LIVERPOOL, ENGLAND – The presence of traditional cardiovascular risk factors may precede the development of polymyalgia rheumatica and giant cell arteritis.

Data from the EPIC-Norfolk study, reported at the British Society for Rheumatology annual conference, showed that raised LDL cholesterol was associated with the onset of polymyalgia rheumatica (PMR) and that high sensitivity C-reactive protein (hsCRP) was associated with giant cell arteritis (GCA).

Sara Freeman/MDedge News

SOURCE: Yates M et al. Rheumatology. 2018 Apr;57[Suppl. 3]:key075.312.

LIVERPOOL, ENGLAND – The presence of traditional cardiovascular risk factors may precede the development of polymyalgia rheumatica and giant cell arteritis.

Data from the EPIC-Norfolk study, reported at the British Society for Rheumatology annual conference, showed that raised LDL cholesterol was associated with the onset of polymyalgia rheumatica (PMR) and that high sensitivity C-reactive protein (hsCRP) was associated with giant cell arteritis (GCA).

Sara Freeman/MDedge News

SOURCE: Yates M et al. Rheumatology. 2018 Apr;57[Suppl. 3]:key075.312.

LIVERPOOL, ENGLAND – The presence of traditional cardiovascular risk factors may precede the development of polymyalgia rheumatica and giant cell arteritis.

Data from the EPIC-Norfolk study, reported at the British Society for Rheumatology annual conference, showed that raised LDL cholesterol was associated with the onset of polymyalgia rheumatica (PMR) and that high sensitivity C-reactive protein (hsCRP) was associated with giant cell arteritis (GCA).

Sara Freeman/MDedge News

SOURCE: Yates M et al. Rheumatology. 2018 Apr;57[Suppl. 3]:key075.312.

BOSTON – Semaglutide was effective in treating type 2 diabetes mellitus among all racial and ethnic subgroups studied in a series of clinical trials; the efficacy did not come at the cost of frequent hypoglycemia or other serious adverse events, according to a pooled subgroup analysis of the SUSTAIN trials.

The trials investigated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the treatment of T2DM. Cyrus V. Desouza, MBBS, presented results of a post hoc analysis of racial and ethnic subgroups, drawing on SUSTAIN trials 1-5 and 7 (SUSTAIN 6 had a different design, focusing on cardiovascular outcomes).

“The trials incorporated patients on the whole spectrum of diabetes, starting from people who are newly diagnosed ... all the way to patients who were on a combination of oral antidiabetic drugs plus insulin,” Dr. Desouza explained in an interview at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists.

The mean time since diagnosis in the SUSTAIN trials varied from 4.2 years in SUSTAIN 1 to 13.3 years in SUSTAIN 5. Dr. Desouza and his colleagues pooled data from the six trials to conduct the subgroup analyses.

Patients in the intervention arms of all trials received once weekly subcutaneous semaglutide, at a dose of either 0.5 mg or 1.0 mg, according to Dr. Desouza, professor of diabetes, endocrinology, and metabolism and Schultz Professor of Diabetes Research, Diabetes, Endocrinology, and Metabolism at the University of Nebraska, Lincoln.

In all, data from 3,066 patients were available. In the racial analysis, 982 low- and 1,328 high-dose semaglutide recipients were white, 243 and 232 were Asian, 82 and 124 were African American, and 25 and 50 identified as “other,” respectively.

An analysis by ethnicity found that 208 low- and 324 high-dose recipients were Hispanic.

At baseline in all trials, mean hemoglobin A_1c levels were similar, ranging from 8% to 8.4%; weights at baseline were a mean 89.6 kg to 96.2 kg across the trials.

The range of reductions in HbA_1c was similar across racial and ethnic groups. “If you look at the proportion of patients who actually achieved an A_1c below 7[%], it’s pretty impressive – it’s between 70% to 80%.” Between 50% and 60% of patients reached an HbA_1c less than 6.5%, said Dr. Desouza.

Looking at the data another way, 62.2%-72.4% of patients saw an HbA_1c reduction of at least 1% on low-dose semaglutide; the range across ethnicities was 74.2%-87.1% on high-dose semaglutide. Dr. Desouza said that the sample sizes weren’t large enough to calculate statistical significance for these subgroup differences.

“But I think what is impressive is that over 50% of patients in all the races and ethnicities were able to achieve a 5% body weight loss, which is metabolically significant in terms of improving outcomes,” he said. “I think that’s a really important fact.” A smaller proportion – around 20% – lost at least 10% of body weight, mostly on high-dose semaglutide.

Severe hypoglycemia, as defined by American Diabetes Association classification, was very rare across trials, except that 4.7% of African Americans saw this adverse event on high-dose semaglutide. Incidence in other subgroups, at either dose, ranged from 0% to 2.4%.

Otherwise, the medication was generally well tolerated, though gastrointestinal side effects were seen. “Asian people have a little higher GI side effects – up to 50% of Asians did develop GI side effects, and between 10% and 13% of Asians had to stop medication due to side effects,” said Dr. Desouza. “So I think that would be the one caveat in terms of tolerance that we did learn.”

The SUSTAIN trials were sponsored by Novo Nordisk. Dr. Desouza has received consulting fees for Novo Nordisk and has received grant support from several other pharmaceutical companies. Two coauthors are Novo Nordisk employees.

[email protected]

SOURCE: Desouza C et al. AACE 2018, Abstract 298

BOSTON – Semaglutide was effective in treating type 2 diabetes mellitus among all racial and ethnic subgroups studied in a series of clinical trials; the efficacy did not come at the cost of frequent hypoglycemia or other serious adverse events, according to a pooled subgroup analysis of the SUSTAIN trials.

The trials investigated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the treatment of T2DM. Cyrus V. Desouza, MBBS, presented results of a post hoc analysis of racial and ethnic subgroups, drawing on SUSTAIN trials 1-5 and 7 (SUSTAIN 6 had a different design, focusing on cardiovascular outcomes).

“The trials incorporated patients on the whole spectrum of diabetes, starting from people who are newly diagnosed ... all the way to patients who were on a combination of oral antidiabetic drugs plus insulin,” Dr. Desouza explained in an interview at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists.

The mean time since diagnosis in the SUSTAIN trials varied from 4.2 years in SUSTAIN 1 to 13.3 years in SUSTAIN 5. Dr. Desouza and his colleagues pooled data from the six trials to conduct the subgroup analyses.

Patients in the intervention arms of all trials received once weekly subcutaneous semaglutide, at a dose of either 0.5 mg or 1.0 mg, according to Dr. Desouza, professor of diabetes, endocrinology, and metabolism and Schultz Professor of Diabetes Research, Diabetes, Endocrinology, and Metabolism at the University of Nebraska, Lincoln.

In all, data from 3,066 patients were available. In the racial analysis, 982 low- and 1,328 high-dose semaglutide recipients were white, 243 and 232 were Asian, 82 and 124 were African American, and 25 and 50 identified as “other,” respectively.

An analysis by ethnicity found that 208 low- and 324 high-dose recipients were Hispanic.

At baseline in all trials, mean hemoglobin A_1c levels were similar, ranging from 8% to 8.4%; weights at baseline were a mean 89.6 kg to 96.2 kg across the trials.

The range of reductions in HbA_1c was similar across racial and ethnic groups. “If you look at the proportion of patients who actually achieved an A_1c below 7[%], it’s pretty impressive – it’s between 70% to 80%.” Between 50% and 60% of patients reached an HbA_1c less than 6.5%, said Dr. Desouza.

Looking at the data another way, 62.2%-72.4% of patients saw an HbA_1c reduction of at least 1% on low-dose semaglutide; the range across ethnicities was 74.2%-87.1% on high-dose semaglutide. Dr. Desouza said that the sample sizes weren’t large enough to calculate statistical significance for these subgroup differences.

“But I think what is impressive is that over 50% of patients in all the races and ethnicities were able to achieve a 5% body weight loss, which is metabolically significant in terms of improving outcomes,” he said. “I think that’s a really important fact.” A smaller proportion – around 20% – lost at least 10% of body weight, mostly on high-dose semaglutide.

Severe hypoglycemia, as defined by American Diabetes Association classification, was very rare across trials, except that 4.7% of African Americans saw this adverse event on high-dose semaglutide. Incidence in other subgroups, at either dose, ranged from 0% to 2.4%.

Otherwise, the medication was generally well tolerated, though gastrointestinal side effects were seen. “Asian people have a little higher GI side effects – up to 50% of Asians did develop GI side effects, and between 10% and 13% of Asians had to stop medication due to side effects,” said Dr. Desouza. “So I think that would be the one caveat in terms of tolerance that we did learn.”

The SUSTAIN trials were sponsored by Novo Nordisk. Dr. Desouza has received consulting fees for Novo Nordisk and has received grant support from several other pharmaceutical companies. Two coauthors are Novo Nordisk employees.

[email protected]

SOURCE: Desouza C et al. AACE 2018, Abstract 298

BOSTON – Semaglutide was effective in treating type 2 diabetes mellitus among all racial and ethnic subgroups studied in a series of clinical trials; the efficacy did not come at the cost of frequent hypoglycemia or other serious adverse events, according to a pooled subgroup analysis of the SUSTAIN trials.

The trials investigated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the treatment of T2DM. Cyrus V. Desouza, MBBS, presented results of a post hoc analysis of racial and ethnic subgroups, drawing on SUSTAIN trials 1-5 and 7 (SUSTAIN 6 had a different design, focusing on cardiovascular outcomes).

“The trials incorporated patients on the whole spectrum of diabetes, starting from people who are newly diagnosed ... all the way to patients who were on a combination of oral antidiabetic drugs plus insulin,” Dr. Desouza explained in an interview at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists.

The mean time since diagnosis in the SUSTAIN trials varied from 4.2 years in SUSTAIN 1 to 13.3 years in SUSTAIN 5. Dr. Desouza and his colleagues pooled data from the six trials to conduct the subgroup analyses.

Patients in the intervention arms of all trials received once weekly subcutaneous semaglutide, at a dose of either 0.5 mg or 1.0 mg, according to Dr. Desouza, professor of diabetes, endocrinology, and metabolism and Schultz Professor of Diabetes Research, Diabetes, Endocrinology, and Metabolism at the University of Nebraska, Lincoln.

In all, data from 3,066 patients were available. In the racial analysis, 982 low- and 1,328 high-dose semaglutide recipients were white, 243 and 232 were Asian, 82 and 124 were African American, and 25 and 50 identified as “other,” respectively.

An analysis by ethnicity found that 208 low- and 324 high-dose recipients were Hispanic.

At baseline in all trials, mean hemoglobin A_1c levels were similar, ranging from 8% to 8.4%; weights at baseline were a mean 89.6 kg to 96.2 kg across the trials.

The range of reductions in HbA_1c was similar across racial and ethnic groups. “If you look at the proportion of patients who actually achieved an A_1c below 7[%], it’s pretty impressive – it’s between 70% to 80%.” Between 50% and 60% of patients reached an HbA_1c less than 6.5%, said Dr. Desouza.

Looking at the data another way, 62.2%-72.4% of patients saw an HbA_1c reduction of at least 1% on low-dose semaglutide; the range across ethnicities was 74.2%-87.1% on high-dose semaglutide. Dr. Desouza said that the sample sizes weren’t large enough to calculate statistical significance for these subgroup differences.

“But I think what is impressive is that over 50% of patients in all the races and ethnicities were able to achieve a 5% body weight loss, which is metabolically significant in terms of improving outcomes,” he said. “I think that’s a really important fact.” A smaller proportion – around 20% – lost at least 10% of body weight, mostly on high-dose semaglutide.

Severe hypoglycemia, as defined by American Diabetes Association classification, was very rare across trials, except that 4.7% of African Americans saw this adverse event on high-dose semaglutide. Incidence in other subgroups, at either dose, ranged from 0% to 2.4%.

Otherwise, the medication was generally well tolerated, though gastrointestinal side effects were seen. “Asian people have a little higher GI side effects – up to 50% of Asians did develop GI side effects, and between 10% and 13% of Asians had to stop medication due to side effects,” said Dr. Desouza. “So I think that would be the one caveat in terms of tolerance that we did learn.”

The SUSTAIN trials were sponsored by Novo Nordisk. Dr. Desouza has received consulting fees for Novo Nordisk and has received grant support from several other pharmaceutical companies. Two coauthors are Novo Nordisk employees.

[email protected]

SOURCE: Desouza C et al. AACE 2018, Abstract 298

About 45,000 individuals in the United States took their own lives in 2016, and about half of them had no known mental health diagnosis at the time of death, based on data from the Centers for Disease Control and Prevention. Suicide rates rose by approximately 30% across all age groups up to age 75 years.

“Suicide is preventable; that’s why it is important to understand all the factors,” Anne Schuchat, MD, principal deputy director of the Centers for Disease Control and Prevention, said in a June 7 teleconference announcing the findings. Although mental health conditions often are seen as the cause of suicide, the results highlight the need to address other factors, including relationship problems, substance abuse, trouble with life transitions, and financial difficulties.

In a Vital Signs report published June 7, a team of CDC researchers led by Deborah M. Stone, ScD, reviewed data from suicide rates by state from 1999-2016. To examine the circumstances of suicide among individuals with and without mental health conditions, the researchers also reviewed data from the CDC’s National Violent Death Reporting System for 2015, which included 27 states.

Although rates increased among all age groups, adults aged 45-64 had the largest absolute increase in suicides, from 13.2 per 100,000 people in 1999 to 19.2 per 100,000 people in 2016.

SOURCE: Stone D et al. MMWR. 2018 Jun 7; 67(22):617-24

About 45,000 individuals in the United States took their own lives in 2016, and about half of them had no known mental health diagnosis at the time of death, based on data from the Centers for Disease Control and Prevention. Suicide rates rose by approximately 30% across all age groups up to age 75 years.

“Suicide is preventable; that’s why it is important to understand all the factors,” Anne Schuchat, MD, principal deputy director of the Centers for Disease Control and Prevention, said in a June 7 teleconference announcing the findings. Although mental health conditions often are seen as the cause of suicide, the results highlight the need to address other factors, including relationship problems, substance abuse, trouble with life transitions, and financial difficulties.

In a Vital Signs report published June 7, a team of CDC researchers led by Deborah M. Stone, ScD, reviewed data from suicide rates by state from 1999-2016. To examine the circumstances of suicide among individuals with and without mental health conditions, the researchers also reviewed data from the CDC’s National Violent Death Reporting System for 2015, which included 27 states.

Although rates increased among all age groups, adults aged 45-64 had the largest absolute increase in suicides, from 13.2 per 100,000 people in 1999 to 19.2 per 100,000 people in 2016.

SOURCE: Stone D et al. MMWR. 2018 Jun 7; 67(22):617-24

About 45,000 individuals in the United States took their own lives in 2016, and about half of them had no known mental health diagnosis at the time of death, based on data from the Centers for Disease Control and Prevention. Suicide rates rose by approximately 30% across all age groups up to age 75 years.

“Suicide is preventable; that’s why it is important to understand all the factors,” Anne Schuchat, MD, principal deputy director of the Centers for Disease Control and Prevention, said in a June 7 teleconference announcing the findings. Although mental health conditions often are seen as the cause of suicide, the results highlight the need to address other factors, including relationship problems, substance abuse, trouble with life transitions, and financial difficulties.

In a Vital Signs report published June 7, a team of CDC researchers led by Deborah M. Stone, ScD, reviewed data from suicide rates by state from 1999-2016. To examine the circumstances of suicide among individuals with and without mental health conditions, the researchers also reviewed data from the CDC’s National Violent Death Reporting System for 2015, which included 27 states.

Although rates increased among all age groups, adults aged 45-64 had the largest absolute increase in suicides, from 13.2 per 100,000 people in 1999 to 19.2 per 100,000 people in 2016.

SOURCE: Stone D et al. MMWR. 2018 Jun 7; 67(22):617-24

The Community Oncology Alliance (COA) is legally challenging the sequestration of Medicare Part B drug reimbursement payments.

Part B drugs administered in the physician’s office are generally reimbursed at average sales price (ASP) plus 6%, a rate set in statute by the Medicare Modernization Act of 2003 (MMA). However, the Budget Control Act of 2011 put a 2% sequestration on the federal budget, effective April 1, 2013, and extended numerous times after, most recently in the Bipartisan Budget Act of 2018. This has the effect of lowering Part B drug reimbursement to ASP + 4.3%.

Kenishirotie/Thinkstock

COA notes in its 2018 Community Oncology Practice Report that since the sequester went into effect in 2013, around 135 independent community cancer clinics have closed and about 190 clinics have been acquired by hospitals.

“Shifting cancer care to the outpatient hospital setting costs all taxpayers, not just Medicare beneficiaries,” the letter states. “The actuarial firm Milliman estimated the shift from 2004 to 2014 to have cost Medicare $2 billion in just one year (2014) and, as a result, an estimated $500 million in the same year to senior beneficiaries responsible for the 20% coinsurance.”

[email protected]

The Community Oncology Alliance (COA) is legally challenging the sequestration of Medicare Part B drug reimbursement payments.

Part B drugs administered in the physician’s office are generally reimbursed at average sales price (ASP) plus 6%, a rate set in statute by the Medicare Modernization Act of 2003 (MMA). However, the Budget Control Act of 2011 put a 2% sequestration on the federal budget, effective April 1, 2013, and extended numerous times after, most recently in the Bipartisan Budget Act of 2018. This has the effect of lowering Part B drug reimbursement to ASP + 4.3%.

Kenishirotie/Thinkstock

COA notes in its 2018 Community Oncology Practice Report that since the sequester went into effect in 2013, around 135 independent community cancer clinics have closed and about 190 clinics have been acquired by hospitals.

“Shifting cancer care to the outpatient hospital setting costs all taxpayers, not just Medicare beneficiaries,” the letter states. “The actuarial firm Milliman estimated the shift from 2004 to 2014 to have cost Medicare $2 billion in just one year (2014) and, as a result, an estimated $500 million in the same year to senior beneficiaries responsible for the 20% coinsurance.”

[email protected]

The Community Oncology Alliance (COA) is legally challenging the sequestration of Medicare Part B drug reimbursement payments.

Part B drugs administered in the physician’s office are generally reimbursed at average sales price (ASP) plus 6%, a rate set in statute by the Medicare Modernization Act of 2003 (MMA). However, the Budget Control Act of 2011 put a 2% sequestration on the federal budget, effective April 1, 2013, and extended numerous times after, most recently in the Bipartisan Budget Act of 2018. This has the effect of lowering Part B drug reimbursement to ASP + 4.3%.

Kenishirotie/Thinkstock

COA notes in its 2018 Community Oncology Practice Report that since the sequester went into effect in 2013, around 135 independent community cancer clinics have closed and about 190 clinics have been acquired by hospitals.

“Shifting cancer care to the outpatient hospital setting costs all taxpayers, not just Medicare beneficiaries,” the letter states. “The actuarial firm Milliman estimated the shift from 2004 to 2014 to have cost Medicare $2 billion in just one year (2014) and, as a result, an estimated $500 million in the same year to senior beneficiaries responsible for the 20% coinsurance.”

[email protected]

Pharmaceutical companies may be in for a more difficult time hiding behind a Risk Evaluation and Mitigation Strategy (REMS) as a way to prevent generic competition from entering the market.

The Food and Drug Administration issued two draft guidance documents on May 31 aimed at spurring on generic competition, items that are part of a broader White House strategy targeting the high price of prescription drugs.

“We have seen REMS requirements exploited in two ways,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “One occurs at the front end of the drug development process, when generic drugs are being developed. The other occurs at the back end of the process, after necessary testing has been completed, when a generic drug seeks approval and market entry.”

On the front end, manufacturers use REMS to restrict the sale of drugs to keep them out of the hands of generic firms, which typically need about 5,000 doses to conduct bioequivalence and bioavailability studies, Dr. Gottlieb noted. The back-end obstacle, which happens after a generic manufacturer files application for generic approval, is what the two guidance documents address.

The first draft guidance document, “Development of a Shared System REMS,” outlines principles and recommendations for brand and generic manufacturers to develop a single REMS program that covers both products, which Dr. Gottlieb said will “enable timelier market entry for products that are part of these REMS.”

The second draft guidance document, “Waivers of the Single Shared System REMS Requirement,” describes the two circumstances under which the generic manufacturer can waive the single, shared REMS requirements:

• If the burden of forming a single, shared systems outweighs the benefits.
• If an aspect of the REMS is covered by a patent or is a trade secret and the generic company was unable to obtain a license for use.

“We believe that by making the process for developing a shared system REMS more efficient, we’ll discourage brand drug makers from using REMS as a way to block generic entry and help end some of the tactics that can delay access,” Dr. Gottlieb said. “Our safety programs shouldn’t be leveraged as a way to forestall generic entry after lawful IP has lapsed on a brand drug.”

“Today’s FDA guidance is a step in the right direction toward our common goal of lowering out-of-control drug prices,” the Campaign for Sustainable Rx Pricing said in a statement “When generic and biosimilar competition is thwarted by these abusive tactics, brand-name manufacturers, who alone control the price of their drugs, keep those prices artificially high. The problem is the price, and more competition is a proven solution.”

Comments on each of the draft guidance documents are due July 31 at www.regulations.gov.

[email protected]

Pharmaceutical companies may be in for a more difficult time hiding behind a Risk Evaluation and Mitigation Strategy (REMS) as a way to prevent generic competition from entering the market.

The Food and Drug Administration issued two draft guidance documents on May 31 aimed at spurring on generic competition, items that are part of a broader White House strategy targeting the high price of prescription drugs.

“We have seen REMS requirements exploited in two ways,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “One occurs at the front end of the drug development process, when generic drugs are being developed. The other occurs at the back end of the process, after necessary testing has been completed, when a generic drug seeks approval and market entry.”

On the front end, manufacturers use REMS to restrict the sale of drugs to keep them out of the hands of generic firms, which typically need about 5,000 doses to conduct bioequivalence and bioavailability studies, Dr. Gottlieb noted. The back-end obstacle, which happens after a generic manufacturer files application for generic approval, is what the two guidance documents address.

The first draft guidance document, “Development of a Shared System REMS,” outlines principles and recommendations for brand and generic manufacturers to develop a single REMS program that covers both products, which Dr. Gottlieb said will “enable timelier market entry for products that are part of these REMS.”

The second draft guidance document, “Waivers of the Single Shared System REMS Requirement,” describes the two circumstances under which the generic manufacturer can waive the single, shared REMS requirements:

• If the burden of forming a single, shared systems outweighs the benefits.
• If an aspect of the REMS is covered by a patent or is a trade secret and the generic company was unable to obtain a license for use.

“We believe that by making the process for developing a shared system REMS more efficient, we’ll discourage brand drug makers from using REMS as a way to block generic entry and help end some of the tactics that can delay access,” Dr. Gottlieb said. “Our safety programs shouldn’t be leveraged as a way to forestall generic entry after lawful IP has lapsed on a brand drug.”

“Today’s FDA guidance is a step in the right direction toward our common goal of lowering out-of-control drug prices,” the Campaign for Sustainable Rx Pricing said in a statement “When generic and biosimilar competition is thwarted by these abusive tactics, brand-name manufacturers, who alone control the price of their drugs, keep those prices artificially high. The problem is the price, and more competition is a proven solution.”

Comments on each of the draft guidance documents are due July 31 at www.regulations.gov.

[email protected]

Pharmaceutical companies may be in for a more difficult time hiding behind a Risk Evaluation and Mitigation Strategy (REMS) as a way to prevent generic competition from entering the market.

The Food and Drug Administration issued two draft guidance documents on May 31 aimed at spurring on generic competition, items that are part of a broader White House strategy targeting the high price of prescription drugs.

“We have seen REMS requirements exploited in two ways,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “One occurs at the front end of the drug development process, when generic drugs are being developed. The other occurs at the back end of the process, after necessary testing has been completed, when a generic drug seeks approval and market entry.”

On the front end, manufacturers use REMS to restrict the sale of drugs to keep them out of the hands of generic firms, which typically need about 5,000 doses to conduct bioequivalence and bioavailability studies, Dr. Gottlieb noted. The back-end obstacle, which happens after a generic manufacturer files application for generic approval, is what the two guidance documents address.

The first draft guidance document, “Development of a Shared System REMS,” outlines principles and recommendations for brand and generic manufacturers to develop a single REMS program that covers both products, which Dr. Gottlieb said will “enable timelier market entry for products that are part of these REMS.”

The second draft guidance document, “Waivers of the Single Shared System REMS Requirement,” describes the two circumstances under which the generic manufacturer can waive the single, shared REMS requirements:

• If the burden of forming a single, shared systems outweighs the benefits.
• If an aspect of the REMS is covered by a patent or is a trade secret and the generic company was unable to obtain a license for use.

“We believe that by making the process for developing a shared system REMS more efficient, we’ll discourage brand drug makers from using REMS as a way to block generic entry and help end some of the tactics that can delay access,” Dr. Gottlieb said. “Our safety programs shouldn’t be leveraged as a way to forestall generic entry after lawful IP has lapsed on a brand drug.”

“Today’s FDA guidance is a step in the right direction toward our common goal of lowering out-of-control drug prices,” the Campaign for Sustainable Rx Pricing said in a statement “When generic and biosimilar competition is thwarted by these abusive tactics, brand-name manufacturers, who alone control the price of their drugs, keep those prices artificially high. The problem is the price, and more competition is a proven solution.”

Comments on each of the draft guidance documents are due July 31 at www.regulations.gov.

[email protected]

CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

CHICAGO – Hyperthermic intraperitoneal chemotherapy (HIPEC) following surgery for colorectal peritoneal carcinomatosis provides no survival benefit and may cause harm, according to findings from the randomized phase 3 UNICANCER Prodige 7 trial.

At a median follow up of 63.8 months, median overall survival – the primary endpoint of the study – was “completely comparable” at 41.7 and 41.2 months, respectively, in 133 patients randomized to receive HIPEC with oxaliplatin after cytoreductive surgery and 132 randomized to the cytoreductive surgery–only arm, François Quenet, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

Sharon Worcester/MDedge News

The use of HIPEC with cytoreductive surgery was introduced about 15 years ago and has become an accepted treatment option – and in some centers, a standard of care; the combination has been considered an effective treatment for peritoneal carcinomatosis, a metastatic tumor of the peritoneum that occurs in about 20% of colorectal cancer patients. The role of HIPEC in the success of the approach, however, has been unclear.

The current findings suggest that cytoreductive surgery alone is as effective as surgery with HIPEC, which “does not influence the survival result,” in most patients, Dr. Quenet said, noting that about 15% of patients were cured.

Additional study is needed to determine if there are certain subsets of patients who might benefit from HIPEC, he added, explaining that a subgroup analysis in the current study suggested that those with a midrange amount of disease in the abdominal cavity (peritoneal cancer index of 11-15) might experience some benefit with HIPEC, but the numbers were too small to be conclusive.

More research also is needed to determine if chemotherapy agents other than the oxaliplatin used with HIPEC in this study might be more effective, he said.

Prodige 7 was funded by UNICANCER. Dr. Quenet has received honoraria from Sanofi/Aventis, Ethicon, and Gamida Cell, as well as travel/accommodations/expenses from Sanofi, Novartis, and Ethicon.

SOURCE: Quenet F et al. ASCO 2018, Abstract LBA3503.

CHICAGO – Hyperthermic intraperitoneal chemotherapy (HIPEC) following surgery for colorectal peritoneal carcinomatosis provides no survival benefit and may cause harm, according to findings from the randomized phase 3 UNICANCER Prodige 7 trial.

At a median follow up of 63.8 months, median overall survival – the primary endpoint of the study – was “completely comparable” at 41.7 and 41.2 months, respectively, in 133 patients randomized to receive HIPEC with oxaliplatin after cytoreductive surgery and 132 randomized to the cytoreductive surgery–only arm, François Quenet, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

Sharon Worcester/MDedge News

The use of HIPEC with cytoreductive surgery was introduced about 15 years ago and has become an accepted treatment option – and in some centers, a standard of care; the combination has been considered an effective treatment for peritoneal carcinomatosis, a metastatic tumor of the peritoneum that occurs in about 20% of colorectal cancer patients. The role of HIPEC in the success of the approach, however, has been unclear.

The current findings suggest that cytoreductive surgery alone is as effective as surgery with HIPEC, which “does not influence the survival result,” in most patients, Dr. Quenet said, noting that about 15% of patients were cured.

Additional study is needed to determine if there are certain subsets of patients who might benefit from HIPEC, he added, explaining that a subgroup analysis in the current study suggested that those with a midrange amount of disease in the abdominal cavity (peritoneal cancer index of 11-15) might experience some benefit with HIPEC, but the numbers were too small to be conclusive.

More research also is needed to determine if chemotherapy agents other than the oxaliplatin used with HIPEC in this study might be more effective, he said.

Prodige 7 was funded by UNICANCER. Dr. Quenet has received honoraria from Sanofi/Aventis, Ethicon, and Gamida Cell, as well as travel/accommodations/expenses from Sanofi, Novartis, and Ethicon.

SOURCE: Quenet F et al. ASCO 2018, Abstract LBA3503.

CHICAGO – Hyperthermic intraperitoneal chemotherapy (HIPEC) following surgery for colorectal peritoneal carcinomatosis provides no survival benefit and may cause harm, according to findings from the randomized phase 3 UNICANCER Prodige 7 trial.

At a median follow up of 63.8 months, median overall survival – the primary endpoint of the study – was “completely comparable” at 41.7 and 41.2 months, respectively, in 133 patients randomized to receive HIPEC with oxaliplatin after cytoreductive surgery and 132 randomized to the cytoreductive surgery–only arm, François Quenet, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

Sharon Worcester/MDedge News

The use of HIPEC with cytoreductive surgery was introduced about 15 years ago and has become an accepted treatment option – and in some centers, a standard of care; the combination has been considered an effective treatment for peritoneal carcinomatosis, a metastatic tumor of the peritoneum that occurs in about 20% of colorectal cancer patients. The role of HIPEC in the success of the approach, however, has been unclear.

The current findings suggest that cytoreductive surgery alone is as effective as surgery with HIPEC, which “does not influence the survival result,” in most patients, Dr. Quenet said, noting that about 15% of patients were cured.

Additional study is needed to determine if there are certain subsets of patients who might benefit from HIPEC, he added, explaining that a subgroup analysis in the current study suggested that those with a midrange amount of disease in the abdominal cavity (peritoneal cancer index of 11-15) might experience some benefit with HIPEC, but the numbers were too small to be conclusive.

More research also is needed to determine if chemotherapy agents other than the oxaliplatin used with HIPEC in this study might be more effective, he said.

Prodige 7 was funded by UNICANCER. Dr. Quenet has received honoraria from Sanofi/Aventis, Ethicon, and Gamida Cell, as well as travel/accommodations/expenses from Sanofi, Novartis, and Ethicon.

SOURCE: Quenet F et al. ASCO 2018, Abstract LBA3503.

About six months ago, the parents of this 1-year-old boy first noticed the lesion on his shoulder. It started as a pinpoint papule but has grown to its current size—at which point, it caught their full attention. Although there are no associated symptoms, the parents request referral to dermatology to clear up the matter.

The child is reportedly healthy in all other respects, maintaining weight as expected, and normally active and reactive to verbal and visual stimuli.

EXAMINATION

A distinctive orangish brown, ovoid, 8 x 4–mm nodule is located on the child’s right superior shoulder. The lesion has a smooth, soft surface, and there is no tenderness on palpation. No additional lesions are seen elsewhere.

Eye examination reveals normal and symmetrical red reflexes.

What is the diagnosis?

Juvenile xanthogranuloma (JXG) is a rare, benign variant of non-Langerhans cell histiocytosis. This patient’s lesion is typical, but JXG can vary in appearance; some patients present with darker or larger lesions—or multiple lesions.

JXGs are essentially granulomatous tumors that, on histologic examination, display multinucleated giant cells called Touton giant cells. These macrophage-derived foam cells are seen in lesions with high lipid content.

JXG tends to favor the neck, face, and trunk but can appear around or (rarely) inside the eye, typically unilaterally in the iris. Benign in all other respects, ocular JXG lesions can cause spontaneous hyphema, glaucoma, or blindness; they must therefore be dealt with by a specialist. Fortunately, only about 10% of patients display ocular involvement.

JXGs can be confused with compound nevi, warts, or Spitz tumors. Therefore, biopsy is often necessary to establish the diagnosis.

TAKE-HOME LEARNING POINTS

• Juvenile xanthogranuloma (JXG) is a rare non-Langerhans cell tumor usually seen on the neck, face, or trunk of children younger than 2.
• The orangish brown, soft appearance of this patient’s papule was typical.
• Although atypical JXG lesions may require shave biopsy to confirm the diagnosis, they typically resolve on their own without treatment.
• When JXG lesions appear in the eye (most commonly in the iris), there is potential for serious complications, including heterochromia, glaucoma, spontaneous hyphema, or even blindness.

About six months ago, the parents of this 1-year-old boy first noticed the lesion on his shoulder. It started as a pinpoint papule but has grown to its current size—at which point, it caught their full attention. Although there are no associated symptoms, the parents request referral to dermatology to clear up the matter.

The child is reportedly healthy in all other respects, maintaining weight as expected, and normally active and reactive to verbal and visual stimuli.

EXAMINATION

A distinctive orangish brown, ovoid, 8 x 4–mm nodule is located on the child’s right superior shoulder. The lesion has a smooth, soft surface, and there is no tenderness on palpation. No additional lesions are seen elsewhere.

Eye examination reveals normal and symmetrical red reflexes.

What is the diagnosis?

Juvenile xanthogranuloma (JXG) is a rare, benign variant of non-Langerhans cell histiocytosis. This patient’s lesion is typical, but JXG can vary in appearance; some patients present with darker or larger lesions—or multiple lesions.

JXGs are essentially granulomatous tumors that, on histologic examination, display multinucleated giant cells called Touton giant cells. These macrophage-derived foam cells are seen in lesions with high lipid content.

JXG tends to favor the neck, face, and trunk but can appear around or (rarely) inside the eye, typically unilaterally in the iris. Benign in all other respects, ocular JXG lesions can cause spontaneous hyphema, glaucoma, or blindness; they must therefore be dealt with by a specialist. Fortunately, only about 10% of patients display ocular involvement.

JXGs can be confused with compound nevi, warts, or Spitz tumors. Therefore, biopsy is often necessary to establish the diagnosis.

TAKE-HOME LEARNING POINTS

• Juvenile xanthogranuloma (JXG) is a rare non-Langerhans cell tumor usually seen on the neck, face, or trunk of children younger than 2.
• The orangish brown, soft appearance of this patient’s papule was typical.
• Although atypical JXG lesions may require shave biopsy to confirm the diagnosis, they typically resolve on their own without treatment.
• When JXG lesions appear in the eye (most commonly in the iris), there is potential for serious complications, including heterochromia, glaucoma, spontaneous hyphema, or even blindness.

About six months ago, the parents of this 1-year-old boy first noticed the lesion on his shoulder. It started as a pinpoint papule but has grown to its current size—at which point, it caught their full attention. Although there are no associated symptoms, the parents request referral to dermatology to clear up the matter.

The child is reportedly healthy in all other respects, maintaining weight as expected, and normally active and reactive to verbal and visual stimuli.

EXAMINATION

A distinctive orangish brown, ovoid, 8 x 4–mm nodule is located on the child’s right superior shoulder. The lesion has a smooth, soft surface, and there is no tenderness on palpation. No additional lesions are seen elsewhere.

Eye examination reveals normal and symmetrical red reflexes.

What is the diagnosis?

Juvenile xanthogranuloma (JXG) is a rare, benign variant of non-Langerhans cell histiocytosis. This patient’s lesion is typical, but JXG can vary in appearance; some patients present with darker or larger lesions—or multiple lesions.

JXGs are essentially granulomatous tumors that, on histologic examination, display multinucleated giant cells called Touton giant cells. These macrophage-derived foam cells are seen in lesions with high lipid content.

JXG tends to favor the neck, face, and trunk but can appear around or (rarely) inside the eye, typically unilaterally in the iris. Benign in all other respects, ocular JXG lesions can cause spontaneous hyphema, glaucoma, or blindness; they must therefore be dealt with by a specialist. Fortunately, only about 10% of patients display ocular involvement.

JXGs can be confused with compound nevi, warts, or Spitz tumors. Therefore, biopsy is often necessary to establish the diagnosis.

TAKE-HOME LEARNING POINTS

• Juvenile xanthogranuloma (JXG) is a rare non-Langerhans cell tumor usually seen on the neck, face, or trunk of children younger than 2.
• The orangish brown, soft appearance of this patient’s papule was typical.
• Although atypical JXG lesions may require shave biopsy to confirm the diagnosis, they typically resolve on their own without treatment.
• When JXG lesions appear in the eye (most commonly in the iris), there is potential for serious complications, including heterochromia, glaucoma, spontaneous hyphema, or even blindness.

Tobacco use among middle and high school students has dropped since 2011, and e-cigarettes have replaced cigarettes as their favorite form of tobacco, according to the Centers for Disease Control and Prevention.

The prevalence of current tobacco use – defined as use on 1 or more days in the past 30 days – among high schoolers fell from 24.2% in 2011 to 19.6% in 2017, and middle school use decreased from 7.5% to 5.6% over that same time. That means the number of youth tobacco users went from almost 4.6 million in 2011 to slightly more than 3.6 million in 2017, Teresa W. Wang, PhD, and her associates said in the Morbidity and Mortality Weekly Report.

[email protected]

SOURCE: Wang TW et al. MMWR. 2018;67(22):629-33.

Tobacco use among middle and high school students has dropped since 2011, and e-cigarettes have replaced cigarettes as their favorite form of tobacco, according to the Centers for Disease Control and Prevention.

The prevalence of current tobacco use – defined as use on 1 or more days in the past 30 days – among high schoolers fell from 24.2% in 2011 to 19.6% in 2017, and middle school use decreased from 7.5% to 5.6% over that same time. That means the number of youth tobacco users went from almost 4.6 million in 2011 to slightly more than 3.6 million in 2017, Teresa W. Wang, PhD, and her associates said in the Morbidity and Mortality Weekly Report.

[email protected]

SOURCE: Wang TW et al. MMWR. 2018;67(22):629-33.

Tobacco use among middle and high school students has dropped since 2011, and e-cigarettes have replaced cigarettes as their favorite form of tobacco, according to the Centers for Disease Control and Prevention.

The prevalence of current tobacco use – defined as use on 1 or more days in the past 30 days – among high schoolers fell from 24.2% in 2011 to 19.6% in 2017, and middle school use decreased from 7.5% to 5.6% over that same time. That means the number of youth tobacco users went from almost 4.6 million in 2011 to slightly more than 3.6 million in 2017, Teresa W. Wang, PhD, and her associates said in the Morbidity and Mortality Weekly Report.

[email protected]

SOURCE: Wang TW et al. MMWR. 2018;67(22):629-33.

Federal officials will not block insurance companies from again using a workaround to cushion a steep rise in health premiums caused by President Donald Trump’s cancellation of a program established under the Affordable Care Act, Health and Human Services Secretary Alex Azar announced June 6.

The technique – called “silver loading” because it pushed price increases onto the silver-level plans in the ACA marketplaces – was used by many states for 2018 policies. But federal officials had hinted they might bar the practice next year.

At a hearing June 6 before the House Education and Workforce Committee, Mr. Azar said stopping this practice “would require regulations, which simply couldn’t be done in time for the 2019 plan period.”

States moved to silver loading after the president in October cut off federal reimbursement for so-called cost-sharing reduction subsidies that the ACA guaranteed to insurance companies. Those payments offset the cost of discounts that insurers are required by the law to provide to some low-income people to help cover their deductibles and other out-of-pocket costs.

States scrambled to let insurers raise rates so they would stay in the market. And many let them use this technique to recoup the lost funding by adding to the premium costs of midlevel silver plans in the health exchanges.

Because the formula for federal premium subsidies offered to people who purchase through the marketplaces is based on the prices of those silver plans, as those premiums rose so did the subsidies to help people afford them. That meant the federal government ended up paying much of the increase in prices.

At the committee hearing June 6, under questioning from Rep. Joe Courtney (D-Conn.), Mr. Azar declined to say if the department was considering a future ban.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Federal officials will not block insurance companies from again using a workaround to cushion a steep rise in health premiums caused by President Donald Trump’s cancellation of a program established under the Affordable Care Act, Health and Human Services Secretary Alex Azar announced June 6.

The technique – called “silver loading” because it pushed price increases onto the silver-level plans in the ACA marketplaces – was used by many states for 2018 policies. But federal officials had hinted they might bar the practice next year.

At a hearing June 6 before the House Education and Workforce Committee, Mr. Azar said stopping this practice “would require regulations, which simply couldn’t be done in time for the 2019 plan period.”

States moved to silver loading after the president in October cut off federal reimbursement for so-called cost-sharing reduction subsidies that the ACA guaranteed to insurance companies. Those payments offset the cost of discounts that insurers are required by the law to provide to some low-income people to help cover their deductibles and other out-of-pocket costs.

States scrambled to let insurers raise rates so they would stay in the market. And many let them use this technique to recoup the lost funding by adding to the premium costs of midlevel silver plans in the health exchanges.

Because the formula for federal premium subsidies offered to people who purchase through the marketplaces is based on the prices of those silver plans, as those premiums rose so did the subsidies to help people afford them. That meant the federal government ended up paying much of the increase in prices.

At the committee hearing June 6, under questioning from Rep. Joe Courtney (D-Conn.), Mr. Azar declined to say if the department was considering a future ban.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Federal officials will not block insurance companies from again using a workaround to cushion a steep rise in health premiums caused by President Donald Trump’s cancellation of a program established under the Affordable Care Act, Health and Human Services Secretary Alex Azar announced June 6.

The technique – called “silver loading” because it pushed price increases onto the silver-level plans in the ACA marketplaces – was used by many states for 2018 policies. But federal officials had hinted they might bar the practice next year.

At a hearing June 6 before the House Education and Workforce Committee, Mr. Azar said stopping this practice “would require regulations, which simply couldn’t be done in time for the 2019 plan period.”

States moved to silver loading after the president in October cut off federal reimbursement for so-called cost-sharing reduction subsidies that the ACA guaranteed to insurance companies. Those payments offset the cost of discounts that insurers are required by the law to provide to some low-income people to help cover their deductibles and other out-of-pocket costs.

States scrambled to let insurers raise rates so they would stay in the market. And many let them use this technique to recoup the lost funding by adding to the premium costs of midlevel silver plans in the health exchanges.

Because the formula for federal premium subsidies offered to people who purchase through the marketplaces is based on the prices of those silver plans, as those premiums rose so did the subsidies to help people afford them. That meant the federal government ended up paying much of the increase in prices.

At the committee hearing June 6, under questioning from Rep. Joe Courtney (D-Conn.), Mr. Azar declined to say if the department was considering a future ban.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.