse events were similar in both groups, and the incidence of symptomatic heart failure was lower than expected among those in the trastuzumab group (less than 2%), which supports “the accumulating evidence that trastuzumab can be given concurrently with anthracyclines with a low frequency of symptomatic cardiac dysfunction, provided that low cumulative doses or less cardiotoxic anthracyclines are used, and careful cardiac monitoring is done,” the authors said.

In an accompanying editorial entitled “Challenging the Dogma on Trastuzumab: A Matter of the Heart,” Dr. Melanie Seal and Dr. Stephen Chia of the division of medical oncology at the British Columbia Cancer Agency, Vancouver, also noted that study results go against the dogma that anthracyclines and trastuzumab should not be given concurrently because of cardiac safety concerns.

“Because HER2-positive breast cancers are sensitive to anthracyclines and preclinical data suggest additive or synergistic effects for the combination of anthracyclines and trastuzumab, … the concomitant delivery of these drugs should be considered with an apparently favourable risk-to-benefit ratio” in patients who present with high-risk disease, such as locally advanced or inflammatory breast cancer, Dr. Seal and Dr. Chia wrote.

Furthermore, they advocated that with “the ability to assess response to systemic treatment and the additional opportunity of correlative studies, neoadjuvant trials should be further exploited in the search for new therapeutic strategies.”

Noting that “almost all new systemic agents being studied in cancer are targeted agents,” they added, “understanding the target, and downstream and redundant effects, is essential if we truly are moving to personalized medicine.”

Women with inflammatory disease 'benefited substantially from trastuzumab.'

Source DR. GIANNI

Major Finding: Adding neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy was tied to a significantly higher 3-year event-free survival rate, compared with neoadjuvant chemotherapy alone.

Data Source: The open-label, phase III NOAH study of 235 women with HER2-positive locally advanced or inflammatory breast cancer.

Disclosures: The study was funded and the drug was provided by Hoffmann-La Roche, the manufacturer of trastuzumab. The 20 authors included a current and a past employee of Roche, and two others who disclosed having served as adviser and/or consultant to several pharmaceutical companies, including Roche. The rest had no disclosures.

Event-free survival at 3 years was significantly greater among women with HER2-positive locally advanced or inflammatory breast cancer who received trastuzumab as neoadjuvant and adjuvant therapy in the international, open-label, phase III NOAH trial, investigators reported.

“Our results suggest that neoadjuvant trastuzumab should be offered to patients with HER2-positive locally advanced or inflammatory breast cancer alongside neoadjuvant chemotherapy, in addition to the established use of adjuvant trastuzumab” post surgery, concluded Dr. Luca Gianni of the Fondazione IRCCS Instituto Nazionale Tumori in Milan and his coauthors.

The 235-patient study appeared in the Lancet (2010;375:377-84).

A monoclonal antibody, trastuzumab (Herceptin) targets HER2—which is overexpressed in about 22% of early breast cancers—in 35% of locally advanced and metastatic tumors, and in 40% of inflammatory breast cancers, according to the authors.

It is widely approved as a monotherapy and a combination therapy for HER2-positive breast cancer, both in its early operable stages and when it has metastasized.

But the authors noted that it has not been “specifically indicated” for patients with locally advanced or inflammatory breast cancer that is positive for HER2.

Patients in the NOAH (Neoadjuvant Herceptin) trial received either neoadjuvant trastuzumab plus a neoadjuvant chemotherapy regimen (doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil) followed by adjuvant trastuzumab, or neoadjuvant chemotherapy alone.

The primary end point was event-free survival, which was defined as the time from randomization to disease recurrence or progression (local, regional, distant, or contralateral), or death from any cause.

After a median follow-up of 3.2 years, 71% of 117 women who received trastuzumab were event free, compared with 56% of 118 women in the chemotherapy-only group—a significant difference that represented a 41% reduction in the risk of recurrence, progression, or death (hazard ratio, 0.59; P = .013).

Pathological complete response, a secondary end point, was also significantly higher among those in the trastuzumab group, compared with the chemotherapy-only group (38.5% vs. 19.5%).

The 3-year overall survival rate was not significantly different at the time of the report (87% with trastuzumab vs. 79% with chemotherapy alone).

These results indicate that in patients with HER2-positive locally advanced or inflammatory breast cancer, adding 1 year of trastuzumab—starting as neoadjuvant and continuing as adjuvant therapy—to neoadjuvant chemotherapy “improved response rates, almost doubled rates of pathological complete response, and reduced risk of relapse, progression, or death compared with patients who did not receive trastuzumab,” the authors wrote.

Trastuzumab showed benefit in all the subgroups tested, including those with inflammatory disease, “who benefited substantially from trastuzumab,” they added.

Adverse events were similar in both groups, and the incidence of symptomatic heart failure was lower than expected among those in the trastuzumab group (less than 2%), which supports “the accumulating evidence that trastuzumab can be given concurrently with anthracyclines with a low frequency of symptomatic cardiac dysfunction, provided that low cumulative doses or less cardiotoxic anthracyclines are used, and careful cardiac monitoring is done,” the authors said.

In an accompanying editorial entitled “Challenging the Dogma on Trastuzumab: A Matter of the Heart,” Dr. Melanie Seal and Dr. Stephen Chia of the division of medical oncology at the British Columbia Cancer Agency, Vancouver, also noted that study results go against the dogma that anthracyclines and trastuzumab should not be given concurrently because of cardiac safety concerns.

“Because HER2-positive breast cancers are sensitive to anthracyclines and preclinical data suggest additive or synergistic effects for the combination of anthracyclines and trastuzumab, … the concomitant delivery of these drugs should be considered with an apparently favourable risk-to-benefit ratio” in patients who present with high-risk disease, such as locally advanced or inflammatory breast cancer, Dr. Seal and Dr. Chia wrote.

Furthermore, they advocated that with “the ability to assess response to systemic treatment and the additional opportunity of correlative studies, neoadjuvant trials should be further exploited in the search for new therapeutic strategies.”

Noting that “almost all new systemic agents being studied in cancer are targeted agents,” they added, “understanding the target, and downstream and redundant effects, is essential if we truly are moving to personalized medicine.”

Women with inflammatory disease 'benefited substantially from trastuzumab.'

Source DR. GIANNI

Major Finding: Adding neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy was tied to a significantly higher 3-year event-free survival rate, compared with neoadjuvant chemotherapy alone.

Data Source: The open-label, phase III NOAH study of 235 women with HER2-positive locally advanced or inflammatory breast cancer.

Disclosures: The study was funded and the drug was provided by Hoffmann-La Roche, the manufacturer of trastuzumab. The 20 authors included a current and a past employee of Roche, and two others who disclosed having served as adviser and/or consultant to several pharmaceutical companies, including Roche. The rest had no disclosures.

Event-free survival at 3 years was significantly greater among women with HER2-positive locally advanced or inflammatory breast cancer who received trastuzumab as neoadjuvant and adjuvant therapy in the international, open-label, phase III NOAH trial, investigators reported.

“Our results suggest that neoadjuvant trastuzumab should be offered to patients with HER2-positive locally advanced or inflammatory breast cancer alongside neoadjuvant chemotherapy, in addition to the established use of adjuvant trastuzumab” post surgery, concluded Dr. Luca Gianni of the Fondazione IRCCS Instituto Nazionale Tumori in Milan and his coauthors.

The 235-patient study appeared in the Lancet (2010;375:377-84).

A monoclonal antibody, trastuzumab (Herceptin) targets HER2—which is overexpressed in about 22% of early breast cancers—in 35% of locally advanced and metastatic tumors, and in 40% of inflammatory breast cancers, according to the authors.

It is widely approved as a monotherapy and a combination therapy for HER2-positive breast cancer, both in its early operable stages and when it has metastasized.

But the authors noted that it has not been “specifically indicated” for patients with locally advanced or inflammatory breast cancer that is positive for HER2.

Patients in the NOAH (Neoadjuvant Herceptin) trial received either neoadjuvant trastuzumab plus a neoadjuvant chemotherapy regimen (doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil) followed by adjuvant trastuzumab, or neoadjuvant chemotherapy alone.

The primary end point was event-free survival, which was defined as the time from randomization to disease recurrence or progression (local, regional, distant, or contralateral), or death from any cause.

After a median follow-up of 3.2 years, 71% of 117 women who received trastuzumab were event free, compared with 56% of 118 women in the chemotherapy-only group—a significant difference that represented a 41% reduction in the risk of recurrence, progression, or death (hazard ratio, 0.59; P = .013).

Pathological complete response, a secondary end point, was also significantly higher among those in the trastuzumab group, compared with the chemotherapy-only group (38.5% vs. 19.5%).

The 3-year overall survival rate was not significantly different at the time of the report (87% with trastuzumab vs. 79% with chemotherapy alone).

These results indicate that in patients with HER2-positive locally advanced or inflammatory breast cancer, adding 1 year of trastuzumab—starting as neoadjuvant and continuing as adjuvant therapy—to neoadjuvant chemotherapy “improved response rates, almost doubled rates of pathological complete response, and reduced risk of relapse, progression, or death compared with patients who did not receive trastuzumab,” the authors wrote.

Trastuzumab showed benefit in all the subgroups tested, including those with inflammatory disease, “who benefited substantially from trastuzumab,” they added.

Adverse events were similar in both groups, and the incidence of symptomatic heart failure was lower than expected among those in the trastuzumab group (less than 2%), which supports “the accumulating evidence that trastuzumab can be given concurrently with anthracyclines with a low frequency of symptomatic cardiac dysfunction, provided that low cumulative doses or less cardiotoxic anthracyclines are used, and careful cardiac monitoring is done,” the authors said.

In an accompanying editorial entitled “Challenging the Dogma on Trastuzumab: A Matter of the Heart,” Dr. Melanie Seal and Dr. Stephen Chia of the division of medical oncology at the British Columbia Cancer Agency, Vancouver, also noted that study results go against the dogma that anthracyclines and trastuzumab should not be given concurrently because of cardiac safety concerns.

“Because HER2-positive breast cancers are sensitive to anthracyclines and preclinical data suggest additive or synergistic effects for the combination of anthracyclines and trastuzumab, … the concomitant delivery of these drugs should be considered with an apparently favourable risk-to-benefit ratio” in patients who present with high-risk disease, such as locally advanced or inflammatory breast cancer, Dr. Seal and Dr. Chia wrote.

Furthermore, they advocated that with “the ability to assess response to systemic treatment and the additional opportunity of correlative studies, neoadjuvant trials should be further exploited in the search for new therapeutic strategies.”

Noting that “almost all new systemic agents being studied in cancer are targeted agents,” they added, “understanding the target, and downstream and redundant effects, is essential if we truly are moving to personalized medicine.”

Women with inflammatory disease 'benefited substantially from trastuzumab.'

Source DR. GIANNI

The Food and Drug Administration has approved lapatinib in combination with letrozole for the treatment of postmenopausal women with advanced breast cancer that is hormone receptor and HER2 positive and for whom hormonal therapy is indicated.

A kinase inhibitor, lapatinib (Tykerb) targets the HER2 protein that is overexpressed in HER2-positive breast cancer. Letrozole (Femara), an aromatase inhibitor, is used in patients with hormone-dependent breast cancer.

In a study sponsored by lapatinib manufacturer GlaxoSmithKline, progression-free survival was more than twofold higher among the women treated with the all-oral combination of these two agents, compared with those who received letrozole alone. “It is too early to determine whether an improvement in overall survival will be observed in the clinical trial,” the FDA statement said.

In the trial, median progression-free survival was 35.4 weeks among the 111 women who received lapatinib (1,500 mg/day) plus letrozole (2.5 mg/day), vs. a median of 13 weeks among the 108 women who received letrozole alone, according to the revised label for lapatinib.

The safety profile of lapatinib was similar to that observed in previous studies of women with advanced breast cancer. Diarrhea, rash, nausea, and fatigue were the most common side effects, according to the FDA. Treatment with lapatinib has been associated with decreased left ventricular ejection fraction and hepatotoxicity, as well as interstitial lung disease and pneumonitis, and it can harm the fetus, the statement added.

Letrozole is marketed by Novartis.

The Food and Drug Administration has approved lapatinib in combination with letrozole for the treatment of postmenopausal women with advanced breast cancer that is hormone receptor and HER2 positive and for whom hormonal therapy is indicated.

A kinase inhibitor, lapatinib (Tykerb) targets the HER2 protein that is overexpressed in HER2-positive breast cancer. Letrozole (Femara), an aromatase inhibitor, is used in patients with hormone-dependent breast cancer.

In a study sponsored by lapatinib manufacturer GlaxoSmithKline, progression-free survival was more than twofold higher among the women treated with the all-oral combination of these two agents, compared with those who received letrozole alone. “It is too early to determine whether an improvement in overall survival will be observed in the clinical trial,” the FDA statement said.

In the trial, median progression-free survival was 35.4 weeks among the 111 women who received lapatinib (1,500 mg/day) plus letrozole (2.5 mg/day), vs. a median of 13 weeks among the 108 women who received letrozole alone, according to the revised label for lapatinib.

The safety profile of lapatinib was similar to that observed in previous studies of women with advanced breast cancer. Diarrhea, rash, nausea, and fatigue were the most common side effects, according to the FDA. Treatment with lapatinib has been associated with decreased left ventricular ejection fraction and hepatotoxicity, as well as interstitial lung disease and pneumonitis, and it can harm the fetus, the statement added.

Letrozole is marketed by Novartis.

The Food and Drug Administration has approved lapatinib in combination with letrozole for the treatment of postmenopausal women with advanced breast cancer that is hormone receptor and HER2 positive and for whom hormonal therapy is indicated.

A kinase inhibitor, lapatinib (Tykerb) targets the HER2 protein that is overexpressed in HER2-positive breast cancer. Letrozole (Femara), an aromatase inhibitor, is used in patients with hormone-dependent breast cancer.

In a study sponsored by lapatinib manufacturer GlaxoSmithKline, progression-free survival was more than twofold higher among the women treated with the all-oral combination of these two agents, compared with those who received letrozole alone. “It is too early to determine whether an improvement in overall survival will be observed in the clinical trial,” the FDA statement said.

In the trial, median progression-free survival was 35.4 weeks among the 111 women who received lapatinib (1,500 mg/day) plus letrozole (2.5 mg/day), vs. a median of 13 weeks among the 108 women who received letrozole alone, according to the revised label for lapatinib.

The safety profile of lapatinib was similar to that observed in previous studies of women with advanced breast cancer. Diarrhea, rash, nausea, and fatigue were the most common side effects, according to the FDA. Treatment with lapatinib has been associated with decreased left ventricular ejection fraction and hepatotoxicity, as well as interstitial lung disease and pneumonitis, and it can harm the fetus, the statement added.

Letrozole is marketed by Novartis.

Major Finding: Overall mortality among children with rheumatic diseases was lower than expected; and although SLE and some other rheumatic conditions were associated with higher mortality, the rates were lower than previously reported for those diseases in this age group.

Data Source: Data from the Indianapolis Pediatric Rheumatology Disease Registry on nearly 49,000 children who were followed for about 8 years.

Disclosures: The study was supported by the Northeast Ohio Chapter of the Arthritis Foundation. The authors had no disclosures.

A study that analyzed data on almost 49,000 children and adolescents enrolled in a U.S. pediatric rheumatology registry found that the overall mortality for pediatric rheumatic diseases was not increased when compared to the general population, results that require further follow-up but were described as “encouraging” by the authors.

“Even for those diseases and conditions associated with increased mortality, the rates were significantly lower than those reported in previous studies,” especially for systemic juvenile rheumatoid arthritis (JRA), childhood systemic lupus erythematosus (SLE), dermatomyositis (DM), and vasculitis, reported Dr. Philip J. Hashkes of the Cleveland Clinic and his associates.

The study, which they said was “the largest systematic mortality outcome study in pediatric rheumatology published to date,” analyzed mortality outcomes among the 48,885 children newly diagnosed with a rheumatic disease between 1992 and 2001 and enrolled in the Indianapolis PRDR (Pediatric Rheumatology Disease Registry), involving patients from 62 centers in the United States. Children with a malignancy were excluded. Patients were followed for a mean of 8 years.

Almost 64% had an inflammatory diagnosis, of which the majority (almost 40%) was JRA, followed by SLE in almost 6% and Raynaud's phenomenon in almost 5%. Arthralgia was the most common noninflammatory diagnosis, affecting 36% of those with a noninflammatory rheumatic disease. Almost 7,000 patients had more than one rheumatic diagnosis.

To compare the observed survival rates to the expected survival rates, the authors calculated the SMR (standardized mortality ratio, defined as the number of observed deaths divided by the number of expected deaths).

The mortality of the patients in the registry was significantly lower than was the expected mortality of the U.S. population, adjusted for age and sex. Overall, there were 110 deaths (0.23%) among the nearly 48,000 patients for whom complete data were available, for an SMR of 0.65.

Put another way: The 5-year survival rate was 99.77% for the entire group, and was slightly lower for those with connective tissue disease, systemic JRA, and those with primary vasculitis other than Kawasaki disease.

There were significant differences in the SMR for several diagnostic categories and specific diseases. SMR was significantly increased for the categories of connective tissue diseases and primary vasculitis, with the exception of Kawasaki disease and Henoch-Schönlein purpura (HSP). The SMR was significantly greater for SLE (3.06) and DM (2.64), but not for systemic JRA (1.8). The SMR was significantly decreased for pain syndromes (0.41) and arthralgia (0.23). The SMR did not differ significantly for other specific diseases, including all subtypes of JRA, Kawasaki disease, and HSP.

The SMRs in the group of patients with noninflammatory diseases (0.58) and those with inflammatory diseases (0.76) were significantly lower than in the general population; the difference was more significant in the noninflammatory group.

Of all the 110 deaths, 64 (58%) were in patients with an inflammatory disease. The rest, with the exception of one patient whose primary diagnosis was not known, were in patients with a noninflammatory disease.

In 39 cases (35%), the cause of death was related to the rheumatic diagnosis. Other causes of death included treatment complications in 11 patients (10%), non-natural causes in 25 (23%), and background disease in 23 (21%). In 12 (11%) patients, the cause of death was unknown or not clear.

The investigators found a significant correlation between the rheumatic diagnosis and cause of death: Among the 64 patients who had been diagnosed with an inflammatory disease before their death, 28 (44%) deaths were related to the diagnosis, for which they were being treated by a rheumatologist, compared with 11 (24%) of the 45 patients diagnosed with a noninflammatory disease.

The cause of death among the patients with SLE included renal disease in six cases, pancreatitis in two patients, pulmonary hemorrhage in one patient, and intracranial hemorrhage in one patient. Four died of an infection, including two who had had a bone marrow transplant. Of the patients with JRA who died, two died of macrophage activation syndrome, which the authors said is “probably currently the most common cause of death” in patients with systemic JRA. Two patients died of heart disease, one died of an infection, and one died of a secondary malignancy.

Significant predictors of mortality identified in the study included the age at the first visit. Being older than 14.5 years was associated with a 2.3-fold greater risk of mortality. Other factors that included sex, ethnicity, time from onset of the disease to diagnosis, and initial medication use were not associated with increased mortality.

Any connective tissue diseases, SLE, DM, primary vasculitis (except for Kawasaki disease and HSP), systemic JRA, and a genetic/chromosomal/metabolic disease were also significant predictors of increased mortality, whereas an arthralgia diagnosis was significantly predictive of better survival.

Morality was higher for systemic JRA, SLE, DM, and vasculitis. But the rates were still significantly lower than in previous studies, they said (Arthritis Rheum. 2010;62:599-608).

Major Finding: Overall mortality among children with rheumatic diseases was lower than expected; and although SLE and some other rheumatic conditions were associated with higher mortality, the rates were lower than previously reported for those diseases in this age group.

Data Source: Data from the Indianapolis Pediatric Rheumatology Disease Registry on nearly 49,000 children who were followed for about 8 years.

Disclosures: The study was supported by the Northeast Ohio Chapter of the Arthritis Foundation. The authors had no disclosures.

A study that analyzed data on almost 49,000 children and adolescents enrolled in a U.S. pediatric rheumatology registry found that the overall mortality for pediatric rheumatic diseases was not increased when compared to the general population, results that require further follow-up but were described as “encouraging” by the authors.

“Even for those diseases and conditions associated with increased mortality, the rates were significantly lower than those reported in previous studies,” especially for systemic juvenile rheumatoid arthritis (JRA), childhood systemic lupus erythematosus (SLE), dermatomyositis (DM), and vasculitis, reported Dr. Philip J. Hashkes of the Cleveland Clinic and his associates.

The study, which they said was “the largest systematic mortality outcome study in pediatric rheumatology published to date,” analyzed mortality outcomes among the 48,885 children newly diagnosed with a rheumatic disease between 1992 and 2001 and enrolled in the Indianapolis PRDR (Pediatric Rheumatology Disease Registry), involving patients from 62 centers in the United States. Children with a malignancy were excluded. Patients were followed for a mean of 8 years.

Almost 64% had an inflammatory diagnosis, of which the majority (almost 40%) was JRA, followed by SLE in almost 6% and Raynaud's phenomenon in almost 5%. Arthralgia was the most common noninflammatory diagnosis, affecting 36% of those with a noninflammatory rheumatic disease. Almost 7,000 patients had more than one rheumatic diagnosis.

To compare the observed survival rates to the expected survival rates, the authors calculated the SMR (standardized mortality ratio, defined as the number of observed deaths divided by the number of expected deaths).

The mortality of the patients in the registry was significantly lower than was the expected mortality of the U.S. population, adjusted for age and sex. Overall, there were 110 deaths (0.23%) among the nearly 48,000 patients for whom complete data were available, for an SMR of 0.65.

Put another way: The 5-year survival rate was 99.77% for the entire group, and was slightly lower for those with connective tissue disease, systemic JRA, and those with primary vasculitis other than Kawasaki disease.

There were significant differences in the SMR for several diagnostic categories and specific diseases. SMR was significantly increased for the categories of connective tissue diseases and primary vasculitis, with the exception of Kawasaki disease and Henoch-Schönlein purpura (HSP). The SMR was significantly greater for SLE (3.06) and DM (2.64), but not for systemic JRA (1.8). The SMR was significantly decreased for pain syndromes (0.41) and arthralgia (0.23). The SMR did not differ significantly for other specific diseases, including all subtypes of JRA, Kawasaki disease, and HSP.

The SMRs in the group of patients with noninflammatory diseases (0.58) and those with inflammatory diseases (0.76) were significantly lower than in the general population; the difference was more significant in the noninflammatory group.

Of all the 110 deaths, 64 (58%) were in patients with an inflammatory disease. The rest, with the exception of one patient whose primary diagnosis was not known, were in patients with a noninflammatory disease.

In 39 cases (35%), the cause of death was related to the rheumatic diagnosis. Other causes of death included treatment complications in 11 patients (10%), non-natural causes in 25 (23%), and background disease in 23 (21%). In 12 (11%) patients, the cause of death was unknown or not clear.

The investigators found a significant correlation between the rheumatic diagnosis and cause of death: Among the 64 patients who had been diagnosed with an inflammatory disease before their death, 28 (44%) deaths were related to the diagnosis, for which they were being treated by a rheumatologist, compared with 11 (24%) of the 45 patients diagnosed with a noninflammatory disease.

The cause of death among the patients with SLE included renal disease in six cases, pancreatitis in two patients, pulmonary hemorrhage in one patient, and intracranial hemorrhage in one patient. Four died of an infection, including two who had had a bone marrow transplant. Of the patients with JRA who died, two died of macrophage activation syndrome, which the authors said is “probably currently the most common cause of death” in patients with systemic JRA. Two patients died of heart disease, one died of an infection, and one died of a secondary malignancy.

Significant predictors of mortality identified in the study included the age at the first visit. Being older than 14.5 years was associated with a 2.3-fold greater risk of mortality. Other factors that included sex, ethnicity, time from onset of the disease to diagnosis, and initial medication use were not associated with increased mortality.

Any connective tissue diseases, SLE, DM, primary vasculitis (except for Kawasaki disease and HSP), systemic JRA, and a genetic/chromosomal/metabolic disease were also significant predictors of increased mortality, whereas an arthralgia diagnosis was significantly predictive of better survival.

Morality was higher for systemic JRA, SLE, DM, and vasculitis. But the rates were still significantly lower than in previous studies, they said (Arthritis Rheum. 2010;62:599-608).

Major Finding: Overall mortality among children with rheumatic diseases was lower than expected; and although SLE and some other rheumatic conditions were associated with higher mortality, the rates were lower than previously reported for those diseases in this age group.

Data Source: Data from the Indianapolis Pediatric Rheumatology Disease Registry on nearly 49,000 children who were followed for about 8 years.

Disclosures: The study was supported by the Northeast Ohio Chapter of the Arthritis Foundation. The authors had no disclosures.

A study that analyzed data on almost 49,000 children and adolescents enrolled in a U.S. pediatric rheumatology registry found that the overall mortality for pediatric rheumatic diseases was not increased when compared to the general population, results that require further follow-up but were described as “encouraging” by the authors.

“Even for those diseases and conditions associated with increased mortality, the rates were significantly lower than those reported in previous studies,” especially for systemic juvenile rheumatoid arthritis (JRA), childhood systemic lupus erythematosus (SLE), dermatomyositis (DM), and vasculitis, reported Dr. Philip J. Hashkes of the Cleveland Clinic and his associates.

The study, which they said was “the largest systematic mortality outcome study in pediatric rheumatology published to date,” analyzed mortality outcomes among the 48,885 children newly diagnosed with a rheumatic disease between 1992 and 2001 and enrolled in the Indianapolis PRDR (Pediatric Rheumatology Disease Registry), involving patients from 62 centers in the United States. Children with a malignancy were excluded. Patients were followed for a mean of 8 years.

Almost 64% had an inflammatory diagnosis, of which the majority (almost 40%) was JRA, followed by SLE in almost 6% and Raynaud's phenomenon in almost 5%. Arthralgia was the most common noninflammatory diagnosis, affecting 36% of those with a noninflammatory rheumatic disease. Almost 7,000 patients had more than one rheumatic diagnosis.

To compare the observed survival rates to the expected survival rates, the authors calculated the SMR (standardized mortality ratio, defined as the number of observed deaths divided by the number of expected deaths).

The mortality of the patients in the registry was significantly lower than was the expected mortality of the U.S. population, adjusted for age and sex. Overall, there were 110 deaths (0.23%) among the nearly 48,000 patients for whom complete data were available, for an SMR of 0.65.

Put another way: The 5-year survival rate was 99.77% for the entire group, and was slightly lower for those with connective tissue disease, systemic JRA, and those with primary vasculitis other than Kawasaki disease.

There were significant differences in the SMR for several diagnostic categories and specific diseases. SMR was significantly increased for the categories of connective tissue diseases and primary vasculitis, with the exception of Kawasaki disease and Henoch-Schönlein purpura (HSP). The SMR was significantly greater for SLE (3.06) and DM (2.64), but not for systemic JRA (1.8). The SMR was significantly decreased for pain syndromes (0.41) and arthralgia (0.23). The SMR did not differ significantly for other specific diseases, including all subtypes of JRA, Kawasaki disease, and HSP.

The SMRs in the group of patients with noninflammatory diseases (0.58) and those with inflammatory diseases (0.76) were significantly lower than in the general population; the difference was more significant in the noninflammatory group.

Of all the 110 deaths, 64 (58%) were in patients with an inflammatory disease. The rest, with the exception of one patient whose primary diagnosis was not known, were in patients with a noninflammatory disease.

In 39 cases (35%), the cause of death was related to the rheumatic diagnosis. Other causes of death included treatment complications in 11 patients (10%), non-natural causes in 25 (23%), and background disease in 23 (21%). In 12 (11%) patients, the cause of death was unknown or not clear.

The investigators found a significant correlation between the rheumatic diagnosis and cause of death: Among the 64 patients who had been diagnosed with an inflammatory disease before their death, 28 (44%) deaths were related to the diagnosis, for which they were being treated by a rheumatologist, compared with 11 (24%) of the 45 patients diagnosed with a noninflammatory disease.

The cause of death among the patients with SLE included renal disease in six cases, pancreatitis in two patients, pulmonary hemorrhage in one patient, and intracranial hemorrhage in one patient. Four died of an infection, including two who had had a bone marrow transplant. Of the patients with JRA who died, two died of macrophage activation syndrome, which the authors said is “probably currently the most common cause of death” in patients with systemic JRA. Two patients died of heart disease, one died of an infection, and one died of a secondary malignancy.

Significant predictors of mortality identified in the study included the age at the first visit. Being older than 14.5 years was associated with a 2.3-fold greater risk of mortality. Other factors that included sex, ethnicity, time from onset of the disease to diagnosis, and initial medication use were not associated with increased mortality.

Any connective tissue diseases, SLE, DM, primary vasculitis (except for Kawasaki disease and HSP), systemic JRA, and a genetic/chromosomal/metabolic disease were also significant predictors of increased mortality, whereas an arthralgia diagnosis was significantly predictive of better survival.

Morality was higher for systemic JRA, SLE, DM, and vasculitis. But the rates were still significantly lower than in previous studies, they said (Arthritis Rheum. 2010;62:599-608).

BETHESDA, MD. — The influenza vaccine for the 2010-2011 influenza season in the United States should include a pandemic 2009 H1N1 strain, instead of one of the two seasonal influenza A strains in the current vaccine, a Food and Drug Administration Advisory Panel recommended.

At a meeting of the FDA's Vaccines and Related Biological Products Advisory Committee, the panel unanimously voted 12 to 0 that the current influenza A(H1N1) strain included in the 2009-2010 seasonal flu vaccine, an A/Brisbane/59/2007 (H1N1)–like virus, should be replaced with a pandemic A(H1N1) vaccine virus, an A/California/7/2009–like virus, the component of the monovalent pandemic vaccine that has been used this season.

Also included in the vaccine should be an A/Perth/16/2009 (H3N2)–like virus and a B/Brisbane/60/2008–like virus (B/Victoria lineage).

The panel's recommendation is based on the finding that the vast majority of influenza A(H1N1) viruses circulating worldwide have been the pandemic strain. At the meeting, Nancy Cox, Ph.D., director of the influenza division, at the Centers for Disease Control and Prevention, Atlanta, told the panel that there has been very little evidence of circulating seasonal A(H1N1) influenza viruses, which “most likely pose a low risk” in the forthcoming season in the northern hemisphere.

The panel meets every year at this time to make preliminary recommendations on the components of the trivalent vaccine for the forthcoming influenza season in the northern hemisphere. It considered information on the strains circulating worldwide as well as recommendations announced by the World Health Organization for the 2010-2011 influenza vaccine.

The panel voted to replace the influenza A(H3N2) strain included in the current vaccine, with a southern hemisphere vaccine virus A/Perth/16/2009 (H3N2)–like virus.

BETHESDA, MD. — The influenza vaccine for the 2010-2011 influenza season in the United States should include a pandemic 2009 H1N1 strain, instead of one of the two seasonal influenza A strains in the current vaccine, a Food and Drug Administration Advisory Panel recommended.

At a meeting of the FDA's Vaccines and Related Biological Products Advisory Committee, the panel unanimously voted 12 to 0 that the current influenza A(H1N1) strain included in the 2009-2010 seasonal flu vaccine, an A/Brisbane/59/2007 (H1N1)–like virus, should be replaced with a pandemic A(H1N1) vaccine virus, an A/California/7/2009–like virus, the component of the monovalent pandemic vaccine that has been used this season.

Also included in the vaccine should be an A/Perth/16/2009 (H3N2)–like virus and a B/Brisbane/60/2008–like virus (B/Victoria lineage).

The panel's recommendation is based on the finding that the vast majority of influenza A(H1N1) viruses circulating worldwide have been the pandemic strain. At the meeting, Nancy Cox, Ph.D., director of the influenza division, at the Centers for Disease Control and Prevention, Atlanta, told the panel that there has been very little evidence of circulating seasonal A(H1N1) influenza viruses, which “most likely pose a low risk” in the forthcoming season in the northern hemisphere.

The panel meets every year at this time to make preliminary recommendations on the components of the trivalent vaccine for the forthcoming influenza season in the northern hemisphere. It considered information on the strains circulating worldwide as well as recommendations announced by the World Health Organization for the 2010-2011 influenza vaccine.

The panel voted to replace the influenza A(H3N2) strain included in the current vaccine, with a southern hemisphere vaccine virus A/Perth/16/2009 (H3N2)–like virus.

BETHESDA, MD. — The influenza vaccine for the 2010-2011 influenza season in the United States should include a pandemic 2009 H1N1 strain, instead of one of the two seasonal influenza A strains in the current vaccine, a Food and Drug Administration Advisory Panel recommended.

At a meeting of the FDA's Vaccines and Related Biological Products Advisory Committee, the panel unanimously voted 12 to 0 that the current influenza A(H1N1) strain included in the 2009-2010 seasonal flu vaccine, an A/Brisbane/59/2007 (H1N1)–like virus, should be replaced with a pandemic A(H1N1) vaccine virus, an A/California/7/2009–like virus, the component of the monovalent pandemic vaccine that has been used this season.

Also included in the vaccine should be an A/Perth/16/2009 (H3N2)–like virus and a B/Brisbane/60/2008–like virus (B/Victoria lineage).

The panel's recommendation is based on the finding that the vast majority of influenza A(H1N1) viruses circulating worldwide have been the pandemic strain. At the meeting, Nancy Cox, Ph.D., director of the influenza division, at the Centers for Disease Control and Prevention, Atlanta, told the panel that there has been very little evidence of circulating seasonal A(H1N1) influenza viruses, which “most likely pose a low risk” in the forthcoming season in the northern hemisphere.

The panel meets every year at this time to make preliminary recommendations on the components of the trivalent vaccine for the forthcoming influenza season in the northern hemisphere. It considered information on the strains circulating worldwide as well as recommendations announced by the World Health Organization for the 2010-2011 influenza vaccine.

The panel voted to replace the influenza A(H3N2) strain included in the current vaccine, with a southern hemisphere vaccine virus A/Perth/16/2009 (H3N2)–like virus.

The approval of the HeartMate II, the continuous-flow left ventricular assist device, has been expanded to include its use as destination therapy for people with severe heart failure who are not acceptable candidates for heart transplantation.

The device can now be used in patients with New York Heart Association class IIIB or IV end-stage left ventricular failure, who have received optimal medical therapy for at least 45 of the last 60 days, according to the statement issued by the manufacturer, Thoratec Corp.

The Food and Drug Administration and Thoratec Corp. announced the approval of the Heart Mate II left ventricular assist device (LVAD) in late January.

It was first approved by the FDA in April 2008 for use as a bridge to transplantation in cardiac transplant candidates at risk of imminent death from nonreversible left ventricular heart failure. The HeartMate II is markedly smaller than previously available devices, including Thoratec's HeartMate XVE, the only other LVAD approved for destination therapy. The HeartMate XVE, a pulsatile flow LVAD, was first approved for use as a bridge to transplantation.

“Its smaller size and mobility should allow more patients, including women and men of smaller stature, access to treatment,” Dr. Jeffrey Shuren, director of the FDA's Center for Devices and Radiological Health, said in the agency's approval statement.

The HeartMate II Destination Therapy study, a randomized trial sponsored by Thoratec, compared the HeartMate II with the HeartMate XVE in 200 patients (median age 64 years) with advanced heart failure who were ineligible for cardiac transplantation. The primary end point—survival at 2 years free of disabling stroke and reoperation to repair or replace the device—was met by 62 (46%) of the 134 patients who received the Heart Mate II, compared with 7 (11%) of the 66 who received the HeartMate XVE (N. Engl J. Med. 2009;361:2241-51).

“In addition, data collected in a separate registry of smaller-stature women and men indicated that the device worked well in this specific population,” the FDA statement said.

As a condition of FDA approval, Thoratec is required to conduct a postmarketing study evaluating the device's performance. The data will be entered into the Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS), which is managed by the FDA; the National Heart, Lung, and Blood Institute; the Center for Medicare & Medicaid Services; and participating hospitals and manufacturers. The study will follow 247 patients for 2 years, and will collect data on outcomes, adverse events, functional status, and quality of life, according to Thoratec.

My Take

Smaller Device Yields Big Results

With this approval, the current state-of-the-art nonpulsatile LVAD can be offered to all appropriate patients without the confines of an investigational study. The approval validates the concept that the smaller LVAD devices confer benefits, compared with the pulsatile device, and it opens up the way to their further development.

Small-stature adults, and many women, are too small for the HeartMate XVE. The HeartMate II is a smaller, nonpulsatile pump, so more patients are eligible candidates. And as the HeartMate II Destination Therapy study showed, there's less morbidity associated with the surgical operation because of the smaller size, which is a big advantage.

Despite better survival and fewer infections with the HeartMate II compared with the HeartMate XVE, the stroke rate was not different, and that's a concern. Investigators will focus more on the mechanisms behind stroke and the resultant anticoagulation strategies.

Typically, destination-therapy patients have class IV heart failure, a low ejection fraction, and poor exercise tolerance, but are not transplant candidates—perhaps because they have had cancer recently, are too old, or have other comorbidities.

Efforts are underway at the NHLBI to study VAD therapy in less ill patients, to determine if patients can be identified as candidates for LVAD therapy before they get desperately ill and need a transplant, or before they are as sick as current LVAD candidates. The HeartMate XVE has shown wear and tear after 1–1½ years of use, but there are people who have had the HeartMate II for more than 3 years.

Considering how far we have come with cardiac resynchronization therapy devices and implantable cardioverter defibrillators—which once were huge, bulky devices that have gotten smaller and smaller and eventually will not even have leads—this is certainly what we expect to happen with LVADS as well.

The approval of the HeartMate II, the continuous-flow left ventricular assist device, has been expanded to include its use as destination therapy for people with severe heart failure who are not acceptable candidates for heart transplantation.

The device can now be used in patients with New York Heart Association class IIIB or IV end-stage left ventricular failure, who have received optimal medical therapy for at least 45 of the last 60 days, according to the statement issued by the manufacturer, Thoratec Corp.

The Food and Drug Administration and Thoratec Corp. announced the approval of the Heart Mate II left ventricular assist device (LVAD) in late January.

It was first approved by the FDA in April 2008 for use as a bridge to transplantation in cardiac transplant candidates at risk of imminent death from nonreversible left ventricular heart failure. The HeartMate II is markedly smaller than previously available devices, including Thoratec's HeartMate XVE, the only other LVAD approved for destination therapy. The HeartMate XVE, a pulsatile flow LVAD, was first approved for use as a bridge to transplantation.

“Its smaller size and mobility should allow more patients, including women and men of smaller stature, access to treatment,” Dr. Jeffrey Shuren, director of the FDA's Center for Devices and Radiological Health, said in the agency's approval statement.

The HeartMate II Destination Therapy study, a randomized trial sponsored by Thoratec, compared the HeartMate II with the HeartMate XVE in 200 patients (median age 64 years) with advanced heart failure who were ineligible for cardiac transplantation. The primary end point—survival at 2 years free of disabling stroke and reoperation to repair or replace the device—was met by 62 (46%) of the 134 patients who received the Heart Mate II, compared with 7 (11%) of the 66 who received the HeartMate XVE (N. Engl J. Med. 2009;361:2241-51).

“In addition, data collected in a separate registry of smaller-stature women and men indicated that the device worked well in this specific population,” the FDA statement said.

As a condition of FDA approval, Thoratec is required to conduct a postmarketing study evaluating the device's performance. The data will be entered into the Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS), which is managed by the FDA; the National Heart, Lung, and Blood Institute; the Center for Medicare & Medicaid Services; and participating hospitals and manufacturers. The study will follow 247 patients for 2 years, and will collect data on outcomes, adverse events, functional status, and quality of life, according to Thoratec.

My Take

Smaller Device Yields Big Results

With this approval, the current state-of-the-art nonpulsatile LVAD can be offered to all appropriate patients without the confines of an investigational study. The approval validates the concept that the smaller LVAD devices confer benefits, compared with the pulsatile device, and it opens up the way to their further development.

Small-stature adults, and many women, are too small for the HeartMate XVE. The HeartMate II is a smaller, nonpulsatile pump, so more patients are eligible candidates. And as the HeartMate II Destination Therapy study showed, there's less morbidity associated with the surgical operation because of the smaller size, which is a big advantage.

Despite better survival and fewer infections with the HeartMate II compared with the HeartMate XVE, the stroke rate was not different, and that's a concern. Investigators will focus more on the mechanisms behind stroke and the resultant anticoagulation strategies.

Typically, destination-therapy patients have class IV heart failure, a low ejection fraction, and poor exercise tolerance, but are not transplant candidates—perhaps because they have had cancer recently, are too old, or have other comorbidities.

Efforts are underway at the NHLBI to study VAD therapy in less ill patients, to determine if patients can be identified as candidates for LVAD therapy before they get desperately ill and need a transplant, or before they are as sick as current LVAD candidates. The HeartMate XVE has shown wear and tear after 1–1½ years of use, but there are people who have had the HeartMate II for more than 3 years.

Considering how far we have come with cardiac resynchronization therapy devices and implantable cardioverter defibrillators—which once were huge, bulky devices that have gotten smaller and smaller and eventually will not even have leads—this is certainly what we expect to happen with LVADS as well.

The approval of the HeartMate II, the continuous-flow left ventricular assist device, has been expanded to include its use as destination therapy for people with severe heart failure who are not acceptable candidates for heart transplantation.

The device can now be used in patients with New York Heart Association class IIIB or IV end-stage left ventricular failure, who have received optimal medical therapy for at least 45 of the last 60 days, according to the statement issued by the manufacturer, Thoratec Corp.

The Food and Drug Administration and Thoratec Corp. announced the approval of the Heart Mate II left ventricular assist device (LVAD) in late January.

It was first approved by the FDA in April 2008 for use as a bridge to transplantation in cardiac transplant candidates at risk of imminent death from nonreversible left ventricular heart failure. The HeartMate II is markedly smaller than previously available devices, including Thoratec's HeartMate XVE, the only other LVAD approved for destination therapy. The HeartMate XVE, a pulsatile flow LVAD, was first approved for use as a bridge to transplantation.

“Its smaller size and mobility should allow more patients, including women and men of smaller stature, access to treatment,” Dr. Jeffrey Shuren, director of the FDA's Center for Devices and Radiological Health, said in the agency's approval statement.

The HeartMate II Destination Therapy study, a randomized trial sponsored by Thoratec, compared the HeartMate II with the HeartMate XVE in 200 patients (median age 64 years) with advanced heart failure who were ineligible for cardiac transplantation. The primary end point—survival at 2 years free of disabling stroke and reoperation to repair or replace the device—was met by 62 (46%) of the 134 patients who received the Heart Mate II, compared with 7 (11%) of the 66 who received the HeartMate XVE (N. Engl J. Med. 2009;361:2241-51).

“In addition, data collected in a separate registry of smaller-stature women and men indicated that the device worked well in this specific population,” the FDA statement said.

As a condition of FDA approval, Thoratec is required to conduct a postmarketing study evaluating the device's performance. The data will be entered into the Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS), which is managed by the FDA; the National Heart, Lung, and Blood Institute; the Center for Medicare & Medicaid Services; and participating hospitals and manufacturers. The study will follow 247 patients for 2 years, and will collect data on outcomes, adverse events, functional status, and quality of life, according to Thoratec.

My Take

Smaller Device Yields Big Results

With this approval, the current state-of-the-art nonpulsatile LVAD can be offered to all appropriate patients without the confines of an investigational study. The approval validates the concept that the smaller LVAD devices confer benefits, compared with the pulsatile device, and it opens up the way to their further development.

Small-stature adults, and many women, are too small for the HeartMate XVE. The HeartMate II is a smaller, nonpulsatile pump, so more patients are eligible candidates. And as the HeartMate II Destination Therapy study showed, there's less morbidity associated with the surgical operation because of the smaller size, which is a big advantage.

Despite better survival and fewer infections with the HeartMate II compared with the HeartMate XVE, the stroke rate was not different, and that's a concern. Investigators will focus more on the mechanisms behind stroke and the resultant anticoagulation strategies.

Typically, destination-therapy patients have class IV heart failure, a low ejection fraction, and poor exercise tolerance, but are not transplant candidates—perhaps because they have had cancer recently, are too old, or have other comorbidities.

Efforts are underway at the NHLBI to study VAD therapy in less ill patients, to determine if patients can be identified as candidates for LVAD therapy before they get desperately ill and need a transplant, or before they are as sick as current LVAD candidates. The HeartMate XVE has shown wear and tear after 1–1½ years of use, but there are people who have had the HeartMate II for more than 3 years.

Considering how far we have come with cardiac resynchronization therapy devices and implantable cardioverter defibrillators—which once were huge, bulky devices that have gotten smaller and smaller and eventually will not even have leads—this is certainly what we expect to happen with LVADS as well.

Immunization rates among U.S. adults remain low, resulting in 40,000-50,000 deaths annually due to diseases that could be prevented by vaccines, according to a report released at a telebriefing.

“Thousands of lives could be saved each year if we could increase the number adults who receive routine and recommended vaccinations,” said Jeffrey Levi, Ph.D., executive director of Trust for America's Health, which contributed to the report.

“To achieve that goal, we need a national strategy to make vaccines a regular part of medical care and to educate Americans about the effectiveness and safety and efficacy of vaccines,” he added. The TFAH is a non-profit organization that is focused on promoting disease prevention, according to its Web site.

The report on the status of adult immunization in the United States was released jointly by the Infectious Diseases Society of America (IDSA), the Robert Wood Johnson Foundation (RWJF), and TFAH. It was supported by a grant from the RWJF.

The most striking findings of the report are pneumococcal vaccine rates, he said. Based on data collected in 2006, 2007, and 2008, 33.1% of adults aged 65 years and older in 36 states were not immunized against pneumonia, even though the Centers for Disease Control and Prevention (CDC) recommends the pneumococcal vaccine for this age group, and most people require one dose only. In Oregon, the state with the highest immunization rate, 26.8% of seniors had not received this vaccine. The lowest rate in the country was Washington, D.C., where 46.5% of seniors had not received it.

Other examples of low adult vaccination rates were highlighted during the briefing: In 2007, only 2.1% of eligible adults (aged 18-64 years) received the diphtheria, tetanus, and pertussis vaccine; only 10% of eligible adult women (aged 18-26 years) received the human papillomavirus vaccine; and just 36.1% of all adults were vaccinated against seasonal flu. In 2008, only 69% of people aged 65 and older got the influenza vaccine.

Annually, “approximately 36,000 Americans die of the seasonal flu, 5,000 die from pneumonia, and more than 1 million adults get shingles,” according to the report. Those types of preventable diseases cost an estimated $10 billion every year.

The lack of a national adult immunization strategy, such as the one in place for children, is one of the main reasons for the low immunization rates, in addition to other factors, including the lack of insurance or inadequate insurance, Dr. William Schaffner, chair of IDSA's Immunization Work Group and coauthor of the report, said during the briefing.

In addition, the health care system is not set up to deliver preventive services and many adults don't have regular checkups. Many physicians who care for adults are not accustomed to providing vaccines in their offices, a factor that contributes to the misunderstanding and misinformation about vaccine safety and effectiveness on the part of both clinicians and patients.

Although primary care physicians are more likely to provide vaccines than are others adult health care providers, many adults receive their medical care only from specialists who do not offer vaccination, noted Dr. Schaffner, who is professor and chair of preventive medicine at Vanderbilt University, Nashville.

He recommended that all clinicians become familiar with the adult immunization schedule, establish a plan to review immunizations patients need, and determine how to order, stock, and keep track of vaccines in the office, which he acknowledged is not an easy task.

During the briefing, Litjen Tan, Ph.D., director of medicine and public health for the American Medical Association, said that all health care providers should provide full coverage for all the adult vaccines recommended by the CDC's Advisory Committee on Immunization Practices (ACIP), and that a vaccine program for uninsured adults should be created.

“We should make reviewing patients' immunization histories a standard part of care and vaccines should be offered in appropriate medical encounters,” when people are already going to see the doctor, when it is convenient for both parties, such as annual physicals, prenatal visits, and cancer screening visits, he added.

Other recommendations for improving adult vaccination rates include requiring coverage of all vaccines under Medicare Part B, increasing public education about the effectiveness and safety of vaccines, and increasing the research, development, and production of vaccines, which would include surveillance and research on safety.

The full report is at the Web sites for IDSA (www.idsociety.orgwww.healthyamericans.orgwww.rwjf.org

Immunization rates among U.S. adults remain low, resulting in 40,000-50,000 deaths annually due to diseases that could be prevented by vaccines, according to a report released at a telebriefing.

“Thousands of lives could be saved each year if we could increase the number adults who receive routine and recommended vaccinations,” said Jeffrey Levi, Ph.D., executive director of Trust for America's Health, which contributed to the report.

“To achieve that goal, we need a national strategy to make vaccines a regular part of medical care and to educate Americans about the effectiveness and safety and efficacy of vaccines,” he added. The TFAH is a non-profit organization that is focused on promoting disease prevention, according to its Web site.

The report on the status of adult immunization in the United States was released jointly by the Infectious Diseases Society of America (IDSA), the Robert Wood Johnson Foundation (RWJF), and TFAH. It was supported by a grant from the RWJF.

The most striking findings of the report are pneumococcal vaccine rates, he said. Based on data collected in 2006, 2007, and 2008, 33.1% of adults aged 65 years and older in 36 states were not immunized against pneumonia, even though the Centers for Disease Control and Prevention (CDC) recommends the pneumococcal vaccine for this age group, and most people require one dose only. In Oregon, the state with the highest immunization rate, 26.8% of seniors had not received this vaccine. The lowest rate in the country was Washington, D.C., where 46.5% of seniors had not received it.

Other examples of low adult vaccination rates were highlighted during the briefing: In 2007, only 2.1% of eligible adults (aged 18-64 years) received the diphtheria, tetanus, and pertussis vaccine; only 10% of eligible adult women (aged 18-26 years) received the human papillomavirus vaccine; and just 36.1% of all adults were vaccinated against seasonal flu. In 2008, only 69% of people aged 65 and older got the influenza vaccine.

Annually, “approximately 36,000 Americans die of the seasonal flu, 5,000 die from pneumonia, and more than 1 million adults get shingles,” according to the report. Those types of preventable diseases cost an estimated $10 billion every year.

The lack of a national adult immunization strategy, such as the one in place for children, is one of the main reasons for the low immunization rates, in addition to other factors, including the lack of insurance or inadequate insurance, Dr. William Schaffner, chair of IDSA's Immunization Work Group and coauthor of the report, said during the briefing.

In addition, the health care system is not set up to deliver preventive services and many adults don't have regular checkups. Many physicians who care for adults are not accustomed to providing vaccines in their offices, a factor that contributes to the misunderstanding and misinformation about vaccine safety and effectiveness on the part of both clinicians and patients.

Although primary care physicians are more likely to provide vaccines than are others adult health care providers, many adults receive their medical care only from specialists who do not offer vaccination, noted Dr. Schaffner, who is professor and chair of preventive medicine at Vanderbilt University, Nashville.

He recommended that all clinicians become familiar with the adult immunization schedule, establish a plan to review immunizations patients need, and determine how to order, stock, and keep track of vaccines in the office, which he acknowledged is not an easy task.

During the briefing, Litjen Tan, Ph.D., director of medicine and public health for the American Medical Association, said that all health care providers should provide full coverage for all the adult vaccines recommended by the CDC's Advisory Committee on Immunization Practices (ACIP), and that a vaccine program for uninsured adults should be created.

“We should make reviewing patients' immunization histories a standard part of care and vaccines should be offered in appropriate medical encounters,” when people are already going to see the doctor, when it is convenient for both parties, such as annual physicals, prenatal visits, and cancer screening visits, he added.

Other recommendations for improving adult vaccination rates include requiring coverage of all vaccines under Medicare Part B, increasing public education about the effectiveness and safety of vaccines, and increasing the research, development, and production of vaccines, which would include surveillance and research on safety.

The full report is at the Web sites for IDSA (www.idsociety.orgwww.healthyamericans.orgwww.rwjf.org

Immunization rates among U.S. adults remain low, resulting in 40,000-50,000 deaths annually due to diseases that could be prevented by vaccines, according to a report released at a telebriefing.

“Thousands of lives could be saved each year if we could increase the number adults who receive routine and recommended vaccinations,” said Jeffrey Levi, Ph.D., executive director of Trust for America's Health, which contributed to the report.

“To achieve that goal, we need a national strategy to make vaccines a regular part of medical care and to educate Americans about the effectiveness and safety and efficacy of vaccines,” he added. The TFAH is a non-profit organization that is focused on promoting disease prevention, according to its Web site.

The report on the status of adult immunization in the United States was released jointly by the Infectious Diseases Society of America (IDSA), the Robert Wood Johnson Foundation (RWJF), and TFAH. It was supported by a grant from the RWJF.

The most striking findings of the report are pneumococcal vaccine rates, he said. Based on data collected in 2006, 2007, and 2008, 33.1% of adults aged 65 years and older in 36 states were not immunized against pneumonia, even though the Centers for Disease Control and Prevention (CDC) recommends the pneumococcal vaccine for this age group, and most people require one dose only. In Oregon, the state with the highest immunization rate, 26.8% of seniors had not received this vaccine. The lowest rate in the country was Washington, D.C., where 46.5% of seniors had not received it.

Other examples of low adult vaccination rates were highlighted during the briefing: In 2007, only 2.1% of eligible adults (aged 18-64 years) received the diphtheria, tetanus, and pertussis vaccine; only 10% of eligible adult women (aged 18-26 years) received the human papillomavirus vaccine; and just 36.1% of all adults were vaccinated against seasonal flu. In 2008, only 69% of people aged 65 and older got the influenza vaccine.

Annually, “approximately 36,000 Americans die of the seasonal flu, 5,000 die from pneumonia, and more than 1 million adults get shingles,” according to the report. Those types of preventable diseases cost an estimated $10 billion every year.

The lack of a national adult immunization strategy, such as the one in place for children, is one of the main reasons for the low immunization rates, in addition to other factors, including the lack of insurance or inadequate insurance, Dr. William Schaffner, chair of IDSA's Immunization Work Group and coauthor of the report, said during the briefing.

In addition, the health care system is not set up to deliver preventive services and many adults don't have regular checkups. Many physicians who care for adults are not accustomed to providing vaccines in their offices, a factor that contributes to the misunderstanding and misinformation about vaccine safety and effectiveness on the part of both clinicians and patients.

Although primary care physicians are more likely to provide vaccines than are others adult health care providers, many adults receive their medical care only from specialists who do not offer vaccination, noted Dr. Schaffner, who is professor and chair of preventive medicine at Vanderbilt University, Nashville.

He recommended that all clinicians become familiar with the adult immunization schedule, establish a plan to review immunizations patients need, and determine how to order, stock, and keep track of vaccines in the office, which he acknowledged is not an easy task.

During the briefing, Litjen Tan, Ph.D., director of medicine and public health for the American Medical Association, said that all health care providers should provide full coverage for all the adult vaccines recommended by the CDC's Advisory Committee on Immunization Practices (ACIP), and that a vaccine program for uninsured adults should be created.

“We should make reviewing patients' immunization histories a standard part of care and vaccines should be offered in appropriate medical encounters,” when people are already going to see the doctor, when it is convenient for both parties, such as annual physicals, prenatal visits, and cancer screening visits, he added.

Other recommendations for improving adult vaccination rates include requiring coverage of all vaccines under Medicare Part B, increasing public education about the effectiveness and safety of vaccines, and increasing the research, development, and production of vaccines, which would include surveillance and research on safety.

The full report is at the Web sites for IDSA (www.idsociety.orgwww.healthyamericans.orgwww.rwjf.org

Evidence indicating the serious effects of psoriasis inflammation to the rest of the body and not just the skin, as once thought, is starting to accumulate, noted Dr. Jeffrey Sobell.

"We are just beginning to understand the impact of uncontrolled inflammation on the body, separate from the effects we're seeing in the skin and joints," Dr. Sobell, of the department of dermatology, Tufts University, Boston, said in an interview. This evidence has raised the question of whether conditions, such as cardiovascular disease (CVD), improve by "treating an individual's underlying psoriasis and controlling that tremendous inflammation" that characterizes the disease.

In addition to CVD, psoriasis patients are at an increased for depression and other conditions such as Crohn's disease, certain cancers, and chronic obstructive pulmonary disease. In a presentation at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation, Dr. Sobell focused on psoriatic arthritis (PsA), depression, and CVD.

PsA
PsA usually appears an average of 10 years after the onset of skin disease (QJ Med. 1987;62:127-41); about 70% of patients have skin manifestations initially, while 15% develop joint symptoms first, and 15% develop joint and skin symptoms simultaneously, he noted.

Dermatologists should screen for arthritis in their psoriasis patients because a prompt diagnosis is critical. Early intervention, particularly with a tumor necrosis factor (TNF) blocker, can reduce the potential for joint deformities and disability, in addition to helping alleviate the signs and symptoms of arthritis, he noted.The FDA-approved biologic treatments for PsA - etanercept, infliximab, adalimumab, and golimumab - are approved for reducing the signs and symptoms of active arthritis, including the progression of structural damage and improving physical function.

"I encourage dermatologists when seeing psoriasis patients to ask questions about arthritis symptoms," such as joint stiffness in the morning, and performing a physical examination that includes looking for asymmetric inflammatory arthritis and tender or swollen joints, said Dr. Sobell. Patients should also be asked about whether they have a family history of PsA, and, if they have joint pain, whether it fluctuates with psoriasis exacerbations, he said, noting that only about 35% of patients with PsA have simultaneous flares of skin and joints.

Depression
Depression affects about 25% of people with psoriasis, and it can be debilitating, sometimes leading to suicidal thoughts, particularly in younger patients, Dr. Sobell said. Although the disease itself has a psychological impact on patients, increased TNF levels are known to be elevated in depression. This "may be part of the pathogenesis of depression" in people with psoriasis, and therefore, TNF levels are a possible target of treatment, he said.

Evidence that treatment with an anti-TNF agent improves symptoms of depression and fatigue includes a phase III study evaluating the efficacy of etanercept, compared with placebo, in over 600 patients with moderate to severe psoriasis (Lancet 2006;367:29-35). At week 12, treatment was associated with improved symptoms of depression and fatigue. Improvements were not strongly correlated with improvements in Psoriasis Area and Severity Index scores and were also seen in patients with little improvement of psoriasis. This "may be a detectable effect of neutralization of TNF" on depression, Dr. Sobell said.

Although these results are intriguing, he added that more studies are needed to further investigate the relationship between TNF levels and depression, and that conclusions cannot be made about the impact of anti-TNF treatment and depression in the general population.

CVD
Psoriasis patients are more likely to have comorbid diseases that are CVD risk factors, such as obesity, hypertension, hyperlipidemia, and insulin resistance. However, psoriasis is also an independent risk factor for MI and CVD, which is thought to be related to the immune and inflammatory activity of skin disease, Dr. Sobell said.

He referred to evidence that TNF, which has a major role in the pathogenesis of RA and psoriasis, also plays a role in cardiovascular disease, including TNF effects on promoting insulin resistance. TNF also induces the cytokine interleukin-6, which increases C-reactive protein (CRP), an inflammatory biomarker that is associated with an increased CVD risk.

This type of evidence raises the issue of whether treatment with systemic psoriasis treatments can reduce cardiovascular risk in these patients, and whether biologic agents improve CVD risk factors and markers, Dr. Sobell said.

Most of the data that have found an association between anti-TNF therapy and improvements in CVD risk factors and markers have been in people with RA, he said. In a small study of RA patients, those treated with adalimumab had significant increases in HDL cholesterol and reduced CRP levels after 2 weeks, compared with those in the placebo group (Ann. Rheum. Dis. 2005; 64:303-5).

Evidence that systemic treatment of RA and psoriasis reduced cardiovascular events was provided in a retrospective study of over 6,000 patients with RA and over 7,000 patients with psoriasis treated between 1998 and 2003 (J.Am. Acad. Dermatol. 2005;52:262-7). The risk of CVD was significantly lower in patients treated with methotrexate in both groups, compared with those who were not (risk was reduced by 23% in those with psoriasis). The addition of folic acid further reduced the risk.

Data on the impact of anti-TNF therapies on CV events include two studies suggesting that CV events in RA patients were reduced during treatment, he said. These include a Swedish registry study of almost 1,000 RA patients, which found a significantly lower risk of cardiovascular events in those treated with an anti-TNF agent compared with controls (J. Rheum. 2005; 32: 1213-8). The impact of treatment in patients with psoriasis is unknown, he pointed out.

^{Photo courtesy Dr. Jeffrey Sobell}

Dr. Sobell disclosed that he is a speaker and consultant for Amgen, Abbott, and Centocor, and is an investigator for Abbott and Centocor. The companies are manufacturers of biologic treatments for psoriasis. SDEF and this news organization are owned by Elsevier.

Evidence indicating the serious effects of psoriasis inflammation to the rest of the body and not just the skin, as once thought, is starting to accumulate, noted Dr. Jeffrey Sobell.

"We are just beginning to understand the impact of uncontrolled inflammation on the body, separate from the effects we're seeing in the skin and joints," Dr. Sobell, of the department of dermatology, Tufts University, Boston, said in an interview. This evidence has raised the question of whether conditions, such as cardiovascular disease (CVD), improve by "treating an individual's underlying psoriasis and controlling that tremendous inflammation" that characterizes the disease.

In addition to CVD, psoriasis patients are at an increased for depression and other conditions such as Crohn's disease, certain cancers, and chronic obstructive pulmonary disease. In a presentation at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation, Dr. Sobell focused on psoriatic arthritis (PsA), depression, and CVD.

PsA
PsA usually appears an average of 10 years after the onset of skin disease (QJ Med. 1987;62:127-41); about 70% of patients have skin manifestations initially, while 15% develop joint symptoms first, and 15% develop joint and skin symptoms simultaneously, he noted.

Dermatologists should screen for arthritis in their psoriasis patients because a prompt diagnosis is critical. Early intervention, particularly with a tumor necrosis factor (TNF) blocker, can reduce the potential for joint deformities and disability, in addition to helping alleviate the signs and symptoms of arthritis, he noted.The FDA-approved biologic treatments for PsA - etanercept, infliximab, adalimumab, and golimumab - are approved for reducing the signs and symptoms of active arthritis, including the progression of structural damage and improving physical function.

"I encourage dermatologists when seeing psoriasis patients to ask questions about arthritis symptoms," such as joint stiffness in the morning, and performing a physical examination that includes looking for asymmetric inflammatory arthritis and tender or swollen joints, said Dr. Sobell. Patients should also be asked about whether they have a family history of PsA, and, if they have joint pain, whether it fluctuates with psoriasis exacerbations, he said, noting that only about 35% of patients with PsA have simultaneous flares of skin and joints.

Depression
Depression affects about 25% of people with psoriasis, and it can be debilitating, sometimes leading to suicidal thoughts, particularly in younger patients, Dr. Sobell said. Although the disease itself has a psychological impact on patients, increased TNF levels are known to be elevated in depression. This "may be part of the pathogenesis of depression" in people with psoriasis, and therefore, TNF levels are a possible target of treatment, he said.

Evidence that treatment with an anti-TNF agent improves symptoms of depression and fatigue includes a phase III study evaluating the efficacy of etanercept, compared with placebo, in over 600 patients with moderate to severe psoriasis (Lancet 2006;367:29-35). At week 12, treatment was associated with improved symptoms of depression and fatigue. Improvements were not strongly correlated with improvements in Psoriasis Area and Severity Index scores and were also seen in patients with little improvement of psoriasis. This "may be a detectable effect of neutralization of TNF" on depression, Dr. Sobell said.

Although these results are intriguing, he added that more studies are needed to further investigate the relationship between TNF levels and depression, and that conclusions cannot be made about the impact of anti-TNF treatment and depression in the general population.

CVD
Psoriasis patients are more likely to have comorbid diseases that are CVD risk factors, such as obesity, hypertension, hyperlipidemia, and insulin resistance. However, psoriasis is also an independent risk factor for MI and CVD, which is thought to be related to the immune and inflammatory activity of skin disease, Dr. Sobell said.

He referred to evidence that TNF, which has a major role in the pathogenesis of RA and psoriasis, also plays a role in cardiovascular disease, including TNF effects on promoting insulin resistance. TNF also induces the cytokine interleukin-6, which increases C-reactive protein (CRP), an inflammatory biomarker that is associated with an increased CVD risk.

This type of evidence raises the issue of whether treatment with systemic psoriasis treatments can reduce cardiovascular risk in these patients, and whether biologic agents improve CVD risk factors and markers, Dr. Sobell said.

Most of the data that have found an association between anti-TNF therapy and improvements in CVD risk factors and markers have been in people with RA, he said. In a small study of RA patients, those treated with adalimumab had significant increases in HDL cholesterol and reduced CRP levels after 2 weeks, compared with those in the placebo group (Ann. Rheum. Dis. 2005; 64:303-5).

Evidence that systemic treatment of RA and psoriasis reduced cardiovascular events was provided in a retrospective study of over 6,000 patients with RA and over 7,000 patients with psoriasis treated between 1998 and 2003 (J.Am. Acad. Dermatol. 2005;52:262-7). The risk of CVD was significantly lower in patients treated with methotrexate in both groups, compared with those who were not (risk was reduced by 23% in those with psoriasis). The addition of folic acid further reduced the risk.

Data on the impact of anti-TNF therapies on CV events include two studies suggesting that CV events in RA patients were reduced during treatment, he said. These include a Swedish registry study of almost 1,000 RA patients, which found a significantly lower risk of cardiovascular events in those treated with an anti-TNF agent compared with controls (J. Rheum. 2005; 32: 1213-8). The impact of treatment in patients with psoriasis is unknown, he pointed out.

^{Photo courtesy Dr. Jeffrey Sobell}

Dr. Sobell disclosed that he is a speaker and consultant for Amgen, Abbott, and Centocor, and is an investigator for Abbott and Centocor. The companies are manufacturers of biologic treatments for psoriasis. SDEF and this news organization are owned by Elsevier.

Evidence indicating the serious effects of psoriasis inflammation to the rest of the body and not just the skin, as once thought, is starting to accumulate, noted Dr. Jeffrey Sobell.

"We are just beginning to understand the impact of uncontrolled inflammation on the body, separate from the effects we're seeing in the skin and joints," Dr. Sobell, of the department of dermatology, Tufts University, Boston, said in an interview. This evidence has raised the question of whether conditions, such as cardiovascular disease (CVD), improve by "treating an individual's underlying psoriasis and controlling that tremendous inflammation" that characterizes the disease.

In addition to CVD, psoriasis patients are at an increased for depression and other conditions such as Crohn's disease, certain cancers, and chronic obstructive pulmonary disease. In a presentation at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation, Dr. Sobell focused on psoriatic arthritis (PsA), depression, and CVD.

PsA
PsA usually appears an average of 10 years after the onset of skin disease (QJ Med. 1987;62:127-41); about 70% of patients have skin manifestations initially, while 15% develop joint symptoms first, and 15% develop joint and skin symptoms simultaneously, he noted.

Dermatologists should screen for arthritis in their psoriasis patients because a prompt diagnosis is critical. Early intervention, particularly with a tumor necrosis factor (TNF) blocker, can reduce the potential for joint deformities and disability, in addition to helping alleviate the signs and symptoms of arthritis, he noted.The FDA-approved biologic treatments for PsA - etanercept, infliximab, adalimumab, and golimumab - are approved for reducing the signs and symptoms of active arthritis, including the progression of structural damage and improving physical function.

"I encourage dermatologists when seeing psoriasis patients to ask questions about arthritis symptoms," such as joint stiffness in the morning, and performing a physical examination that includes looking for asymmetric inflammatory arthritis and tender or swollen joints, said Dr. Sobell. Patients should also be asked about whether they have a family history of PsA, and, if they have joint pain, whether it fluctuates with psoriasis exacerbations, he said, noting that only about 35% of patients with PsA have simultaneous flares of skin and joints.

Depression
Depression affects about 25% of people with psoriasis, and it can be debilitating, sometimes leading to suicidal thoughts, particularly in younger patients, Dr. Sobell said. Although the disease itself has a psychological impact on patients, increased TNF levels are known to be elevated in depression. This "may be part of the pathogenesis of depression" in people with psoriasis, and therefore, TNF levels are a possible target of treatment, he said.

Evidence that treatment with an anti-TNF agent improves symptoms of depression and fatigue includes a phase III study evaluating the efficacy of etanercept, compared with placebo, in over 600 patients with moderate to severe psoriasis (Lancet 2006;367:29-35). At week 12, treatment was associated with improved symptoms of depression and fatigue. Improvements were not strongly correlated with improvements in Psoriasis Area and Severity Index scores and were also seen in patients with little improvement of psoriasis. This "may be a detectable effect of neutralization of TNF" on depression, Dr. Sobell said.

Although these results are intriguing, he added that more studies are needed to further investigate the relationship between TNF levels and depression, and that conclusions cannot be made about the impact of anti-TNF treatment and depression in the general population.

CVD
Psoriasis patients are more likely to have comorbid diseases that are CVD risk factors, such as obesity, hypertension, hyperlipidemia, and insulin resistance. However, psoriasis is also an independent risk factor for MI and CVD, which is thought to be related to the immune and inflammatory activity of skin disease, Dr. Sobell said.

He referred to evidence that TNF, which has a major role in the pathogenesis of RA and psoriasis, also plays a role in cardiovascular disease, including TNF effects on promoting insulin resistance. TNF also induces the cytokine interleukin-6, which increases C-reactive protein (CRP), an inflammatory biomarker that is associated with an increased CVD risk.

This type of evidence raises the issue of whether treatment with systemic psoriasis treatments can reduce cardiovascular risk in these patients, and whether biologic agents improve CVD risk factors and markers, Dr. Sobell said.

Most of the data that have found an association between anti-TNF therapy and improvements in CVD risk factors and markers have been in people with RA, he said. In a small study of RA patients, those treated with adalimumab had significant increases in HDL cholesterol and reduced CRP levels after 2 weeks, compared with those in the placebo group (Ann. Rheum. Dis. 2005; 64:303-5).

Evidence that systemic treatment of RA and psoriasis reduced cardiovascular events was provided in a retrospective study of over 6,000 patients with RA and over 7,000 patients with psoriasis treated between 1998 and 2003 (J.Am. Acad. Dermatol. 2005;52:262-7). The risk of CVD was significantly lower in patients treated with methotrexate in both groups, compared with those who were not (risk was reduced by 23% in those with psoriasis). The addition of folic acid further reduced the risk.

Data on the impact of anti-TNF therapies on CV events include two studies suggesting that CV events in RA patients were reduced during treatment, he said. These include a Swedish registry study of almost 1,000 RA patients, which found a significantly lower risk of cardiovascular events in those treated with an anti-TNF agent compared with controls (J. Rheum. 2005; 32: 1213-8). The impact of treatment in patients with psoriasis is unknown, he pointed out.

^{Photo courtesy Dr. Jeffrey Sobell}

Dr. Sobell disclosed that he is a speaker and consultant for Amgen, Abbott, and Centocor, and is an investigator for Abbott and Centocor. The companies are manufacturers of biologic treatments for psoriasis. SDEF and this news organization are owned by Elsevier.

A sustained-release formulation of the potassium channel blocker dalfampridine has been approved by the Food and Drug Administration as a treatment to improve walking in people with multiple sclerosis.

In a statement, the FDA announced that dalfampridine extended-release tablets had been approved for this indication, based on studies that found patients treated with the drug had faster walking speeds than did those treated with placebo. This is the first drug approved for this indication, according to the FDA.

Dalfampridine will be marketed as Ampyra by Acorda Therapeutics Inc. of Hawthorne, N.Y.

At a meeting in October 2009, the majority of an FDA advisory panel voted that Acorda had provided “substantial evidence” of effectiveness for this indication, although only one-third of the patients in the two pivotal trials were considered responders. Most of the panel also agreed that the drug could be considered safe for use in people with MS, but not in patients who have a history of seizures and those with severe renal insufficiency.

The recommended dose of dalfampridine is 10 mg twice a day. However, higher doses have been associated with seizures, and the drug should not be taken by patients with moderate to severe kidney disease, whose blood levels with dalfampridine approach the levels that have been associated with seizures, according to the FDA statement.

The drug has a long history of use in the United States despite never having been approved, according to background documents filed by the FDA for the advisory panel meeting. For more than 20 years, dalfampridine has been compounded in pharmacies and used off-label to improve walking in people with various neurologic conditions. However, fampridine's narrow therapeutic range makes plasma levels difficult to regulate with the immediate-release formulation, which is associated with an increased risk of seizures. The sustained formulation was developed to overcome these limitations.

In clinical trials, the most common adverse reactions in patients taking dalfampridine included urinary tract infections, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhea, indigestion, throat pain, and skin sensations including burning, tingling, and itching.

At the meeting, representatives of Acorda said that dalfampridine improves conduction in demyelinated axons.

A sustained-release formulation of the potassium channel blocker dalfampridine has been approved by the Food and Drug Administration as a treatment to improve walking in people with multiple sclerosis.

In a statement, the FDA announced that dalfampridine extended-release tablets had been approved for this indication, based on studies that found patients treated with the drug had faster walking speeds than did those treated with placebo. This is the first drug approved for this indication, according to the FDA.

Dalfampridine will be marketed as Ampyra by Acorda Therapeutics Inc. of Hawthorne, N.Y.

At a meeting in October 2009, the majority of an FDA advisory panel voted that Acorda had provided “substantial evidence” of effectiveness for this indication, although only one-third of the patients in the two pivotal trials were considered responders. Most of the panel also agreed that the drug could be considered safe for use in people with MS, but not in patients who have a history of seizures and those with severe renal insufficiency.

The recommended dose of dalfampridine is 10 mg twice a day. However, higher doses have been associated with seizures, and the drug should not be taken by patients with moderate to severe kidney disease, whose blood levels with dalfampridine approach the levels that have been associated with seizures, according to the FDA statement.

The drug has a long history of use in the United States despite never having been approved, according to background documents filed by the FDA for the advisory panel meeting. For more than 20 years, dalfampridine has been compounded in pharmacies and used off-label to improve walking in people with various neurologic conditions. However, fampridine's narrow therapeutic range makes plasma levels difficult to regulate with the immediate-release formulation, which is associated with an increased risk of seizures. The sustained formulation was developed to overcome these limitations.

In clinical trials, the most common adverse reactions in patients taking dalfampridine included urinary tract infections, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhea, indigestion, throat pain, and skin sensations including burning, tingling, and itching.

At the meeting, representatives of Acorda said that dalfampridine improves conduction in demyelinated axons.

A sustained-release formulation of the potassium channel blocker dalfampridine has been approved by the Food and Drug Administration as a treatment to improve walking in people with multiple sclerosis.

In a statement, the FDA announced that dalfampridine extended-release tablets had been approved for this indication, based on studies that found patients treated with the drug had faster walking speeds than did those treated with placebo. This is the first drug approved for this indication, according to the FDA.

Dalfampridine will be marketed as Ampyra by Acorda Therapeutics Inc. of Hawthorne, N.Y.

At a meeting in October 2009, the majority of an FDA advisory panel voted that Acorda had provided “substantial evidence” of effectiveness for this indication, although only one-third of the patients in the two pivotal trials were considered responders. Most of the panel also agreed that the drug could be considered safe for use in people with MS, but not in patients who have a history of seizures and those with severe renal insufficiency.

The recommended dose of dalfampridine is 10 mg twice a day. However, higher doses have been associated with seizures, and the drug should not be taken by patients with moderate to severe kidney disease, whose blood levels with dalfampridine approach the levels that have been associated with seizures, according to the FDA statement.

The drug has a long history of use in the United States despite never having been approved, according to background documents filed by the FDA for the advisory panel meeting. For more than 20 years, dalfampridine has been compounded in pharmacies and used off-label to improve walking in people with various neurologic conditions. However, fampridine's narrow therapeutic range makes plasma levels difficult to regulate with the immediate-release formulation, which is associated with an increased risk of seizures. The sustained formulation was developed to overcome these limitations.

In clinical trials, the most common adverse reactions in patients taking dalfampridine included urinary tract infections, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhea, indigestion, throat pain, and skin sensations including burning, tingling, and itching.

At the meeting, representatives of Acorda said that dalfampridine improves conduction in demyelinated axons.

The weight-loss drug sibutramine is now contraindicated in people with a history of cardiovascular disease, the Food and Drug Administration announced last month.

The recommendation was based on a review of data indicating an increased risk of myocardial infarction and stroke is associated with the use of the drug in this population. On the same day, the European Medicines Agency (EMEA) announced that after its review of the same data, the EMEA's Committee for Medicinal Products for Human Use had recommended that the marketing of sibutramine be suspended in the European Union.

Until now, the sibutramine label had included a warning against its use in patients with cardiovascular disease, but “based on the serious nature of the review findings, FDA requested and the manufacturer agreed to add a new contraindication,” according to the agency's statement. The FDA is advising that clinicians regularly monitor the blood pressure and heart rate of their patients on sibutramine, and “if sustained increases in blood pressure and/or heart rate are observed, sibutramine should be discontinued.”

The advisory adds that sibutramine should be discontinued in patients who do not lose at least 5% of their baseline body weight within the first 3-6 months of treatment, “as continued treatment is unlikely to be effective and exposes the patient to unnecessary risk.”

Sibutramine, a serotonin-norepinephrine reuptake inhibitor marketed as Meridia by Abbott Laboratories, was approved in 1997.

Concerns about increases in blood pressure and heart rate associated with sibutramine date back to a 1996, when an FDA advisory panel agreed the drug was effective in trials, but voted 5-4 against approval, based largely on concerns over increases in mean blood pressure and heart rate over placebo at all doses studied.

The new contraindication states that sibutramine “is not to be used in patients with a history of cardiovascular disease,” including history of coronary artery disease, history of stroke or transient ischemic attack, history of heart arrhythmias, history of heart failure, history of peripheral arterial disease, and uncontrolled hypertension (such as over 145/90 mm Hg).

The data reviewed by the FDA and EMEA were from the Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT) study, which compared placebo plus standard care to sibutramine and standard care in about 10,000 overweight or obese patients aged at least 55 years, with a history of cardiovascular disease (CVD) or type 2 diabetes and one additional cardiovascular risk factor.

The study was designed to show that weight loss with sibutramine was more effective in lowering the number of cardiovascular events than with placebo, according to the FDA. But the rate of cardiovascular events among those on sibutramine was 11.4%, compared with 10% in placebo patients, according to preliminary data reported by the FDA in November 2009.

Further review of the data showed that only those participants who had a history of CVD were at an increased risk for cardiovascular events, according to the Jan. 21 statement. Among those with a history of CVD only, and not diabetes, the event rate was 8.3% in those taking placebo, compared with 10.1% in those on sibutramine, a nonsignificant difference.

The difference in cardiovascular event rates between groups did reach statistical significance in patients with both CVD and diabetes, at 11.9% in placebo patients vs. 13.9% in those taking sibutramine. But in patients with diabetes and no history of CVD, the event rates were identical, at 6.5%.

The FDA is planning to hold another advisory panel meeting to discuss the risk-benefit profile of sibutramine and whether any further regulatory action is needed to ensure the safe use of the drug, the statement said.

The weight-loss drug sibutramine is now contraindicated in people with a history of cardiovascular disease, the Food and Drug Administration announced last month.

The recommendation was based on a review of data indicating an increased risk of myocardial infarction and stroke is associated with the use of the drug in this population. On the same day, the European Medicines Agency (EMEA) announced that after its review of the same data, the EMEA's Committee for Medicinal Products for Human Use had recommended that the marketing of sibutramine be suspended in the European Union.

Until now, the sibutramine label had included a warning against its use in patients with cardiovascular disease, but “based on the serious nature of the review findings, FDA requested and the manufacturer agreed to add a new contraindication,” according to the agency's statement. The FDA is advising that clinicians regularly monitor the blood pressure and heart rate of their patients on sibutramine, and “if sustained increases in blood pressure and/or heart rate are observed, sibutramine should be discontinued.”

The advisory adds that sibutramine should be discontinued in patients who do not lose at least 5% of their baseline body weight within the first 3-6 months of treatment, “as continued treatment is unlikely to be effective and exposes the patient to unnecessary risk.”

Sibutramine, a serotonin-norepinephrine reuptake inhibitor marketed as Meridia by Abbott Laboratories, was approved in 1997.

Concerns about increases in blood pressure and heart rate associated with sibutramine date back to a 1996, when an FDA advisory panel agreed the drug was effective in trials, but voted 5-4 against approval, based largely on concerns over increases in mean blood pressure and heart rate over placebo at all doses studied.

The new contraindication states that sibutramine “is not to be used in patients with a history of cardiovascular disease,” including history of coronary artery disease, history of stroke or transient ischemic attack, history of heart arrhythmias, history of heart failure, history of peripheral arterial disease, and uncontrolled hypertension (such as over 145/90 mm Hg).

The data reviewed by the FDA and EMEA were from the Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT) study, which compared placebo plus standard care to sibutramine and standard care in about 10,000 overweight or obese patients aged at least 55 years, with a history of cardiovascular disease (CVD) or type 2 diabetes and one additional cardiovascular risk factor.

The study was designed to show that weight loss with sibutramine was more effective in lowering the number of cardiovascular events than with placebo, according to the FDA. But the rate of cardiovascular events among those on sibutramine was 11.4%, compared with 10% in placebo patients, according to preliminary data reported by the FDA in November 2009.

Further review of the data showed that only those participants who had a history of CVD were at an increased risk for cardiovascular events, according to the Jan. 21 statement. Among those with a history of CVD only, and not diabetes, the event rate was 8.3% in those taking placebo, compared with 10.1% in those on sibutramine, a nonsignificant difference.

The difference in cardiovascular event rates between groups did reach statistical significance in patients with both CVD and diabetes, at 11.9% in placebo patients vs. 13.9% in those taking sibutramine. But in patients with diabetes and no history of CVD, the event rates were identical, at 6.5%.

The FDA is planning to hold another advisory panel meeting to discuss the risk-benefit profile of sibutramine and whether any further regulatory action is needed to ensure the safe use of the drug, the statement said.

The weight-loss drug sibutramine is now contraindicated in people with a history of cardiovascular disease, the Food and Drug Administration announced last month.

The recommendation was based on a review of data indicating an increased risk of myocardial infarction and stroke is associated with the use of the drug in this population. On the same day, the European Medicines Agency (EMEA) announced that after its review of the same data, the EMEA's Committee for Medicinal Products for Human Use had recommended that the marketing of sibutramine be suspended in the European Union.

Until now, the sibutramine label had included a warning against its use in patients with cardiovascular disease, but “based on the serious nature of the review findings, FDA requested and the manufacturer agreed to add a new contraindication,” according to the agency's statement. The FDA is advising that clinicians regularly monitor the blood pressure and heart rate of their patients on sibutramine, and “if sustained increases in blood pressure and/or heart rate are observed, sibutramine should be discontinued.”

The advisory adds that sibutramine should be discontinued in patients who do not lose at least 5% of their baseline body weight within the first 3-6 months of treatment, “as continued treatment is unlikely to be effective and exposes the patient to unnecessary risk.”

Sibutramine, a serotonin-norepinephrine reuptake inhibitor marketed as Meridia by Abbott Laboratories, was approved in 1997.

Concerns about increases in blood pressure and heart rate associated with sibutramine date back to a 1996, when an FDA advisory panel agreed the drug was effective in trials, but voted 5-4 against approval, based largely on concerns over increases in mean blood pressure and heart rate over placebo at all doses studied.

The new contraindication states that sibutramine “is not to be used in patients with a history of cardiovascular disease,” including history of coronary artery disease, history of stroke or transient ischemic attack, history of heart arrhythmias, history of heart failure, history of peripheral arterial disease, and uncontrolled hypertension (such as over 145/90 mm Hg).

The data reviewed by the FDA and EMEA were from the Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT) study, which compared placebo plus standard care to sibutramine and standard care in about 10,000 overweight or obese patients aged at least 55 years, with a history of cardiovascular disease (CVD) or type 2 diabetes and one additional cardiovascular risk factor.

The study was designed to show that weight loss with sibutramine was more effective in lowering the number of cardiovascular events than with placebo, according to the FDA. But the rate of cardiovascular events among those on sibutramine was 11.4%, compared with 10% in placebo patients, according to preliminary data reported by the FDA in November 2009.

Further review of the data showed that only those participants who had a history of CVD were at an increased risk for cardiovascular events, according to the Jan. 21 statement. Among those with a history of CVD only, and not diabetes, the event rate was 8.3% in those taking placebo, compared with 10.1% in those on sibutramine, a nonsignificant difference.

The difference in cardiovascular event rates between groups did reach statistical significance in patients with both CVD and diabetes, at 11.9% in placebo patients vs. 13.9% in those taking sibutramine. But in patients with diabetes and no history of CVD, the event rates were identical, at 6.5%.

The FDA is planning to hold another advisory panel meeting to discuss the risk-benefit profile of sibutramine and whether any further regulatory action is needed to ensure the safe use of the drug, the statement said.

The potential health effects of exposure to bisphenol A, the chemical compound used in baby bottles and many different food and beverage packages, will be studied in short- and long-term trials in animals and humans, William Corr, deputy secretary of the Department of Health and Human Services, announced during a briefing.

More than $30 million will be provided by the National Institute of Environmental Health Sciences for studies to be conducted by the Food and Drug Administration, the National Institutes of Health, and other institutions. Results are expected in 18-24 months, he said.

In the meantime, HHS has issued recommendations for consumers on simple steps they can take now to reduce infants' exposure to BPA, including discarding scratched baby bottles and infant “sippie” cups and being careful about how breast milk or formula is heated, he said.

The recommendations, with information on what is currently understood about the effects of BPA on health, are posted on the HHS Web site (www.hhs.gov/safety/bpa

BPA is a component of the epoxy resin that lines many food containers, as well as plastic used in a range of products that includes baby bottles and water bottles. Small amounts of BPA have been detected in canned liquid infant formula, but powdered formula generally does not have detectable levels, said the HHS.

During the briefing, Linda Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences and director of the National Toxicology Program (NTP), said that a “growing body of evidence” indicates that BPA exposure may be harmful to humans, but more data are needed on the potential health effects, which might involve behavior, obesity, reproductive disorders, diabetes, cardiovascular disease, asthma, and cancer.

FDA commissioner Dr. Margaret Hamburg said at the briefing that the FDA's assessment of the potential risks of BPA exposure is now in line with the NTP's assessment that there is a basis for “some concern.” In an August 2008 draft assessment of the health risks of BPA, the FDA said that, based on a review of toxicology research and other information, exposure to BPA-containing materials is safe. However, the NTP followed with a report that concluded there was a basis for “some concern” about the potential health effects of BPA. The FDA's change in position was a result of the agency's evaluation of data that became available since the NTP report was released, Dr. Hamburg said.

The recommendations for parents include the advice to follow guidelines for feeding infants, which includes breastfeeding for at least 12 months. If breastfeeding is not an option, iron-fortified formula is the safest and most nutritious alternative, and although trace amounts of BPA have been detected in canned formula, good nutrition “outweighs any potential risks of BPA,” Mr. Corr said.

The recommendations also advise letting boiled water cool to a lukewarm temperature before mixing it with powdered formula, avoiding heating baby bottles in a microwave, allowing bottles to cool to room temperature before adding infant formula, and avoiding putting boiling or very hot water, formula, or any other liquids in bottles that contain BPA.

According to the HHS information sheet, the six major manufacturers of baby bottles and infant feeding cups—which represent over 90% of the U.S. market—have not manufactured these products with BPA for the U.S. market since January 2009.

The potential health effects of exposure to bisphenol A, the chemical compound used in baby bottles and many different food and beverage packages, will be studied in short- and long-term trials in animals and humans, William Corr, deputy secretary of the Department of Health and Human Services, announced during a briefing.

More than $30 million will be provided by the National Institute of Environmental Health Sciences for studies to be conducted by the Food and Drug Administration, the National Institutes of Health, and other institutions. Results are expected in 18-24 months, he said.

In the meantime, HHS has issued recommendations for consumers on simple steps they can take now to reduce infants' exposure to BPA, including discarding scratched baby bottles and infant “sippie” cups and being careful about how breast milk or formula is heated, he said.

The recommendations, with information on what is currently understood about the effects of BPA on health, are posted on the HHS Web site (www.hhs.gov/safety/bpa

BPA is a component of the epoxy resin that lines many food containers, as well as plastic used in a range of products that includes baby bottles and water bottles. Small amounts of BPA have been detected in canned liquid infant formula, but powdered formula generally does not have detectable levels, said the HHS.

During the briefing, Linda Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences and director of the National Toxicology Program (NTP), said that a “growing body of evidence” indicates that BPA exposure may be harmful to humans, but more data are needed on the potential health effects, which might involve behavior, obesity, reproductive disorders, diabetes, cardiovascular disease, asthma, and cancer.

FDA commissioner Dr. Margaret Hamburg said at the briefing that the FDA's assessment of the potential risks of BPA exposure is now in line with the NTP's assessment that there is a basis for “some concern.” In an August 2008 draft assessment of the health risks of BPA, the FDA said that, based on a review of toxicology research and other information, exposure to BPA-containing materials is safe. However, the NTP followed with a report that concluded there was a basis for “some concern” about the potential health effects of BPA. The FDA's change in position was a result of the agency's evaluation of data that became available since the NTP report was released, Dr. Hamburg said.

The recommendations for parents include the advice to follow guidelines for feeding infants, which includes breastfeeding for at least 12 months. If breastfeeding is not an option, iron-fortified formula is the safest and most nutritious alternative, and although trace amounts of BPA have been detected in canned formula, good nutrition “outweighs any potential risks of BPA,” Mr. Corr said.

The recommendations also advise letting boiled water cool to a lukewarm temperature before mixing it with powdered formula, avoiding heating baby bottles in a microwave, allowing bottles to cool to room temperature before adding infant formula, and avoiding putting boiling or very hot water, formula, or any other liquids in bottles that contain BPA.

According to the HHS information sheet, the six major manufacturers of baby bottles and infant feeding cups—which represent over 90% of the U.S. market—have not manufactured these products with BPA for the U.S. market since January 2009.

The potential health effects of exposure to bisphenol A, the chemical compound used in baby bottles and many different food and beverage packages, will be studied in short- and long-term trials in animals and humans, William Corr, deputy secretary of the Department of Health and Human Services, announced during a briefing.

More than $30 million will be provided by the National Institute of Environmental Health Sciences for studies to be conducted by the Food and Drug Administration, the National Institutes of Health, and other institutions. Results are expected in 18-24 months, he said.

In the meantime, HHS has issued recommendations for consumers on simple steps they can take now to reduce infants' exposure to BPA, including discarding scratched baby bottles and infant “sippie” cups and being careful about how breast milk or formula is heated, he said.

The recommendations, with information on what is currently understood about the effects of BPA on health, are posted on the HHS Web site (www.hhs.gov/safety/bpa

BPA is a component of the epoxy resin that lines many food containers, as well as plastic used in a range of products that includes baby bottles and water bottles. Small amounts of BPA have been detected in canned liquid infant formula, but powdered formula generally does not have detectable levels, said the HHS.

During the briefing, Linda Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences and director of the National Toxicology Program (NTP), said that a “growing body of evidence” indicates that BPA exposure may be harmful to humans, but more data are needed on the potential health effects, which might involve behavior, obesity, reproductive disorders, diabetes, cardiovascular disease, asthma, and cancer.

FDA commissioner Dr. Margaret Hamburg said at the briefing that the FDA's assessment of the potential risks of BPA exposure is now in line with the NTP's assessment that there is a basis for “some concern.” In an August 2008 draft assessment of the health risks of BPA, the FDA said that, based on a review of toxicology research and other information, exposure to BPA-containing materials is safe. However, the NTP followed with a report that concluded there was a basis for “some concern” about the potential health effects of BPA. The FDA's change in position was a result of the agency's evaluation of data that became available since the NTP report was released, Dr. Hamburg said.

The recommendations for parents include the advice to follow guidelines for feeding infants, which includes breastfeeding for at least 12 months. If breastfeeding is not an option, iron-fortified formula is the safest and most nutritious alternative, and although trace amounts of BPA have been detected in canned formula, good nutrition “outweighs any potential risks of BPA,” Mr. Corr said.

The recommendations also advise letting boiled water cool to a lukewarm temperature before mixing it with powdered formula, avoiding heating baby bottles in a microwave, allowing bottles to cool to room temperature before adding infant formula, and avoiding putting boiling or very hot water, formula, or any other liquids in bottles that contain BPA.

According to the HHS information sheet, the six major manufacturers of baby bottles and infant feeding cups—which represent over 90% of the U.S. market—have not manufactured these products with BPA for the U.S. market since January 2009.