Elizabeth Mechcatie

The Food and Drug Administration wants more information on denosumab before completing its review of the monoclonal antibody for the treatment and prevention of postmenopausal osteoporosis, the manufacturer, Amgen Inc., announced.

In a “Complete Response Letter,” the FDA requested more information on the design of Amgen's planned postmarketing surveillance program, and has asked the company to conduct a new clinical program for the postmenopausal osteoporosis prevention indication, according to an Amgen statement.

The agency also has requested updated safety data and has determined that a Risk Evaluation and Mitigation Strategy (REMS) is needed for the drug, the statement said. (The FDA requires REMS for drugs with safety issues to ensure that their benefits exceed their risks.) The company plans to respond quickly to the FDA's requests pertaining to the postmenopausal osteoporosis treatment indication.

In another statement reporting the company's third-quarter earnings, Amgen announced that it also had received a separate Complete Response Letter from the FDA regarding its approval application for denosumab for the treatment and prevention of bone loss caused by hormone ablation therapy in patients with breast or prostate cancer. In that letter, the agency requested more safety information in these populations, specifically results from “additional adequate and well-controlled clinical trials” showing that denosumab does not have detrimental effects on time-to-disease progression or overall survival in patients with breast cancer who are treated with an aromatase inhibitor, and in patients with prostate cancer who receive androgen deprivation therapy, according to the company. Amgen is reviewing both letters “and will work with the FDA to determine the appropriate next steps regarding these applications,” the company indicated.

At a meeting in August, an FDA advisory committee voted that the benefits of denosumab for treating postmenopausal osteoporosis outweighed its risks, but did not support use of the drug for other indications, including osteoporosis prevention, primarily because of concerns about its long-term safety. Denosumab, a human IgG2 monoclonal antibody, targets “an essential regulator” of osteoclasts, according to Amgen. It is also being studied for other conditions associated with bone loss, including rheumatoid arthritis, and for its potential to delay bone metastases. If approved, its trade name would be Prolia.

The Food and Drug Administration wants more information on denosumab before completing its review of the monoclonal antibody for the treatment and prevention of postmenopausal osteoporosis, the manufacturer, Amgen Inc., announced.

In a “Complete Response Letter,” the FDA requested more information on the design of Amgen's planned postmarketing surveillance program, and has asked the company to conduct a new clinical program for the postmenopausal osteoporosis prevention indication, according to an Amgen statement.

The agency also has requested updated safety data and has determined that a Risk Evaluation and Mitigation Strategy (REMS) is needed for the drug, the statement said. (The FDA requires REMS for drugs with safety issues to ensure that their benefits exceed their risks.) The company plans to respond quickly to the FDA's requests pertaining to the postmenopausal osteoporosis treatment indication.

In another statement reporting the company's third-quarter earnings, Amgen announced that it also had received a separate Complete Response Letter from the FDA regarding its approval application for denosumab for the treatment and prevention of bone loss caused by hormone ablation therapy in patients with breast or prostate cancer. In that letter, the agency requested more safety information in these populations, specifically results from “additional adequate and well-controlled clinical trials” showing that denosumab does not have detrimental effects on time-to-disease progression or overall survival in patients with breast cancer who are treated with an aromatase inhibitor, and in patients with prostate cancer who receive androgen deprivation therapy, according to the company. Amgen is reviewing both letters “and will work with the FDA to determine the appropriate next steps regarding these applications,” the company indicated.

At a meeting in August, an FDA advisory committee voted that the benefits of denosumab for treating postmenopausal osteoporosis outweighed its risks, but did not support use of the drug for other indications, including osteoporosis prevention, primarily because of concerns about its long-term safety. Denosumab, a human IgG2 monoclonal antibody, targets “an essential regulator” of osteoclasts, according to Amgen. It is also being studied for other conditions associated with bone loss, including rheumatoid arthritis, and for its potential to delay bone metastases. If approved, its trade name would be Prolia.

The Food and Drug Administration wants more information on denosumab before completing its review of the monoclonal antibody for the treatment and prevention of postmenopausal osteoporosis, the manufacturer, Amgen Inc., announced.

In a “Complete Response Letter,” the FDA requested more information on the design of Amgen's planned postmarketing surveillance program, and has asked the company to conduct a new clinical program for the postmenopausal osteoporosis prevention indication, according to an Amgen statement.

The agency also has requested updated safety data and has determined that a Risk Evaluation and Mitigation Strategy (REMS) is needed for the drug, the statement said. (The FDA requires REMS for drugs with safety issues to ensure that their benefits exceed their risks.) The company plans to respond quickly to the FDA's requests pertaining to the postmenopausal osteoporosis treatment indication.

In another statement reporting the company's third-quarter earnings, Amgen announced that it also had received a separate Complete Response Letter from the FDA regarding its approval application for denosumab for the treatment and prevention of bone loss caused by hormone ablation therapy in patients with breast or prostate cancer. In that letter, the agency requested more safety information in these populations, specifically results from “additional adequate and well-controlled clinical trials” showing that denosumab does not have detrimental effects on time-to-disease progression or overall survival in patients with breast cancer who are treated with an aromatase inhibitor, and in patients with prostate cancer who receive androgen deprivation therapy, according to the company. Amgen is reviewing both letters “and will work with the FDA to determine the appropriate next steps regarding these applications,” the company indicated.

At a meeting in August, an FDA advisory committee voted that the benefits of denosumab for treating postmenopausal osteoporosis outweighed its risks, but did not support use of the drug for other indications, including osteoporosis prevention, primarily because of concerns about its long-term safety. Denosumab, a human IgG2 monoclonal antibody, targets “an essential regulator” of osteoclasts, according to Amgen. It is also being studied for other conditions associated with bone loss, including rheumatoid arthritis, and for its potential to delay bone metastases. If approved, its trade name would be Prolia.

As part of an ongoing safety review of the weight-loss drug sibutramine, the Food and Drug Administration is looking at recent data suggesting that the cardiovascular event rate among patients on the medication was higher than among those on placebo.

“The analysis of these data is ongoing and FDA is making no conclusions about the preliminary findings at this time,” according to a statement posted on the agency's MedWatch site. These findings, the statement adds, “highlight the importance of avoiding the use of sibutramine” in patients with a history of coronary artery disease, congestive heart failure, arrhythmias, or stroke, which is recommended in the current sibutramine label.

Sibutramine is an orally administered drug marketed as Meridia by Abbott Laboratories. Its therapeutic effects result from norepinephrine, serotonin, and dopamine reuptake inhibition, according to the label. It was approved in 1997 for the management of obesity, including weight loss and maintenance of weight loss, in conjunction with a reduced-calorie diet, and is recommended only for obese patients with an initial body mass index at or above 30 kg/m

The FDA reported results from a study of about 10,000 patients aged 55 years or older who were overweight or obese and had a history of heart disease or type 2 diabetes and one additional cardiovascular risk factor. The preliminary results of the study's primary end point—MI, stroke, resuscitated cardiac arrest, or death—were reported in 11.4% of those on sibutramine, compared with 10% of those on placebo. The difference was described in the FDA statement as “higher than expected, suggesting that sibutramine is associated with an increased cardiovascular risk in the study population.”

Abbott started the study, Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT), in 2002 at the request of the FDA's European counterpart, the European Medicines Agency (EMEA), as one of the conditions for keeping the drug on the market in Europe after serious cardiovascular events were reported in people on sibutramine in the early 2000s. The aim of the study was to evaluate the safety and efficacy of sibutramine in overweight and obese people.

The FDA was apprised of the results in mid-November.

The Health Research Group of health advocacy organization Public Citizen filed a citizen's petition with the FDA early this month, calling on the agency to withdraw the drug from the market immediately, because of the new data indicating that the drug increases the risk of MIs, strokes, resuscitated cardiac arrest, or deaths in obese patients treated with the drug.

This is the second such petition filed by the group. In 2005, the FDA denied the first petition requesting that sibutramine be taken off the market because of concerns over the drug's safety, related to the increased heart rate and/or blood pressure seen in some patients in preapproval clinical studies.

In an interview, Dr. Sidney Wolfe, director of the Washington-based Health Research Group, said that the preliminary results of the SCOUT trial are a concern. The advocacy group continues to support the withdrawal of sibutramine from the market and is currently conducting an analysis of sibutramine-related reports in the FDA's adverse event reporting system database, he said.

Despite the label's recommendation that patients with risk factors such as cardiovascular disease not be treated with sibutramine, the drug is still prescribed to patients who are obese and have some of these risk factors, he noted.

Clinicians can report adverse events associated with sibutramine to the FDA's MedWatch program at 800-332-1088 or www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm

As part of an ongoing safety review of the weight-loss drug sibutramine, the Food and Drug Administration is looking at recent data suggesting that the cardiovascular event rate among patients on the medication was higher than among those on placebo.

“The analysis of these data is ongoing and FDA is making no conclusions about the preliminary findings at this time,” according to a statement posted on the agency's MedWatch site. These findings, the statement adds, “highlight the importance of avoiding the use of sibutramine” in patients with a history of coronary artery disease, congestive heart failure, arrhythmias, or stroke, which is recommended in the current sibutramine label.

Sibutramine is an orally administered drug marketed as Meridia by Abbott Laboratories. Its therapeutic effects result from norepinephrine, serotonin, and dopamine reuptake inhibition, according to the label. It was approved in 1997 for the management of obesity, including weight loss and maintenance of weight loss, in conjunction with a reduced-calorie diet, and is recommended only for obese patients with an initial body mass index at or above 30 kg/m

The FDA reported results from a study of about 10,000 patients aged 55 years or older who were overweight or obese and had a history of heart disease or type 2 diabetes and one additional cardiovascular risk factor. The preliminary results of the study's primary end point—MI, stroke, resuscitated cardiac arrest, or death—were reported in 11.4% of those on sibutramine, compared with 10% of those on placebo. The difference was described in the FDA statement as “higher than expected, suggesting that sibutramine is associated with an increased cardiovascular risk in the study population.”

Abbott started the study, Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT), in 2002 at the request of the FDA's European counterpart, the European Medicines Agency (EMEA), as one of the conditions for keeping the drug on the market in Europe after serious cardiovascular events were reported in people on sibutramine in the early 2000s. The aim of the study was to evaluate the safety and efficacy of sibutramine in overweight and obese people.

The FDA was apprised of the results in mid-November.

The Health Research Group of health advocacy organization Public Citizen filed a citizen's petition with the FDA early this month, calling on the agency to withdraw the drug from the market immediately, because of the new data indicating that the drug increases the risk of MIs, strokes, resuscitated cardiac arrest, or deaths in obese patients treated with the drug.

This is the second such petition filed by the group. In 2005, the FDA denied the first petition requesting that sibutramine be taken off the market because of concerns over the drug's safety, related to the increased heart rate and/or blood pressure seen in some patients in preapproval clinical studies.

In an interview, Dr. Sidney Wolfe, director of the Washington-based Health Research Group, said that the preliminary results of the SCOUT trial are a concern. The advocacy group continues to support the withdrawal of sibutramine from the market and is currently conducting an analysis of sibutramine-related reports in the FDA's adverse event reporting system database, he said.

Despite the label's recommendation that patients with risk factors such as cardiovascular disease not be treated with sibutramine, the drug is still prescribed to patients who are obese and have some of these risk factors, he noted.

Clinicians can report adverse events associated with sibutramine to the FDA's MedWatch program at 800-332-1088 or www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm

As part of an ongoing safety review of the weight-loss drug sibutramine, the Food and Drug Administration is looking at recent data suggesting that the cardiovascular event rate among patients on the medication was higher than among those on placebo.

“The analysis of these data is ongoing and FDA is making no conclusions about the preliminary findings at this time,” according to a statement posted on the agency's MedWatch site. These findings, the statement adds, “highlight the importance of avoiding the use of sibutramine” in patients with a history of coronary artery disease, congestive heart failure, arrhythmias, or stroke, which is recommended in the current sibutramine label.

Sibutramine is an orally administered drug marketed as Meridia by Abbott Laboratories. Its therapeutic effects result from norepinephrine, serotonin, and dopamine reuptake inhibition, according to the label. It was approved in 1997 for the management of obesity, including weight loss and maintenance of weight loss, in conjunction with a reduced-calorie diet, and is recommended only for obese patients with an initial body mass index at or above 30 kg/m

The FDA reported results from a study of about 10,000 patients aged 55 years or older who were overweight or obese and had a history of heart disease or type 2 diabetes and one additional cardiovascular risk factor. The preliminary results of the study's primary end point—MI, stroke, resuscitated cardiac arrest, or death—were reported in 11.4% of those on sibutramine, compared with 10% of those on placebo. The difference was described in the FDA statement as “higher than expected, suggesting that sibutramine is associated with an increased cardiovascular risk in the study population.”

Abbott started the study, Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT), in 2002 at the request of the FDA's European counterpart, the European Medicines Agency (EMEA), as one of the conditions for keeping the drug on the market in Europe after serious cardiovascular events were reported in people on sibutramine in the early 2000s. The aim of the study was to evaluate the safety and efficacy of sibutramine in overweight and obese people.

The FDA was apprised of the results in mid-November.

The Health Research Group of health advocacy organization Public Citizen filed a citizen's petition with the FDA early this month, calling on the agency to withdraw the drug from the market immediately, because of the new data indicating that the drug increases the risk of MIs, strokes, resuscitated cardiac arrest, or deaths in obese patients treated with the drug.

This is the second such petition filed by the group. In 2005, the FDA denied the first petition requesting that sibutramine be taken off the market because of concerns over the drug's safety, related to the increased heart rate and/or blood pressure seen in some patients in preapproval clinical studies.

In an interview, Dr. Sidney Wolfe, director of the Washington-based Health Research Group, said that the preliminary results of the SCOUT trial are a concern. The advocacy group continues to support the withdrawal of sibutramine from the market and is currently conducting an analysis of sibutramine-related reports in the FDA's adverse event reporting system database, he said.

Despite the label's recommendation that patients with risk factors such as cardiovascular disease not be treated with sibutramine, the drug is still prescribed to patients who are obese and have some of these risk factors, he noted.

Clinicians can report adverse events associated with sibutramine to the FDA's MedWatch program at 800-332-1088 or www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm

SILVER SPRING, MD. — The majority of a Food and Drug Administration advisory panel did not support expanding the approval of omalizumab as a treatment for moderate to severe persistent asthma to include children aged 6-11 years, based on available safety and efficacy data.

The FDA's Pulmonary-Allergy Drugs Advisory Committee voted 10-4 that the safety and efficacy data on omalizumab did not provide “substantial and convincing evidence” to support approval for the proposed indication: the treatment of asthma in patients aged 6-11 years with moderate to severe persistent asthma whose symptoms are inadequately controlled with inhaled corticosteroids (ICS) and who have a positive skin test or in vitro reactivity to a perennial aeroallergen. Omalizumab, a monoclonal antibody that reduces serum IgE levels, was approved in 2003 for the same indication in adolescents and adults aged 12 years and older.

It is marketed as Xolair by Genentech USA Inc. and Novartis Pharmaceuticals.

A marginal effect on efficacy and outstanding safety issues, including concerns about long-term safety, anaphylaxis risk, and unknown implications of circulating levels of omalizumab-IgE immune complexes in some treated patients, were among the reasons panelists said they voted against approval.

Oma lizumab is administered subcutaneously, every 2-4 weeks in a health care setting, at a dose based on serum IgE levels and body weight. The current label includes warnings about the potential risks of anaphylaxis and malignancies associated with treatment, based on data in clinical trials and postmarketing reports. In July 2009, the FDA reported that a cardiovascular safety signal associated with omalizumab was identified in post-marketing reports.

Omalizumab was evaluated in a pivotal 52-week study of 627 children aged 6-11 years with moderate to severe persistent, inadequately controlled allergic asthma, despite treatment with fluticasone at a dose of 200 mcg or more per day (or the equivalent), with or without other controller medications, which included short-acting beta-agonists (a mean of 2.8 puffs/day) and leukotriene antagonists (37%).

The primary end point, the rate of clinically significant asthma exacerbations (defined as worsening of symptoms requiring a doubling of the baseline ICS dose for 3 days or more and/or treatment with rescue systemic intravenous or oral steroids for 3 days) at 24 weeks, was 0.45 among those treated with omalizumab, compared with 0.64 among those on placebo, which was statistically significant.

One secondary efficacy end point, the asthma exacerbation rate at 52 weeks, was significant in favor of omalizumab (0.78 among those on omalizumab, compared with 1.30 among those on placebo).

The other secondary end points—nocturnal symptom scores, asthma medication rescue use, and quality of life scores at 24 weeks—were not significantly different between the two groups. The most common adverse effects in pediatric studies were nasopharyngitis, upper respiratory tract infections, and headache; these were reported at similar rates in those on placebo and omalizumab.

No new safety signals were identified, and there were no malignancies among omalizumab-treated patients. The one case of anaphylaxis in an omalizumab-treated patient was associated with a meperidine hydrochloride (Demerol) injection.

The FDA usually follows the recommendations of its advisory panels.

SILVER SPRING, MD. — The majority of a Food and Drug Administration advisory panel did not support expanding the approval of omalizumab as a treatment for moderate to severe persistent asthma to include children aged 6-11 years, based on available safety and efficacy data.

The FDA's Pulmonary-Allergy Drugs Advisory Committee voted 10-4 that the safety and efficacy data on omalizumab did not provide “substantial and convincing evidence” to support approval for the proposed indication: the treatment of asthma in patients aged 6-11 years with moderate to severe persistent asthma whose symptoms are inadequately controlled with inhaled corticosteroids (ICS) and who have a positive skin test or in vitro reactivity to a perennial aeroallergen. Omalizumab, a monoclonal antibody that reduces serum IgE levels, was approved in 2003 for the same indication in adolescents and adults aged 12 years and older.

It is marketed as Xolair by Genentech USA Inc. and Novartis Pharmaceuticals.

A marginal effect on efficacy and outstanding safety issues, including concerns about long-term safety, anaphylaxis risk, and unknown implications of circulating levels of omalizumab-IgE immune complexes in some treated patients, were among the reasons panelists said they voted against approval.

Oma lizumab is administered subcutaneously, every 2-4 weeks in a health care setting, at a dose based on serum IgE levels and body weight. The current label includes warnings about the potential risks of anaphylaxis and malignancies associated with treatment, based on data in clinical trials and postmarketing reports. In July 2009, the FDA reported that a cardiovascular safety signal associated with omalizumab was identified in post-marketing reports.

Omalizumab was evaluated in a pivotal 52-week study of 627 children aged 6-11 years with moderate to severe persistent, inadequately controlled allergic asthma, despite treatment with fluticasone at a dose of 200 mcg or more per day (or the equivalent), with or without other controller medications, which included short-acting beta-agonists (a mean of 2.8 puffs/day) and leukotriene antagonists (37%).

The primary end point, the rate of clinically significant asthma exacerbations (defined as worsening of symptoms requiring a doubling of the baseline ICS dose for 3 days or more and/or treatment with rescue systemic intravenous or oral steroids for 3 days) at 24 weeks, was 0.45 among those treated with omalizumab, compared with 0.64 among those on placebo, which was statistically significant.

One secondary efficacy end point, the asthma exacerbation rate at 52 weeks, was significant in favor of omalizumab (0.78 among those on omalizumab, compared with 1.30 among those on placebo).

The other secondary end points—nocturnal symptom scores, asthma medication rescue use, and quality of life scores at 24 weeks—were not significantly different between the two groups. The most common adverse effects in pediatric studies were nasopharyngitis, upper respiratory tract infections, and headache; these were reported at similar rates in those on placebo and omalizumab.

No new safety signals were identified, and there were no malignancies among omalizumab-treated patients. The one case of anaphylaxis in an omalizumab-treated patient was associated with a meperidine hydrochloride (Demerol) injection.

The FDA usually follows the recommendations of its advisory panels.

SILVER SPRING, MD. — The majority of a Food and Drug Administration advisory panel did not support expanding the approval of omalizumab as a treatment for moderate to severe persistent asthma to include children aged 6-11 years, based on available safety and efficacy data.

The FDA's Pulmonary-Allergy Drugs Advisory Committee voted 10-4 that the safety and efficacy data on omalizumab did not provide “substantial and convincing evidence” to support approval for the proposed indication: the treatment of asthma in patients aged 6-11 years with moderate to severe persistent asthma whose symptoms are inadequately controlled with inhaled corticosteroids (ICS) and who have a positive skin test or in vitro reactivity to a perennial aeroallergen. Omalizumab, a monoclonal antibody that reduces serum IgE levels, was approved in 2003 for the same indication in adolescents and adults aged 12 years and older.

It is marketed as Xolair by Genentech USA Inc. and Novartis Pharmaceuticals.

A marginal effect on efficacy and outstanding safety issues, including concerns about long-term safety, anaphylaxis risk, and unknown implications of circulating levels of omalizumab-IgE immune complexes in some treated patients, were among the reasons panelists said they voted against approval.

Oma lizumab is administered subcutaneously, every 2-4 weeks in a health care setting, at a dose based on serum IgE levels and body weight. The current label includes warnings about the potential risks of anaphylaxis and malignancies associated with treatment, based on data in clinical trials and postmarketing reports. In July 2009, the FDA reported that a cardiovascular safety signal associated with omalizumab was identified in post-marketing reports.

Omalizumab was evaluated in a pivotal 52-week study of 627 children aged 6-11 years with moderate to severe persistent, inadequately controlled allergic asthma, despite treatment with fluticasone at a dose of 200 mcg or more per day (or the equivalent), with or without other controller medications, which included short-acting beta-agonists (a mean of 2.8 puffs/day) and leukotriene antagonists (37%).

The primary end point, the rate of clinically significant asthma exacerbations (defined as worsening of symptoms requiring a doubling of the baseline ICS dose for 3 days or more and/or treatment with rescue systemic intravenous or oral steroids for 3 days) at 24 weeks, was 0.45 among those treated with omalizumab, compared with 0.64 among those on placebo, which was statistically significant.

One secondary efficacy end point, the asthma exacerbation rate at 52 weeks, was significant in favor of omalizumab (0.78 among those on omalizumab, compared with 1.30 among those on placebo).

The other secondary end points—nocturnal symptom scores, asthma medication rescue use, and quality of life scores at 24 weeks—were not significantly different between the two groups. The most common adverse effects in pediatric studies were nasopharyngitis, upper respiratory tract infections, and headache; these were reported at similar rates in those on placebo and omalizumab.

No new safety signals were identified, and there were no malignancies among omalizumab-treated patients. The one case of anaphylaxis in an omalizumab-treated patient was associated with a meperidine hydrochloride (Demerol) injection.

The FDA usually follows the recommendations of its advisory panels.

SILVER SPRING, MD. — A Food and Drug Administration advisory panel voted 11-1 that evidence from two studies provided enough evidence to support approval of a claim that treatment with the inhaled, dry-powder formulation of tiotropium reduces exacerbations in patients with chronic obstructive pulmonary disease.

At the meeting, 11 of the 12 members of the FDA's Pulmonary-Allergy Drugs Advisory Committee also voted that data from one of those studies, the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, “adequately addressed” the potential safety signals of an increased risk of stroke and adverse cardiovascular outcomes associated with this product that have been recently identified in pooled data and meta-analyses of tiotropium studies.

The dry-powder formulation of tiotropium is marketed as the Spiriva HandiHaler by Boehringer Ingelheim and Pfizer. It was approved in the United States in January 2004 for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It is administered once daily; each inhalation contains a dose of 18 mcg of tiotropium, an anticholinergic.

The companies proposed that Spiriva be approved for reductions in COPD exacerbations based on the UPLIFT trial and the Veterans Affairs (VA) Exacerbations Trial. In the 6-month VA study, there were approximately 1,800 patients with COPD, most of whom were men and whose mean age was 68 years. The two primary end points—the proportion of patients with COPD exacerbations and the proportion of patients hospitalized for exacerbations—were significantly lower among those on Spiriva, compared with those on placebo: 27.9% of those on Spiriva and 32.3% of those on placebo had at least one exacerbation during the study, a significant difference (P value .037), and 7% of those on Spiriva had at least one exacerbation requiring hospitalization, compared with 9.5% of those on placebo, which approached significance (P value .056). The median time to the first exacerbation and to the first exacerbation resulting in hospitalization, secondary end points, were also reduced among those on Spiriva, compared with those on placebo.

In the UPLIFT study, a multinational, randomized, placebo-controlled, 4-year study comparing tiotropium to placebo in almost 3,000 COPD patients, the number of COPD exacerbations, which was a secondary end point, was significantly lower among those on Spiriva over 4 years, compared with those on placebo.

Also in the UPLIFT study, the risks for stroke, cardiovascular events, and mortality were all lower among those on Spiriva when compared to placebo. The FDA's analysis concluded that the UPLIFT data did not suggest an increased risk for stroke or cardiovascular events, and suggested that the data supported a decrease in mortality associated with treatment. (The risk of mortality was reduced by 27% in this study.)

The FDA usually follows the recommendations of its advisory panels. Another treatment approved for COPD, the combination of fluticasone propionate and salmeterol inhalation powder marketed as Advair Diskus, has been approved for reducing COPD exacerbations.

SILVER SPRING, MD. — A Food and Drug Administration advisory panel voted 11-1 that evidence from two studies provided enough evidence to support approval of a claim that treatment with the inhaled, dry-powder formulation of tiotropium reduces exacerbations in patients with chronic obstructive pulmonary disease.

At the meeting, 11 of the 12 members of the FDA's Pulmonary-Allergy Drugs Advisory Committee also voted that data from one of those studies, the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, “adequately addressed” the potential safety signals of an increased risk of stroke and adverse cardiovascular outcomes associated with this product that have been recently identified in pooled data and meta-analyses of tiotropium studies.

The dry-powder formulation of tiotropium is marketed as the Spiriva HandiHaler by Boehringer Ingelheim and Pfizer. It was approved in the United States in January 2004 for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It is administered once daily; each inhalation contains a dose of 18 mcg of tiotropium, an anticholinergic.

The companies proposed that Spiriva be approved for reductions in COPD exacerbations based on the UPLIFT trial and the Veterans Affairs (VA) Exacerbations Trial. In the 6-month VA study, there were approximately 1,800 patients with COPD, most of whom were men and whose mean age was 68 years. The two primary end points—the proportion of patients with COPD exacerbations and the proportion of patients hospitalized for exacerbations—were significantly lower among those on Spiriva, compared with those on placebo: 27.9% of those on Spiriva and 32.3% of those on placebo had at least one exacerbation during the study, a significant difference (P value .037), and 7% of those on Spiriva had at least one exacerbation requiring hospitalization, compared with 9.5% of those on placebo, which approached significance (P value .056). The median time to the first exacerbation and to the first exacerbation resulting in hospitalization, secondary end points, were also reduced among those on Spiriva, compared with those on placebo.

In the UPLIFT study, a multinational, randomized, placebo-controlled, 4-year study comparing tiotropium to placebo in almost 3,000 COPD patients, the number of COPD exacerbations, which was a secondary end point, was significantly lower among those on Spiriva over 4 years, compared with those on placebo.

Also in the UPLIFT study, the risks for stroke, cardiovascular events, and mortality were all lower among those on Spiriva when compared to placebo. The FDA's analysis concluded that the UPLIFT data did not suggest an increased risk for stroke or cardiovascular events, and suggested that the data supported a decrease in mortality associated with treatment. (The risk of mortality was reduced by 27% in this study.)

The FDA usually follows the recommendations of its advisory panels. Another treatment approved for COPD, the combination of fluticasone propionate and salmeterol inhalation powder marketed as Advair Diskus, has been approved for reducing COPD exacerbations.

SILVER SPRING, MD. — A Food and Drug Administration advisory panel voted 11-1 that evidence from two studies provided enough evidence to support approval of a claim that treatment with the inhaled, dry-powder formulation of tiotropium reduces exacerbations in patients with chronic obstructive pulmonary disease.

At the meeting, 11 of the 12 members of the FDA's Pulmonary-Allergy Drugs Advisory Committee also voted that data from one of those studies, the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, “adequately addressed” the potential safety signals of an increased risk of stroke and adverse cardiovascular outcomes associated with this product that have been recently identified in pooled data and meta-analyses of tiotropium studies.

The dry-powder formulation of tiotropium is marketed as the Spiriva HandiHaler by Boehringer Ingelheim and Pfizer. It was approved in the United States in January 2004 for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It is administered once daily; each inhalation contains a dose of 18 mcg of tiotropium, an anticholinergic.

The companies proposed that Spiriva be approved for reductions in COPD exacerbations based on the UPLIFT trial and the Veterans Affairs (VA) Exacerbations Trial. In the 6-month VA study, there were approximately 1,800 patients with COPD, most of whom were men and whose mean age was 68 years. The two primary end points—the proportion of patients with COPD exacerbations and the proportion of patients hospitalized for exacerbations—were significantly lower among those on Spiriva, compared with those on placebo: 27.9% of those on Spiriva and 32.3% of those on placebo had at least one exacerbation during the study, a significant difference (P value .037), and 7% of those on Spiriva had at least one exacerbation requiring hospitalization, compared with 9.5% of those on placebo, which approached significance (P value .056). The median time to the first exacerbation and to the first exacerbation resulting in hospitalization, secondary end points, were also reduced among those on Spiriva, compared with those on placebo.

In the UPLIFT study, a multinational, randomized, placebo-controlled, 4-year study comparing tiotropium to placebo in almost 3,000 COPD patients, the number of COPD exacerbations, which was a secondary end point, was significantly lower among those on Spiriva over 4 years, compared with those on placebo.

Also in the UPLIFT study, the risks for stroke, cardiovascular events, and mortality were all lower among those on Spiriva when compared to placebo. The FDA's analysis concluded that the UPLIFT data did not suggest an increased risk for stroke or cardiovascular events, and suggested that the data supported a decrease in mortality associated with treatment. (The risk of mortality was reduced by 27% in this study.)

The FDA usually follows the recommendations of its advisory panels. Another treatment approved for COPD, the combination of fluticasone propionate and salmeterol inhalation powder marketed as Advair Diskus, has been approved for reducing COPD exacerbations.

The atypical antipsychotic aripiprazole has been approved for treating irritability associated with autistic disorder in children and adolescents aged 6-17 years. Irritability includes symptoms of aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods, the manufacturers announced.

Aripiprazole is marketed as Abilify by the manufacturers, Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co. The recommended dose for the new indication is 5 mg to 10 mg day (starting at 2 mg/day, with the maximum dose of 15 mg/day).

Since it was initially approved by the Food and Drug Administration in 2002 for schizophrenia, it has been approved for several other adult and pediatric indications, including treatment of schizophrenia in adolescents aged 13-17 years, and bipolar disorder indications down to age 10 years.

The effectiveness of aripiprazole for the autistic disorder indication was established in two 8-week multicenter studies of children and adolescents aged 6-17 years (more than 75% were younger than age 13 years), according to the revised label. They met the DSM-IV criteria for autistic disorder and exhibited behaviors that included tantrums, aggression, and/or self-injurious behavior.

In one study of 98 children and adolescents, those who were on aripiprazole (starting at a dose of 2 mg/day and increasing up to 15 mg/day based on clinical response) had significantly improved scores when compared to those on placebo at 8 weeks on two scales: the irritability subscale of the Aberrant Behavior Checklist (ABC-I), a caregiver rated assessment tool, and the Clinical Global Impression-Improvement (CGI-I) scale, a tool used to monitor treatment outcomes in psychiatric disorders.

In the second study of 218 children and adolescents, those on a fixed dose of aripiprazole (5 mg, 10 mg, or 15 mg per day) had significantly improved scores on the ABC-I subscale compared with those on placebo.

In a pooled analysis of the two studies, mean weight gain among those on aripiprazole was 1.6 kg, compared with 0.4 kg among those on placebo. During the study, 26% of those on aripiprazole and 7% of those on placebo experienced clinically significant weight gain, defined as at least a 7% change from baseline, according to the company statement.

Other adverse events more common among treated patients included sedation, affecting 21% of those on aripiprazole compared with 4% of those on placebo, fatigue (17% vs. 2%), vomiting (14% vs. 7%), somnolence (10% vs. 4%), tremor (10% vs. 0%), drooling (9% vs. 0%), and extrapyramidal disorder (6% vs. 0%).

These studies were “not designed or intended to evaluate” aripiprazole for treatment of the core symptoms of autistic disorder, the company statement said.

The atypical antipsychotic aripiprazole has been approved for treating irritability associated with autistic disorder in children and adolescents aged 6-17 years. Irritability includes symptoms of aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods, the manufacturers announced.

Aripiprazole is marketed as Abilify by the manufacturers, Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co. The recommended dose for the new indication is 5 mg to 10 mg day (starting at 2 mg/day, with the maximum dose of 15 mg/day).

Since it was initially approved by the Food and Drug Administration in 2002 for schizophrenia, it has been approved for several other adult and pediatric indications, including treatment of schizophrenia in adolescents aged 13-17 years, and bipolar disorder indications down to age 10 years.

The effectiveness of aripiprazole for the autistic disorder indication was established in two 8-week multicenter studies of children and adolescents aged 6-17 years (more than 75% were younger than age 13 years), according to the revised label. They met the DSM-IV criteria for autistic disorder and exhibited behaviors that included tantrums, aggression, and/or self-injurious behavior.

In one study of 98 children and adolescents, those who were on aripiprazole (starting at a dose of 2 mg/day and increasing up to 15 mg/day based on clinical response) had significantly improved scores when compared to those on placebo at 8 weeks on two scales: the irritability subscale of the Aberrant Behavior Checklist (ABC-I), a caregiver rated assessment tool, and the Clinical Global Impression-Improvement (CGI-I) scale, a tool used to monitor treatment outcomes in psychiatric disorders.

In the second study of 218 children and adolescents, those on a fixed dose of aripiprazole (5 mg, 10 mg, or 15 mg per day) had significantly improved scores on the ABC-I subscale compared with those on placebo.

In a pooled analysis of the two studies, mean weight gain among those on aripiprazole was 1.6 kg, compared with 0.4 kg among those on placebo. During the study, 26% of those on aripiprazole and 7% of those on placebo experienced clinically significant weight gain, defined as at least a 7% change from baseline, according to the company statement.

Other adverse events more common among treated patients included sedation, affecting 21% of those on aripiprazole compared with 4% of those on placebo, fatigue (17% vs. 2%), vomiting (14% vs. 7%), somnolence (10% vs. 4%), tremor (10% vs. 0%), drooling (9% vs. 0%), and extrapyramidal disorder (6% vs. 0%).

These studies were “not designed or intended to evaluate” aripiprazole for treatment of the core symptoms of autistic disorder, the company statement said.

The atypical antipsychotic aripiprazole has been approved for treating irritability associated with autistic disorder in children and adolescents aged 6-17 years. Irritability includes symptoms of aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods, the manufacturers announced.

Aripiprazole is marketed as Abilify by the manufacturers, Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co. The recommended dose for the new indication is 5 mg to 10 mg day (starting at 2 mg/day, with the maximum dose of 15 mg/day).

Since it was initially approved by the Food and Drug Administration in 2002 for schizophrenia, it has been approved for several other adult and pediatric indications, including treatment of schizophrenia in adolescents aged 13-17 years, and bipolar disorder indications down to age 10 years.

The effectiveness of aripiprazole for the autistic disorder indication was established in two 8-week multicenter studies of children and adolescents aged 6-17 years (more than 75% were younger than age 13 years), according to the revised label. They met the DSM-IV criteria for autistic disorder and exhibited behaviors that included tantrums, aggression, and/or self-injurious behavior.

In one study of 98 children and adolescents, those who were on aripiprazole (starting at a dose of 2 mg/day and increasing up to 15 mg/day based on clinical response) had significantly improved scores when compared to those on placebo at 8 weeks on two scales: the irritability subscale of the Aberrant Behavior Checklist (ABC-I), a caregiver rated assessment tool, and the Clinical Global Impression-Improvement (CGI-I) scale, a tool used to monitor treatment outcomes in psychiatric disorders.

In the second study of 218 children and adolescents, those on a fixed dose of aripiprazole (5 mg, 10 mg, or 15 mg per day) had significantly improved scores on the ABC-I subscale compared with those on placebo.

In a pooled analysis of the two studies, mean weight gain among those on aripiprazole was 1.6 kg, compared with 0.4 kg among those on placebo. During the study, 26% of those on aripiprazole and 7% of those on placebo experienced clinically significant weight gain, defined as at least a 7% change from baseline, according to the company statement.

Other adverse events more common among treated patients included sedation, affecting 21% of those on aripiprazole compared with 4% of those on placebo, fatigue (17% vs. 2%), vomiting (14% vs. 7%), somnolence (10% vs. 4%), tremor (10% vs. 0%), drooling (9% vs. 0%), and extrapyramidal disorder (6% vs. 0%).

These studies were “not designed or intended to evaluate” aripiprazole for treatment of the core symptoms of autistic disorder, the company statement said.

The longer a woman breastfeeds, the less likely she will develop metabolic syndrome over time, even if she has a history of gestational diabetes, according to the results of a prospective study that followed almost 1,400 women for 20 years.

Having breastfed for more than 1 month was associated with a 39%-46% lower incidence of metabolic syndrome (depending on duration of breastfeeding) among women with no history of gestational diabetes, and with a 44%-86% lower incidence among those with gestational diabetes.“The findings indicate that breastfeeding a child may have lasting favorable effects on a woman's risk factors for later developing diabetes or heart disease,” the lead author, Erica P. Gunderson, Ph.D., said in a statement released by Kaiser Permanente. The study was published online, [doi.org/10.2337/db09-1197]), and will appear in print in Diabetes in February.

Their findings did not appear to be caused by differences in weight gain, physical activity, or other health behaviors, but less abdominal fat and higher levels of high-density lipoprotein were characteristic of women who did not develop metabolic syndrome, added Dr. Gunderson of the division of research, epidemiology and prevention at Kaiser Permanente, Oakland, Calif.

The study followed 1,399 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, who were aged 18-30 years when they were enrolled, had never delivered a baby, and did not have metabolic syndrome at baseline. Of these women, 704 had at least one singleton live birth in 1986-2006, including 84 who had gestational diabetes; over 20 years, 120 cases of metabolic syndrome were diagnosed among these women. The overall incidence of metabolic syndrome was 12.0 cases/1,000 person years. The incidence was significantly higher among those who had been diagnosed with gestational diabetes during pregnancy, than those who had not (22.1 cases/1,000 person years, compared with 10.8 cases/1,000 person years.)

The study was funded by the National Institutes of Health.

The longer a woman breastfeeds, the less likely she will develop metabolic syndrome over time, even if she has a history of gestational diabetes, according to the results of a prospective study that followed almost 1,400 women for 20 years.

Having breastfed for more than 1 month was associated with a 39%-46% lower incidence of metabolic syndrome (depending on duration of breastfeeding) among women with no history of gestational diabetes, and with a 44%-86% lower incidence among those with gestational diabetes.“The findings indicate that breastfeeding a child may have lasting favorable effects on a woman's risk factors for later developing diabetes or heart disease,” the lead author, Erica P. Gunderson, Ph.D., said in a statement released by Kaiser Permanente. The study was published online, [doi.org/10.2337/db09-1197]), and will appear in print in Diabetes in February.

Their findings did not appear to be caused by differences in weight gain, physical activity, or other health behaviors, but less abdominal fat and higher levels of high-density lipoprotein were characteristic of women who did not develop metabolic syndrome, added Dr. Gunderson of the division of research, epidemiology and prevention at Kaiser Permanente, Oakland, Calif.

The study followed 1,399 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, who were aged 18-30 years when they were enrolled, had never delivered a baby, and did not have metabolic syndrome at baseline. Of these women, 704 had at least one singleton live birth in 1986-2006, including 84 who had gestational diabetes; over 20 years, 120 cases of metabolic syndrome were diagnosed among these women. The overall incidence of metabolic syndrome was 12.0 cases/1,000 person years. The incidence was significantly higher among those who had been diagnosed with gestational diabetes during pregnancy, than those who had not (22.1 cases/1,000 person years, compared with 10.8 cases/1,000 person years.)

The study was funded by the National Institutes of Health.

The longer a woman breastfeeds, the less likely she will develop metabolic syndrome over time, even if she has a history of gestational diabetes, according to the results of a prospective study that followed almost 1,400 women for 20 years.

Having breastfed for more than 1 month was associated with a 39%-46% lower incidence of metabolic syndrome (depending on duration of breastfeeding) among women with no history of gestational diabetes, and with a 44%-86% lower incidence among those with gestational diabetes.“The findings indicate that breastfeeding a child may have lasting favorable effects on a woman's risk factors for later developing diabetes or heart disease,” the lead author, Erica P. Gunderson, Ph.D., said in a statement released by Kaiser Permanente. The study was published online, [doi.org/10.2337/db09-1197]), and will appear in print in Diabetes in February.

Their findings did not appear to be caused by differences in weight gain, physical activity, or other health behaviors, but less abdominal fat and higher levels of high-density lipoprotein were characteristic of women who did not develop metabolic syndrome, added Dr. Gunderson of the division of research, epidemiology and prevention at Kaiser Permanente, Oakland, Calif.

The study followed 1,399 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, who were aged 18-30 years when they were enrolled, had never delivered a baby, and did not have metabolic syndrome at baseline. Of these women, 704 had at least one singleton live birth in 1986-2006, including 84 who had gestational diabetes; over 20 years, 120 cases of metabolic syndrome were diagnosed among these women. The overall incidence of metabolic syndrome was 12.0 cases/1,000 person years. The incidence was significantly higher among those who had been diagnosed with gestational diabetes during pregnancy, than those who had not (22.1 cases/1,000 person years, compared with 10.8 cases/1,000 person years.)

The study was funded by the National Institutes of Health.

Cases of chondrolysis diagnosed a median of 8.5 months after administration of a continuous intra-articular infusion of a local anesthetic for postsurgical pain with an infusion pump have prompted the Food and Drug Administration to issue a statement recommending against this practice.

“Because the reported cases involved significant injury to otherwise healthy young adults, the FDA wants to advise health care professionals that elastomeric infusion devices or any other infusion pump are not cleared by [the agency] to deliver intra-articular infusions of local anesthetics and should not be used for this purpose,” according to the statement, which lists bupivacaine, chlorprocaine, lidocaine, mepivacaine, procaine, and ropivacaine as the marketed local anesthetics.

The statement also pointed out that local anesthetics are approved as injections “for the production of local or regional anesthesia or analgesia” and are not approved for continuous intra-articular postoperative infusions. “It is important to note that single intra-articular injections of local anesthetics in orthopedic procedures have been used for many years” without any reports of chondrolysis, the statement added.

The 35 reports of chondrolysis—the necrosis and destruction of cartilage—reviewed by the FDA were reported between 2006 and 2008 in people aged 16–58 years (median 25 years), mostly after shoulder surgery; 6 were in people aged 16–18. They were given continuous infusions of a local anesthetic over 48–72 hours, administered directly into the intra-articular space with an elastomeric infusion pump, with and without epinephrine. Of the 35 cases, 34 (97%) involved shoulder surgeries; the remaining case was in the knee. Almost half (46%) of the infusions involved the glenohumeral (glenoid) space. Most of the cases (32 or 91%) involved bupivacaine.

Symptoms of chondrolysis—joint pain, stiffness, and loss of motion—were reported as early as the second month after the infusion. In more than half of the cases, additional surgery, such as arthroscopy or joint replacement, was needed, according to the FDA. The cases were not associated with any single brand of infusion device.

Although the cause of the 35 cases is not known, “the infused local anesthetic drugs, the device materials, and/or other sources may have resulted in the development of chondrolysis,” the statement said. There have also been recent reports of chondrolysis in the literature of people who have had bupivacaine infusions, as well as preclinical studies that found that exposure of chondrocytes to bupivacaine, lidocaine, and ropivacaine resulted in chondrolysis.

Cases of chondrolysis diagnosed a median of 8.5 months after administration of a continuous intra-articular infusion of a local anesthetic for postsurgical pain with an infusion pump have prompted the Food and Drug Administration to issue a statement recommending against this practice.

“Because the reported cases involved significant injury to otherwise healthy young adults, the FDA wants to advise health care professionals that elastomeric infusion devices or any other infusion pump are not cleared by [the agency] to deliver intra-articular infusions of local anesthetics and should not be used for this purpose,” according to the statement, which lists bupivacaine, chlorprocaine, lidocaine, mepivacaine, procaine, and ropivacaine as the marketed local anesthetics.

The statement also pointed out that local anesthetics are approved as injections “for the production of local or regional anesthesia or analgesia” and are not approved for continuous intra-articular postoperative infusions. “It is important to note that single intra-articular injections of local anesthetics in orthopedic procedures have been used for many years” without any reports of chondrolysis, the statement added.

The 35 reports of chondrolysis—the necrosis and destruction of cartilage—reviewed by the FDA were reported between 2006 and 2008 in people aged 16–58 years (median 25 years), mostly after shoulder surgery; 6 were in people aged 16–18. They were given continuous infusions of a local anesthetic over 48–72 hours, administered directly into the intra-articular space with an elastomeric infusion pump, with and without epinephrine. Of the 35 cases, 34 (97%) involved shoulder surgeries; the remaining case was in the knee. Almost half (46%) of the infusions involved the glenohumeral (glenoid) space. Most of the cases (32 or 91%) involved bupivacaine.

Symptoms of chondrolysis—joint pain, stiffness, and loss of motion—were reported as early as the second month after the infusion. In more than half of the cases, additional surgery, such as arthroscopy or joint replacement, was needed, according to the FDA. The cases were not associated with any single brand of infusion device.

Although the cause of the 35 cases is not known, “the infused local anesthetic drugs, the device materials, and/or other sources may have resulted in the development of chondrolysis,” the statement said. There have also been recent reports of chondrolysis in the literature of people who have had bupivacaine infusions, as well as preclinical studies that found that exposure of chondrocytes to bupivacaine, lidocaine, and ropivacaine resulted in chondrolysis.

Cases of chondrolysis diagnosed a median of 8.5 months after administration of a continuous intra-articular infusion of a local anesthetic for postsurgical pain with an infusion pump have prompted the Food and Drug Administration to issue a statement recommending against this practice.

“Because the reported cases involved significant injury to otherwise healthy young adults, the FDA wants to advise health care professionals that elastomeric infusion devices or any other infusion pump are not cleared by [the agency] to deliver intra-articular infusions of local anesthetics and should not be used for this purpose,” according to the statement, which lists bupivacaine, chlorprocaine, lidocaine, mepivacaine, procaine, and ropivacaine as the marketed local anesthetics.

The statement also pointed out that local anesthetics are approved as injections “for the production of local or regional anesthesia or analgesia” and are not approved for continuous intra-articular postoperative infusions. “It is important to note that single intra-articular injections of local anesthetics in orthopedic procedures have been used for many years” without any reports of chondrolysis, the statement added.

The 35 reports of chondrolysis—the necrosis and destruction of cartilage—reviewed by the FDA were reported between 2006 and 2008 in people aged 16–58 years (median 25 years), mostly after shoulder surgery; 6 were in people aged 16–18. They were given continuous infusions of a local anesthetic over 48–72 hours, administered directly into the intra-articular space with an elastomeric infusion pump, with and without epinephrine. Of the 35 cases, 34 (97%) involved shoulder surgeries; the remaining case was in the knee. Almost half (46%) of the infusions involved the glenohumeral (glenoid) space. Most of the cases (32 or 91%) involved bupivacaine.

Symptoms of chondrolysis—joint pain, stiffness, and loss of motion—were reported as early as the second month after the infusion. In more than half of the cases, additional surgery, such as arthroscopy or joint replacement, was needed, according to the FDA. The cases were not associated with any single brand of infusion device.

Although the cause of the 35 cases is not known, “the infused local anesthetic drugs, the device materials, and/or other sources may have resulted in the development of chondrolysis,” the statement said. There have also been recent reports of chondrolysis in the literature of people who have had bupivacaine infusions, as well as preclinical studies that found that exposure of chondrocytes to bupivacaine, lidocaine, and ropivacaine resulted in chondrolysis.

The American Medical Association has launched an interactive Web site for the public to evaluate the severity of influenza symptoms of individuals or family members and share that information with their health care providers, who in turn can use the site to monitor their patients' symptoms, the AMA announced during a telephone briefing.

The Web site, AMAfluhelp.org, is described as the country's first "comprehensive Web-based patient flu-assessment program," which "walks patients through a series of questions to determine the severity of their flu symptoms," based on the latest guidelines from the Centers for Disease Control and Prevention, according to an AMA statement announcing the launch.

The free site features physician-designed online tools "to help physicians monitor their patients' symptoms, facilitate care and treatment decisions, and efficiently manage their practices' patient flow."

For example, a physician can use the site to determine whether a patient can return to school or work, and a patient can use the site to generate a note from the physician to that effect. Also, a patient can use the site to determine whether to seek medical care for themselves or a family member. A patient who indicates that he or she has a high fever will receive a prompt to call his or her physician immediately or seek urgent medical care. The site also can be used to help patients monitor symptoms after vaccination, prompting them on when they should seek medical help.

People can log in to the Web site or can participate anonymously and can "invite" family members and their physicians and other health care providers to connect with the system. The information they enter is private and secured, and personal data cannot be accessed without a user's consent, according to the AMA statement.

Dr. James Mault, chairman and CEO of HealthyCircles, the company powering the AMA portal, said during the briefing that a physician can enter the program and monitor all the patients he or she is following, and communicate with them through online questions and answers.

During the briefing, Chris Lindley, director of emergency preparedness and response in the Colorado Department of Public Health and Environment, said that a link to the Web site will be added to the department's Web site, as part of the state's response to the influenza pandemic.

The AMA is promoting the Web site in collaboration with a coalition that includes Blue Cross NEPA, CVS Caremark, Merck & Co., Microsoft Corp., Minute Clinic, and the state of Colorado.

The American Medical Association has launched an interactive Web site for the public to evaluate the severity of influenza symptoms of individuals or family members and share that information with their health care providers, who in turn can use the site to monitor their patients' symptoms, the AMA announced during a telephone briefing.

The Web site, AMAfluhelp.org, is described as the country's first "comprehensive Web-based patient flu-assessment program," which "walks patients through a series of questions to determine the severity of their flu symptoms," based on the latest guidelines from the Centers for Disease Control and Prevention, according to an AMA statement announcing the launch.

The free site features physician-designed online tools "to help physicians monitor their patients' symptoms, facilitate care and treatment decisions, and efficiently manage their practices' patient flow."

For example, a physician can use the site to determine whether a patient can return to school or work, and a patient can use the site to generate a note from the physician to that effect. Also, a patient can use the site to determine whether to seek medical care for themselves or a family member. A patient who indicates that he or she has a high fever will receive a prompt to call his or her physician immediately or seek urgent medical care. The site also can be used to help patients monitor symptoms after vaccination, prompting them on when they should seek medical help.

People can log in to the Web site or can participate anonymously and can "invite" family members and their physicians and other health care providers to connect with the system. The information they enter is private and secured, and personal data cannot be accessed without a user's consent, according to the AMA statement.

Dr. James Mault, chairman and CEO of HealthyCircles, the company powering the AMA portal, said during the briefing that a physician can enter the program and monitor all the patients he or she is following, and communicate with them through online questions and answers.

During the briefing, Chris Lindley, director of emergency preparedness and response in the Colorado Department of Public Health and Environment, said that a link to the Web site will be added to the department's Web site, as part of the state's response to the influenza pandemic.

The AMA is promoting the Web site in collaboration with a coalition that includes Blue Cross NEPA, CVS Caremark, Merck & Co., Microsoft Corp., Minute Clinic, and the state of Colorado.

The American Medical Association has launched an interactive Web site for the public to evaluate the severity of influenza symptoms of individuals or family members and share that information with their health care providers, who in turn can use the site to monitor their patients' symptoms, the AMA announced during a telephone briefing.

The Web site, AMAfluhelp.org, is described as the country's first "comprehensive Web-based patient flu-assessment program," which "walks patients through a series of questions to determine the severity of their flu symptoms," based on the latest guidelines from the Centers for Disease Control and Prevention, according to an AMA statement announcing the launch.

The free site features physician-designed online tools "to help physicians monitor their patients' symptoms, facilitate care and treatment decisions, and efficiently manage their practices' patient flow."

For example, a physician can use the site to determine whether a patient can return to school or work, and a patient can use the site to generate a note from the physician to that effect. Also, a patient can use the site to determine whether to seek medical care for themselves or a family member. A patient who indicates that he or she has a high fever will receive a prompt to call his or her physician immediately or seek urgent medical care. The site also can be used to help patients monitor symptoms after vaccination, prompting them on when they should seek medical help.

People can log in to the Web site or can participate anonymously and can "invite" family members and their physicians and other health care providers to connect with the system. The information they enter is private and secured, and personal data cannot be accessed without a user's consent, according to the AMA statement.

Dr. James Mault, chairman and CEO of HealthyCircles, the company powering the AMA portal, said during the briefing that a physician can enter the program and monitor all the patients he or she is following, and communicate with them through online questions and answers.

During the briefing, Chris Lindley, director of emergency preparedness and response in the Colorado Department of Public Health and Environment, said that a link to the Web site will be added to the department's Web site, as part of the state's response to the influenza pandemic.

The AMA is promoting the Web site in collaboration with a coalition that includes Blue Cross NEPA, CVS Caremark, Merck & Co., Microsoft Corp., Minute Clinic, and the state of Colorado.

GAITHERSBURG, MD. — A Food and Drug Administration advisory panel voted 6 to 1 that a novel device that uses thermal energy to ablate smooth muscle in the airway during bronchoscopy could be approved under certain conditions as a treatment for severe, persistent asthma in people aged 18 years and older.

At the meeting, members of the FDA's Anesthesiology and Respiratory Therapy Devices Panel agreed that there was reasonable evidence that the device was safe and effective for this indication, but stipulated several conditions for approval.

The conditions included requiring the manufacturer to enroll all patients treated with the device after approval in a registry, which would follow the durability of the therapeutic effects and safety; and not using the device in patients with impaired coagulation or on those who are on anticoagulant medication, because hemoptysis was reported in six treated patients in the pivotal study.

Other conditions for approval were that physicians who use the device be adequately trained, and that patients not be retreated with the device until clinical trial data on the effects of retreatment are available. The panel also unanimously recommended postmarketing studies of the device.

Components of the Alair Bronchial Thermoplasty system include a radiofrequency generator and a single-use catheter with an electrode basket at the tip that delivers radiofrequency (RF) energy to surrounding tissue. Treatment results in clinical improvements in people with severe asthma by using thermal energy “to reduce the airway smooth muscle responsible for airway constriction in asthma patients,” according to the manufacturer Asthmatx.

The pivotal study conducted in six countries compared treatment with the device in 190 patients to sham bronchoscopy in 98 patients (where the catheter was deployed, without RF). Patients, whose median age was 41 years, had severe persistent asthma that was “not well controlled” (30%) or “very poorly controlled” (70%), and required high doses of inhaled corticosteroids and long-acting beta agonist therapy. Treatment was administered during three separate outpatient bronchoscopies 3 weeks apart.

The primary end point was the average of the changes in 6, 9, and 12 month Asthma Quality of Life Questionnaire (AQLQ) scores, a patient self-administered validated questionnaire, from baseline. Scores increased among patients in both groups, but the average of the three scores was 0.21 points greater among those in the active treatment group, compared with those in the sham group, which just missed statistical significance, according to the FDA's analysis.

The largest effects of treatment were seen at U.S. study sites, but in Brazil, improvements in the scores were somewhat higher among those in the sham group, which some panelists thought may have been due to the free maintenance medications received by all the patients enrolled at the Brazil sites.

Some of the study's secondary end points, including rates of severe exacerbations after treatment; days lost from work, school, or other daily activities due to asthma symptoms; and emergency room visits for respiratory symptoms, were lower among those treated with the device. Nearly 79% of those on Alair had a change in the AQLQ score of at least 0.5 (which the company said is the threshold for a clinically meaningful change), compared with 64.3% of those on sham treatment, the company reported.

Respiratory related-events, including asthma symptoms, were higher among those in the device-treated patients during the treatment phase (from the time of the first bronchoscopy through 6 weeks after the third bronchoscopy) but lower than among those in the sham group after that tine. A total of 6 patients (3%) treated with the device had hemoptysis, but there were no cases in sham-treated patients. There were no treatment related-deaths or withdrawals for worsening asthma in the study.

GAITHERSBURG, MD. — A Food and Drug Administration advisory panel voted 6 to 1 that a novel device that uses thermal energy to ablate smooth muscle in the airway during bronchoscopy could be approved under certain conditions as a treatment for severe, persistent asthma in people aged 18 years and older.

At the meeting, members of the FDA's Anesthesiology and Respiratory Therapy Devices Panel agreed that there was reasonable evidence that the device was safe and effective for this indication, but stipulated several conditions for approval.

The conditions included requiring the manufacturer to enroll all patients treated with the device after approval in a registry, which would follow the durability of the therapeutic effects and safety; and not using the device in patients with impaired coagulation or on those who are on anticoagulant medication, because hemoptysis was reported in six treated patients in the pivotal study.

Other conditions for approval were that physicians who use the device be adequately trained, and that patients not be retreated with the device until clinical trial data on the effects of retreatment are available. The panel also unanimously recommended postmarketing studies of the device.

Components of the Alair Bronchial Thermoplasty system include a radiofrequency generator and a single-use catheter with an electrode basket at the tip that delivers radiofrequency (RF) energy to surrounding tissue. Treatment results in clinical improvements in people with severe asthma by using thermal energy “to reduce the airway smooth muscle responsible for airway constriction in asthma patients,” according to the manufacturer Asthmatx.

The pivotal study conducted in six countries compared treatment with the device in 190 patients to sham bronchoscopy in 98 patients (where the catheter was deployed, without RF). Patients, whose median age was 41 years, had severe persistent asthma that was “not well controlled” (30%) or “very poorly controlled” (70%), and required high doses of inhaled corticosteroids and long-acting beta agonist therapy. Treatment was administered during three separate outpatient bronchoscopies 3 weeks apart.

The primary end point was the average of the changes in 6, 9, and 12 month Asthma Quality of Life Questionnaire (AQLQ) scores, a patient self-administered validated questionnaire, from baseline. Scores increased among patients in both groups, but the average of the three scores was 0.21 points greater among those in the active treatment group, compared with those in the sham group, which just missed statistical significance, according to the FDA's analysis.

The largest effects of treatment were seen at U.S. study sites, but in Brazil, improvements in the scores were somewhat higher among those in the sham group, which some panelists thought may have been due to the free maintenance medications received by all the patients enrolled at the Brazil sites.

Some of the study's secondary end points, including rates of severe exacerbations after treatment; days lost from work, school, or other daily activities due to asthma symptoms; and emergency room visits for respiratory symptoms, were lower among those treated with the device. Nearly 79% of those on Alair had a change in the AQLQ score of at least 0.5 (which the company said is the threshold for a clinically meaningful change), compared with 64.3% of those on sham treatment, the company reported.

Respiratory related-events, including asthma symptoms, were higher among those in the device-treated patients during the treatment phase (from the time of the first bronchoscopy through 6 weeks after the third bronchoscopy) but lower than among those in the sham group after that tine. A total of 6 patients (3%) treated with the device had hemoptysis, but there were no cases in sham-treated patients. There were no treatment related-deaths or withdrawals for worsening asthma in the study.

GAITHERSBURG, MD. — A Food and Drug Administration advisory panel voted 6 to 1 that a novel device that uses thermal energy to ablate smooth muscle in the airway during bronchoscopy could be approved under certain conditions as a treatment for severe, persistent asthma in people aged 18 years and older.

At the meeting, members of the FDA's Anesthesiology and Respiratory Therapy Devices Panel agreed that there was reasonable evidence that the device was safe and effective for this indication, but stipulated several conditions for approval.

The conditions included requiring the manufacturer to enroll all patients treated with the device after approval in a registry, which would follow the durability of the therapeutic effects and safety; and not using the device in patients with impaired coagulation or on those who are on anticoagulant medication, because hemoptysis was reported in six treated patients in the pivotal study.

Other conditions for approval were that physicians who use the device be adequately trained, and that patients not be retreated with the device until clinical trial data on the effects of retreatment are available. The panel also unanimously recommended postmarketing studies of the device.

Components of the Alair Bronchial Thermoplasty system include a radiofrequency generator and a single-use catheter with an electrode basket at the tip that delivers radiofrequency (RF) energy to surrounding tissue. Treatment results in clinical improvements in people with severe asthma by using thermal energy “to reduce the airway smooth muscle responsible for airway constriction in asthma patients,” according to the manufacturer Asthmatx.

The pivotal study conducted in six countries compared treatment with the device in 190 patients to sham bronchoscopy in 98 patients (where the catheter was deployed, without RF). Patients, whose median age was 41 years, had severe persistent asthma that was “not well controlled” (30%) or “very poorly controlled” (70%), and required high doses of inhaled corticosteroids and long-acting beta agonist therapy. Treatment was administered during three separate outpatient bronchoscopies 3 weeks apart.

The primary end point was the average of the changes in 6, 9, and 12 month Asthma Quality of Life Questionnaire (AQLQ) scores, a patient self-administered validated questionnaire, from baseline. Scores increased among patients in both groups, but the average of the three scores was 0.21 points greater among those in the active treatment group, compared with those in the sham group, which just missed statistical significance, according to the FDA's analysis.

The largest effects of treatment were seen at U.S. study sites, but in Brazil, improvements in the scores were somewhat higher among those in the sham group, which some panelists thought may have been due to the free maintenance medications received by all the patients enrolled at the Brazil sites.

Some of the study's secondary end points, including rates of severe exacerbations after treatment; days lost from work, school, or other daily activities due to asthma symptoms; and emergency room visits for respiratory symptoms, were lower among those treated with the device. Nearly 79% of those on Alair had a change in the AQLQ score of at least 0.5 (which the company said is the threshold for a clinically meaningful change), compared with 64.3% of those on sham treatment, the company reported.

Respiratory related-events, including asthma symptoms, were higher among those in the device-treated patients during the treatment phase (from the time of the first bronchoscopy through 6 weeks after the third bronchoscopy) but lower than among those in the sham group after that tine. A total of 6 patients (3%) treated with the device had hemoptysis, but there were no cases in sham-treated patients. There were no treatment related-deaths or withdrawals for worsening asthma in the study.

Different doses of liraglutide, an investigational human glucagon-like peptide-1 analogue developed to treat type 2 diabetes, were associated with significantly greater weight loss when compared with orlistat and placebo in a European multicenter study of over 500 obese adults who did not have type 2 diabetes.

“Overall, the results of this study indicate the potential benefit of liraglutide, in conjunction with an energy-deficit diet, in the treatment of obesity and associated risk factors,” according to the investigators lead by Dr. Arne Astrup of the University of Copenhagen, Denmark. Liraglutide, which stimulates the release of insulin when serum glucose levels are elevated, “offers a new mode of action for the treatment of obesity and improved efficacy compared with currently available therapies,” they said, noting that the long-term risk/benefit profile and the effect on maintaining weight must be established.

Liraglutide, which is under review by the Food and Drug Administration as a treatment for type 2 diabetes, has been associated with a dose-dependent weight loss, which the authors said is “most probably” due to a combination of effects on the GI tract and brain, since “native [glucagon-like peptide-1 (GLP-1)] suppresses appetite and energy intake in both normal-weight and obese individuals,” the authors said.

The study was funded by liraglutide manufacturer, Novo-Nordisk A/S. Dr. Astrup has been paid for lectures and has conducted sponsored research for the company. All authors reported performing commercially sponsored research for and advising Novo Nordisk, as well as competitive manufacturers. Two authors are employees of the company.

In the double-blind, placebo-controlled study, individuals ages 18-65, with body mass index ranging from 30 to 40 kg/m

After 20 weeks, the individuals on liraglutide lost a mean of 4.8 kg to 7.2 kg, compared with a mean of 2.8 kg among those on placebo and 4.1 kg among those on orlistat. The differences between all doses of liraglutide and placebo were significant.

In addition, 61% of those on liraglutide lost more than 5% of their body weight, which was significantly greater than those on placebo, and 76% of those on 3.0 mg of liraglutide lost more than 5% of their weight, when compared with 30% of those on placebo and 44% of those on orlistat, all significant differences.

Those on all doses of liraglutide saw reductions in blood pressure, and the prevalence of prediabetes was reduced by 84%-96% among those on the different doses of liraglutide. Weight loss was associated with reduced waist circumference, lowered systolic and diastolic blood pressure, and the proportion of patients with metabolic syndrome and prediabetes.

Overall, liraglutide was well tolerated, the investigators wrote. Having to self-administer injections did not appear to affect compliance, and while those on liragltuide experienced a higher rate of nausea and vomiting than did those on placebo, it was transient and mild to moderate for the most part.

In an editorial, Dr. George Bray of Louisiana State University, Baton Rouge, said that a limitation to using peptides like liraglutide for treating obesity is that they have to be injected, and “whether long-term use of an injectable drug is palatable as a treatment for obesity is yet to be established.” But he added, “from what we do know about GLP-1 agonists and their mechanisms, we can be optimistic that their promise for the treatment of obesity will be fulfilled.” Dr. Bray disclosed no conflicts of interest.

Different doses of liraglutide, an investigational human glucagon-like peptide-1 analogue developed to treat type 2 diabetes, were associated with significantly greater weight loss when compared with orlistat and placebo in a European multicenter study of over 500 obese adults who did not have type 2 diabetes.

“Overall, the results of this study indicate the potential benefit of liraglutide, in conjunction with an energy-deficit diet, in the treatment of obesity and associated risk factors,” according to the investigators lead by Dr. Arne Astrup of the University of Copenhagen, Denmark. Liraglutide, which stimulates the release of insulin when serum glucose levels are elevated, “offers a new mode of action for the treatment of obesity and improved efficacy compared with currently available therapies,” they said, noting that the long-term risk/benefit profile and the effect on maintaining weight must be established.

Liraglutide, which is under review by the Food and Drug Administration as a treatment for type 2 diabetes, has been associated with a dose-dependent weight loss, which the authors said is “most probably” due to a combination of effects on the GI tract and brain, since “native [glucagon-like peptide-1 (GLP-1)] suppresses appetite and energy intake in both normal-weight and obese individuals,” the authors said.

The study was funded by liraglutide manufacturer, Novo-Nordisk A/S. Dr. Astrup has been paid for lectures and has conducted sponsored research for the company. All authors reported performing commercially sponsored research for and advising Novo Nordisk, as well as competitive manufacturers. Two authors are employees of the company.

In the double-blind, placebo-controlled study, individuals ages 18-65, with body mass index ranging from 30 to 40 kg/m

After 20 weeks, the individuals on liraglutide lost a mean of 4.8 kg to 7.2 kg, compared with a mean of 2.8 kg among those on placebo and 4.1 kg among those on orlistat. The differences between all doses of liraglutide and placebo were significant.

In addition, 61% of those on liraglutide lost more than 5% of their body weight, which was significantly greater than those on placebo, and 76% of those on 3.0 mg of liraglutide lost more than 5% of their weight, when compared with 30% of those on placebo and 44% of those on orlistat, all significant differences.

Those on all doses of liraglutide saw reductions in blood pressure, and the prevalence of prediabetes was reduced by 84%-96% among those on the different doses of liraglutide. Weight loss was associated with reduced waist circumference, lowered systolic and diastolic blood pressure, and the proportion of patients with metabolic syndrome and prediabetes.

Overall, liraglutide was well tolerated, the investigators wrote. Having to self-administer injections did not appear to affect compliance, and while those on liragltuide experienced a higher rate of nausea and vomiting than did those on placebo, it was transient and mild to moderate for the most part.

In an editorial, Dr. George Bray of Louisiana State University, Baton Rouge, said that a limitation to using peptides like liraglutide for treating obesity is that they have to be injected, and “whether long-term use of an injectable drug is palatable as a treatment for obesity is yet to be established.” But he added, “from what we do know about GLP-1 agonists and their mechanisms, we can be optimistic that their promise for the treatment of obesity will be fulfilled.” Dr. Bray disclosed no conflicts of interest.

Different doses of liraglutide, an investigational human glucagon-like peptide-1 analogue developed to treat type 2 diabetes, were associated with significantly greater weight loss when compared with orlistat and placebo in a European multicenter study of over 500 obese adults who did not have type 2 diabetes.

“Overall, the results of this study indicate the potential benefit of liraglutide, in conjunction with an energy-deficit diet, in the treatment of obesity and associated risk factors,” according to the investigators lead by Dr. Arne Astrup of the University of Copenhagen, Denmark. Liraglutide, which stimulates the release of insulin when serum glucose levels are elevated, “offers a new mode of action for the treatment of obesity and improved efficacy compared with currently available therapies,” they said, noting that the long-term risk/benefit profile and the effect on maintaining weight must be established.

Liraglutide, which is under review by the Food and Drug Administration as a treatment for type 2 diabetes, has been associated with a dose-dependent weight loss, which the authors said is “most probably” due to a combination of effects on the GI tract and brain, since “native [glucagon-like peptide-1 (GLP-1)] suppresses appetite and energy intake in both normal-weight and obese individuals,” the authors said.

The study was funded by liraglutide manufacturer, Novo-Nordisk A/S. Dr. Astrup has been paid for lectures and has conducted sponsored research for the company. All authors reported performing commercially sponsored research for and advising Novo Nordisk, as well as competitive manufacturers. Two authors are employees of the company.

In the double-blind, placebo-controlled study, individuals ages 18-65, with body mass index ranging from 30 to 40 kg/m

After 20 weeks, the individuals on liraglutide lost a mean of 4.8 kg to 7.2 kg, compared with a mean of 2.8 kg among those on placebo and 4.1 kg among those on orlistat. The differences between all doses of liraglutide and placebo were significant.

In addition, 61% of those on liraglutide lost more than 5% of their body weight, which was significantly greater than those on placebo, and 76% of those on 3.0 mg of liraglutide lost more than 5% of their weight, when compared with 30% of those on placebo and 44% of those on orlistat, all significant differences.

Those on all doses of liraglutide saw reductions in blood pressure, and the prevalence of prediabetes was reduced by 84%-96% among those on the different doses of liraglutide. Weight loss was associated with reduced waist circumference, lowered systolic and diastolic blood pressure, and the proportion of patients with metabolic syndrome and prediabetes.

Overall, liraglutide was well tolerated, the investigators wrote. Having to self-administer injections did not appear to affect compliance, and while those on liragltuide experienced a higher rate of nausea and vomiting than did those on placebo, it was transient and mild to moderate for the most part.

In an editorial, Dr. George Bray of Louisiana State University, Baton Rouge, said that a limitation to using peptides like liraglutide for treating obesity is that they have to be injected, and “whether long-term use of an injectable drug is palatable as a treatment for obesity is yet to be established.” But he added, “from what we do know about GLP-1 agonists and their mechanisms, we can be optimistic that their promise for the treatment of obesity will be fulfilled.” Dr. Bray disclosed no conflicts of interest.