A Food and Drug Administration advisory panel voted 14-2 against recommending approval of a supplemental New Drug Application for empagliflozin (Jardiance) as an adjunct to insulin therapy to improve glycemic control in adults with type 1 diabetes. The drug is already is approved for people with type 2 diabetes.

Members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee cited persisting concerns about the risk for diabetic ketoacidosis (DKA) seen with the drug, as well as the limited pool of evidence Boehringer Ingelheim presented. Patients with type 1 diabetes are at increased risk for DKA.

The agency said it typically gets two major studies to support applications for drug approvals, but the application reviewed Nov. 13 rested largely on a single phase 3 trial, in which 241 people with type 1 diabetes took a low dose (2.5 mg) of empagliflozin for about 6 months. Panelists repeatedly objected to the paucity of data they had to consider this expanded approval.

“We owe it to patients with type 1 diabetes to do this right,” said Brendan M. Everett, MD, MPH, of Harvard Medical School, Boston, who served as a panelist. “It’s out of respect for them that I voted no.”

Boehringer Ingelheim, and members of the public argued that people with type 1 diabetes want access to new medicines such as empagliflozin that already are available for people with type 2 diabetes. The agency approved the drug in 2014 at doses of 10 mg and 25 mg as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. In 2016, it approved a new indication for empagliflozin for reducing risk of cardiovascular death in people with type 2 disease.

The panelists said they were sympathetic to that point of view, but stressed the need for further larger studies of empagliflozin in people with type 1 diabetes.

“I do think this is promising,” said panelist Michael Blaha, MD, MPH, of Johns Hopkins University, Baltimore. “But I’m not sure we are here to evaluate promising things. We’re here to evaluate proven things.”

The FDA advisers also said there was a need for greater clarity about reporting of adverse events in testing of this drug. The FDA reviewers reported disagreements with Boehringer about some cases classified as “unlikely ketoacidosis but ketosis” in the study.

“Some events adjudicated as ‘unlikely ketoacidosis but ketosis’ were clinically significant serious events requiring hospitalizations and prompt intervention, such as discontinuation of study drug,” wrote Mahtab Niyyati, MD, an FDA clinical reviewer, in her slides for the meeting.

The FDA is not obliged to accept the suggestions of its advisory panels, but it often does.

The agency did not ask the panel to weigh in directly on whether to approve the drug. Instead, the question put to the panel for a vote was whether the available data suggest that the benefits outweigh the risks of empagliflozin and support approval of a 2.5-mg dose as an adjunct to insulin for people with type 1 diabetes.

Empagliflozin is part of the sodium-glucose cotransporter 2 (SGLT2) inhibitor class of medicines, already known to have a risk for DKA, the agency noted in its briefing document for the meeting. DKA occurs as a result of insulin deficiency and subsequent ketogenesis.

There are no SGLT2 inhibitors approved for type 1 diabetes, the staff said in the review. The agency has rebuffed recent bids by makers of other SGLT2 drugs for people with type 1 diabetes. In July, AstraZeneca said the FDA had not approved its application for use of dapagliflozin (Farxiga) as an adjunct treatment to insulin to improve glycemic control in adult patients with type1 diabetes, when insulin alone does not provide adequate glycemic control. AstraZeneca said it was working with the agency on issues raised in the response letter it received.

In March, the FDA blocked a bid by Sanofi for approval of its investigational SGLT1/2 inhibitor, sotagliflozin (Zynquista) for use in people with type 1 diabetes. A panel had voted 8-8 in January on a question about the additional approval for this drug.

At the Nov. 13 meeting, panel members offered comments about the potential design of a new test for empagliflozin in type 1 diabetes, including a suggestion for a 2-year trial.

Anna McCollister-Slipp, the consumer representative on the FDA panel, cast one of the two votes in favor of use of the drug for people with type 1 diabetes. She said the agency needed to press for more research in this field but also argued that patients can manage the risks of treatments they find valuable. She cited, as an example, how she has stuck with an insulin pump to manage her own type 1 diabetes, despite having setbacks with the device that sent her to the emergency department.

The other vote in support of the empagliflozin application came from panelist Kashif M. Munir, MD, medical director of the University of Maryland Center for Diabetes and Endrocrinology, Baltimore. In explaining his vote, Dr. Munir noted that he and other physicians already are prescribing medications such as empagliflozin for people with type 1 diabetes, even though it is an off-label use. Boehringer’s strategy of using a lower dose of the drug for this group of patients would mean a reduction in effectiveness but also would lower the risk for side effects.

“Some of us do use existing medications” and have patients take partial doses, Dr. Munir said, adding that the current off-label use of the drug persuaded him to vote in favor of expanded approval, despite his concerns about the data.

Empagliflozin given at 2.5 mg resulted in a statistically significant difference of 0.26% in change in hemoglobin HbA_1c at week 26, compared with placebo, said Roberto Crackel, PhD, an FDA mathematical statistician, during the presentation. There was a numerically small benefit in body weight and systolic blood pressure, but no benefit in reducing hypoglycemic events, he said.

In concluding, the agency’s presentation, Dr. Niyyati presented a slide depicting potential risk and benefit for empagliflozin with 6 months and then 6.5 years of follow-up. It showed that in terms of the benefit of HbA_1c control, there is a potential but undemonstrated reduction in the risk of microvascular complications at 6 months and an estimated 2.8% reduction in microvascular complications after 6.5 years.

In terms of risk of DKA, there are limited data with unstable estimates, ranging to perhaps as many as 468 additional patients-with-events per 10,000 patients at the 6-month point. By the 6.5-year mark, treating 10,000 patients could result in 1,494 additional events.

In a statement issued after the panel’s vote, Boehringer and its partner on empagliflozin, Eli Lilly, stressed the benefit seen with the drug, a statistically significant reduction in HbA_1c (0.28%), compared with insulin given with a matched placebo in adults with type 1 diabetes. Secondary endpoints of the trial demonstrated reductions in weight (1.8 kg) and systolic blood pressure (2.1 mm Hg), compared with insulin plus placebo, the companies said.

“We continue to believe the totality of data from the EASE [Empagliflozin as Adjunctive to Insulin Therapy] program indicates a favorable benefit-risk profile for empagliflozin 2.5 mg in adults with type 1 diabetes and look forward to continuing to work with the FDA in this review process,” said Mohamed Eid, MD, MPH, vice president, clinical development & medical affairs, cardiometabolism & respiratory medicine, Boehringer Ingelheim, in a statement.

Speaking as a member of the public, Kelly L. Close, founder of the diaTribe Foundation, urged the FDA to “think creatively” about approval of the drug.” Many people already are using empagliflozin off label, she said. An FDA approval would help physicians and their patients manage the risks of this medicine. Without such help, patients may be needlessly exposed to harm, she argued.

“That’s what happens with popular unregulated drugs that payers cover, and we know that many, many payers are covering this drug for people with type 1,” she said.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen’s health research group, made the opposing argument during the public session. The trial, in which 241 took the low dose of the drug and 241 on placebo, was “underpowered” in Dr. Wolfe’s view. He also stressed the issue that the FDA had raised about adjudication of the cases of side effects.

An FDA approval of the 2.5-mg dose would send “a dangerous false green signal to those doctors who are already prescribing off-label” drugs in SGLT2 inhibitor class, he said.

That would foster a misleading perception “that we have found the sweet spot” balancing safety and risk, he added. “I can’t see how the FDA or the advisory committee would suggest approval” of empagliflozin for type 1 diabetes.”

A Food and Drug Administration advisory panel voted 14-2 against recommending approval of a supplemental New Drug Application for empagliflozin (Jardiance) as an adjunct to insulin therapy to improve glycemic control in adults with type 1 diabetes. The drug is already is approved for people with type 2 diabetes.

Members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee cited persisting concerns about the risk for diabetic ketoacidosis (DKA) seen with the drug, as well as the limited pool of evidence Boehringer Ingelheim presented. Patients with type 1 diabetes are at increased risk for DKA.

The agency said it typically gets two major studies to support applications for drug approvals, but the application reviewed Nov. 13 rested largely on a single phase 3 trial, in which 241 people with type 1 diabetes took a low dose (2.5 mg) of empagliflozin for about 6 months. Panelists repeatedly objected to the paucity of data they had to consider this expanded approval.

“We owe it to patients with type 1 diabetes to do this right,” said Brendan M. Everett, MD, MPH, of Harvard Medical School, Boston, who served as a panelist. “It’s out of respect for them that I voted no.”

Boehringer Ingelheim, and members of the public argued that people with type 1 diabetes want access to new medicines such as empagliflozin that already are available for people with type 2 diabetes. The agency approved the drug in 2014 at doses of 10 mg and 25 mg as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. In 2016, it approved a new indication for empagliflozin for reducing risk of cardiovascular death in people with type 2 disease.

The panelists said they were sympathetic to that point of view, but stressed the need for further larger studies of empagliflozin in people with type 1 diabetes.

“I do think this is promising,” said panelist Michael Blaha, MD, MPH, of Johns Hopkins University, Baltimore. “But I’m not sure we are here to evaluate promising things. We’re here to evaluate proven things.”

The FDA advisers also said there was a need for greater clarity about reporting of adverse events in testing of this drug. The FDA reviewers reported disagreements with Boehringer about some cases classified as “unlikely ketoacidosis but ketosis” in the study.

“Some events adjudicated as ‘unlikely ketoacidosis but ketosis’ were clinically significant serious events requiring hospitalizations and prompt intervention, such as discontinuation of study drug,” wrote Mahtab Niyyati, MD, an FDA clinical reviewer, in her slides for the meeting.

The FDA is not obliged to accept the suggestions of its advisory panels, but it often does.

The agency did not ask the panel to weigh in directly on whether to approve the drug. Instead, the question put to the panel for a vote was whether the available data suggest that the benefits outweigh the risks of empagliflozin and support approval of a 2.5-mg dose as an adjunct to insulin for people with type 1 diabetes.

Empagliflozin is part of the sodium-glucose cotransporter 2 (SGLT2) inhibitor class of medicines, already known to have a risk for DKA, the agency noted in its briefing document for the meeting. DKA occurs as a result of insulin deficiency and subsequent ketogenesis.

There are no SGLT2 inhibitors approved for type 1 diabetes, the staff said in the review. The agency has rebuffed recent bids by makers of other SGLT2 drugs for people with type 1 diabetes. In July, AstraZeneca said the FDA had not approved its application for use of dapagliflozin (Farxiga) as an adjunct treatment to insulin to improve glycemic control in adult patients with type1 diabetes, when insulin alone does not provide adequate glycemic control. AstraZeneca said it was working with the agency on issues raised in the response letter it received.

In March, the FDA blocked a bid by Sanofi for approval of its investigational SGLT1/2 inhibitor, sotagliflozin (Zynquista) for use in people with type 1 diabetes. A panel had voted 8-8 in January on a question about the additional approval for this drug.

At the Nov. 13 meeting, panel members offered comments about the potential design of a new test for empagliflozin in type 1 diabetes, including a suggestion for a 2-year trial.

Anna McCollister-Slipp, the consumer representative on the FDA panel, cast one of the two votes in favor of use of the drug for people with type 1 diabetes. She said the agency needed to press for more research in this field but also argued that patients can manage the risks of treatments they find valuable. She cited, as an example, how she has stuck with an insulin pump to manage her own type 1 diabetes, despite having setbacks with the device that sent her to the emergency department.

The other vote in support of the empagliflozin application came from panelist Kashif M. Munir, MD, medical director of the University of Maryland Center for Diabetes and Endrocrinology, Baltimore. In explaining his vote, Dr. Munir noted that he and other physicians already are prescribing medications such as empagliflozin for people with type 1 diabetes, even though it is an off-label use. Boehringer’s strategy of using a lower dose of the drug for this group of patients would mean a reduction in effectiveness but also would lower the risk for side effects.

“Some of us do use existing medications” and have patients take partial doses, Dr. Munir said, adding that the current off-label use of the drug persuaded him to vote in favor of expanded approval, despite his concerns about the data.

Empagliflozin given at 2.5 mg resulted in a statistically significant difference of 0.26% in change in hemoglobin HbA_1c at week 26, compared with placebo, said Roberto Crackel, PhD, an FDA mathematical statistician, during the presentation. There was a numerically small benefit in body weight and systolic blood pressure, but no benefit in reducing hypoglycemic events, he said.

In concluding, the agency’s presentation, Dr. Niyyati presented a slide depicting potential risk and benefit for empagliflozin with 6 months and then 6.5 years of follow-up. It showed that in terms of the benefit of HbA_1c control, there is a potential but undemonstrated reduction in the risk of microvascular complications at 6 months and an estimated 2.8% reduction in microvascular complications after 6.5 years.

In terms of risk of DKA, there are limited data with unstable estimates, ranging to perhaps as many as 468 additional patients-with-events per 10,000 patients at the 6-month point. By the 6.5-year mark, treating 10,000 patients could result in 1,494 additional events.

In a statement issued after the panel’s vote, Boehringer and its partner on empagliflozin, Eli Lilly, stressed the benefit seen with the drug, a statistically significant reduction in HbA_1c (0.28%), compared with insulin given with a matched placebo in adults with type 1 diabetes. Secondary endpoints of the trial demonstrated reductions in weight (1.8 kg) and systolic blood pressure (2.1 mm Hg), compared with insulin plus placebo, the companies said.

“We continue to believe the totality of data from the EASE [Empagliflozin as Adjunctive to Insulin Therapy] program indicates a favorable benefit-risk profile for empagliflozin 2.5 mg in adults with type 1 diabetes and look forward to continuing to work with the FDA in this review process,” said Mohamed Eid, MD, MPH, vice president, clinical development & medical affairs, cardiometabolism & respiratory medicine, Boehringer Ingelheim, in a statement.

Speaking as a member of the public, Kelly L. Close, founder of the diaTribe Foundation, urged the FDA to “think creatively” about approval of the drug.” Many people already are using empagliflozin off label, she said. An FDA approval would help physicians and their patients manage the risks of this medicine. Without such help, patients may be needlessly exposed to harm, she argued.

“That’s what happens with popular unregulated drugs that payers cover, and we know that many, many payers are covering this drug for people with type 1,” she said.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen’s health research group, made the opposing argument during the public session. The trial, in which 241 took the low dose of the drug and 241 on placebo, was “underpowered” in Dr. Wolfe’s view. He also stressed the issue that the FDA had raised about adjudication of the cases of side effects.

An FDA approval of the 2.5-mg dose would send “a dangerous false green signal to those doctors who are already prescribing off-label” drugs in SGLT2 inhibitor class, he said.

That would foster a misleading perception “that we have found the sweet spot” balancing safety and risk, he added. “I can’t see how the FDA or the advisory committee would suggest approval” of empagliflozin for type 1 diabetes.”

A Food and Drug Administration advisory panel voted 14-2 against recommending approval of a supplemental New Drug Application for empagliflozin (Jardiance) as an adjunct to insulin therapy to improve glycemic control in adults with type 1 diabetes. The drug is already is approved for people with type 2 diabetes.

Members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee cited persisting concerns about the risk for diabetic ketoacidosis (DKA) seen with the drug, as well as the limited pool of evidence Boehringer Ingelheim presented. Patients with type 1 diabetes are at increased risk for DKA.

The agency said it typically gets two major studies to support applications for drug approvals, but the application reviewed Nov. 13 rested largely on a single phase 3 trial, in which 241 people with type 1 diabetes took a low dose (2.5 mg) of empagliflozin for about 6 months. Panelists repeatedly objected to the paucity of data they had to consider this expanded approval.

“We owe it to patients with type 1 diabetes to do this right,” said Brendan M. Everett, MD, MPH, of Harvard Medical School, Boston, who served as a panelist. “It’s out of respect for them that I voted no.”

Boehringer Ingelheim, and members of the public argued that people with type 1 diabetes want access to new medicines such as empagliflozin that already are available for people with type 2 diabetes. The agency approved the drug in 2014 at doses of 10 mg and 25 mg as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. In 2016, it approved a new indication for empagliflozin for reducing risk of cardiovascular death in people with type 2 disease.

The panelists said they were sympathetic to that point of view, but stressed the need for further larger studies of empagliflozin in people with type 1 diabetes.

“I do think this is promising,” said panelist Michael Blaha, MD, MPH, of Johns Hopkins University, Baltimore. “But I’m not sure we are here to evaluate promising things. We’re here to evaluate proven things.”

The FDA advisers also said there was a need for greater clarity about reporting of adverse events in testing of this drug. The FDA reviewers reported disagreements with Boehringer about some cases classified as “unlikely ketoacidosis but ketosis” in the study.

“Some events adjudicated as ‘unlikely ketoacidosis but ketosis’ were clinically significant serious events requiring hospitalizations and prompt intervention, such as discontinuation of study drug,” wrote Mahtab Niyyati, MD, an FDA clinical reviewer, in her slides for the meeting.

The FDA is not obliged to accept the suggestions of its advisory panels, but it often does.

The agency did not ask the panel to weigh in directly on whether to approve the drug. Instead, the question put to the panel for a vote was whether the available data suggest that the benefits outweigh the risks of empagliflozin and support approval of a 2.5-mg dose as an adjunct to insulin for people with type 1 diabetes.

Empagliflozin is part of the sodium-glucose cotransporter 2 (SGLT2) inhibitor class of medicines, already known to have a risk for DKA, the agency noted in its briefing document for the meeting. DKA occurs as a result of insulin deficiency and subsequent ketogenesis.

There are no SGLT2 inhibitors approved for type 1 diabetes, the staff said in the review. The agency has rebuffed recent bids by makers of other SGLT2 drugs for people with type 1 diabetes. In July, AstraZeneca said the FDA had not approved its application for use of dapagliflozin (Farxiga) as an adjunct treatment to insulin to improve glycemic control in adult patients with type1 diabetes, when insulin alone does not provide adequate glycemic control. AstraZeneca said it was working with the agency on issues raised in the response letter it received.

In March, the FDA blocked a bid by Sanofi for approval of its investigational SGLT1/2 inhibitor, sotagliflozin (Zynquista) for use in people with type 1 diabetes. A panel had voted 8-8 in January on a question about the additional approval for this drug.

At the Nov. 13 meeting, panel members offered comments about the potential design of a new test for empagliflozin in type 1 diabetes, including a suggestion for a 2-year trial.

Anna McCollister-Slipp, the consumer representative on the FDA panel, cast one of the two votes in favor of use of the drug for people with type 1 diabetes. She said the agency needed to press for more research in this field but also argued that patients can manage the risks of treatments they find valuable. She cited, as an example, how she has stuck with an insulin pump to manage her own type 1 diabetes, despite having setbacks with the device that sent her to the emergency department.

The other vote in support of the empagliflozin application came from panelist Kashif M. Munir, MD, medical director of the University of Maryland Center for Diabetes and Endrocrinology, Baltimore. In explaining his vote, Dr. Munir noted that he and other physicians already are prescribing medications such as empagliflozin for people with type 1 diabetes, even though it is an off-label use. Boehringer’s strategy of using a lower dose of the drug for this group of patients would mean a reduction in effectiveness but also would lower the risk for side effects.

“Some of us do use existing medications” and have patients take partial doses, Dr. Munir said, adding that the current off-label use of the drug persuaded him to vote in favor of expanded approval, despite his concerns about the data.

Empagliflozin given at 2.5 mg resulted in a statistically significant difference of 0.26% in change in hemoglobin HbA_1c at week 26, compared with placebo, said Roberto Crackel, PhD, an FDA mathematical statistician, during the presentation. There was a numerically small benefit in body weight and systolic blood pressure, but no benefit in reducing hypoglycemic events, he said.

In concluding, the agency’s presentation, Dr. Niyyati presented a slide depicting potential risk and benefit for empagliflozin with 6 months and then 6.5 years of follow-up. It showed that in terms of the benefit of HbA_1c control, there is a potential but undemonstrated reduction in the risk of microvascular complications at 6 months and an estimated 2.8% reduction in microvascular complications after 6.5 years.

In terms of risk of DKA, there are limited data with unstable estimates, ranging to perhaps as many as 468 additional patients-with-events per 10,000 patients at the 6-month point. By the 6.5-year mark, treating 10,000 patients could result in 1,494 additional events.

In a statement issued after the panel’s vote, Boehringer and its partner on empagliflozin, Eli Lilly, stressed the benefit seen with the drug, a statistically significant reduction in HbA_1c (0.28%), compared with insulin given with a matched placebo in adults with type 1 diabetes. Secondary endpoints of the trial demonstrated reductions in weight (1.8 kg) and systolic blood pressure (2.1 mm Hg), compared with insulin plus placebo, the companies said.

“We continue to believe the totality of data from the EASE [Empagliflozin as Adjunctive to Insulin Therapy] program indicates a favorable benefit-risk profile for empagliflozin 2.5 mg in adults with type 1 diabetes and look forward to continuing to work with the FDA in this review process,” said Mohamed Eid, MD, MPH, vice president, clinical development & medical affairs, cardiometabolism & respiratory medicine, Boehringer Ingelheim, in a statement.

Speaking as a member of the public, Kelly L. Close, founder of the diaTribe Foundation, urged the FDA to “think creatively” about approval of the drug.” Many people already are using empagliflozin off label, she said. An FDA approval would help physicians and their patients manage the risks of this medicine. Without such help, patients may be needlessly exposed to harm, she argued.

“That’s what happens with popular unregulated drugs that payers cover, and we know that many, many payers are covering this drug for people with type 1,” she said.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen’s health research group, made the opposing argument during the public session. The trial, in which 241 took the low dose of the drug and 241 on placebo, was “underpowered” in Dr. Wolfe’s view. He also stressed the issue that the FDA had raised about adjudication of the cases of side effects.

An FDA approval of the 2.5-mg dose would send “a dangerous false green signal to those doctors who are already prescribing off-label” drugs in SGLT2 inhibitor class, he said.

That would foster a misleading perception “that we have found the sweet spot” balancing safety and risk, he added. “I can’t see how the FDA or the advisory committee would suggest approval” of empagliflozin for type 1 diabetes.”

When added to maximally tolerated statin therapy, bempedoic acid reduced LDL cholesterol by more than 15%, compared with placebo, Anne C. Goldberg, MD, and colleagues reported in JAMA.

The prodrug also improved non-HDL cholesterol, total cholesterol, apolipoprotein B, and C-reactive protein in a group of patients who remained at high risk of cardiovascular events despite maximally tolerated statin treatment, said Dr. Goldberg of Washington University, St. Louis, and coauthors in reporting the results of CLEAR Wisdom (Evaluation of Long-Term Efficacy of Bempedoic Acid [ETC-1002] in Patients With Hyperlipidemia at High Cardiovascular Risk).

The prodrug bempedoic acid works differently than most statins. In the liver, the drug activates into bempedoyl-CoA. It interrupts ATP-citrate lyase, an enzyme critical to the main statin target, 3-hydroxy-3-methylglutaryl-CoA reductase. Although it reduces cholesterol synthesis in the liver, bempedoic acid isn’t active in skeletal muscle, unlike statins.

The 52-week placebo-controlled trial included 2,300 patients enrolled at 91 international sites. All of them had atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both. They were randomized 2:1 to bempedoic acid 180 mg daily or placebo. Patients were a mean of 64 years old, with a mean LDL cholesterol level of 120.4 mg/dL. Most (89.6%) were receiving statin therapy, with 53% receiving high-intensity treatment.

The primary endpoint was change in LDL cholesterol. Secondary measures included overall lipid changes and changes in lipoprotein and biomarkers of cardiovascular disease.

After 12 weeks, patients taking bempedoic acid experienced significantly lowered LDL cholesterol, compared with those taking placebo (–15% vs. 2.4%; between-group difference, 17.4%). The key secondary endpoints were also positive, including non–LDL cholesterol (–10.8% vs. 2.3%), total cholesterol (–9.9% vs. 1.3%), apolipoprotein B (–9.3% vs 3.7%), and high-sensitivity C-reactive protein (median, –18.7% vs –9.4%)

Most patients in both groups (about 70%) experienced at least one adverse event. However, the majority of those (77.6%) were not related to the study drug. Most were mild to moderate and included myalgia (1% vs. 0.8%), increased aspartate aminotransferase level (0.6% vs. 0%), and arthralgia (0.6% vs. 0%).

Serious adverse events occurred in 19.8% of patients, with three possibly related to bempedoic acid. These were ulcerative colitis and ischemic stroke in the bempedoic acid group and upper abdominal pain in the placebo group.

Eight fatalities occurred during the CLEAR Wisdom. There were single cases of cardiac arrest, coronary artery arteriosclerosis, acute poisoning with carbon dioxide, myocardial infarction, and septic shock related to a prescheduled abdominal surgical procedure. One patient in the active group died from an unknown cause.

Four events in the bempedoic acid group and two events in the placebo group were cardiovascular deaths.

New or worsening diabetes developed in approximately 7% of each group, and less than 3% of those taking bempedoic acid developed gout or increased blood uric acid, as was the case for less than 1% of patients taking placebo.

In May, the Food and Drug Administration accepted a New Drug Application from Esperion for bempedoic acid. A response is expected in February 2020.

Dr. Goldberg reporter receiving research grants/support from Amgen, Amarin, Pfizer, Regeneron, Sanofi, IONIS, Novartis, and Merck and serving as a consultant for Esperion, Novartis, Akcea, OptumRX, 23andMe, Sanofi/Regeneron, and Merck.

[email protected]

SOURCE: Goldberg AC et al. JAMA. 2019 Nov 12;322:1780-8.

When added to maximally tolerated statin therapy, bempedoic acid reduced LDL cholesterol by more than 15%, compared with placebo, Anne C. Goldberg, MD, and colleagues reported in JAMA.

The prodrug also improved non-HDL cholesterol, total cholesterol, apolipoprotein B, and C-reactive protein in a group of patients who remained at high risk of cardiovascular events despite maximally tolerated statin treatment, said Dr. Goldberg of Washington University, St. Louis, and coauthors in reporting the results of CLEAR Wisdom (Evaluation of Long-Term Efficacy of Bempedoic Acid [ETC-1002] in Patients With Hyperlipidemia at High Cardiovascular Risk).

The prodrug bempedoic acid works differently than most statins. In the liver, the drug activates into bempedoyl-CoA. It interrupts ATP-citrate lyase, an enzyme critical to the main statin target, 3-hydroxy-3-methylglutaryl-CoA reductase. Although it reduces cholesterol synthesis in the liver, bempedoic acid isn’t active in skeletal muscle, unlike statins.

The 52-week placebo-controlled trial included 2,300 patients enrolled at 91 international sites. All of them had atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both. They were randomized 2:1 to bempedoic acid 180 mg daily or placebo. Patients were a mean of 64 years old, with a mean LDL cholesterol level of 120.4 mg/dL. Most (89.6%) were receiving statin therapy, with 53% receiving high-intensity treatment.

The primary endpoint was change in LDL cholesterol. Secondary measures included overall lipid changes and changes in lipoprotein and biomarkers of cardiovascular disease.

After 12 weeks, patients taking bempedoic acid experienced significantly lowered LDL cholesterol, compared with those taking placebo (–15% vs. 2.4%; between-group difference, 17.4%). The key secondary endpoints were also positive, including non–LDL cholesterol (–10.8% vs. 2.3%), total cholesterol (–9.9% vs. 1.3%), apolipoprotein B (–9.3% vs 3.7%), and high-sensitivity C-reactive protein (median, –18.7% vs –9.4%)

Most patients in both groups (about 70%) experienced at least one adverse event. However, the majority of those (77.6%) were not related to the study drug. Most were mild to moderate and included myalgia (1% vs. 0.8%), increased aspartate aminotransferase level (0.6% vs. 0%), and arthralgia (0.6% vs. 0%).

Serious adverse events occurred in 19.8% of patients, with three possibly related to bempedoic acid. These were ulcerative colitis and ischemic stroke in the bempedoic acid group and upper abdominal pain in the placebo group.

Eight fatalities occurred during the CLEAR Wisdom. There were single cases of cardiac arrest, coronary artery arteriosclerosis, acute poisoning with carbon dioxide, myocardial infarction, and septic shock related to a prescheduled abdominal surgical procedure. One patient in the active group died from an unknown cause.

Four events in the bempedoic acid group and two events in the placebo group were cardiovascular deaths.

New or worsening diabetes developed in approximately 7% of each group, and less than 3% of those taking bempedoic acid developed gout or increased blood uric acid, as was the case for less than 1% of patients taking placebo.

In May, the Food and Drug Administration accepted a New Drug Application from Esperion for bempedoic acid. A response is expected in February 2020.

Dr. Goldberg reporter receiving research grants/support from Amgen, Amarin, Pfizer, Regeneron, Sanofi, IONIS, Novartis, and Merck and serving as a consultant for Esperion, Novartis, Akcea, OptumRX, 23andMe, Sanofi/Regeneron, and Merck.

[email protected]

SOURCE: Goldberg AC et al. JAMA. 2019 Nov 12;322:1780-8.

When added to maximally tolerated statin therapy, bempedoic acid reduced LDL cholesterol by more than 15%, compared with placebo, Anne C. Goldberg, MD, and colleagues reported in JAMA.

The prodrug also improved non-HDL cholesterol, total cholesterol, apolipoprotein B, and C-reactive protein in a group of patients who remained at high risk of cardiovascular events despite maximally tolerated statin treatment, said Dr. Goldberg of Washington University, St. Louis, and coauthors in reporting the results of CLEAR Wisdom (Evaluation of Long-Term Efficacy of Bempedoic Acid [ETC-1002] in Patients With Hyperlipidemia at High Cardiovascular Risk).

The prodrug bempedoic acid works differently than most statins. In the liver, the drug activates into bempedoyl-CoA. It interrupts ATP-citrate lyase, an enzyme critical to the main statin target, 3-hydroxy-3-methylglutaryl-CoA reductase. Although it reduces cholesterol synthesis in the liver, bempedoic acid isn’t active in skeletal muscle, unlike statins.

The 52-week placebo-controlled trial included 2,300 patients enrolled at 91 international sites. All of them had atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both. They were randomized 2:1 to bempedoic acid 180 mg daily or placebo. Patients were a mean of 64 years old, with a mean LDL cholesterol level of 120.4 mg/dL. Most (89.6%) were receiving statin therapy, with 53% receiving high-intensity treatment.

The primary endpoint was change in LDL cholesterol. Secondary measures included overall lipid changes and changes in lipoprotein and biomarkers of cardiovascular disease.

After 12 weeks, patients taking bempedoic acid experienced significantly lowered LDL cholesterol, compared with those taking placebo (–15% vs. 2.4%; between-group difference, 17.4%). The key secondary endpoints were also positive, including non–LDL cholesterol (–10.8% vs. 2.3%), total cholesterol (–9.9% vs. 1.3%), apolipoprotein B (–9.3% vs 3.7%), and high-sensitivity C-reactive protein (median, –18.7% vs –9.4%)

Most patients in both groups (about 70%) experienced at least one adverse event. However, the majority of those (77.6%) were not related to the study drug. Most were mild to moderate and included myalgia (1% vs. 0.8%), increased aspartate aminotransferase level (0.6% vs. 0%), and arthralgia (0.6% vs. 0%).

Serious adverse events occurred in 19.8% of patients, with three possibly related to bempedoic acid. These were ulcerative colitis and ischemic stroke in the bempedoic acid group and upper abdominal pain in the placebo group.

Eight fatalities occurred during the CLEAR Wisdom. There were single cases of cardiac arrest, coronary artery arteriosclerosis, acute poisoning with carbon dioxide, myocardial infarction, and septic shock related to a prescheduled abdominal surgical procedure. One patient in the active group died from an unknown cause.

Four events in the bempedoic acid group and two events in the placebo group were cardiovascular deaths.

New or worsening diabetes developed in approximately 7% of each group, and less than 3% of those taking bempedoic acid developed gout or increased blood uric acid, as was the case for less than 1% of patients taking placebo.

In May, the Food and Drug Administration accepted a New Drug Application from Esperion for bempedoic acid. A response is expected in February 2020.

Dr. Goldberg reporter receiving research grants/support from Amgen, Amarin, Pfizer, Regeneron, Sanofi, IONIS, Novartis, and Merck and serving as a consultant for Esperion, Novartis, Akcea, OptumRX, 23andMe, Sanofi/Regeneron, and Merck.

[email protected]

SOURCE: Goldberg AC et al. JAMA. 2019 Nov 12;322:1780-8.

The rising cost of prescription drugs in the United States has prompted new recommendations by the American College of Physicians such as promoting the use of lower-cost generics and introducing annual out-of-pocket spending caps.

Darwin Brandis/Getty Images

Two position papers, published in Annals of Internal Medicine, outlined the College’s concerns about the increasing price of prescription drugs for Medicare and Medicaid, pointing out that the United States has an average annual per capita spend of $1,443 on pharmaceutical drugs and $1,026 on retail prescription drugs.

“The primary differences between health care expenditures in the United States versus other high-income nations are pricing of medical goods and services and the lack of direct price controls or negotiating power by centralized government health care systems,” wrote Hilary Daniel and Sue S. Bornstein, MD, of the Health Public Policy Committee of the American College of Physicians, in one of the papers.

They cited the example of new drugs for hepatitis C which, at more than $80,000 for a treatment course, accounted for 40% of the net growth in prescription drug spending in 2014.

Their first recommendation was to modify the Medicare Part D low-income subsidy (LIS) program, which currently supports approximately 12 million beneficiaries, to encourage the use of lower-cost generic or biosimilar drugs.

The rate of generic drug dispensing among LIS enrollees has been consistently 4%-5% lower than among non-LIS enrollees, they wrote. The Centers for Medicare & Medicaid Services estimated that Medicare could have saved nearly $9 billion, and passed on $3 billion in savings to the Part D program and its beneficiaries, if available equivalent generics were prescribed instead of brand-name drugs.

The authors wrote that zero-copay generics have had the strongest effect on generic drug use, both for LIS and non-LIS enrollees.

“Reducing or eliminating cost sharing for LIS enrollees would not require legislative action, because it would not increase cost sharing, would reduce overall out-of pocket costs for LIS enrollees, and would encourage use of generics among them,” they wrote. They authors of the paper also argued that this move could reduce Medicare spending on reinsurance payments, because most enrollees who reach the ‘catastrophic’ phase of coverage were in the LIS program.

The second recommendation was for annual out-of-pocket spending caps for Medicare Part D beneficiaries who reach the catastrophic phase of coverage. During 2007-2015, the number of seniors in Medicare Part D who reached this catastrophic limit of coverage doubled to more than 1 million, with those enrollees paying an average of more than $3,000 out of pocket in 2015 alone, the authors noted.

“Caps have been proposed in other areas of Medicare; a 2016 resolution from the House Committee on the Budget included a Medicare proposal with a catastrophic coverage cap on annual out-of-pocket expenses, which it called, ‘an important aspect of the private insurance market currently absent from Medicare that would safeguard the sickest and poorest beneficiaries,’ ” they wrote.

In an accompanying editorial, Shelley A. Jazowski of the University of North Carolina at Chapel Hill and coauthor Stacie B. Dusetzina, PhD, of Vanderbilt University, in Nashville, Tenn., said that, while a cap would improve financial protection for beneficiaries, it could result in trade-offs such as increased premiums to accommodate lower spending by some beneficiaries.

The American College of Physicians (ACP) supports a full repeal of the noninterference clause in the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, wrote the position paper’s authors. This Act prohibits Medicare from negotiating directly with pharmaceutical manufacturers over the price of drugs.

The position paper also advocated for interim approaches, such as allowing the Secretary of Health and Human Services to negotiate on the price of a limited set of high-cost or sole-source drugs.

“Although negotiation alone may not be enough to rein in drug prices, this approach would allow the government to leverage its purchasing power to reduce Medicare program costs while also allowing plan sponsors to maintain the power to negotiate for the vast majority of drugs covered in the program,” they wrote.

The editorial’s authors pointed out that the success of these negotiations would rely on the ability of Medicare to walk away from a bad deal, which could delay or limit the availability of some drugs with limited competitors.

The ACP also called for efforts to minimize the financial impact of misclassifications of prescription drugs in the Medicaid Drug Rebate Program on the federal government. One study found that these misclassifications occurred in 885 of the 30,000 drugs in the program. The EpiPen and EpiPen Jr autoinjectors, for example, were improperly classified as generic drugs, the paper states.

The authors’ final recommendation in the position paper was for further study of payment models that could reduce incentives to prescribe higher-priced drugs instead of lower-cost and similarly effective options.

In the second position paper, Ms. Daniel and Dr. Bornstein made policy recommendations targeted at pharmacy benefit managers. The first was to improve transparency for pharmacy benefit managers, such as by banning gag clauses that might prevent pharmacies from sharing pricing information with consumers.

“The continued lack of transparency from [pharmacy benefit managers] and insurers can hinder how patients, physicians, and others view the drug supply chain and can make it difficult to identify whether a particular entity is inappropriately driving up drug prices,” the authors wrote in the second position paper.

This was accompanied by a recommendation that accurate, understandable and actionable information on the price of prescription medication should be made available to physicians and patients at the point of prescription. They also called for health plans, pharmacy benefit managers and pharmaceutical manufacturers to share information on the amount paid for prescription drugs, aggregate amount of rebates, and pricing decisions to the Department of Health & Human Services and make that information publicly available, with exceptions for confidential data.

The editorial’s authors commented that many of the policy recommendations raised in the position paper were currently being debated in Congress, and there was clear support from physician groups to address drug pricing, out-of-pocket spending, and access.

“Although trade-offs will need to be considered before selection or implementation of policy solutions, policymakers must act to ensure that patients have access to the prescription drugs they need at a price that reflects the benefits to patients and society,” they wrote.

One author declared book royalties but no other conflicts of interest were declared.

SOURCES: Daniel H et al. Ann Intern Med. 2019 Nov 12. doi. 10.7326/M19-0013; doi. 10.7326/M19-0035.

The rising cost of prescription drugs in the United States has prompted new recommendations by the American College of Physicians such as promoting the use of lower-cost generics and introducing annual out-of-pocket spending caps.

Darwin Brandis/Getty Images

Two position papers, published in Annals of Internal Medicine, outlined the College’s concerns about the increasing price of prescription drugs for Medicare and Medicaid, pointing out that the United States has an average annual per capita spend of $1,443 on pharmaceutical drugs and $1,026 on retail prescription drugs.

“The primary differences between health care expenditures in the United States versus other high-income nations are pricing of medical goods and services and the lack of direct price controls or negotiating power by centralized government health care systems,” wrote Hilary Daniel and Sue S. Bornstein, MD, of the Health Public Policy Committee of the American College of Physicians, in one of the papers.

They cited the example of new drugs for hepatitis C which, at more than $80,000 for a treatment course, accounted for 40% of the net growth in prescription drug spending in 2014.

Their first recommendation was to modify the Medicare Part D low-income subsidy (LIS) program, which currently supports approximately 12 million beneficiaries, to encourage the use of lower-cost generic or biosimilar drugs.

The rate of generic drug dispensing among LIS enrollees has been consistently 4%-5% lower than among non-LIS enrollees, they wrote. The Centers for Medicare & Medicaid Services estimated that Medicare could have saved nearly $9 billion, and passed on $3 billion in savings to the Part D program and its beneficiaries, if available equivalent generics were prescribed instead of brand-name drugs.

The authors wrote that zero-copay generics have had the strongest effect on generic drug use, both for LIS and non-LIS enrollees.

“Reducing or eliminating cost sharing for LIS enrollees would not require legislative action, because it would not increase cost sharing, would reduce overall out-of pocket costs for LIS enrollees, and would encourage use of generics among them,” they wrote. They authors of the paper also argued that this move could reduce Medicare spending on reinsurance payments, because most enrollees who reach the ‘catastrophic’ phase of coverage were in the LIS program.

The second recommendation was for annual out-of-pocket spending caps for Medicare Part D beneficiaries who reach the catastrophic phase of coverage. During 2007-2015, the number of seniors in Medicare Part D who reached this catastrophic limit of coverage doubled to more than 1 million, with those enrollees paying an average of more than $3,000 out of pocket in 2015 alone, the authors noted.

“Caps have been proposed in other areas of Medicare; a 2016 resolution from the House Committee on the Budget included a Medicare proposal with a catastrophic coverage cap on annual out-of-pocket expenses, which it called, ‘an important aspect of the private insurance market currently absent from Medicare that would safeguard the sickest and poorest beneficiaries,’ ” they wrote.

In an accompanying editorial, Shelley A. Jazowski of the University of North Carolina at Chapel Hill and coauthor Stacie B. Dusetzina, PhD, of Vanderbilt University, in Nashville, Tenn., said that, while a cap would improve financial protection for beneficiaries, it could result in trade-offs such as increased premiums to accommodate lower spending by some beneficiaries.

The American College of Physicians (ACP) supports a full repeal of the noninterference clause in the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, wrote the position paper’s authors. This Act prohibits Medicare from negotiating directly with pharmaceutical manufacturers over the price of drugs.

The position paper also advocated for interim approaches, such as allowing the Secretary of Health and Human Services to negotiate on the price of a limited set of high-cost or sole-source drugs.

“Although negotiation alone may not be enough to rein in drug prices, this approach would allow the government to leverage its purchasing power to reduce Medicare program costs while also allowing plan sponsors to maintain the power to negotiate for the vast majority of drugs covered in the program,” they wrote.

The editorial’s authors pointed out that the success of these negotiations would rely on the ability of Medicare to walk away from a bad deal, which could delay or limit the availability of some drugs with limited competitors.

The ACP also called for efforts to minimize the financial impact of misclassifications of prescription drugs in the Medicaid Drug Rebate Program on the federal government. One study found that these misclassifications occurred in 885 of the 30,000 drugs in the program. The EpiPen and EpiPen Jr autoinjectors, for example, were improperly classified as generic drugs, the paper states.

The authors’ final recommendation in the position paper was for further study of payment models that could reduce incentives to prescribe higher-priced drugs instead of lower-cost and similarly effective options.

In the second position paper, Ms. Daniel and Dr. Bornstein made policy recommendations targeted at pharmacy benefit managers. The first was to improve transparency for pharmacy benefit managers, such as by banning gag clauses that might prevent pharmacies from sharing pricing information with consumers.

“The continued lack of transparency from [pharmacy benefit managers] and insurers can hinder how patients, physicians, and others view the drug supply chain and can make it difficult to identify whether a particular entity is inappropriately driving up drug prices,” the authors wrote in the second position paper.

This was accompanied by a recommendation that accurate, understandable and actionable information on the price of prescription medication should be made available to physicians and patients at the point of prescription. They also called for health plans, pharmacy benefit managers and pharmaceutical manufacturers to share information on the amount paid for prescription drugs, aggregate amount of rebates, and pricing decisions to the Department of Health & Human Services and make that information publicly available, with exceptions for confidential data.

The editorial’s authors commented that many of the policy recommendations raised in the position paper were currently being debated in Congress, and there was clear support from physician groups to address drug pricing, out-of-pocket spending, and access.

“Although trade-offs will need to be considered before selection or implementation of policy solutions, policymakers must act to ensure that patients have access to the prescription drugs they need at a price that reflects the benefits to patients and society,” they wrote.

One author declared book royalties but no other conflicts of interest were declared.

SOURCES: Daniel H et al. Ann Intern Med. 2019 Nov 12. doi. 10.7326/M19-0013; doi. 10.7326/M19-0035.

The rising cost of prescription drugs in the United States has prompted new recommendations by the American College of Physicians such as promoting the use of lower-cost generics and introducing annual out-of-pocket spending caps.

Darwin Brandis/Getty Images

Two position papers, published in Annals of Internal Medicine, outlined the College’s concerns about the increasing price of prescription drugs for Medicare and Medicaid, pointing out that the United States has an average annual per capita spend of $1,443 on pharmaceutical drugs and $1,026 on retail prescription drugs.

“The primary differences between health care expenditures in the United States versus other high-income nations are pricing of medical goods and services and the lack of direct price controls or negotiating power by centralized government health care systems,” wrote Hilary Daniel and Sue S. Bornstein, MD, of the Health Public Policy Committee of the American College of Physicians, in one of the papers.

They cited the example of new drugs for hepatitis C which, at more than $80,000 for a treatment course, accounted for 40% of the net growth in prescription drug spending in 2014.

Their first recommendation was to modify the Medicare Part D low-income subsidy (LIS) program, which currently supports approximately 12 million beneficiaries, to encourage the use of lower-cost generic or biosimilar drugs.

The rate of generic drug dispensing among LIS enrollees has been consistently 4%-5% lower than among non-LIS enrollees, they wrote. The Centers for Medicare & Medicaid Services estimated that Medicare could have saved nearly $9 billion, and passed on $3 billion in savings to the Part D program and its beneficiaries, if available equivalent generics were prescribed instead of brand-name drugs.

The authors wrote that zero-copay generics have had the strongest effect on generic drug use, both for LIS and non-LIS enrollees.

“Reducing or eliminating cost sharing for LIS enrollees would not require legislative action, because it would not increase cost sharing, would reduce overall out-of pocket costs for LIS enrollees, and would encourage use of generics among them,” they wrote. They authors of the paper also argued that this move could reduce Medicare spending on reinsurance payments, because most enrollees who reach the ‘catastrophic’ phase of coverage were in the LIS program.

The second recommendation was for annual out-of-pocket spending caps for Medicare Part D beneficiaries who reach the catastrophic phase of coverage. During 2007-2015, the number of seniors in Medicare Part D who reached this catastrophic limit of coverage doubled to more than 1 million, with those enrollees paying an average of more than $3,000 out of pocket in 2015 alone, the authors noted.

“Caps have been proposed in other areas of Medicare; a 2016 resolution from the House Committee on the Budget included a Medicare proposal with a catastrophic coverage cap on annual out-of-pocket expenses, which it called, ‘an important aspect of the private insurance market currently absent from Medicare that would safeguard the sickest and poorest beneficiaries,’ ” they wrote.

In an accompanying editorial, Shelley A. Jazowski of the University of North Carolina at Chapel Hill and coauthor Stacie B. Dusetzina, PhD, of Vanderbilt University, in Nashville, Tenn., said that, while a cap would improve financial protection for beneficiaries, it could result in trade-offs such as increased premiums to accommodate lower spending by some beneficiaries.

The American College of Physicians (ACP) supports a full repeal of the noninterference clause in the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, wrote the position paper’s authors. This Act prohibits Medicare from negotiating directly with pharmaceutical manufacturers over the price of drugs.

The position paper also advocated for interim approaches, such as allowing the Secretary of Health and Human Services to negotiate on the price of a limited set of high-cost or sole-source drugs.

“Although negotiation alone may not be enough to rein in drug prices, this approach would allow the government to leverage its purchasing power to reduce Medicare program costs while also allowing plan sponsors to maintain the power to negotiate for the vast majority of drugs covered in the program,” they wrote.

The editorial’s authors pointed out that the success of these negotiations would rely on the ability of Medicare to walk away from a bad deal, which could delay or limit the availability of some drugs with limited competitors.

The ACP also called for efforts to minimize the financial impact of misclassifications of prescription drugs in the Medicaid Drug Rebate Program on the federal government. One study found that these misclassifications occurred in 885 of the 30,000 drugs in the program. The EpiPen and EpiPen Jr autoinjectors, for example, were improperly classified as generic drugs, the paper states.

The authors’ final recommendation in the position paper was for further study of payment models that could reduce incentives to prescribe higher-priced drugs instead of lower-cost and similarly effective options.

In the second position paper, Ms. Daniel and Dr. Bornstein made policy recommendations targeted at pharmacy benefit managers. The first was to improve transparency for pharmacy benefit managers, such as by banning gag clauses that might prevent pharmacies from sharing pricing information with consumers.

“The continued lack of transparency from [pharmacy benefit managers] and insurers can hinder how patients, physicians, and others view the drug supply chain and can make it difficult to identify whether a particular entity is inappropriately driving up drug prices,” the authors wrote in the second position paper.

This was accompanied by a recommendation that accurate, understandable and actionable information on the price of prescription medication should be made available to physicians and patients at the point of prescription. They also called for health plans, pharmacy benefit managers and pharmaceutical manufacturers to share information on the amount paid for prescription drugs, aggregate amount of rebates, and pricing decisions to the Department of Health & Human Services and make that information publicly available, with exceptions for confidential data.

The editorial’s authors commented that many of the policy recommendations raised in the position paper were currently being debated in Congress, and there was clear support from physician groups to address drug pricing, out-of-pocket spending, and access.

“Although trade-offs will need to be considered before selection or implementation of policy solutions, policymakers must act to ensure that patients have access to the prescription drugs they need at a price that reflects the benefits to patients and society,” they wrote.

One author declared book royalties but no other conflicts of interest were declared.

SOURCES: Daniel H et al. Ann Intern Med. 2019 Nov 12. doi. 10.7326/M19-0013; doi. 10.7326/M19-0035.

SAN FRANCISCO – Volume matters when it comes to mitral valve repair/replacement for primary mitral regurgitation. The more cases a physician and hospital do, the better the outcomes, according to a review of 55,311 cases in the Society of Thoracic Surgeons Adult Cardiac Surgery Database.

Investigators “found a clear inflection point at approximately 75 cases” for hospitals and 35 cases for individual surgeons when the curves for successful mitral repair and 30-day operative mortality start to level out. Nationwide, 148 hospitals (14%) in the analysis did 75 or more mitral cases a year, and 303 surgeons (13%) did at least 35.

Lead investigator Vinay Badhwar, MD, professor and chair of cardiovascular and thoracic surgery at West Virginia University, Morgantown, estimated that about 90% of Americans have access to a regional hospital that does at least 25 mitral procedures annually, and about 82% can use a regional hospital that does at least 40. Meanwhile, the rate of mitral valve repair for primary mitral regurgitation was 81% (44,692/55,311) in the study, up from about 60% a decade ago.

“We are getting there; we are getting better,” Dr. Badhwar said at the Transcatheter Cardiovascular Therapeutics annual meeting. By defining volume cut points, he said the findings could be useful in future guidelines to steer referrals to higher-volume centers.

“We really needed these data, because we’ve had so many other pieces pointing to the volume repair rates and technical success, which clearly is related to volume. Now we have the outcome data we’ve been looking for; this ties it together. There really is an impact on patient outcomes,” Robert Bonow, MD, a professor of cardiology at Northwestern University, Chicago, commented.

The team divided annual case volume into quartiles. The lowest hospital quartile did fewer than 11 cases a year, and the highest more than 46. The lowest-quartile surgeons did fewer than 6 cases a year, and the highest more than 20. Lowest-quartile surgeons and hospitals, versus the highest, had higher operative mortality and 30-day morbidity and mortality, and lower 1-year survival.

Patients in the lowest quartile were also more likely to be black or Hispanic (14.8% versus 10.2%); have no insurance (4.0% versus 2.4%); and more severe symptom presentation (31.9% versus 23.8% class III or IV heart failure). The differences were highly statistically significant.

Study moderator Ajay Kirtane, MD, an interventional cardiologist and associate professor of medicine at Columbia University, New York, said there’s a role for advocacy to get more people to high-volume centers. “Just because you live in an area that has a good program doesn’t mean that you are actually going to get referred to that program. We find a lot that it’s advocacy that is important,” especially with the disparities noted in the study. “Not everybody has an advocate who says, ‘Don’t do it here; do it someplace else,’ ” he said at the meeting sponsored by the Cardiovascular Research Foundation.

And not everyone has an advocate to get them to the right surgeon, even if they get to the right program. “There are cardiac procedures that most surgeons can do well. Mitral valve surgery is one of those that should be super specialized,” said cardiothoracic surgeon Michael Mack, MD, director of the cardiovascular service line at Baylor Scott and White Health System, Dallas.

No industry funding was reported. Dr. Badhwar had no relevant disclosures.

[email protected]

SOURCE: Badhwar V et al. TCT 2019.

SAN FRANCISCO – Volume matters when it comes to mitral valve repair/replacement for primary mitral regurgitation. The more cases a physician and hospital do, the better the outcomes, according to a review of 55,311 cases in the Society of Thoracic Surgeons Adult Cardiac Surgery Database.

Investigators “found a clear inflection point at approximately 75 cases” for hospitals and 35 cases for individual surgeons when the curves for successful mitral repair and 30-day operative mortality start to level out. Nationwide, 148 hospitals (14%) in the analysis did 75 or more mitral cases a year, and 303 surgeons (13%) did at least 35.

Lead investigator Vinay Badhwar, MD, professor and chair of cardiovascular and thoracic surgery at West Virginia University, Morgantown, estimated that about 90% of Americans have access to a regional hospital that does at least 25 mitral procedures annually, and about 82% can use a regional hospital that does at least 40. Meanwhile, the rate of mitral valve repair for primary mitral regurgitation was 81% (44,692/55,311) in the study, up from about 60% a decade ago.

“We are getting there; we are getting better,” Dr. Badhwar said at the Transcatheter Cardiovascular Therapeutics annual meeting. By defining volume cut points, he said the findings could be useful in future guidelines to steer referrals to higher-volume centers.

“We really needed these data, because we’ve had so many other pieces pointing to the volume repair rates and technical success, which clearly is related to volume. Now we have the outcome data we’ve been looking for; this ties it together. There really is an impact on patient outcomes,” Robert Bonow, MD, a professor of cardiology at Northwestern University, Chicago, commented.

The team divided annual case volume into quartiles. The lowest hospital quartile did fewer than 11 cases a year, and the highest more than 46. The lowest-quartile surgeons did fewer than 6 cases a year, and the highest more than 20. Lowest-quartile surgeons and hospitals, versus the highest, had higher operative mortality and 30-day morbidity and mortality, and lower 1-year survival.

Patients in the lowest quartile were also more likely to be black or Hispanic (14.8% versus 10.2%); have no insurance (4.0% versus 2.4%); and more severe symptom presentation (31.9% versus 23.8% class III or IV heart failure). The differences were highly statistically significant.

Study moderator Ajay Kirtane, MD, an interventional cardiologist and associate professor of medicine at Columbia University, New York, said there’s a role for advocacy to get more people to high-volume centers. “Just because you live in an area that has a good program doesn’t mean that you are actually going to get referred to that program. We find a lot that it’s advocacy that is important,” especially with the disparities noted in the study. “Not everybody has an advocate who says, ‘Don’t do it here; do it someplace else,’ ” he said at the meeting sponsored by the Cardiovascular Research Foundation.

And not everyone has an advocate to get them to the right surgeon, even if they get to the right program. “There are cardiac procedures that most surgeons can do well. Mitral valve surgery is one of those that should be super specialized,” said cardiothoracic surgeon Michael Mack, MD, director of the cardiovascular service line at Baylor Scott and White Health System, Dallas.

No industry funding was reported. Dr. Badhwar had no relevant disclosures.

[email protected]

SOURCE: Badhwar V et al. TCT 2019.

SAN FRANCISCO – Volume matters when it comes to mitral valve repair/replacement for primary mitral regurgitation. The more cases a physician and hospital do, the better the outcomes, according to a review of 55,311 cases in the Society of Thoracic Surgeons Adult Cardiac Surgery Database.

Investigators “found a clear inflection point at approximately 75 cases” for hospitals and 35 cases for individual surgeons when the curves for successful mitral repair and 30-day operative mortality start to level out. Nationwide, 148 hospitals (14%) in the analysis did 75 or more mitral cases a year, and 303 surgeons (13%) did at least 35.

Lead investigator Vinay Badhwar, MD, professor and chair of cardiovascular and thoracic surgery at West Virginia University, Morgantown, estimated that about 90% of Americans have access to a regional hospital that does at least 25 mitral procedures annually, and about 82% can use a regional hospital that does at least 40. Meanwhile, the rate of mitral valve repair for primary mitral regurgitation was 81% (44,692/55,311) in the study, up from about 60% a decade ago.

“We are getting there; we are getting better,” Dr. Badhwar said at the Transcatheter Cardiovascular Therapeutics annual meeting. By defining volume cut points, he said the findings could be useful in future guidelines to steer referrals to higher-volume centers.

“We really needed these data, because we’ve had so many other pieces pointing to the volume repair rates and technical success, which clearly is related to volume. Now we have the outcome data we’ve been looking for; this ties it together. There really is an impact on patient outcomes,” Robert Bonow, MD, a professor of cardiology at Northwestern University, Chicago, commented.

The team divided annual case volume into quartiles. The lowest hospital quartile did fewer than 11 cases a year, and the highest more than 46. The lowest-quartile surgeons did fewer than 6 cases a year, and the highest more than 20. Lowest-quartile surgeons and hospitals, versus the highest, had higher operative mortality and 30-day morbidity and mortality, and lower 1-year survival.

Patients in the lowest quartile were also more likely to be black or Hispanic (14.8% versus 10.2%); have no insurance (4.0% versus 2.4%); and more severe symptom presentation (31.9% versus 23.8% class III or IV heart failure). The differences were highly statistically significant.

Study moderator Ajay Kirtane, MD, an interventional cardiologist and associate professor of medicine at Columbia University, New York, said there’s a role for advocacy to get more people to high-volume centers. “Just because you live in an area that has a good program doesn’t mean that you are actually going to get referred to that program. We find a lot that it’s advocacy that is important,” especially with the disparities noted in the study. “Not everybody has an advocate who says, ‘Don’t do it here; do it someplace else,’ ” he said at the meeting sponsored by the Cardiovascular Research Foundation.

And not everyone has an advocate to get them to the right surgeon, even if they get to the right program. “There are cardiac procedures that most surgeons can do well. Mitral valve surgery is one of those that should be super specialized,” said cardiothoracic surgeon Michael Mack, MD, director of the cardiovascular service line at Baylor Scott and White Health System, Dallas.

No industry funding was reported. Dr. Badhwar had no relevant disclosures.

[email protected]

SOURCE: Badhwar V et al. TCT 2019.

PHILADELPHIA – Women who underwent either hysterectomy or myomectomy had similar short-term outcomes between 6 weeks and 12 weeks after surgery despite different baseline characteristics, according to recent results from the COMPARE-UF study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

“Both hysterectomy and myomectomy can substantially improve women’s quality of life scores and substantially reduce symptom severity,” reported Wanda K. Nicholson, MD, MPH, lead investigator for COMPARE-UF and professor of general obstetrics and gynecology at the University of North Carolina at Chapel Hill.

Researchers included 1,295 women in the COMPARE-UF study who were at least 30 years old, not attempting pregnancy, and undergoing hysterectomy or myomectomy for treatment of fibroids. Overall, 727 patients underwent hysterectomy, and 568 patients underwent myomectomy.

The researchers measured QoL and symptom severity using the Uterine Fibroid Scale-QoL, the EQ-5D, and Visual Analog Scale (VAS). The UFS-QoL contained subscales for concern, activities, energy and mood, control, self-consciousness, and sexual function, while the EQ-5D had subscales for mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.

After surgery, UFS-QoL overall scores were similar in both hysterectomy and myomectomy groups between 6 weeks and 12 weeks (77 vs. 76), but there was less postsurgery symptom severity in the hysterectomy group over the same time period (16 vs. 20; P less than .05). However, both groups had a significant improvement in overall UFS-QoL post surgery (hysterectomy, 31; myomectomy, 30) and in UFS-QoL symptom severity (hysterectomy, 41; myomectomy, 37), Dr. Nicholson noted. EQ-5D VAS scores also were similar in both hysterectomy and myomectomy groups after treatment (82 vs. 79), and showed a 10.9 score improvement in hysterectomy patients and an 8.6 score improvement in myomectomy patients.

“This is really important, because it shows that, regardless of which procedure that you’ve chosen, at least at short-term follow up, it appears that you will have improvement in quality of life,” she said.

When researchers analyzed the UFS-QoL subscale scores, they found patients who underwent abdominal myomectomy scored better than abdominal hysterectomy on the activities subscale (79 vs. 72; P equals .01) and energy/mood subscale (82 vs. 75; P equals .03). In examining minimally invasive procedures, Dr. Nicholson and colleagues found higher improvements in health-related QoL scores among patients undergoing minimally invasive hysterectomy (45-80 vs. 45 vs. 75), and these patients also had lower symptom severity, compared with patients who underwent myomectomy (59-13 vs. 58-21).

“At least at the short-term follow-up, we think that some of that difference that we see in minimally invasive procedures vs. nonminimally invasive may be in part due to women’s perceptions or what their expectations are having minimally invasive surgery, and how they might feel in the short-term follow-up period,” said Dr. Nicholson.

These similar short-term outcomes occurred even though there were significant differences in baseline patient characteristics for the hysterectomy and myomectomy groups, with women undergoing hysterectomy being significantly younger (40 years) than patients undergoing hysterectomy (45 years). Differences also were significant between hysterectomy and myomectomy groups in the percentage of patients who were white (50% vs. 41%; P less than .01), African-American (38% vs. 41%; P less than .01) or other races (12% vs. 18%; P less than .01). There also were significant differences in baseline body mass index between hysterectomy (31 kg/m²) and myomectomy (29 kg/m²) groups.

Patients in both groups further differed in presurgery quality-of-life (QoL) scores.

Women in the hysterectomy group had lower presurgery overall QoL (44 vs. 50), greater symptom severity (60 vs. 52), and lower VAS (69 vs. 73) scores, compared with the myomectomy group (P less than .05). This difference continued in the UFS-QoL subscale scores, where women in the hysterectomy group had significantly lower scores in the concern (38 vs. 45), activities (46 vs. 52), energy/mood (45 vs. 51), control (48 vs. 52), self-consciousness (41 vs. 50), and sexual function (45 vs. 50) subscales, compared with women in the myomectomy group (P less than .05). The researchers used propensity scoring to adjust for baseline characteristics, and inverse propensity weighting to adjust for potential confounding in the multivariate analysis.

COMPARE-UF is funded by the Agency for Healthcare Research and Quality (AHRQ), Patient-Centered Outcomes Research Institute (PCORI), and the National Institutes of Health. Dr. Nicholson reported no relevant conflicts of interest.

SOURCE: Nicholson WK et al. ASRM 2019, Abstract SYT07.

PHILADELPHIA – Women who underwent either hysterectomy or myomectomy had similar short-term outcomes between 6 weeks and 12 weeks after surgery despite different baseline characteristics, according to recent results from the COMPARE-UF study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

“Both hysterectomy and myomectomy can substantially improve women’s quality of life scores and substantially reduce symptom severity,” reported Wanda K. Nicholson, MD, MPH, lead investigator for COMPARE-UF and professor of general obstetrics and gynecology at the University of North Carolina at Chapel Hill.

Researchers included 1,295 women in the COMPARE-UF study who were at least 30 years old, not attempting pregnancy, and undergoing hysterectomy or myomectomy for treatment of fibroids. Overall, 727 patients underwent hysterectomy, and 568 patients underwent myomectomy.

The researchers measured QoL and symptom severity using the Uterine Fibroid Scale-QoL, the EQ-5D, and Visual Analog Scale (VAS). The UFS-QoL contained subscales for concern, activities, energy and mood, control, self-consciousness, and sexual function, while the EQ-5D had subscales for mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.

After surgery, UFS-QoL overall scores were similar in both hysterectomy and myomectomy groups between 6 weeks and 12 weeks (77 vs. 76), but there was less postsurgery symptom severity in the hysterectomy group over the same time period (16 vs. 20; P less than .05). However, both groups had a significant improvement in overall UFS-QoL post surgery (hysterectomy, 31; myomectomy, 30) and in UFS-QoL symptom severity (hysterectomy, 41; myomectomy, 37), Dr. Nicholson noted. EQ-5D VAS scores also were similar in both hysterectomy and myomectomy groups after treatment (82 vs. 79), and showed a 10.9 score improvement in hysterectomy patients and an 8.6 score improvement in myomectomy patients.

“This is really important, because it shows that, regardless of which procedure that you’ve chosen, at least at short-term follow up, it appears that you will have improvement in quality of life,” she said.

When researchers analyzed the UFS-QoL subscale scores, they found patients who underwent abdominal myomectomy scored better than abdominal hysterectomy on the activities subscale (79 vs. 72; P equals .01) and energy/mood subscale (82 vs. 75; P equals .03). In examining minimally invasive procedures, Dr. Nicholson and colleagues found higher improvements in health-related QoL scores among patients undergoing minimally invasive hysterectomy (45-80 vs. 45 vs. 75), and these patients also had lower symptom severity, compared with patients who underwent myomectomy (59-13 vs. 58-21).

“At least at the short-term follow-up, we think that some of that difference that we see in minimally invasive procedures vs. nonminimally invasive may be in part due to women’s perceptions or what their expectations are having minimally invasive surgery, and how they might feel in the short-term follow-up period,” said Dr. Nicholson.

These similar short-term outcomes occurred even though there were significant differences in baseline patient characteristics for the hysterectomy and myomectomy groups, with women undergoing hysterectomy being significantly younger (40 years) than patients undergoing hysterectomy (45 years). Differences also were significant between hysterectomy and myomectomy groups in the percentage of patients who were white (50% vs. 41%; P less than .01), African-American (38% vs. 41%; P less than .01) or other races (12% vs. 18%; P less than .01). There also were significant differences in baseline body mass index between hysterectomy (31 kg/m²) and myomectomy (29 kg/m²) groups.

Patients in both groups further differed in presurgery quality-of-life (QoL) scores.

Women in the hysterectomy group had lower presurgery overall QoL (44 vs. 50), greater symptom severity (60 vs. 52), and lower VAS (69 vs. 73) scores, compared with the myomectomy group (P less than .05). This difference continued in the UFS-QoL subscale scores, where women in the hysterectomy group had significantly lower scores in the concern (38 vs. 45), activities (46 vs. 52), energy/mood (45 vs. 51), control (48 vs. 52), self-consciousness (41 vs. 50), and sexual function (45 vs. 50) subscales, compared with women in the myomectomy group (P less than .05). The researchers used propensity scoring to adjust for baseline characteristics, and inverse propensity weighting to adjust for potential confounding in the multivariate analysis.

COMPARE-UF is funded by the Agency for Healthcare Research and Quality (AHRQ), Patient-Centered Outcomes Research Institute (PCORI), and the National Institutes of Health. Dr. Nicholson reported no relevant conflicts of interest.

SOURCE: Nicholson WK et al. ASRM 2019, Abstract SYT07.

PHILADELPHIA – Women who underwent either hysterectomy or myomectomy had similar short-term outcomes between 6 weeks and 12 weeks after surgery despite different baseline characteristics, according to recent results from the COMPARE-UF study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

“Both hysterectomy and myomectomy can substantially improve women’s quality of life scores and substantially reduce symptom severity,” reported Wanda K. Nicholson, MD, MPH, lead investigator for COMPARE-UF and professor of general obstetrics and gynecology at the University of North Carolina at Chapel Hill.

Researchers included 1,295 women in the COMPARE-UF study who were at least 30 years old, not attempting pregnancy, and undergoing hysterectomy or myomectomy for treatment of fibroids. Overall, 727 patients underwent hysterectomy, and 568 patients underwent myomectomy.

The researchers measured QoL and symptom severity using the Uterine Fibroid Scale-QoL, the EQ-5D, and Visual Analog Scale (VAS). The UFS-QoL contained subscales for concern, activities, energy and mood, control, self-consciousness, and sexual function, while the EQ-5D had subscales for mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.

After surgery, UFS-QoL overall scores were similar in both hysterectomy and myomectomy groups between 6 weeks and 12 weeks (77 vs. 76), but there was less postsurgery symptom severity in the hysterectomy group over the same time period (16 vs. 20; P less than .05). However, both groups had a significant improvement in overall UFS-QoL post surgery (hysterectomy, 31; myomectomy, 30) and in UFS-QoL symptom severity (hysterectomy, 41; myomectomy, 37), Dr. Nicholson noted. EQ-5D VAS scores also were similar in both hysterectomy and myomectomy groups after treatment (82 vs. 79), and showed a 10.9 score improvement in hysterectomy patients and an 8.6 score improvement in myomectomy patients.

“This is really important, because it shows that, regardless of which procedure that you’ve chosen, at least at short-term follow up, it appears that you will have improvement in quality of life,” she said.

When researchers analyzed the UFS-QoL subscale scores, they found patients who underwent abdominal myomectomy scored better than abdominal hysterectomy on the activities subscale (79 vs. 72; P equals .01) and energy/mood subscale (82 vs. 75; P equals .03). In examining minimally invasive procedures, Dr. Nicholson and colleagues found higher improvements in health-related QoL scores among patients undergoing minimally invasive hysterectomy (45-80 vs. 45 vs. 75), and these patients also had lower symptom severity, compared with patients who underwent myomectomy (59-13 vs. 58-21).

“At least at the short-term follow-up, we think that some of that difference that we see in minimally invasive procedures vs. nonminimally invasive may be in part due to women’s perceptions or what their expectations are having minimally invasive surgery, and how they might feel in the short-term follow-up period,” said Dr. Nicholson.

These similar short-term outcomes occurred even though there were significant differences in baseline patient characteristics for the hysterectomy and myomectomy groups, with women undergoing hysterectomy being significantly younger (40 years) than patients undergoing hysterectomy (45 years). Differences also were significant between hysterectomy and myomectomy groups in the percentage of patients who were white (50% vs. 41%; P less than .01), African-American (38% vs. 41%; P less than .01) or other races (12% vs. 18%; P less than .01). There also were significant differences in baseline body mass index between hysterectomy (31 kg/m²) and myomectomy (29 kg/m²) groups.

Patients in both groups further differed in presurgery quality-of-life (QoL) scores.

Women in the hysterectomy group had lower presurgery overall QoL (44 vs. 50), greater symptom severity (60 vs. 52), and lower VAS (69 vs. 73) scores, compared with the myomectomy group (P less than .05). This difference continued in the UFS-QoL subscale scores, where women in the hysterectomy group had significantly lower scores in the concern (38 vs. 45), activities (46 vs. 52), energy/mood (45 vs. 51), control (48 vs. 52), self-consciousness (41 vs. 50), and sexual function (45 vs. 50) subscales, compared with women in the myomectomy group (P less than .05). The researchers used propensity scoring to adjust for baseline characteristics, and inverse propensity weighting to adjust for potential confounding in the multivariate analysis.

COMPARE-UF is funded by the Agency for Healthcare Research and Quality (AHRQ), Patient-Centered Outcomes Research Institute (PCORI), and the National Institutes of Health. Dr. Nicholson reported no relevant conflicts of interest.

SOURCE: Nicholson WK et al. ASRM 2019, Abstract SYT07.

SAN ANTONIO – The first new treatment for Helicobacter pylori infection to receive Food and Drug Administration approval in 22 years performed so well in a pivotal phase 3 trial that it is worthy of consideration as best-in-class first-line therapy, David Y. Graham, MD, asserted at the annual meeting of the American College of Gastroenterology.

The drug, recently approved as Talicia, is a rifabutin-based triple therapy. Each capsule contains 50 mg of rifabutin, 1,000 mg of amoxicillin, and 40 mg of omeprazole. As in the pivotal phase 3 trial led by Dr. Graham, the approved treatment regimen calls for adults to take four capsules every 8 hours for 14 days.

The impetus for developing the new therapy centers on the growing problem of resistance to long-standard agents for H. pylori eradication, including metronidazole and clarithromycin. The World Health Organization has declared H. pylori eradication to be a high priority for therapeutic development. Rifabutin resistance is rare: In one study, 413 of 414 strains of H. pylori were sensitive to the antibiotic, noted Dr. Graham, professor of medicine at Baylor College of Medicine, Houston.

He presented the results of the pivotal phase 3, double-blind, multicenter, active comparator trial, known as ERADICATE Hp2, in which 455 participants with confirmed H. pylori infection were randomized to a course of the all-in-one-capsule triple drug combo or to dual therapy with four capsules, each containing 1,000 mg of amoxicillin and 40 mg of omeprazole, every 8 hours for 14 days.

The primary endpoint was H. pylori eradication as documented by a negative urea breath test obtained 4-6 weeks after completing 14 days of treatment. The rate was 84% with the rifabutin-based combo, compared with 58% seen with the high-dose dual therapy. Moreover, in a prespecified secondary analysis restricted to the 391 participants who were confirmed to be actually taking their medication as evidenced by a positive blood level measured on day 13, the eradication rates rose to 90% and 65%, respectively.

The antimicrobial resistance rates documented in this study were eye opening: 17% of patients’ strains were resistant to clarithromycin, 44% to metronidazole, and 10.5% to both. Of concern, 6.4% of participants’ strains were amoxicillin resistant.

“For the first time we saw a low level – but a definite level – of amoxicillin resistance. That’s something we had not seen previously,” Dr. Graham said.

No rifabutin resistance was detected before or after treatment.

The side effect profiles of the two treatment regimens were similar. Diarrhea was reported by 9% of participants, headache by 7%, and nausea by 5%. No serious adverse events occurred in the 14-day study.

The efficacy of the rifabutin-based therapy wasn’t affected by metronidazole or clarithromycin resistance.

The ERADICATE Hp2 trial was sponsored by RedHill Biopharma of Tel Aviv. Dr. Graham reported having no financial conflicts.

[email protected]

SAN ANTONIO – The first new treatment for Helicobacter pylori infection to receive Food and Drug Administration approval in 22 years performed so well in a pivotal phase 3 trial that it is worthy of consideration as best-in-class first-line therapy, David Y. Graham, MD, asserted at the annual meeting of the American College of Gastroenterology.

The drug, recently approved as Talicia, is a rifabutin-based triple therapy. Each capsule contains 50 mg of rifabutin, 1,000 mg of amoxicillin, and 40 mg of omeprazole. As in the pivotal phase 3 trial led by Dr. Graham, the approved treatment regimen calls for adults to take four capsules every 8 hours for 14 days.

The impetus for developing the new therapy centers on the growing problem of resistance to long-standard agents for H. pylori eradication, including metronidazole and clarithromycin. The World Health Organization has declared H. pylori eradication to be a high priority for therapeutic development. Rifabutin resistance is rare: In one study, 413 of 414 strains of H. pylori were sensitive to the antibiotic, noted Dr. Graham, professor of medicine at Baylor College of Medicine, Houston.

He presented the results of the pivotal phase 3, double-blind, multicenter, active comparator trial, known as ERADICATE Hp2, in which 455 participants with confirmed H. pylori infection were randomized to a course of the all-in-one-capsule triple drug combo or to dual therapy with four capsules, each containing 1,000 mg of amoxicillin and 40 mg of omeprazole, every 8 hours for 14 days.

The primary endpoint was H. pylori eradication as documented by a negative urea breath test obtained 4-6 weeks after completing 14 days of treatment. The rate was 84% with the rifabutin-based combo, compared with 58% seen with the high-dose dual therapy. Moreover, in a prespecified secondary analysis restricted to the 391 participants who were confirmed to be actually taking their medication as evidenced by a positive blood level measured on day 13, the eradication rates rose to 90% and 65%, respectively.

The antimicrobial resistance rates documented in this study were eye opening: 17% of patients’ strains were resistant to clarithromycin, 44% to metronidazole, and 10.5% to both. Of concern, 6.4% of participants’ strains were amoxicillin resistant.

“For the first time we saw a low level – but a definite level – of amoxicillin resistance. That’s something we had not seen previously,” Dr. Graham said.

No rifabutin resistance was detected before or after treatment.

The side effect profiles of the two treatment regimens were similar. Diarrhea was reported by 9% of participants, headache by 7%, and nausea by 5%. No serious adverse events occurred in the 14-day study.

The efficacy of the rifabutin-based therapy wasn’t affected by metronidazole or clarithromycin resistance.

The ERADICATE Hp2 trial was sponsored by RedHill Biopharma of Tel Aviv. Dr. Graham reported having no financial conflicts.

[email protected]

SAN ANTONIO – The first new treatment for Helicobacter pylori infection to receive Food and Drug Administration approval in 22 years performed so well in a pivotal phase 3 trial that it is worthy of consideration as best-in-class first-line therapy, David Y. Graham, MD, asserted at the annual meeting of the American College of Gastroenterology.

The drug, recently approved as Talicia, is a rifabutin-based triple therapy. Each capsule contains 50 mg of rifabutin, 1,000 mg of amoxicillin, and 40 mg of omeprazole. As in the pivotal phase 3 trial led by Dr. Graham, the approved treatment regimen calls for adults to take four capsules every 8 hours for 14 days.

The impetus for developing the new therapy centers on the growing problem of resistance to long-standard agents for H. pylori eradication, including metronidazole and clarithromycin. The World Health Organization has declared H. pylori eradication to be a high priority for therapeutic development. Rifabutin resistance is rare: In one study, 413 of 414 strains of H. pylori were sensitive to the antibiotic, noted Dr. Graham, professor of medicine at Baylor College of Medicine, Houston.

He presented the results of the pivotal phase 3, double-blind, multicenter, active comparator trial, known as ERADICATE Hp2, in which 455 participants with confirmed H. pylori infection were randomized to a course of the all-in-one-capsule triple drug combo or to dual therapy with four capsules, each containing 1,000 mg of amoxicillin and 40 mg of omeprazole, every 8 hours for 14 days.

The primary endpoint was H. pylori eradication as documented by a negative urea breath test obtained 4-6 weeks after completing 14 days of treatment. The rate was 84% with the rifabutin-based combo, compared with 58% seen with the high-dose dual therapy. Moreover, in a prespecified secondary analysis restricted to the 391 participants who were confirmed to be actually taking their medication as evidenced by a positive blood level measured on day 13, the eradication rates rose to 90% and 65%, respectively.

The antimicrobial resistance rates documented in this study were eye opening: 17% of patients’ strains were resistant to clarithromycin, 44% to metronidazole, and 10.5% to both. Of concern, 6.4% of participants’ strains were amoxicillin resistant.

“For the first time we saw a low level – but a definite level – of amoxicillin resistance. That’s something we had not seen previously,” Dr. Graham said.

No rifabutin resistance was detected before or after treatment.

The side effect profiles of the two treatment regimens were similar. Diarrhea was reported by 9% of participants, headache by 7%, and nausea by 5%. No serious adverse events occurred in the 14-day study.

The efficacy of the rifabutin-based therapy wasn’t affected by metronidazole or clarithromycin resistance.

The ERADICATE Hp2 trial was sponsored by RedHill Biopharma of Tel Aviv. Dr. Graham reported having no financial conflicts.

[email protected]

He’s not quite dead yet!

sdominick/iStock/Getty Images Plus

In 2015, Benjamin Schreiber, an Iowa man convicted of murder and sentenced to life in prison without parole, developed a case of septic poisoning because of large, untreated kidney stones. While at the hospital, his heart stopped several times, requiring resuscitation. After being stabilized, he underwent surgery to remove the kidney stones and was then released back to his prison cell.

Fast forward to 2018. Mr. Schreiber filed for relief from his conviction, arguing that, because he technically died, his life sentence had been served and he should be released. While the logic is impeccable, an Iowa district court didn’t buy it, noting that the fact that Mr. Schreiber was able to submit a petition for his release “confirms the petitioner’s current status as living.”

Sadly for Mr. Schreiber, the Iowa Court of Appeals agreed with the lower court’s decision. In a wonderfully pithy summation of the case, Judge Amanda Potterfield wrote: “Schreiber is either still alive, in which case he must remain in prison, or he is actually dead, in which case this appeal is moot.”

While the Livin’ on the MDedge team is glad that a convicted murderer will not be released back into the public, we salute his devotion to the art of technicality. The judges may not have been convinced, but you’re dead to us, Mr. Schreiber.
 

Breaking news: Drug companies gouge consumers

BrianAJackson/iStock/Getty Images Plus

Canada. It’s home to many things: Trees, glaciers, beavers, and several people. But we Americans also know it as the home of cheap drugs. It may be borderline illegal, but that’s never stopped America from taking things that don’t belong to us before.

You’d think then that it’d be great being sick in Canada. But it turns out that many of those poor, desperate souls living in the frozen tundra of the north are actually overpaying for drugs just like the rest of us, according to research published in the Canadian Medical Association Journal.

It all comes down to those strange items called drug discount cards. They’re coupons offered by brand-name drug manufacturers to keep patients from switching to cheap generics.

Sounds great, right? Well, while a few patients saw savings, the average cost to patients with public insurance increased by 1.3% over generics. And if you were unfortunate enough to have private insurance, you’d be paying 46% more using the cards rather than generics. In some instances, patients were paying a whole $10 more for a prescription of the name brand, compared with the generic. And we thought Tim Hortons was our northern neighbor’s only company making a lot of dough. Ten loonies more per Rx ain’t Timbits.

So, Canada, how does it feel to have your health care made fun of? U-S-A! U-S-A! Now, if you’ll excuse us, we’re off to pay $1,000 a pill to cure us some hepatitis C. That’s some real red-blooded American price gouging right there.
 

This looks like a job for vacuum science

urbazon/E+

The LOTME staff, of course, scans a veritable buffet of sources to come up with the tasty tidbits we present each week to our deliciously wonderful and highly scrumptious readers each week.

One of our favorite sauces … umm, we mean sources, and the home of a tantalizing medical morsel (can you tell it’s almost lunch time?), is the Journal of Vacuum Science and Technology B. That’s B, not A. Anyone, at least anyone who’s serious about vacuum science, will tell you that the Journal of Vacuum Science and Technology A is pretty much a bottomless pit of trolling, political bickering, and popular nonsense. But B, now that’s a different story.

B is where we meet the EStAD (electrostatic and air driven) device. EStAD is a portable device that may someday offer physicians and first responders a way to treat wounds in rural areas where immediate care may not be available, the investigators said.

EStAD, using a process called electrospinning along with a confined electric field, works like a can of spray paint to deposit a fiber mat, which could be a bandage or a drug, onto a wound.

The device is still under development, but the research team reports that it has been successfully tested on a porcine skin incision and a gloved human hand.

The next step in EStAD development is to bring it to Washington, where the investigators will see if spray-on bandages can stand up to the hot air coming out of politicians’ mouths. We’re hoping that they sell tickets.

He’s not quite dead yet!

sdominick/iStock/Getty Images Plus

In 2015, Benjamin Schreiber, an Iowa man convicted of murder and sentenced to life in prison without parole, developed a case of septic poisoning because of large, untreated kidney stones. While at the hospital, his heart stopped several times, requiring resuscitation. After being stabilized, he underwent surgery to remove the kidney stones and was then released back to his prison cell.

Fast forward to 2018. Mr. Schreiber filed for relief from his conviction, arguing that, because he technically died, his life sentence had been served and he should be released. While the logic is impeccable, an Iowa district court didn’t buy it, noting that the fact that Mr. Schreiber was able to submit a petition for his release “confirms the petitioner’s current status as living.”

Sadly for Mr. Schreiber, the Iowa Court of Appeals agreed with the lower court’s decision. In a wonderfully pithy summation of the case, Judge Amanda Potterfield wrote: “Schreiber is either still alive, in which case he must remain in prison, or he is actually dead, in which case this appeal is moot.”

While the Livin’ on the MDedge team is glad that a convicted murderer will not be released back into the public, we salute his devotion to the art of technicality. The judges may not have been convinced, but you’re dead to us, Mr. Schreiber.
 

Breaking news: Drug companies gouge consumers

BrianAJackson/iStock/Getty Images Plus

Canada. It’s home to many things: Trees, glaciers, beavers, and several people. But we Americans also know it as the home of cheap drugs. It may be borderline illegal, but that’s never stopped America from taking things that don’t belong to us before.

You’d think then that it’d be great being sick in Canada. But it turns out that many of those poor, desperate souls living in the frozen tundra of the north are actually overpaying for drugs just like the rest of us, according to research published in the Canadian Medical Association Journal.

It all comes down to those strange items called drug discount cards. They’re coupons offered by brand-name drug manufacturers to keep patients from switching to cheap generics.

Sounds great, right? Well, while a few patients saw savings, the average cost to patients with public insurance increased by 1.3% over generics. And if you were unfortunate enough to have private insurance, you’d be paying 46% more using the cards rather than generics. In some instances, patients were paying a whole $10 more for a prescription of the name brand, compared with the generic. And we thought Tim Hortons was our northern neighbor’s only company making a lot of dough. Ten loonies more per Rx ain’t Timbits.

So, Canada, how does it feel to have your health care made fun of? U-S-A! U-S-A! Now, if you’ll excuse us, we’re off to pay $1,000 a pill to cure us some hepatitis C. That’s some real red-blooded American price gouging right there.
 

This looks like a job for vacuum science

urbazon/E+

The LOTME staff, of course, scans a veritable buffet of sources to come up with the tasty tidbits we present each week to our deliciously wonderful and highly scrumptious readers each week.

One of our favorite sauces … umm, we mean sources, and the home of a tantalizing medical morsel (can you tell it’s almost lunch time?), is the Journal of Vacuum Science and Technology B. That’s B, not A. Anyone, at least anyone who’s serious about vacuum science, will tell you that the Journal of Vacuum Science and Technology A is pretty much a bottomless pit of trolling, political bickering, and popular nonsense. But B, now that’s a different story.

B is where we meet the EStAD (electrostatic and air driven) device. EStAD is a portable device that may someday offer physicians and first responders a way to treat wounds in rural areas where immediate care may not be available, the investigators said.

EStAD, using a process called electrospinning along with a confined electric field, works like a can of spray paint to deposit a fiber mat, which could be a bandage or a drug, onto a wound.

The device is still under development, but the research team reports that it has been successfully tested on a porcine skin incision and a gloved human hand.

The next step in EStAD development is to bring it to Washington, where the investigators will see if spray-on bandages can stand up to the hot air coming out of politicians’ mouths. We’re hoping that they sell tickets.

He’s not quite dead yet!

sdominick/iStock/Getty Images Plus

In 2015, Benjamin Schreiber, an Iowa man convicted of murder and sentenced to life in prison without parole, developed a case of septic poisoning because of large, untreated kidney stones. While at the hospital, his heart stopped several times, requiring resuscitation. After being stabilized, he underwent surgery to remove the kidney stones and was then released back to his prison cell.

Fast forward to 2018. Mr. Schreiber filed for relief from his conviction, arguing that, because he technically died, his life sentence had been served and he should be released. While the logic is impeccable, an Iowa district court didn’t buy it, noting that the fact that Mr. Schreiber was able to submit a petition for his release “confirms the petitioner’s current status as living.”

Sadly for Mr. Schreiber, the Iowa Court of Appeals agreed with the lower court’s decision. In a wonderfully pithy summation of the case, Judge Amanda Potterfield wrote: “Schreiber is either still alive, in which case he must remain in prison, or he is actually dead, in which case this appeal is moot.”

While the Livin’ on the MDedge team is glad that a convicted murderer will not be released back into the public, we salute his devotion to the art of technicality. The judges may not have been convinced, but you’re dead to us, Mr. Schreiber.
 

Breaking news: Drug companies gouge consumers

BrianAJackson/iStock/Getty Images Plus

Canada. It’s home to many things: Trees, glaciers, beavers, and several people. But we Americans also know it as the home of cheap drugs. It may be borderline illegal, but that’s never stopped America from taking things that don’t belong to us before.

You’d think then that it’d be great being sick in Canada. But it turns out that many of those poor, desperate souls living in the frozen tundra of the north are actually overpaying for drugs just like the rest of us, according to research published in the Canadian Medical Association Journal.

It all comes down to those strange items called drug discount cards. They’re coupons offered by brand-name drug manufacturers to keep patients from switching to cheap generics.

Sounds great, right? Well, while a few patients saw savings, the average cost to patients with public insurance increased by 1.3% over generics. And if you were unfortunate enough to have private insurance, you’d be paying 46% more using the cards rather than generics. In some instances, patients were paying a whole $10 more for a prescription of the name brand, compared with the generic. And we thought Tim Hortons was our northern neighbor’s only company making a lot of dough. Ten loonies more per Rx ain’t Timbits.

So, Canada, how does it feel to have your health care made fun of? U-S-A! U-S-A! Now, if you’ll excuse us, we’re off to pay $1,000 a pill to cure us some hepatitis C. That’s some real red-blooded American price gouging right there.
 

This looks like a job for vacuum science

urbazon/E+

The LOTME staff, of course, scans a veritable buffet of sources to come up with the tasty tidbits we present each week to our deliciously wonderful and highly scrumptious readers each week.

One of our favorite sauces … umm, we mean sources, and the home of a tantalizing medical morsel (can you tell it’s almost lunch time?), is the Journal of Vacuum Science and Technology B. That’s B, not A. Anyone, at least anyone who’s serious about vacuum science, will tell you that the Journal of Vacuum Science and Technology A is pretty much a bottomless pit of trolling, political bickering, and popular nonsense. But B, now that’s a different story.

B is where we meet the EStAD (electrostatic and air driven) device. EStAD is a portable device that may someday offer physicians and first responders a way to treat wounds in rural areas where immediate care may not be available, the investigators said.

EStAD, using a process called electrospinning along with a confined electric field, works like a can of spray paint to deposit a fiber mat, which could be a bandage or a drug, onto a wound.

The device is still under development, but the research team reports that it has been successfully tested on a porcine skin incision and a gloved human hand.

The next step in EStAD development is to bring it to Washington, where the investigators will see if spray-on bandages can stand up to the hot air coming out of politicians’ mouths. We’re hoping that they sell tickets.

Price increases are the main source of the increase in spending on oral anticancer drugs in the Medicare Part D prescription drug program, according to new research.

Dynamic Graphics/Thinkstockphotos

“Annualized spending on the same oral anticancer drugs more than doubled in a 5-year period,” Kira Seiger from Harvard Medical School, Boston, and colleagues wrote in a research letter published online in JAMA Oncology.

“Use increased substantially, likely owing to expanded drug indications, increased Medicare Part D enrollment, and declining cancer mortality yielding longer treatment courses,” the authors continued. “However, increased spending was predominantly driven (56%) by rising drug costs, which is reflective of pharmaceutical pricing strategies.”

Increased use of these drugs accounted for 44% of the annualized spending on the 56 oral anticancer drugs in this study.

Researchers found that from 2007 through 2013, “anticancer drugs prices increased 5% above inflation annually, plus 10% per subsequent indication approved. Results of this study demonstrated a continued rise from 2013 through 2017 with a compound annual growth rate of 13% above inflation for drug cost per beneficiary.”

Ms. Seiger and colleagues noted that, from 2013 through 2017, more than $41.4 billion was spent on the 56 oral anticancer drugs examined for the study. These drugs carried an average out-of-pocket cost of $551, accounting for $2.1 billion of the amount spent on these drugs.

“High drug prices on market entry are often attributed to research and development expenses, though research and development may not explain the subsequent increases in drug costs demonstrated in this study,” the researchers stated.

They recommended policy makers consider capping price increases at a set percentage above inflation, “especially given that rising use reflects increased need for these therapies.”

The study was sponsored in part by the department of dermatology at Brigham and Women’s Hospital, Boston. Three of the five authors reported received fees from pharmaceutical manufacturers, and one reported serving as chair for the National Comprehensive Cancer Network.

SOURCE: Kira Seiger et al. JAMA Oncology. doi: 10.1001/jamaoncol.2019.4906.

Price increases are the main source of the increase in spending on oral anticancer drugs in the Medicare Part D prescription drug program, according to new research.

Dynamic Graphics/Thinkstockphotos

“Annualized spending on the same oral anticancer drugs more than doubled in a 5-year period,” Kira Seiger from Harvard Medical School, Boston, and colleagues wrote in a research letter published online in JAMA Oncology.

“Use increased substantially, likely owing to expanded drug indications, increased Medicare Part D enrollment, and declining cancer mortality yielding longer treatment courses,” the authors continued. “However, increased spending was predominantly driven (56%) by rising drug costs, which is reflective of pharmaceutical pricing strategies.”

Increased use of these drugs accounted for 44% of the annualized spending on the 56 oral anticancer drugs in this study.

Researchers found that from 2007 through 2013, “anticancer drugs prices increased 5% above inflation annually, plus 10% per subsequent indication approved. Results of this study demonstrated a continued rise from 2013 through 2017 with a compound annual growth rate of 13% above inflation for drug cost per beneficiary.”

Ms. Seiger and colleagues noted that, from 2013 through 2017, more than $41.4 billion was spent on the 56 oral anticancer drugs examined for the study. These drugs carried an average out-of-pocket cost of $551, accounting for $2.1 billion of the amount spent on these drugs.

“High drug prices on market entry are often attributed to research and development expenses, though research and development may not explain the subsequent increases in drug costs demonstrated in this study,” the researchers stated.

They recommended policy makers consider capping price increases at a set percentage above inflation, “especially given that rising use reflects increased need for these therapies.”

The study was sponsored in part by the department of dermatology at Brigham and Women’s Hospital, Boston. Three of the five authors reported received fees from pharmaceutical manufacturers, and one reported serving as chair for the National Comprehensive Cancer Network.

SOURCE: Kira Seiger et al. JAMA Oncology. doi: 10.1001/jamaoncol.2019.4906.

Price increases are the main source of the increase in spending on oral anticancer drugs in the Medicare Part D prescription drug program, according to new research.

Dynamic Graphics/Thinkstockphotos

“Annualized spending on the same oral anticancer drugs more than doubled in a 5-year period,” Kira Seiger from Harvard Medical School, Boston, and colleagues wrote in a research letter published online in JAMA Oncology.

“Use increased substantially, likely owing to expanded drug indications, increased Medicare Part D enrollment, and declining cancer mortality yielding longer treatment courses,” the authors continued. “However, increased spending was predominantly driven (56%) by rising drug costs, which is reflective of pharmaceutical pricing strategies.”

Increased use of these drugs accounted for 44% of the annualized spending on the 56 oral anticancer drugs in this study.

Researchers found that from 2007 through 2013, “anticancer drugs prices increased 5% above inflation annually, plus 10% per subsequent indication approved. Results of this study demonstrated a continued rise from 2013 through 2017 with a compound annual growth rate of 13% above inflation for drug cost per beneficiary.”

Ms. Seiger and colleagues noted that, from 2013 through 2017, more than $41.4 billion was spent on the 56 oral anticancer drugs examined for the study. These drugs carried an average out-of-pocket cost of $551, accounting for $2.1 billion of the amount spent on these drugs.

“High drug prices on market entry are often attributed to research and development expenses, though research and development may not explain the subsequent increases in drug costs demonstrated in this study,” the researchers stated.

They recommended policy makers consider capping price increases at a set percentage above inflation, “especially given that rising use reflects increased need for these therapies.”

The study was sponsored in part by the department of dermatology at Brigham and Women’s Hospital, Boston. Three of the five authors reported received fees from pharmaceutical manufacturers, and one reported serving as chair for the National Comprehensive Cancer Network.

SOURCE: Kira Seiger et al. JAMA Oncology. doi: 10.1001/jamaoncol.2019.4906.

Women with vulval cancer who have a negative sentinel node biopsy have a low risk of recurrence and good disease-specific survival outcomes, investigators report.

One of two current standard treatment approaches for early-stage vulval cancer is radical excision of the tumor and inguinofemoral lymph node dissection, wrote Ligita P. Froeding, MD, of Copenhagen University Hospital Rigshospitalet, and coauthors. Their report is in Gynecologic Oncology. However, this procedure is associated with the disabling complication of leg lymphedema, which can significantly affect a woman’s quality of life.

Radical excision with sentinel biopsy is also an option, but the authors said large, population-based studies on the safety of this procedure when performed outside multicenter clinical trials were lacking.

In a prospective, nationwide cohort study, researchers analyzed data from 190 patients with vulval cancer who underwent the sentinel node procedure and had a negative biopsy. Of these, 73 patients had a unilateral procedure and 117 had a bilateral biopsy.

Over a median follow-up of 30 months’ follow-up, 32 patients (16.8%) died – 12 (37.5%) of vulval cancer and 20 (62.5%) from other causes. The 3-year overall survival rate was 84% and disease-specific survival was 93%.

The overall rate of recurrence in these sentinel node–negative women was 12.1% during the follow-up period. Fourteen patients (7.4%) experienced an isolated local vulval recurrence at a median time of 16 months after their primary treatment, and eight of these patients subsequently underwent inguinofemoral lymph node dissection following treatment of the recurrence. Three patients in this group died from vulval cancer, so the 3-year overall survival rate for patients with recurrent disease was 58%.

Four patients developed an isolated groin recurrence at a median of 12 months, and were treated with a combination of inguinofemoral lymph node dissection and chemoradiation. Two then developed a second recurrence.

Histopathological revision of original sentinel node specimens from the four women who experienced groin recurrences revealed that two patients actually had metastases at the time of the sentinel node procedure. In one case there were scattered tumor cells measuring less than 0.1 mm, while in the other there was a metastasis measuring 0.9 mm that was seen in six consecutive slides.

The authors noted that the failure to detect these metastases occurred despite strict adherence to histopathological procedure protocols. They suggested the first misdiagnosis may have been the result of the pathologist’s reluctance to make a histological diagnosis with so few tumor cells present. The second slide was originally screened microscopically by a specially trained medical laboratory technician, before being signed out by a pathologist, which “potentially decreases the pathologist’s diagnostic awareness,” they suggested.

“In conclusion, our study showed that the SN procedure is safe in selected VC patients when the current guidelines are strictly followed, and the procedure is performed in specialized gynecological oncology centers with a high volume of patients.”

No conflicts of interest were declared.

SOURCE: Froeding L et al. Gynecol Oncol 2019 Nov 8. doi: 10.1016/j.ygyno.2019.10.024.

Women with vulval cancer who have a negative sentinel node biopsy have a low risk of recurrence and good disease-specific survival outcomes, investigators report.

One of two current standard treatment approaches for early-stage vulval cancer is radical excision of the tumor and inguinofemoral lymph node dissection, wrote Ligita P. Froeding, MD, of Copenhagen University Hospital Rigshospitalet, and coauthors. Their report is in Gynecologic Oncology. However, this procedure is associated with the disabling complication of leg lymphedema, which can significantly affect a woman’s quality of life.

Radical excision with sentinel biopsy is also an option, but the authors said large, population-based studies on the safety of this procedure when performed outside multicenter clinical trials were lacking.

In a prospective, nationwide cohort study, researchers analyzed data from 190 patients with vulval cancer who underwent the sentinel node procedure and had a negative biopsy. Of these, 73 patients had a unilateral procedure and 117 had a bilateral biopsy.

Over a median follow-up of 30 months’ follow-up, 32 patients (16.8%) died – 12 (37.5%) of vulval cancer and 20 (62.5%) from other causes. The 3-year overall survival rate was 84% and disease-specific survival was 93%.

The overall rate of recurrence in these sentinel node–negative women was 12.1% during the follow-up period. Fourteen patients (7.4%) experienced an isolated local vulval recurrence at a median time of 16 months after their primary treatment, and eight of these patients subsequently underwent inguinofemoral lymph node dissection following treatment of the recurrence. Three patients in this group died from vulval cancer, so the 3-year overall survival rate for patients with recurrent disease was 58%.

Four patients developed an isolated groin recurrence at a median of 12 months, and were treated with a combination of inguinofemoral lymph node dissection and chemoradiation. Two then developed a second recurrence.

Histopathological revision of original sentinel node specimens from the four women who experienced groin recurrences revealed that two patients actually had metastases at the time of the sentinel node procedure. In one case there were scattered tumor cells measuring less than 0.1 mm, while in the other there was a metastasis measuring 0.9 mm that was seen in six consecutive slides.

The authors noted that the failure to detect these metastases occurred despite strict adherence to histopathological procedure protocols. They suggested the first misdiagnosis may have been the result of the pathologist’s reluctance to make a histological diagnosis with so few tumor cells present. The second slide was originally screened microscopically by a specially trained medical laboratory technician, before being signed out by a pathologist, which “potentially decreases the pathologist’s diagnostic awareness,” they suggested.

“In conclusion, our study showed that the SN procedure is safe in selected VC patients when the current guidelines are strictly followed, and the procedure is performed in specialized gynecological oncology centers with a high volume of patients.”

No conflicts of interest were declared.

SOURCE: Froeding L et al. Gynecol Oncol 2019 Nov 8. doi: 10.1016/j.ygyno.2019.10.024.

Women with vulval cancer who have a negative sentinel node biopsy have a low risk of recurrence and good disease-specific survival outcomes, investigators report.

One of two current standard treatment approaches for early-stage vulval cancer is radical excision of the tumor and inguinofemoral lymph node dissection, wrote Ligita P. Froeding, MD, of Copenhagen University Hospital Rigshospitalet, and coauthors. Their report is in Gynecologic Oncology. However, this procedure is associated with the disabling complication of leg lymphedema, which can significantly affect a woman’s quality of life.

Radical excision with sentinel biopsy is also an option, but the authors said large, population-based studies on the safety of this procedure when performed outside multicenter clinical trials were lacking.

In a prospective, nationwide cohort study, researchers analyzed data from 190 patients with vulval cancer who underwent the sentinel node procedure and had a negative biopsy. Of these, 73 patients had a unilateral procedure and 117 had a bilateral biopsy.

Over a median follow-up of 30 months’ follow-up, 32 patients (16.8%) died – 12 (37.5%) of vulval cancer and 20 (62.5%) from other causes. The 3-year overall survival rate was 84% and disease-specific survival was 93%.

The overall rate of recurrence in these sentinel node–negative women was 12.1% during the follow-up period. Fourteen patients (7.4%) experienced an isolated local vulval recurrence at a median time of 16 months after their primary treatment, and eight of these patients subsequently underwent inguinofemoral lymph node dissection following treatment of the recurrence. Three patients in this group died from vulval cancer, so the 3-year overall survival rate for patients with recurrent disease was 58%.

Four patients developed an isolated groin recurrence at a median of 12 months, and were treated with a combination of inguinofemoral lymph node dissection and chemoradiation. Two then developed a second recurrence.

Histopathological revision of original sentinel node specimens from the four women who experienced groin recurrences revealed that two patients actually had metastases at the time of the sentinel node procedure. In one case there were scattered tumor cells measuring less than 0.1 mm, while in the other there was a metastasis measuring 0.9 mm that was seen in six consecutive slides.

The authors noted that the failure to detect these metastases occurred despite strict adherence to histopathological procedure protocols. They suggested the first misdiagnosis may have been the result of the pathologist’s reluctance to make a histological diagnosis with so few tumor cells present. The second slide was originally screened microscopically by a specially trained medical laboratory technician, before being signed out by a pathologist, which “potentially decreases the pathologist’s diagnostic awareness,” they suggested.

“In conclusion, our study showed that the SN procedure is safe in selected VC patients when the current guidelines are strictly followed, and the procedure is performed in specialized gynecological oncology centers with a high volume of patients.”

No conflicts of interest were declared.

SOURCE: Froeding L et al. Gynecol Oncol 2019 Nov 8. doi: 10.1016/j.ygyno.2019.10.024.

‘Tis the season to reflect and take stock: What did you do this year? Perhaps you made it to Portugal, or published a paper, or added another doctor to your practice? Maybe you had a baby, or learned a new procedure, or bought a Tesla? Of course, you made (loads of?) money and treated many patients. Imagine if I asked you this in person, what would you reply? And what made you most proud? I’d tell you this story.

Last week I saw a 50-something-year-old woman for her annual skin screening. She asked if I remembered her mother, who was also my patient. Squinting through my dermatoscope at the nevi on her back, I tried to recall. “Yes, I think so.” (Actually, I was unsure.)

“Well she passed away last week from breast cancer,” she said.

“Oh, I’m sorry to hear that,” I replied.

She added: “Yes, yet she lived much longer than we thought. I want you to know we believe it was in large part because of you.”

I stopped and wheeled around to face her. How could that possibly be true? I had only treated her for a simple skin cancer. She explained that I had seen her mom about a year ago and cut out a skin cancer on her face. Her mom was afraid of needles and of surgery. Apparently when she asked me if it would hurt, I replied: “Well, most patients, yes, but not you.” Pausing, I added: “Because you’re a tough old bird.” She laughed. Apparently that warmth I conveyed and display of confidence in her was just what she needed at that moment. She didn’t flinch.

Not long after, she was diagnosed with breast cancer. When given the news with her children present, she replied, “well, I’ll just fight it. I’m a tough old bird.” It was just what they needed in that moment. “I’m a tough old bird” became their rally cry. Apparently with each stage, surgery, radiation, chemo, they fell back on it. Her son had “Tough Old Bird” made into a magnet and prominently posted on the refrigerator door where she would see it every day.

Sadly, she ultimately succumbed to her disease, but did so later than had been expected and having fought all the way. My patient teared up and asked if she could give me a hug on behalf of her mom. “Thank you, Dr. Benabio. We won’t forget what you did for her.”

I did recall her now, remembering even what exam room she was in when I said it. Yet, I had no idea what I had done. I wonder how many others there were. Of the many things you accomplished this year, try to recall these achievements. Not the psoriasis cleared, or tumor extirpated, or new homes bought. But the comfort and care you brought to the mother with worry, the father with anguish, the daughter with anxieties, or the son with misdeeds.

It is a beautiful, hard, and joyous life we have as physicians, for our “happiness lies in the absorption in some vocation which satisfies the soul; that we are here to add what we can to, not get what we can from life.”* How fortunate are we. Take stock.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

Reference

*William Osler, “Doctor and Nurse.” Address given at Training School for Nurses at Johns Hopkins Hospital, June 4, 1891

‘Tis the season to reflect and take stock: What did you do this year? Perhaps you made it to Portugal, or published a paper, or added another doctor to your practice? Maybe you had a baby, or learned a new procedure, or bought a Tesla? Of course, you made (loads of?) money and treated many patients. Imagine if I asked you this in person, what would you reply? And what made you most proud? I’d tell you this story.

Last week I saw a 50-something-year-old woman for her annual skin screening. She asked if I remembered her mother, who was also my patient. Squinting through my dermatoscope at the nevi on her back, I tried to recall. “Yes, I think so.” (Actually, I was unsure.)

“Well she passed away last week from breast cancer,” she said.

“Oh, I’m sorry to hear that,” I replied.

She added: “Yes, yet she lived much longer than we thought. I want you to know we believe it was in large part because of you.”

I stopped and wheeled around to face her. How could that possibly be true? I had only treated her for a simple skin cancer. She explained that I had seen her mom about a year ago and cut out a skin cancer on her face. Her mom was afraid of needles and of surgery. Apparently when she asked me if it would hurt, I replied: “Well, most patients, yes, but not you.” Pausing, I added: “Because you’re a tough old bird.” She laughed. Apparently that warmth I conveyed and display of confidence in her was just what she needed at that moment. She didn’t flinch.

Not long after, she was diagnosed with breast cancer. When given the news with her children present, she replied, “well, I’ll just fight it. I’m a tough old bird.” It was just what they needed in that moment. “I’m a tough old bird” became their rally cry. Apparently with each stage, surgery, radiation, chemo, they fell back on it. Her son had “Tough Old Bird” made into a magnet and prominently posted on the refrigerator door where she would see it every day.

Sadly, she ultimately succumbed to her disease, but did so later than had been expected and having fought all the way. My patient teared up and asked if she could give me a hug on behalf of her mom. “Thank you, Dr. Benabio. We won’t forget what you did for her.”

I did recall her now, remembering even what exam room she was in when I said it. Yet, I had no idea what I had done. I wonder how many others there were. Of the many things you accomplished this year, try to recall these achievements. Not the psoriasis cleared, or tumor extirpated, or new homes bought. But the comfort and care you brought to the mother with worry, the father with anguish, the daughter with anxieties, or the son with misdeeds.

It is a beautiful, hard, and joyous life we have as physicians, for our “happiness lies in the absorption in some vocation which satisfies the soul; that we are here to add what we can to, not get what we can from life.”* How fortunate are we. Take stock.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

Reference

*William Osler, “Doctor and Nurse.” Address given at Training School for Nurses at Johns Hopkins Hospital, June 4, 1891

‘Tis the season to reflect and take stock: What did you do this year? Perhaps you made it to Portugal, or published a paper, or added another doctor to your practice? Maybe you had a baby, or learned a new procedure, or bought a Tesla? Of course, you made (loads of?) money and treated many patients. Imagine if I asked you this in person, what would you reply? And what made you most proud? I’d tell you this story.

Last week I saw a 50-something-year-old woman for her annual skin screening. She asked if I remembered her mother, who was also my patient. Squinting through my dermatoscope at the nevi on her back, I tried to recall. “Yes, I think so.” (Actually, I was unsure.)

“Well she passed away last week from breast cancer,” she said.

“Oh, I’m sorry to hear that,” I replied.

She added: “Yes, yet she lived much longer than we thought. I want you to know we believe it was in large part because of you.”

I stopped and wheeled around to face her. How could that possibly be true? I had only treated her for a simple skin cancer. She explained that I had seen her mom about a year ago and cut out a skin cancer on her face. Her mom was afraid of needles and of surgery. Apparently when she asked me if it would hurt, I replied: “Well, most patients, yes, but not you.” Pausing, I added: “Because you’re a tough old bird.” She laughed. Apparently that warmth I conveyed and display of confidence in her was just what she needed at that moment. She didn’t flinch.

Not long after, she was diagnosed with breast cancer. When given the news with her children present, she replied, “well, I’ll just fight it. I’m a tough old bird.” It was just what they needed in that moment. “I’m a tough old bird” became their rally cry. Apparently with each stage, surgery, radiation, chemo, they fell back on it. Her son had “Tough Old Bird” made into a magnet and prominently posted on the refrigerator door where she would see it every day.

Sadly, she ultimately succumbed to her disease, but did so later than had been expected and having fought all the way. My patient teared up and asked if she could give me a hug on behalf of her mom. “Thank you, Dr. Benabio. We won’t forget what you did for her.”

I did recall her now, remembering even what exam room she was in when I said it. Yet, I had no idea what I had done. I wonder how many others there were. Of the many things you accomplished this year, try to recall these achievements. Not the psoriasis cleared, or tumor extirpated, or new homes bought. But the comfort and care you brought to the mother with worry, the father with anguish, the daughter with anxieties, or the son with misdeeds.

It is a beautiful, hard, and joyous life we have as physicians, for our “happiness lies in the absorption in some vocation which satisfies the soul; that we are here to add what we can to, not get what we can from life.”* How fortunate are we. Take stock.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

Reference

*William Osler, “Doctor and Nurse.” Address given at Training School for Nurses at Johns Hopkins Hospital, June 4, 1891