Drug Therapy

Prescription pricing is a primary reason why Medicaid spending on multiple sclerosis disease-modifying therapies (DMTs) has more than doubled between 2011 and 2017 and the introduction of a generic glatiramer acetate is having nominal effect on pricing and utilization within the class, new research is showing.

Kenishirotie/Thinkstock

“Gross spending on self-administered and infusible MS DMTs in the Medicaid program increased 2.9-fold from $453 million in 2011 to $1.32 billion in 2017,” Daniel Hartung, PharmD, of Oregon Health and Science University, Portland, and his colleagues wrote in a research report published Jan. 15 in Neurology. Net spending after accounting for rebates during this period showed a doubling of spending from $278 million per year to $600 million per year.

Use of MS DMTs during this period overall remained stable, but there was a shift from injectable DMTs to oral DMTs during this time window, the researchers found, with the plurality of utilization attributed to glatiramer acetate.

Sandoz began marketing a generic version of glatiramer acetate 20 mg in the second quarter of 2015, which led to an immediate increase in the cost per prescription of $441 for the branded version of glatiramer acetate 20 mg, although that cost has come down gradually by $52 per prescription over time. Other DMTs saw minimal price changes at that time, Dr. Hartung and his colleagues noted.

The researchers attributed the increased Medicaid spending to rising prices of DMTs.

“Although some of this increase is attributable to the 2014 Medicaid expansion, the primary driver was rising DMT costs per prescription, which doubled over the period,” the researchers wrote. “Thus, we assert that rising prices, not increasing use, are the primary driver of spending for DMTs in the Medicaid program.”

In addition, the introduction of the first generic DMT “appeared to have little effect on the overall trajectory of DMT costs,” they continued. “In fact, the cost of Teva’s 20-mg glatiramer acetate increased significantly following the release of Sandoz’s generic. ... The increase possibly signified efforts to both retain revenue and further push market share to the 40-mg version. Although the costs for generic glatiramer acetate declined over time, its introduction appears not to have fundamentally affected the overall trend in DMT costs.”

Indeed, the researchers’ examination of utilization trends found that Teva executed a successful preemptive strategy of converting 20-mg users of glatiramer acetate to 40-mg users, something that is not interchangeable with the generic product.

“Low generic penetration is also due to the fact that Sandoz’s product was only 15% less expensive than branded glatiramer acetate 20 mg and approximately the same cost as the 40-mg version at launch,” Dr. Hartung and his colleagues stated. “This difference may have been further diminished by rebates that Teva may have provided to maintain preferred status on state Medicaid formularies.”

These factors reflect an “urgent need for robust generic competition within the DMT class,” the authors wrote.

The study was supported by the National Multiple Sclerosis Society. Lead author Dr. Hartung reported receiving research support from AbbVie.

[email protected]

SOURCE: Hartung D et al. Neurology. Jan 15. doi: 10.1212/WNL.0000000000008936.

Prescription pricing is a primary reason why Medicaid spending on multiple sclerosis disease-modifying therapies (DMTs) has more than doubled between 2011 and 2017 and the introduction of a generic glatiramer acetate is having nominal effect on pricing and utilization within the class, new research is showing.

Kenishirotie/Thinkstock

“Gross spending on self-administered and infusible MS DMTs in the Medicaid program increased 2.9-fold from $453 million in 2011 to $1.32 billion in 2017,” Daniel Hartung, PharmD, of Oregon Health and Science University, Portland, and his colleagues wrote in a research report published Jan. 15 in Neurology. Net spending after accounting for rebates during this period showed a doubling of spending from $278 million per year to $600 million per year.

Use of MS DMTs during this period overall remained stable, but there was a shift from injectable DMTs to oral DMTs during this time window, the researchers found, with the plurality of utilization attributed to glatiramer acetate.

Sandoz began marketing a generic version of glatiramer acetate 20 mg in the second quarter of 2015, which led to an immediate increase in the cost per prescription of $441 for the branded version of glatiramer acetate 20 mg, although that cost has come down gradually by $52 per prescription over time. Other DMTs saw minimal price changes at that time, Dr. Hartung and his colleagues noted.

The researchers attributed the increased Medicaid spending to rising prices of DMTs.

“Although some of this increase is attributable to the 2014 Medicaid expansion, the primary driver was rising DMT costs per prescription, which doubled over the period,” the researchers wrote. “Thus, we assert that rising prices, not increasing use, are the primary driver of spending for DMTs in the Medicaid program.”

In addition, the introduction of the first generic DMT “appeared to have little effect on the overall trajectory of DMT costs,” they continued. “In fact, the cost of Teva’s 20-mg glatiramer acetate increased significantly following the release of Sandoz’s generic. ... The increase possibly signified efforts to both retain revenue and further push market share to the 40-mg version. Although the costs for generic glatiramer acetate declined over time, its introduction appears not to have fundamentally affected the overall trend in DMT costs.”

Indeed, the researchers’ examination of utilization trends found that Teva executed a successful preemptive strategy of converting 20-mg users of glatiramer acetate to 40-mg users, something that is not interchangeable with the generic product.

“Low generic penetration is also due to the fact that Sandoz’s product was only 15% less expensive than branded glatiramer acetate 20 mg and approximately the same cost as the 40-mg version at launch,” Dr. Hartung and his colleagues stated. “This difference may have been further diminished by rebates that Teva may have provided to maintain preferred status on state Medicaid formularies.”

These factors reflect an “urgent need for robust generic competition within the DMT class,” the authors wrote.

The study was supported by the National Multiple Sclerosis Society. Lead author Dr. Hartung reported receiving research support from AbbVie.

[email protected]

SOURCE: Hartung D et al. Neurology. Jan 15. doi: 10.1212/WNL.0000000000008936.

Prescription pricing is a primary reason why Medicaid spending on multiple sclerosis disease-modifying therapies (DMTs) has more than doubled between 2011 and 2017 and the introduction of a generic glatiramer acetate is having nominal effect on pricing and utilization within the class, new research is showing.

Kenishirotie/Thinkstock

“Gross spending on self-administered and infusible MS DMTs in the Medicaid program increased 2.9-fold from $453 million in 2011 to $1.32 billion in 2017,” Daniel Hartung, PharmD, of Oregon Health and Science University, Portland, and his colleagues wrote in a research report published Jan. 15 in Neurology. Net spending after accounting for rebates during this period showed a doubling of spending from $278 million per year to $600 million per year.

Use of MS DMTs during this period overall remained stable, but there was a shift from injectable DMTs to oral DMTs during this time window, the researchers found, with the plurality of utilization attributed to glatiramer acetate.

Sandoz began marketing a generic version of glatiramer acetate 20 mg in the second quarter of 2015, which led to an immediate increase in the cost per prescription of $441 for the branded version of glatiramer acetate 20 mg, although that cost has come down gradually by $52 per prescription over time. Other DMTs saw minimal price changes at that time, Dr. Hartung and his colleagues noted.

The researchers attributed the increased Medicaid spending to rising prices of DMTs.

“Although some of this increase is attributable to the 2014 Medicaid expansion, the primary driver was rising DMT costs per prescription, which doubled over the period,” the researchers wrote. “Thus, we assert that rising prices, not increasing use, are the primary driver of spending for DMTs in the Medicaid program.”

In addition, the introduction of the first generic DMT “appeared to have little effect on the overall trajectory of DMT costs,” they continued. “In fact, the cost of Teva’s 20-mg glatiramer acetate increased significantly following the release of Sandoz’s generic. ... The increase possibly signified efforts to both retain revenue and further push market share to the 40-mg version. Although the costs for generic glatiramer acetate declined over time, its introduction appears not to have fundamentally affected the overall trend in DMT costs.”

Indeed, the researchers’ examination of utilization trends found that Teva executed a successful preemptive strategy of converting 20-mg users of glatiramer acetate to 40-mg users, something that is not interchangeable with the generic product.

“Low generic penetration is also due to the fact that Sandoz’s product was only 15% less expensive than branded glatiramer acetate 20 mg and approximately the same cost as the 40-mg version at launch,” Dr. Hartung and his colleagues stated. “This difference may have been further diminished by rebates that Teva may have provided to maintain preferred status on state Medicaid formularies.”

These factors reflect an “urgent need for robust generic competition within the DMT class,” the authors wrote.

The study was supported by the National Multiple Sclerosis Society. Lead author Dr. Hartung reported receiving research support from AbbVie.

[email protected]

SOURCE: Hartung D et al. Neurology. Jan 15. doi: 10.1212/WNL.0000000000008936.

A Food and Drug Administration advisory committee voted 27-0 on Jan. 14 against recommending agency approval of oxycodegol, a new type of opioid molecule designed to slow passage of the drug through the blood-brain barrier and hence cause less of a “high” and potentially blunt the drug’s abuse potential.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

But the panel, which includes members from both the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee, unanimously shared the opinion that the data submitted by the drug developer, Nektar, failed to clearly demonstrate the drug’s safety and efficacy.

“There was a lot of ambiguity [in the data] about safety and efficacy, and this is too important an issue to have so much ambiguity,” summed up Ronald S. Litman, DO, professor of anesthesiology and critical care at the University of Pennsylvania in Philadelphia and chair of the combined committee.

“The subliminal message” that would surround oxycodegol if it received FDA approval would be that it is a “safer” opioid, “and that would make it a blockbuster drug, and for that to happen you need data that [prove] the benefits outweigh risks, but we didn’t see those data. It was all speculation, and we can’t approve a potential blockbuster opioid in the middle of a public health opioid crisis based on speculation,” commented Steve B. Meisel, PharmD, system director of medication safety for Fairview Health Services in Minneapolis and a committee member.

According to Nektar, oxycodegol is a new molecular entity that combines a morphinan pharmacophore, oxycodol, with a six-unit chain of polyethylene glycol, a design that slows movement of the drug into the brain by about an hour after an oral dose when compared with oxycodone. It works as a full mu opioid receptor agonist that inhibits the nociceptive pathways while it reduces reinforcing or euphoric effects and other negative CNS-mediated side effects because of its slowed entry into the central nervous system.

But, as became apparent during the course of the day’s presentations and questions, while the clinical evidence in general supported this mechanism, the data were flawed by many limitations and caveats. FDA staffers critiqued the company’s data set for a variety of issues, including testing dosages that were “arbitrary and flawed,” evidence for “high oral abuse potential” in one study, including “a high rate of euphoria” of 17% even at the recommended dosage level (and a higher euphoria incidence at a higher dosage), limited information on additional pain medications that enrolled patients had used both before enrollment and during the study, and possible enrollment bias. Many panel members also raised concerns that included the efficacy data coming from a single randomized study, incomplete data on possible hepatic toxicity, no data to address potential abuse via injection or inhalation, a very modest demonstrated increment in pain relief, and abuse potential studies that relied on a single dose of the drug.

On the other hand, many committee members, and others in the pain field, applauded the general concept behind oxycodegol and urged the developer to run additional studies and collect more data for a future FDA application.

There has been “a lot of controversy” about oxycodegol, often centered on the question “why do we need another opioid,” commented Steven P. Cohen, MD, professor of anesthesiology, neurology, and pain medicine and chief of pain medicine at Johns Hopkins Health in Baltimore. “Having another opioid on the market with a different pain indication and possibly lower abuse potential” would be welcome and “almost certainly would not result in more prescriptions or abuse,” said Dr. Cohen, who was not a committee member but addressed in an interview the need for new and effective pain medications that offer an alternative to conventional opioids. “Patients who might otherwise be prescribed a different opioid might receive oxycodegol instead,” he suggested. But first, the developing company will need to collect a lot more clinical data than it has reported so far.

[email protected]

A Food and Drug Administration advisory committee voted 27-0 on Jan. 14 against recommending agency approval of oxycodegol, a new type of opioid molecule designed to slow passage of the drug through the blood-brain barrier and hence cause less of a “high” and potentially blunt the drug’s abuse potential.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

But the panel, which includes members from both the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee, unanimously shared the opinion that the data submitted by the drug developer, Nektar, failed to clearly demonstrate the drug’s safety and efficacy.

“There was a lot of ambiguity [in the data] about safety and efficacy, and this is too important an issue to have so much ambiguity,” summed up Ronald S. Litman, DO, professor of anesthesiology and critical care at the University of Pennsylvania in Philadelphia and chair of the combined committee.

“The subliminal message” that would surround oxycodegol if it received FDA approval would be that it is a “safer” opioid, “and that would make it a blockbuster drug, and for that to happen you need data that [prove] the benefits outweigh risks, but we didn’t see those data. It was all speculation, and we can’t approve a potential blockbuster opioid in the middle of a public health opioid crisis based on speculation,” commented Steve B. Meisel, PharmD, system director of medication safety for Fairview Health Services in Minneapolis and a committee member.

According to Nektar, oxycodegol is a new molecular entity that combines a morphinan pharmacophore, oxycodol, with a six-unit chain of polyethylene glycol, a design that slows movement of the drug into the brain by about an hour after an oral dose when compared with oxycodone. It works as a full mu opioid receptor agonist that inhibits the nociceptive pathways while it reduces reinforcing or euphoric effects and other negative CNS-mediated side effects because of its slowed entry into the central nervous system.

But, as became apparent during the course of the day’s presentations and questions, while the clinical evidence in general supported this mechanism, the data were flawed by many limitations and caveats. FDA staffers critiqued the company’s data set for a variety of issues, including testing dosages that were “arbitrary and flawed,” evidence for “high oral abuse potential” in one study, including “a high rate of euphoria” of 17% even at the recommended dosage level (and a higher euphoria incidence at a higher dosage), limited information on additional pain medications that enrolled patients had used both before enrollment and during the study, and possible enrollment bias. Many panel members also raised concerns that included the efficacy data coming from a single randomized study, incomplete data on possible hepatic toxicity, no data to address potential abuse via injection or inhalation, a very modest demonstrated increment in pain relief, and abuse potential studies that relied on a single dose of the drug.

On the other hand, many committee members, and others in the pain field, applauded the general concept behind oxycodegol and urged the developer to run additional studies and collect more data for a future FDA application.

There has been “a lot of controversy” about oxycodegol, often centered on the question “why do we need another opioid,” commented Steven P. Cohen, MD, professor of anesthesiology, neurology, and pain medicine and chief of pain medicine at Johns Hopkins Health in Baltimore. “Having another opioid on the market with a different pain indication and possibly lower abuse potential” would be welcome and “almost certainly would not result in more prescriptions or abuse,” said Dr. Cohen, who was not a committee member but addressed in an interview the need for new and effective pain medications that offer an alternative to conventional opioids. “Patients who might otherwise be prescribed a different opioid might receive oxycodegol instead,” he suggested. But first, the developing company will need to collect a lot more clinical data than it has reported so far.

[email protected]

A Food and Drug Administration advisory committee voted 27-0 on Jan. 14 against recommending agency approval of oxycodegol, a new type of opioid molecule designed to slow passage of the drug through the blood-brain barrier and hence cause less of a “high” and potentially blunt the drug’s abuse potential.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

But the panel, which includes members from both the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee, unanimously shared the opinion that the data submitted by the drug developer, Nektar, failed to clearly demonstrate the drug’s safety and efficacy.

“There was a lot of ambiguity [in the data] about safety and efficacy, and this is too important an issue to have so much ambiguity,” summed up Ronald S. Litman, DO, professor of anesthesiology and critical care at the University of Pennsylvania in Philadelphia and chair of the combined committee.

“The subliminal message” that would surround oxycodegol if it received FDA approval would be that it is a “safer” opioid, “and that would make it a blockbuster drug, and for that to happen you need data that [prove] the benefits outweigh risks, but we didn’t see those data. It was all speculation, and we can’t approve a potential blockbuster opioid in the middle of a public health opioid crisis based on speculation,” commented Steve B. Meisel, PharmD, system director of medication safety for Fairview Health Services in Minneapolis and a committee member.

According to Nektar, oxycodegol is a new molecular entity that combines a morphinan pharmacophore, oxycodol, with a six-unit chain of polyethylene glycol, a design that slows movement of the drug into the brain by about an hour after an oral dose when compared with oxycodone. It works as a full mu opioid receptor agonist that inhibits the nociceptive pathways while it reduces reinforcing or euphoric effects and other negative CNS-mediated side effects because of its slowed entry into the central nervous system.

But, as became apparent during the course of the day’s presentations and questions, while the clinical evidence in general supported this mechanism, the data were flawed by many limitations and caveats. FDA staffers critiqued the company’s data set for a variety of issues, including testing dosages that were “arbitrary and flawed,” evidence for “high oral abuse potential” in one study, including “a high rate of euphoria” of 17% even at the recommended dosage level (and a higher euphoria incidence at a higher dosage), limited information on additional pain medications that enrolled patients had used both before enrollment and during the study, and possible enrollment bias. Many panel members also raised concerns that included the efficacy data coming from a single randomized study, incomplete data on possible hepatic toxicity, no data to address potential abuse via injection or inhalation, a very modest demonstrated increment in pain relief, and abuse potential studies that relied on a single dose of the drug.

On the other hand, many committee members, and others in the pain field, applauded the general concept behind oxycodegol and urged the developer to run additional studies and collect more data for a future FDA application.

There has been “a lot of controversy” about oxycodegol, often centered on the question “why do we need another opioid,” commented Steven P. Cohen, MD, professor of anesthesiology, neurology, and pain medicine and chief of pain medicine at Johns Hopkins Health in Baltimore. “Having another opioid on the market with a different pain indication and possibly lower abuse potential” would be welcome and “almost certainly would not result in more prescriptions or abuse,” said Dr. Cohen, who was not a committee member but addressed in an interview the need for new and effective pain medications that offer an alternative to conventional opioids. “Patients who might otherwise be prescribed a different opioid might receive oxycodegol instead,” he suggested. But first, the developing company will need to collect a lot more clinical data than it has reported so far.

[email protected]

The Food and Drug Administration has issued a Safety Alert regarding the weight-management medication lorcaserin (Belviq, Belviq XR) after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.

bankrx/Getty Images

“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.

The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.

“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.

Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.

Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.

Lorcaserin is distributed by Eisai.*

[email protected]

*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin. 

The Food and Drug Administration has issued a Safety Alert regarding the weight-management medication lorcaserin (Belviq, Belviq XR) after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.

bankrx/Getty Images

“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.

The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.

“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.

Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.

Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.

Lorcaserin is distributed by Eisai.*

[email protected]

*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin. 

The Food and Drug Administration has issued a Safety Alert regarding the weight-management medication lorcaserin (Belviq, Belviq XR) after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.

bankrx/Getty Images

“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.

The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.

“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.

Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.

Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.

Lorcaserin is distributed by Eisai.*

[email protected]

*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin. 

Drug development times are not showing any signs of decreasing even though application review times at the Food and Drug Administration are improving, new research has shown.

Olivier Le Moal/Getty Images

“Despite the accumulation of expedited programs that have reduced FDA review times, overall clinical development times have not become shorter, although it is not possible to know what role these programs may have played in preventing an increase in development times,” Jonathan Darrow of Harvard Medical School, Boston, and colleagues wrote in a study published Jan. 14 in JAMA.

Researchers noted that FDA approval times declined from more than 3 years in 1983 to less than 1 year in 2017, although total time from the authorization of clinical testing to approval has remained steady across that period at about 8 years.

“The resistance of total development times to efforts to shorten them could be the result of more submissions of applications for rare disease drugs, which can sometimes pose trial recruitment challenges; a shifting emphasis to more challenging therapeutic categories, such as central nervous system disorder treatments; longer time horizons needed to establish efficacy when early intervention is important (e.g., cancer); or other factors,” wrote Mr. Darrow and colleagues.

The authors also note that the value of the expanded review toolbox the FDA now employs is “unclear” as “the number of new drug approvals has not increased substantially over the past three decades.” This observation does not count biologics or generic approvals.

Research revealed that the mean annual number of new drug approvals (including biologics) was 34 from 1990 to 1999, 25 from 2000 to 2009, and 41 from 2010 to 2018. In addition, while the number of new drug approvals has remained at or below 60 per year, the portion of drugs using at least one expedited review program increased over time, with more than 80% of the 59 new drugs approved in 2018 being subject to at least one expedited review program.

“Although the FDA has on average applied its expedited programs to drugs offering larger health gains, it is difficult to assess whether these programs have incentivized greater therapeutic innovation or merely allowed more appropriate agency prioritization,” noted Mr. Darrow and colleagues.

And while it may be hard to truly understand the impact of the many expedited review programs that have been introduced at the FDA, there is still room for improvement in the process.

In an editorial published in JAMA, Joshua Sharfstein, MD, of Johns Hopkins University, Baltimore, suggested four reforms the FDA could examine.

“First, Congress and the FDA should rationalize the various programs for expedited review,” he wrote, noting that companies are using the Orphan Drug Act to prevent competition. “Fixing the system requires, at a minimum, promoting meaningful competition for non-orphan uses.”

Second, he wrote, the FDA needs to strengthen oversight of postmarket safety though more diligence in the operation of its Risk Evaluation and Management Strategies (REMS) program.

“Third, Congress should recalibrate the programs that provide companies with special marketing protections,” added Dr. Sharfstein, former FDA principal deputy commissioner. “One place to look is pediatric exclusivity, which has been estimated to cost the health care system more than $6 for every $1 spent by a company on a pediatric trial.”

And finally, “Congress should use patent and pricing incentives to accelerate the generation of definitive evidence under accelerated approval,” citing proposals to limit pricing or market exclusivity until companies complete studies that assess clinically relevant endpoints.

“These changes would reflect an evolution, not a revolution, of the FDA’s approach to new drug approval,” Dr. Sharfstein said. “These reforms could also bring greater order and thoughtfulness to the regulation of important new therapies, while enhancing safety and creating greater capability to afford truly transformative medical products.”

[email protected]

SOURCE: Jonathan Darrow et al. JAMA 2020 Jan 14. doi: 10.1001/jama.2019.20288.

Drug development times are not showing any signs of decreasing even though application review times at the Food and Drug Administration are improving, new research has shown.

Olivier Le Moal/Getty Images

“Despite the accumulation of expedited programs that have reduced FDA review times, overall clinical development times have not become shorter, although it is not possible to know what role these programs may have played in preventing an increase in development times,” Jonathan Darrow of Harvard Medical School, Boston, and colleagues wrote in a study published Jan. 14 in JAMA.

Researchers noted that FDA approval times declined from more than 3 years in 1983 to less than 1 year in 2017, although total time from the authorization of clinical testing to approval has remained steady across that period at about 8 years.

“The resistance of total development times to efforts to shorten them could be the result of more submissions of applications for rare disease drugs, which can sometimes pose trial recruitment challenges; a shifting emphasis to more challenging therapeutic categories, such as central nervous system disorder treatments; longer time horizons needed to establish efficacy when early intervention is important (e.g., cancer); or other factors,” wrote Mr. Darrow and colleagues.

The authors also note that the value of the expanded review toolbox the FDA now employs is “unclear” as “the number of new drug approvals has not increased substantially over the past three decades.” This observation does not count biologics or generic approvals.

Research revealed that the mean annual number of new drug approvals (including biologics) was 34 from 1990 to 1999, 25 from 2000 to 2009, and 41 from 2010 to 2018. In addition, while the number of new drug approvals has remained at or below 60 per year, the portion of drugs using at least one expedited review program increased over time, with more than 80% of the 59 new drugs approved in 2018 being subject to at least one expedited review program.

“Although the FDA has on average applied its expedited programs to drugs offering larger health gains, it is difficult to assess whether these programs have incentivized greater therapeutic innovation or merely allowed more appropriate agency prioritization,” noted Mr. Darrow and colleagues.

And while it may be hard to truly understand the impact of the many expedited review programs that have been introduced at the FDA, there is still room for improvement in the process.

In an editorial published in JAMA, Joshua Sharfstein, MD, of Johns Hopkins University, Baltimore, suggested four reforms the FDA could examine.

“First, Congress and the FDA should rationalize the various programs for expedited review,” he wrote, noting that companies are using the Orphan Drug Act to prevent competition. “Fixing the system requires, at a minimum, promoting meaningful competition for non-orphan uses.”

Second, he wrote, the FDA needs to strengthen oversight of postmarket safety though more diligence in the operation of its Risk Evaluation and Management Strategies (REMS) program.

“Third, Congress should recalibrate the programs that provide companies with special marketing protections,” added Dr. Sharfstein, former FDA principal deputy commissioner. “One place to look is pediatric exclusivity, which has been estimated to cost the health care system more than $6 for every $1 spent by a company on a pediatric trial.”

And finally, “Congress should use patent and pricing incentives to accelerate the generation of definitive evidence under accelerated approval,” citing proposals to limit pricing or market exclusivity until companies complete studies that assess clinically relevant endpoints.

“These changes would reflect an evolution, not a revolution, of the FDA’s approach to new drug approval,” Dr. Sharfstein said. “These reforms could also bring greater order and thoughtfulness to the regulation of important new therapies, while enhancing safety and creating greater capability to afford truly transformative medical products.”

[email protected]

SOURCE: Jonathan Darrow et al. JAMA 2020 Jan 14. doi: 10.1001/jama.2019.20288.

Drug development times are not showing any signs of decreasing even though application review times at the Food and Drug Administration are improving, new research has shown.

Olivier Le Moal/Getty Images

“Despite the accumulation of expedited programs that have reduced FDA review times, overall clinical development times have not become shorter, although it is not possible to know what role these programs may have played in preventing an increase in development times,” Jonathan Darrow of Harvard Medical School, Boston, and colleagues wrote in a study published Jan. 14 in JAMA.

Researchers noted that FDA approval times declined from more than 3 years in 1983 to less than 1 year in 2017, although total time from the authorization of clinical testing to approval has remained steady across that period at about 8 years.

“The resistance of total development times to efforts to shorten them could be the result of more submissions of applications for rare disease drugs, which can sometimes pose trial recruitment challenges; a shifting emphasis to more challenging therapeutic categories, such as central nervous system disorder treatments; longer time horizons needed to establish efficacy when early intervention is important (e.g., cancer); or other factors,” wrote Mr. Darrow and colleagues.

The authors also note that the value of the expanded review toolbox the FDA now employs is “unclear” as “the number of new drug approvals has not increased substantially over the past three decades.” This observation does not count biologics or generic approvals.

Research revealed that the mean annual number of new drug approvals (including biologics) was 34 from 1990 to 1999, 25 from 2000 to 2009, and 41 from 2010 to 2018. In addition, while the number of new drug approvals has remained at or below 60 per year, the portion of drugs using at least one expedited review program increased over time, with more than 80% of the 59 new drugs approved in 2018 being subject to at least one expedited review program.

“Although the FDA has on average applied its expedited programs to drugs offering larger health gains, it is difficult to assess whether these programs have incentivized greater therapeutic innovation or merely allowed more appropriate agency prioritization,” noted Mr. Darrow and colleagues.

And while it may be hard to truly understand the impact of the many expedited review programs that have been introduced at the FDA, there is still room for improvement in the process.

In an editorial published in JAMA, Joshua Sharfstein, MD, of Johns Hopkins University, Baltimore, suggested four reforms the FDA could examine.

“First, Congress and the FDA should rationalize the various programs for expedited review,” he wrote, noting that companies are using the Orphan Drug Act to prevent competition. “Fixing the system requires, at a minimum, promoting meaningful competition for non-orphan uses.”

Second, he wrote, the FDA needs to strengthen oversight of postmarket safety though more diligence in the operation of its Risk Evaluation and Management Strategies (REMS) program.

“Third, Congress should recalibrate the programs that provide companies with special marketing protections,” added Dr. Sharfstein, former FDA principal deputy commissioner. “One place to look is pediatric exclusivity, which has been estimated to cost the health care system more than $6 for every $1 spent by a company on a pediatric trial.”

And finally, “Congress should use patent and pricing incentives to accelerate the generation of definitive evidence under accelerated approval,” citing proposals to limit pricing or market exclusivity until companies complete studies that assess clinically relevant endpoints.

“These changes would reflect an evolution, not a revolution, of the FDA’s approach to new drug approval,” Dr. Sharfstein said. “These reforms could also bring greater order and thoughtfulness to the regulation of important new therapies, while enhancing safety and creating greater capability to afford truly transformative medical products.”

[email protected]

SOURCE: Jonathan Darrow et al. JAMA 2020 Jan 14. doi: 10.1001/jama.2019.20288.

Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.

In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.

Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
 

Demographics and etiologies

The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.

The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).

The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.

In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).

In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).

“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
 

Management

Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.

Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).

However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.

This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.

“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.

Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.

However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.

Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.

Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
 

Outcomes

The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).

Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.

Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.

Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.

The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
 

Implications of the findings

Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.

Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.

The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.

The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.

Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.

“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.

The authors reported having no disclosures.

[email protected]

SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.

Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.

In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.

Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
 

Demographics and etiologies

The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.

The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).

The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.

In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).

In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).

“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
 

Management

Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.

Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).

However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.

This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.

“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.

Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.

However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.

Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.

Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
 

Outcomes

The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).

Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.

Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.

Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.

The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
 

Implications of the findings

Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.

Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.

The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.

The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.

Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.

“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.

The authors reported having no disclosures.

[email protected]

SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.

Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.

In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.

Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
 

Demographics and etiologies

The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.

The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).

The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.

In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).

In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).

“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
 

Management

Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.

Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).

However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.

This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.

“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.

Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.

However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.

Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.

Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
 

Outcomes

The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).

Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.

Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.

Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.

The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
 

Implications of the findings

Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.

Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.

The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.

The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.

Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.

“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.

The authors reported having no disclosures.

[email protected]

SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.

The National Comprehensive Cancer Network (NCCN) has released its first set of guidelines for managing pediatric aggressive mature B-cell lymphomas.

The guidelines highlight the complexities of treating pediatric Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as recommendations include a range of multiagent regimens for different patient groups at various time points.

“The treatment of this disease is relatively complicated,” said Kimberly J. Davies, MD, a pediatric hematologist/oncologist at Dana-Farber Cancer Institute in Boston and chair of the guidelines panel. “The chemotherapy regimens have a lot of drugs, a lot of nuances to how they’re supposed to be given. These guidelines delineate that treatment and help the provider … make sure they are delivering the treatment a patient needs.”

The guidelines recommend different regimens according to a patient’s risk group, but the same treatment approach should be used for patients with BL and those with DLBCL.

“The biggest difference between pediatric and adult patients is that pediatric patients are more uniformly treated, regardless of what type of aggressive B-cell lymphoma they have,” said Matthew Barth, MD, a pediatric hematologist/oncologist at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and vice chair of the NCCN guidelines panel.

“Adults with diffuse large B-cell lymphoma and Burkitt lymphoma are generally treated with different chemotherapy regimens, but, in pediatrics, we use the same treatment regimens for both diffuse large B-cell lymphoma and Burkitt lymphoma,” he added.

As an example, the new guidelines recommend that pediatric patients with low-risk BL/DLBCL receive the POG9219 regimen (N Engl J Med. 1997 Oct 30;337[18]:1259-66) or FAB/LMB96 regimen A (Br J Haematol. 2008 Jun;141[6]:840-7) as induction, or they should be enrolled in a clinical trial.

On the other hand, induction for high-risk pediatric BL/DLBCL patients should consist of rituximab and a chemotherapy regimen used in the COG ANHL1131 trial. The recommendation to incorporate rituximab in high-risk pediatric patients is based on results from that trial (J Clin Oncol. 2016 May 20. doi: 10.1200/JCO.2016.34.15_suppl.10507).

“Until recent clinical trial data was available, we weren’t really sure how to incorporate rituximab into the treatment of pediatric patients with mature B-cell lymphomas,” Dr. Barth said. “We now have evidence that rituximab is clearly beneficial for patients who are in higher-risk groups.”

Dr. Barth and Dr. Davies both noted that pediatric BL and DLBCL have high cure rates. Long-term survival rates range from about 80% to more than 90%, according to the American Cancer Society. However, the patients who do relapse or progress can be difficult to treat.

“We have quite good cure rates at this point in time, which is a great success, but that means that a very small population of patients don’t respond to initial therapy, and … it’s hard to know what the best treatment for those patients is,” Dr. Davies said.

She noted that studies are underway to determine if immunotherapies, including chimeric antigen receptor T-cell therapy, might improve outcomes in patients with relapsed or refractory disease.

For now, the NCCN guidelines recommend clinical trial enrollment for relapsed/refractory patients. Alternatively, these patients can receive additional chemotherapy, and responders can proceed to transplant. Patients who don’t achieve at least a partial response may go on to a clinical trial or receive best supportive care.

Dr. Davies and Dr. Barth reported having no conflicts of interest.

[email protected]

The National Comprehensive Cancer Network (NCCN) has released its first set of guidelines for managing pediatric aggressive mature B-cell lymphomas.

The guidelines highlight the complexities of treating pediatric Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as recommendations include a range of multiagent regimens for different patient groups at various time points.

“The treatment of this disease is relatively complicated,” said Kimberly J. Davies, MD, a pediatric hematologist/oncologist at Dana-Farber Cancer Institute in Boston and chair of the guidelines panel. “The chemotherapy regimens have a lot of drugs, a lot of nuances to how they’re supposed to be given. These guidelines delineate that treatment and help the provider … make sure they are delivering the treatment a patient needs.”

The guidelines recommend different regimens according to a patient’s risk group, but the same treatment approach should be used for patients with BL and those with DLBCL.

“The biggest difference between pediatric and adult patients is that pediatric patients are more uniformly treated, regardless of what type of aggressive B-cell lymphoma they have,” said Matthew Barth, MD, a pediatric hematologist/oncologist at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and vice chair of the NCCN guidelines panel.

“Adults with diffuse large B-cell lymphoma and Burkitt lymphoma are generally treated with different chemotherapy regimens, but, in pediatrics, we use the same treatment regimens for both diffuse large B-cell lymphoma and Burkitt lymphoma,” he added.

As an example, the new guidelines recommend that pediatric patients with low-risk BL/DLBCL receive the POG9219 regimen (N Engl J Med. 1997 Oct 30;337[18]:1259-66) or FAB/LMB96 regimen A (Br J Haematol. 2008 Jun;141[6]:840-7) as induction, or they should be enrolled in a clinical trial.

On the other hand, induction for high-risk pediatric BL/DLBCL patients should consist of rituximab and a chemotherapy regimen used in the COG ANHL1131 trial. The recommendation to incorporate rituximab in high-risk pediatric patients is based on results from that trial (J Clin Oncol. 2016 May 20. doi: 10.1200/JCO.2016.34.15_suppl.10507).

“Until recent clinical trial data was available, we weren’t really sure how to incorporate rituximab into the treatment of pediatric patients with mature B-cell lymphomas,” Dr. Barth said. “We now have evidence that rituximab is clearly beneficial for patients who are in higher-risk groups.”

Dr. Barth and Dr. Davies both noted that pediatric BL and DLBCL have high cure rates. Long-term survival rates range from about 80% to more than 90%, according to the American Cancer Society. However, the patients who do relapse or progress can be difficult to treat.

“We have quite good cure rates at this point in time, which is a great success, but that means that a very small population of patients don’t respond to initial therapy, and … it’s hard to know what the best treatment for those patients is,” Dr. Davies said.

She noted that studies are underway to determine if immunotherapies, including chimeric antigen receptor T-cell therapy, might improve outcomes in patients with relapsed or refractory disease.

For now, the NCCN guidelines recommend clinical trial enrollment for relapsed/refractory patients. Alternatively, these patients can receive additional chemotherapy, and responders can proceed to transplant. Patients who don’t achieve at least a partial response may go on to a clinical trial or receive best supportive care.

Dr. Davies and Dr. Barth reported having no conflicts of interest.

[email protected]

The National Comprehensive Cancer Network (NCCN) has released its first set of guidelines for managing pediatric aggressive mature B-cell lymphomas.

The guidelines highlight the complexities of treating pediatric Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as recommendations include a range of multiagent regimens for different patient groups at various time points.

“The treatment of this disease is relatively complicated,” said Kimberly J. Davies, MD, a pediatric hematologist/oncologist at Dana-Farber Cancer Institute in Boston and chair of the guidelines panel. “The chemotherapy regimens have a lot of drugs, a lot of nuances to how they’re supposed to be given. These guidelines delineate that treatment and help the provider … make sure they are delivering the treatment a patient needs.”

The guidelines recommend different regimens according to a patient’s risk group, but the same treatment approach should be used for patients with BL and those with DLBCL.

“The biggest difference between pediatric and adult patients is that pediatric patients are more uniformly treated, regardless of what type of aggressive B-cell lymphoma they have,” said Matthew Barth, MD, a pediatric hematologist/oncologist at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and vice chair of the NCCN guidelines panel.

“Adults with diffuse large B-cell lymphoma and Burkitt lymphoma are generally treated with different chemotherapy regimens, but, in pediatrics, we use the same treatment regimens for both diffuse large B-cell lymphoma and Burkitt lymphoma,” he added.

As an example, the new guidelines recommend that pediatric patients with low-risk BL/DLBCL receive the POG9219 regimen (N Engl J Med. 1997 Oct 30;337[18]:1259-66) or FAB/LMB96 regimen A (Br J Haematol. 2008 Jun;141[6]:840-7) as induction, or they should be enrolled in a clinical trial.

On the other hand, induction for high-risk pediatric BL/DLBCL patients should consist of rituximab and a chemotherapy regimen used in the COG ANHL1131 trial. The recommendation to incorporate rituximab in high-risk pediatric patients is based on results from that trial (J Clin Oncol. 2016 May 20. doi: 10.1200/JCO.2016.34.15_suppl.10507).

“Until recent clinical trial data was available, we weren’t really sure how to incorporate rituximab into the treatment of pediatric patients with mature B-cell lymphomas,” Dr. Barth said. “We now have evidence that rituximab is clearly beneficial for patients who are in higher-risk groups.”

Dr. Barth and Dr. Davies both noted that pediatric BL and DLBCL have high cure rates. Long-term survival rates range from about 80% to more than 90%, according to the American Cancer Society. However, the patients who do relapse or progress can be difficult to treat.

“We have quite good cure rates at this point in time, which is a great success, but that means that a very small population of patients don’t respond to initial therapy, and … it’s hard to know what the best treatment for those patients is,” Dr. Davies said.

She noted that studies are underway to determine if immunotherapies, including chimeric antigen receptor T-cell therapy, might improve outcomes in patients with relapsed or refractory disease.

For now, the NCCN guidelines recommend clinical trial enrollment for relapsed/refractory patients. Alternatively, these patients can receive additional chemotherapy, and responders can proceed to transplant. Patients who don’t achieve at least a partial response may go on to a clinical trial or receive best supportive care.

Dr. Davies and Dr. Barth reported having no conflicts of interest.

[email protected]

The incidence of gout was approximately 40% lower in diabetes patients who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2) than it was in those who were prescribed glucagonlike peptide–1 receptor (GLP-1) agonists in a population-based new-user cohort study.

Hyperuricemia is a known cause of gout and common in type 2 diabetes patients. SGLT2 inhibitors may reduce the risk of gout by preventing the reabsorption of glucose and lowering serum uric acid levels; however, the impact on gout risk remains uncertain, wrote Michael Fralick, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

In a study published in the Annals of Internal Medicine, the researchers compared SGLT2 inhibitors and GLP-1 agonists in patients with type 2 diabetes to assess protection against gout.

The study population included adults with type 2 diabetes mellitus who had a new prescription for an SGTL2 inhibitor or GLP-1 agonist. The average age of the patients was 54 years; approximately half were women. Baseline characteristics were similar between the groups.

Overall, the researchers found a relative risk reduction of approximately 40% and an absolute risk reduction of approximately three fewer cases per 1,000 person-years in patients who received SGLT2 inhibitors, compared with those who received GLP-1 agonists. The incidence rate for gout in the SGLT2 and GLP-1 groups were 4.9 per 1,000 person-years and 7.8 per 1,000 person-years, respectively.

The study findings were limited by the investigators’ inability to measure potential confounding variables such as body mass index, alcohol use, and high purine diet; incomplete lab data on creatinine and hemoglobin A; and a low baseline risk for gout in the study population, the researchers noted. However, the results persisted across sensitivity analysis and, if replicated, suggest that “SGLT2 inhibitors might be an effective class of medication for the prevention of gout for patients with diabetes or metabolic disorders,” they wrote.

The study was supported in part by Brigham and Women’s Hospital; lead author Dr. Fralick disclosed funding from the Eliot Phillipson Clinician-Scientist Training Program at the University of Toronto and the Canadian Institutes of Health Research.

SOURCE: Fralick M et al. Ann Intern Med. 2020 Jan 14. doi: 10.7326/M19-2610.

The incidence of gout was approximately 40% lower in diabetes patients who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2) than it was in those who were prescribed glucagonlike peptide–1 receptor (GLP-1) agonists in a population-based new-user cohort study.

Hyperuricemia is a known cause of gout and common in type 2 diabetes patients. SGLT2 inhibitors may reduce the risk of gout by preventing the reabsorption of glucose and lowering serum uric acid levels; however, the impact on gout risk remains uncertain, wrote Michael Fralick, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

In a study published in the Annals of Internal Medicine, the researchers compared SGLT2 inhibitors and GLP-1 agonists in patients with type 2 diabetes to assess protection against gout.

The study population included adults with type 2 diabetes mellitus who had a new prescription for an SGTL2 inhibitor or GLP-1 agonist. The average age of the patients was 54 years; approximately half were women. Baseline characteristics were similar between the groups.

Overall, the researchers found a relative risk reduction of approximately 40% and an absolute risk reduction of approximately three fewer cases per 1,000 person-years in patients who received SGLT2 inhibitors, compared with those who received GLP-1 agonists. The incidence rate for gout in the SGLT2 and GLP-1 groups were 4.9 per 1,000 person-years and 7.8 per 1,000 person-years, respectively.

The study findings were limited by the investigators’ inability to measure potential confounding variables such as body mass index, alcohol use, and high purine diet; incomplete lab data on creatinine and hemoglobin A; and a low baseline risk for gout in the study population, the researchers noted. However, the results persisted across sensitivity analysis and, if replicated, suggest that “SGLT2 inhibitors might be an effective class of medication for the prevention of gout for patients with diabetes or metabolic disorders,” they wrote.

The study was supported in part by Brigham and Women’s Hospital; lead author Dr. Fralick disclosed funding from the Eliot Phillipson Clinician-Scientist Training Program at the University of Toronto and the Canadian Institutes of Health Research.

SOURCE: Fralick M et al. Ann Intern Med. 2020 Jan 14. doi: 10.7326/M19-2610.

The incidence of gout was approximately 40% lower in diabetes patients who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2) than it was in those who were prescribed glucagonlike peptide–1 receptor (GLP-1) agonists in a population-based new-user cohort study.

Hyperuricemia is a known cause of gout and common in type 2 diabetes patients. SGLT2 inhibitors may reduce the risk of gout by preventing the reabsorption of glucose and lowering serum uric acid levels; however, the impact on gout risk remains uncertain, wrote Michael Fralick, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

In a study published in the Annals of Internal Medicine, the researchers compared SGLT2 inhibitors and GLP-1 agonists in patients with type 2 diabetes to assess protection against gout.

The study population included adults with type 2 diabetes mellitus who had a new prescription for an SGTL2 inhibitor or GLP-1 agonist. The average age of the patients was 54 years; approximately half were women. Baseline characteristics were similar between the groups.

Overall, the researchers found a relative risk reduction of approximately 40% and an absolute risk reduction of approximately three fewer cases per 1,000 person-years in patients who received SGLT2 inhibitors, compared with those who received GLP-1 agonists. The incidence rate for gout in the SGLT2 and GLP-1 groups were 4.9 per 1,000 person-years and 7.8 per 1,000 person-years, respectively.

The study findings were limited by the investigators’ inability to measure potential confounding variables such as body mass index, alcohol use, and high purine diet; incomplete lab data on creatinine and hemoglobin A; and a low baseline risk for gout in the study population, the researchers noted. However, the results persisted across sensitivity analysis and, if replicated, suggest that “SGLT2 inhibitors might be an effective class of medication for the prevention of gout for patients with diabetes or metabolic disorders,” they wrote.

The study was supported in part by Brigham and Women’s Hospital; lead author Dr. Fralick disclosed funding from the Eliot Phillipson Clinician-Scientist Training Program at the University of Toronto and the Canadian Institutes of Health Research.

SOURCE: Fralick M et al. Ann Intern Med. 2020 Jan 14. doi: 10.7326/M19-2610.

Women whose rheumatoid arthritis is carefully managed before and during pregnancy have a significantly lower risk of adverse pregnancy outcomes, including miscarriage or perinatal death, new research suggests.

zoranm/Getty Images

A study published in Arthritis Care & Research presents the outcomes of a retrospective, observational study examining health care data from 443 first pregnancies in women with RA and 6,097 women without the disease.

First author Alessandra Bortoluzzi, MD, PhD, from the Rheumatology Unit at the University of Ferrara (Italy) and coauthors looked at seven diagnostic, therapeutic, and follow-up health care quality indicators during the prepregnancy and perinatal period. They included having at least one blood test in the 18 months before conception and during pregnancy, preconception musculoskeletal imaging, no exposure or wash-out from teratogenic drugs, and no exposure to biologic drugs between conception and delivery or end of pregnancy.

An ideal clinical pathway included at least one element from each of the diagnostic, therapeutic, and prenatal follow-up quality indicators.

Overall, women with RA had a significantly higher rate of thyroid diseases, adverse pregnancy outcomes, and miscarriage or perinatal death when compared with controls. However, those who followed the ideal clinical pathway for management of their disease during pregnancy had a 40% lower odds of adverse pregnancy outcomes (odds ratio, 0.60; 95% confidence interval, 0.39-0.94) and a 60% lower odds of miscarriage or perinatal death (OR, 0.40; 95% CI, 0.24-0.69) in comparison with women with RA who were not managed to the same standard. The researchers adjusted both comparisons for age, Charlson comorbidity index, and thyroid diseases.

Women with RA who met diagnostic, therapeutic, and prenatal follow-up quality indicators showed no significant differences from the general population in terms of the risk of adverse pregnancy outcomes, miscarriage, or perinatal death after adjusting for hypertension in addition to the same variables as before.

When researchers looked at some of the individual health care quality indicators, they found that testing for antiphospholipid (aPL) antibodies within 18 months of conception or pregnancy was associated with a 44% lower rate of adverse pregnancy outcomes. Similarly, antinuclear antibody or anti–extractable nuclear antigen antibody testing was associated with 36% lower odds of adverse pregnancy outcomes.

Dr. Bortoluzzi and her coauthors wrote that their findings pointed to the value of testing for aPL antibodies in women with RA who wish to get pregnant.

“In fact, despite the absence of formal recommendation or validated health care quality indicators focused on stratification of preconceptional obstetric risk in patients with RA, we started from the basic and universally accepted assumption that aPL antibodies are pathogenic autoantibodies and therefore recognized risk factors for adverse pregnancy outcome,” they wrote.

Women with RA who had either no exposure to methotrexate or leflunomide or who had a washout period from 6 months prior to conception had 72% lower odds of adverse pregnancy outcomes.

The authors also looked at the effects of drugs such as aspirin, glucocorticoids, and low-molecular-weight heparin that are used during pregnancy. They found that the relative risk of adverse pregnancy outcomes was 40% higher in women with RA who were taking glucocorticoids, compared with those with the disease but not taking that type of medication. However, low-molecular-weight heparin use was associated with an 80% lower relative risk of miscarriage or perinatal death in comparison with those not taking it. Researchers saw no significant effects of aspirin or conventional synthetic disease-modifying antirheumatic drugs on either adverse pregnancy outcomes or the risk of miscarriage or perinatal death.

“This reinforces the importance of adjustment of therapy for RA before conception and throughout pregnancy, because medication use could affect pregnancy course not only influencing maternal disease activity but also the gestational outcome,” the authors wrote. “Although this is a study conducted on administrative data, we can hypothesize that exposure to therapy represents a marker of high RA disease activity and severity. In our setting, it is possible that, the more active the disease, the greater the probability of being included in the ideal clinical pathway, but in any case, this resulted in a lower odds ratio of adverse pregnancy outcome and miscarriage/perinatal death.”

The study was supported by the Italian Society for Rheumatology. No conflicts of interest were declared.

SOURCE: Bortoluzzi A et al. Arthritis Care Res. 2020 Jan 8. doi: 10.1002/ACR.24116.

Women whose rheumatoid arthritis is carefully managed before and during pregnancy have a significantly lower risk of adverse pregnancy outcomes, including miscarriage or perinatal death, new research suggests.

zoranm/Getty Images

A study published in Arthritis Care & Research presents the outcomes of a retrospective, observational study examining health care data from 443 first pregnancies in women with RA and 6,097 women without the disease.

First author Alessandra Bortoluzzi, MD, PhD, from the Rheumatology Unit at the University of Ferrara (Italy) and coauthors looked at seven diagnostic, therapeutic, and follow-up health care quality indicators during the prepregnancy and perinatal period. They included having at least one blood test in the 18 months before conception and during pregnancy, preconception musculoskeletal imaging, no exposure or wash-out from teratogenic drugs, and no exposure to biologic drugs between conception and delivery or end of pregnancy.

An ideal clinical pathway included at least one element from each of the diagnostic, therapeutic, and prenatal follow-up quality indicators.

Overall, women with RA had a significantly higher rate of thyroid diseases, adverse pregnancy outcomes, and miscarriage or perinatal death when compared with controls. However, those who followed the ideal clinical pathway for management of their disease during pregnancy had a 40% lower odds of adverse pregnancy outcomes (odds ratio, 0.60; 95% confidence interval, 0.39-0.94) and a 60% lower odds of miscarriage or perinatal death (OR, 0.40; 95% CI, 0.24-0.69) in comparison with women with RA who were not managed to the same standard. The researchers adjusted both comparisons for age, Charlson comorbidity index, and thyroid diseases.

Women with RA who met diagnostic, therapeutic, and prenatal follow-up quality indicators showed no significant differences from the general population in terms of the risk of adverse pregnancy outcomes, miscarriage, or perinatal death after adjusting for hypertension in addition to the same variables as before.

When researchers looked at some of the individual health care quality indicators, they found that testing for antiphospholipid (aPL) antibodies within 18 months of conception or pregnancy was associated with a 44% lower rate of adverse pregnancy outcomes. Similarly, antinuclear antibody or anti–extractable nuclear antigen antibody testing was associated with 36% lower odds of adverse pregnancy outcomes.

Dr. Bortoluzzi and her coauthors wrote that their findings pointed to the value of testing for aPL antibodies in women with RA who wish to get pregnant.

“In fact, despite the absence of formal recommendation or validated health care quality indicators focused on stratification of preconceptional obstetric risk in patients with RA, we started from the basic and universally accepted assumption that aPL antibodies are pathogenic autoantibodies and therefore recognized risk factors for adverse pregnancy outcome,” they wrote.

Women with RA who had either no exposure to methotrexate or leflunomide or who had a washout period from 6 months prior to conception had 72% lower odds of adverse pregnancy outcomes.

The authors also looked at the effects of drugs such as aspirin, glucocorticoids, and low-molecular-weight heparin that are used during pregnancy. They found that the relative risk of adverse pregnancy outcomes was 40% higher in women with RA who were taking glucocorticoids, compared with those with the disease but not taking that type of medication. However, low-molecular-weight heparin use was associated with an 80% lower relative risk of miscarriage or perinatal death in comparison with those not taking it. Researchers saw no significant effects of aspirin or conventional synthetic disease-modifying antirheumatic drugs on either adverse pregnancy outcomes or the risk of miscarriage or perinatal death.

“This reinforces the importance of adjustment of therapy for RA before conception and throughout pregnancy, because medication use could affect pregnancy course not only influencing maternal disease activity but also the gestational outcome,” the authors wrote. “Although this is a study conducted on administrative data, we can hypothesize that exposure to therapy represents a marker of high RA disease activity and severity. In our setting, it is possible that, the more active the disease, the greater the probability of being included in the ideal clinical pathway, but in any case, this resulted in a lower odds ratio of adverse pregnancy outcome and miscarriage/perinatal death.”

The study was supported by the Italian Society for Rheumatology. No conflicts of interest were declared.

SOURCE: Bortoluzzi A et al. Arthritis Care Res. 2020 Jan 8. doi: 10.1002/ACR.24116.

Women whose rheumatoid arthritis is carefully managed before and during pregnancy have a significantly lower risk of adverse pregnancy outcomes, including miscarriage or perinatal death, new research suggests.

zoranm/Getty Images

A study published in Arthritis Care & Research presents the outcomes of a retrospective, observational study examining health care data from 443 first pregnancies in women with RA and 6,097 women without the disease.

First author Alessandra Bortoluzzi, MD, PhD, from the Rheumatology Unit at the University of Ferrara (Italy) and coauthors looked at seven diagnostic, therapeutic, and follow-up health care quality indicators during the prepregnancy and perinatal period. They included having at least one blood test in the 18 months before conception and during pregnancy, preconception musculoskeletal imaging, no exposure or wash-out from teratogenic drugs, and no exposure to biologic drugs between conception and delivery or end of pregnancy.

An ideal clinical pathway included at least one element from each of the diagnostic, therapeutic, and prenatal follow-up quality indicators.

Overall, women with RA had a significantly higher rate of thyroid diseases, adverse pregnancy outcomes, and miscarriage or perinatal death when compared with controls. However, those who followed the ideal clinical pathway for management of their disease during pregnancy had a 40% lower odds of adverse pregnancy outcomes (odds ratio, 0.60; 95% confidence interval, 0.39-0.94) and a 60% lower odds of miscarriage or perinatal death (OR, 0.40; 95% CI, 0.24-0.69) in comparison with women with RA who were not managed to the same standard. The researchers adjusted both comparisons for age, Charlson comorbidity index, and thyroid diseases.

Women with RA who met diagnostic, therapeutic, and prenatal follow-up quality indicators showed no significant differences from the general population in terms of the risk of adverse pregnancy outcomes, miscarriage, or perinatal death after adjusting for hypertension in addition to the same variables as before.

When researchers looked at some of the individual health care quality indicators, they found that testing for antiphospholipid (aPL) antibodies within 18 months of conception or pregnancy was associated with a 44% lower rate of adverse pregnancy outcomes. Similarly, antinuclear antibody or anti–extractable nuclear antigen antibody testing was associated with 36% lower odds of adverse pregnancy outcomes.

Dr. Bortoluzzi and her coauthors wrote that their findings pointed to the value of testing for aPL antibodies in women with RA who wish to get pregnant.

“In fact, despite the absence of formal recommendation or validated health care quality indicators focused on stratification of preconceptional obstetric risk in patients with RA, we started from the basic and universally accepted assumption that aPL antibodies are pathogenic autoantibodies and therefore recognized risk factors for adverse pregnancy outcome,” they wrote.

Women with RA who had either no exposure to methotrexate or leflunomide or who had a washout period from 6 months prior to conception had 72% lower odds of adverse pregnancy outcomes.

The authors also looked at the effects of drugs such as aspirin, glucocorticoids, and low-molecular-weight heparin that are used during pregnancy. They found that the relative risk of adverse pregnancy outcomes was 40% higher in women with RA who were taking glucocorticoids, compared with those with the disease but not taking that type of medication. However, low-molecular-weight heparin use was associated with an 80% lower relative risk of miscarriage or perinatal death in comparison with those not taking it. Researchers saw no significant effects of aspirin or conventional synthetic disease-modifying antirheumatic drugs on either adverse pregnancy outcomes or the risk of miscarriage or perinatal death.

“This reinforces the importance of adjustment of therapy for RA before conception and throughout pregnancy, because medication use could affect pregnancy course not only influencing maternal disease activity but also the gestational outcome,” the authors wrote. “Although this is a study conducted on administrative data, we can hypothesize that exposure to therapy represents a marker of high RA disease activity and severity. In our setting, it is possible that, the more active the disease, the greater the probability of being included in the ideal clinical pathway, but in any case, this resulted in a lower odds ratio of adverse pregnancy outcome and miscarriage/perinatal death.”

The study was supported by the Italian Society for Rheumatology. No conflicts of interest were declared.

SOURCE: Bortoluzzi A et al. Arthritis Care Res. 2020 Jan 8. doi: 10.1002/ACR.24116.

PHILADELPHIA – Treatment with the PCSK9 inhibitor alirocumab linked with a significant cut in the rates of peripheral artery disease events and ischemic strokes without increasing the rate of hemorrhagic strokes, and alirocumab treatment also showed a trend toward an association with a reduced rate of venous thromboembolic events in prespecified, ancillary analyses of data collected from more than 18,000 patients in the ODYSSEY Outcomes trial.

Mitchel L. Zoler/MDedge News

The analyses that looked at peripheral artery disease (PAD) events and venous thromboembolism (VTE) events also suggested that the apparent ability of alirocumab to reduce their incidence may have been largely mediated through a reduction in Lp(a) lipoprotein, with less of a contribution from the drug’s primary action of reducing LDL cholesterol, Gregory G. Schwartz, MD, said at the American Heart Association scientific sessions.

When used on top of intensive statin treatment, as in the ODYSSEY Outcomes trial, treatment with the PCSK9 inhibitor alirocumab “may be useful to prevent PAD events, particularly in patients with high levels of Lp(a),” said Dr. Schwartz, professor of medicine at the University of Colorado Denver in Aurora. In the analysis he reported, patients treated with alirocumab for a median of 2.8 years had a statistically significant 31% reduced rate of PAD or VTE event and a significant 31% reduced rate of PAD events alone, compared with control patients who received placebo, he reported. Alirocumab treatment was also associated with a 33% lower rate of VTE events only, but the overall rate of these events was low, and this difference just missed statistical significance with a P value of .06.

“Levels of Lp(a), but not LDL cholesterol, predicted the risk of PAD events,” and in patients on alirocumab treatment “the magnitude of Lp(a) reduction, but not LDL-cholesterol reduction, was associated with a reduction in PAD events and VTE.” The reduction in PAD events linked with alirocumab treatment “may be related to Lp(a) lowering,” Dr. Schwartz suggested.

The link between alirocumab treatment and a reduction in ischemic stroke with no increase in hemorrhagic strokes appeared in a separate prespecified analysis from ODYSSEY Outcomes that looked at the rates of ischemic stroke, hemorrhagic stroke, and their combined incidence during the median 2.8 year of study follow-up. Patients treated with alirocumab had a statistically significant 27% reduction in their rate of ischemic strokes compared with patients on placebo, and a statistically significant 28% relative reduction in the rate of any stroke with alirocumab treatment, J. Wouter Jukema, MD, said in a separate report at the meeting. The rate of hemorrhagic strokes was small, and showed a nominal 17% reduction in patients treated with alirocumab, compared with controls, a difference that was not statistically significant.

Mitchel L. Zoler/MDedge News

Further analysis of the stroke outcomes also showed that these reductions in total strokes occurred with alirocumab treatment at roughly similar rates regardless of baseline level of LDL cholesterol or history of a prior cerebrovascular event. Analysis also showed that the rate of hemorrhagic strokes was consistently low regardless of the on-treatment level of LDL cholesterol. Even among patients whose LDL cholesterol level fell below 25 mg/dL on alirocumab treatment, the incidence of hemorrhagic strokes during follow-up was 0.1%, “a very reassuring finding,” said Dr. Jukema, professor of cardiology at Leiden (The Netherlands) University. The stroke analyses did not examine possible linkages of these effects with changes in level of Lp(a).

ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) included 18,924 patients who had experienced an acute coronary syndrome event within the prior 12 months and had an LDL cholesterol level of at least 70 mg/dL despite maximally tolerated statin treatment and randomized them to treatment with alirocumab or placebo. The primary endpoint was the combination of coronary heart disease death, nonfatal MI, ischemic stroke, and hospitalization for unstable angina, which alirocumab effectively reduced compared with placebo (N Engl J Med. 2018 Nov 29;379[22]:2097-107).

The PAD analysis tallied the combined rate of acute limb ischemia, revascularization, or amputation related to PAD, and the VTE cases included patients who developed deep vein thrombosis or pulmonary embolism. All cases were nonadjudicated reports from participating investigators. Because Lp(a) makes up a portion of LDL cholesterol, Dr. Schwartz and associates calculated adjusted values for LDL cholesterol that were independent of Lp(a).

In a multivariable analysis that adjusted for demographic and clinical characteristics as well as baseline Lp(a) and the calculated level of LDL cholesterol, every 1 mg/dL decrease in Lp(a) linked with a statistically significant, nearly 1% decrease in the rate of either a PAD or VTE event, while the change in LDL cholesterol had no significant relationship with this endpoint, said Dr. Schwartz.

The impact of Lp(a) lowering was most dramatic among the subgroups of patients who entered the study with the highest levels of Lp(a). “In the lowest quartile [for baseline level of Lp(a)] the effect of treatment [with alirocumab] was inconsequential; all of the action was in the upper two quartiles,” he said. Dr. Schwartz highlighted that 90% of patients in the study were on an “intense” statin dosage, and 97% received some statin treatment. Against that treatment background, the findings showed that patients still had residual cardiovascular disease risk that did not appear to respond to changes in LDL cholesterol but which did appear to respond to a reduction in Lp(a) produced by alirocumab. Dr. Schwartz further suggested that alirocumab’s reduction of Lp(a) might also mediate the drug’s apparent effect on reducing VTE incidence, possibly because Lp(a) is structurally similar to plasminogen and hence can have prothrombotic effects.

ODYSSEY Outcomes was sponsored by Sanofi and Regeneron, the companies that market alirocumab (Praluent). Dr. Schwartz has received research support from Sanofi and from Resverlogix, Roche, and The Medicines Company. Dr. Jukema has been a speaker for and received research support from Sanofi Regeneron, and has also been a speaker for Amgen, MSD, and Roche and has also received research support from Biotronik

[email protected]

SOURCE: Schwartz GG et al. AHA 2019, Abstract 309; Jukema JW et al. AHA 2019, Abstract 334.

PHILADELPHIA – Treatment with the PCSK9 inhibitor alirocumab linked with a significant cut in the rates of peripheral artery disease events and ischemic strokes without increasing the rate of hemorrhagic strokes, and alirocumab treatment also showed a trend toward an association with a reduced rate of venous thromboembolic events in prespecified, ancillary analyses of data collected from more than 18,000 patients in the ODYSSEY Outcomes trial.

Mitchel L. Zoler/MDedge News

The analyses that looked at peripheral artery disease (PAD) events and venous thromboembolism (VTE) events also suggested that the apparent ability of alirocumab to reduce their incidence may have been largely mediated through a reduction in Lp(a) lipoprotein, with less of a contribution from the drug’s primary action of reducing LDL cholesterol, Gregory G. Schwartz, MD, said at the American Heart Association scientific sessions.

When used on top of intensive statin treatment, as in the ODYSSEY Outcomes trial, treatment with the PCSK9 inhibitor alirocumab “may be useful to prevent PAD events, particularly in patients with high levels of Lp(a),” said Dr. Schwartz, professor of medicine at the University of Colorado Denver in Aurora. In the analysis he reported, patients treated with alirocumab for a median of 2.8 years had a statistically significant 31% reduced rate of PAD or VTE event and a significant 31% reduced rate of PAD events alone, compared with control patients who received placebo, he reported. Alirocumab treatment was also associated with a 33% lower rate of VTE events only, but the overall rate of these events was low, and this difference just missed statistical significance with a P value of .06.

“Levels of Lp(a), but not LDL cholesterol, predicted the risk of PAD events,” and in patients on alirocumab treatment “the magnitude of Lp(a) reduction, but not LDL-cholesterol reduction, was associated with a reduction in PAD events and VTE.” The reduction in PAD events linked with alirocumab treatment “may be related to Lp(a) lowering,” Dr. Schwartz suggested.

The link between alirocumab treatment and a reduction in ischemic stroke with no increase in hemorrhagic strokes appeared in a separate prespecified analysis from ODYSSEY Outcomes that looked at the rates of ischemic stroke, hemorrhagic stroke, and their combined incidence during the median 2.8 year of study follow-up. Patients treated with alirocumab had a statistically significant 27% reduction in their rate of ischemic strokes compared with patients on placebo, and a statistically significant 28% relative reduction in the rate of any stroke with alirocumab treatment, J. Wouter Jukema, MD, said in a separate report at the meeting. The rate of hemorrhagic strokes was small, and showed a nominal 17% reduction in patients treated with alirocumab, compared with controls, a difference that was not statistically significant.

Mitchel L. Zoler/MDedge News

Further analysis of the stroke outcomes also showed that these reductions in total strokes occurred with alirocumab treatment at roughly similar rates regardless of baseline level of LDL cholesterol or history of a prior cerebrovascular event. Analysis also showed that the rate of hemorrhagic strokes was consistently low regardless of the on-treatment level of LDL cholesterol. Even among patients whose LDL cholesterol level fell below 25 mg/dL on alirocumab treatment, the incidence of hemorrhagic strokes during follow-up was 0.1%, “a very reassuring finding,” said Dr. Jukema, professor of cardiology at Leiden (The Netherlands) University. The stroke analyses did not examine possible linkages of these effects with changes in level of Lp(a).

ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) included 18,924 patients who had experienced an acute coronary syndrome event within the prior 12 months and had an LDL cholesterol level of at least 70 mg/dL despite maximally tolerated statin treatment and randomized them to treatment with alirocumab or placebo. The primary endpoint was the combination of coronary heart disease death, nonfatal MI, ischemic stroke, and hospitalization for unstable angina, which alirocumab effectively reduced compared with placebo (N Engl J Med. 2018 Nov 29;379[22]:2097-107).

The PAD analysis tallied the combined rate of acute limb ischemia, revascularization, or amputation related to PAD, and the VTE cases included patients who developed deep vein thrombosis or pulmonary embolism. All cases were nonadjudicated reports from participating investigators. Because Lp(a) makes up a portion of LDL cholesterol, Dr. Schwartz and associates calculated adjusted values for LDL cholesterol that were independent of Lp(a).

In a multivariable analysis that adjusted for demographic and clinical characteristics as well as baseline Lp(a) and the calculated level of LDL cholesterol, every 1 mg/dL decrease in Lp(a) linked with a statistically significant, nearly 1% decrease in the rate of either a PAD or VTE event, while the change in LDL cholesterol had no significant relationship with this endpoint, said Dr. Schwartz.

The impact of Lp(a) lowering was most dramatic among the subgroups of patients who entered the study with the highest levels of Lp(a). “In the lowest quartile [for baseline level of Lp(a)] the effect of treatment [with alirocumab] was inconsequential; all of the action was in the upper two quartiles,” he said. Dr. Schwartz highlighted that 90% of patients in the study were on an “intense” statin dosage, and 97% received some statin treatment. Against that treatment background, the findings showed that patients still had residual cardiovascular disease risk that did not appear to respond to changes in LDL cholesterol but which did appear to respond to a reduction in Lp(a) produced by alirocumab. Dr. Schwartz further suggested that alirocumab’s reduction of Lp(a) might also mediate the drug’s apparent effect on reducing VTE incidence, possibly because Lp(a) is structurally similar to plasminogen and hence can have prothrombotic effects.

ODYSSEY Outcomes was sponsored by Sanofi and Regeneron, the companies that market alirocumab (Praluent). Dr. Schwartz has received research support from Sanofi and from Resverlogix, Roche, and The Medicines Company. Dr. Jukema has been a speaker for and received research support from Sanofi Regeneron, and has also been a speaker for Amgen, MSD, and Roche and has also received research support from Biotronik

[email protected]

SOURCE: Schwartz GG et al. AHA 2019, Abstract 309; Jukema JW et al. AHA 2019, Abstract 334.

PHILADELPHIA – Treatment with the PCSK9 inhibitor alirocumab linked with a significant cut in the rates of peripheral artery disease events and ischemic strokes without increasing the rate of hemorrhagic strokes, and alirocumab treatment also showed a trend toward an association with a reduced rate of venous thromboembolic events in prespecified, ancillary analyses of data collected from more than 18,000 patients in the ODYSSEY Outcomes trial.

Mitchel L. Zoler/MDedge News

The analyses that looked at peripheral artery disease (PAD) events and venous thromboembolism (VTE) events also suggested that the apparent ability of alirocumab to reduce their incidence may have been largely mediated through a reduction in Lp(a) lipoprotein, with less of a contribution from the drug’s primary action of reducing LDL cholesterol, Gregory G. Schwartz, MD, said at the American Heart Association scientific sessions.

When used on top of intensive statin treatment, as in the ODYSSEY Outcomes trial, treatment with the PCSK9 inhibitor alirocumab “may be useful to prevent PAD events, particularly in patients with high levels of Lp(a),” said Dr. Schwartz, professor of medicine at the University of Colorado Denver in Aurora. In the analysis he reported, patients treated with alirocumab for a median of 2.8 years had a statistically significant 31% reduced rate of PAD or VTE event and a significant 31% reduced rate of PAD events alone, compared with control patients who received placebo, he reported. Alirocumab treatment was also associated with a 33% lower rate of VTE events only, but the overall rate of these events was low, and this difference just missed statistical significance with a P value of .06.

“Levels of Lp(a), but not LDL cholesterol, predicted the risk of PAD events,” and in patients on alirocumab treatment “the magnitude of Lp(a) reduction, but not LDL-cholesterol reduction, was associated with a reduction in PAD events and VTE.” The reduction in PAD events linked with alirocumab treatment “may be related to Lp(a) lowering,” Dr. Schwartz suggested.

The link between alirocumab treatment and a reduction in ischemic stroke with no increase in hemorrhagic strokes appeared in a separate prespecified analysis from ODYSSEY Outcomes that looked at the rates of ischemic stroke, hemorrhagic stroke, and their combined incidence during the median 2.8 year of study follow-up. Patients treated with alirocumab had a statistically significant 27% reduction in their rate of ischemic strokes compared with patients on placebo, and a statistically significant 28% relative reduction in the rate of any stroke with alirocumab treatment, J. Wouter Jukema, MD, said in a separate report at the meeting. The rate of hemorrhagic strokes was small, and showed a nominal 17% reduction in patients treated with alirocumab, compared with controls, a difference that was not statistically significant.

Mitchel L. Zoler/MDedge News

Further analysis of the stroke outcomes also showed that these reductions in total strokes occurred with alirocumab treatment at roughly similar rates regardless of baseline level of LDL cholesterol or history of a prior cerebrovascular event. Analysis also showed that the rate of hemorrhagic strokes was consistently low regardless of the on-treatment level of LDL cholesterol. Even among patients whose LDL cholesterol level fell below 25 mg/dL on alirocumab treatment, the incidence of hemorrhagic strokes during follow-up was 0.1%, “a very reassuring finding,” said Dr. Jukema, professor of cardiology at Leiden (The Netherlands) University. The stroke analyses did not examine possible linkages of these effects with changes in level of Lp(a).

ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) included 18,924 patients who had experienced an acute coronary syndrome event within the prior 12 months and had an LDL cholesterol level of at least 70 mg/dL despite maximally tolerated statin treatment and randomized them to treatment with alirocumab or placebo. The primary endpoint was the combination of coronary heart disease death, nonfatal MI, ischemic stroke, and hospitalization for unstable angina, which alirocumab effectively reduced compared with placebo (N Engl J Med. 2018 Nov 29;379[22]:2097-107).

The PAD analysis tallied the combined rate of acute limb ischemia, revascularization, or amputation related to PAD, and the VTE cases included patients who developed deep vein thrombosis or pulmonary embolism. All cases were nonadjudicated reports from participating investigators. Because Lp(a) makes up a portion of LDL cholesterol, Dr. Schwartz and associates calculated adjusted values for LDL cholesterol that were independent of Lp(a).

In a multivariable analysis that adjusted for demographic and clinical characteristics as well as baseline Lp(a) and the calculated level of LDL cholesterol, every 1 mg/dL decrease in Lp(a) linked with a statistically significant, nearly 1% decrease in the rate of either a PAD or VTE event, while the change in LDL cholesterol had no significant relationship with this endpoint, said Dr. Schwartz.

The impact of Lp(a) lowering was most dramatic among the subgroups of patients who entered the study with the highest levels of Lp(a). “In the lowest quartile [for baseline level of Lp(a)] the effect of treatment [with alirocumab] was inconsequential; all of the action was in the upper two quartiles,” he said. Dr. Schwartz highlighted that 90% of patients in the study were on an “intense” statin dosage, and 97% received some statin treatment. Against that treatment background, the findings showed that patients still had residual cardiovascular disease risk that did not appear to respond to changes in LDL cholesterol but which did appear to respond to a reduction in Lp(a) produced by alirocumab. Dr. Schwartz further suggested that alirocumab’s reduction of Lp(a) might also mediate the drug’s apparent effect on reducing VTE incidence, possibly because Lp(a) is structurally similar to plasminogen and hence can have prothrombotic effects.

ODYSSEY Outcomes was sponsored by Sanofi and Regeneron, the companies that market alirocumab (Praluent). Dr. Schwartz has received research support from Sanofi and from Resverlogix, Roche, and The Medicines Company. Dr. Jukema has been a speaker for and received research support from Sanofi Regeneron, and has also been a speaker for Amgen, MSD, and Roche and has also received research support from Biotronik

[email protected]

SOURCE: Schwartz GG et al. AHA 2019, Abstract 309; Jukema JW et al. AHA 2019, Abstract 334.

LAS VEGAS – Nearly a quarter of American adults are on a prescription drug that often produces obesity as a side effect, and use of such obesogenic drugs was significantly higher among patients who already are obese, based on national U.S. data collected during 2013-2016.

Mitchel L. Zoler/MDedge News

The Endocrine Society, the STOP Obesity Alliance, and other medical societies have recommended that clinicians try to minimize use of obesogenic drugs and focus on prescribing agents that are weight neutral or that trigger weight loss when those options are available and appropriate, and the new findings add further evidence that clinicians need to be more mindful of this issue, Craig M. Hales, MD, said at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Among the American adults interviewed for the survey, 40% of those on at least one prescription medication were on at least one drug that is considered obesogenic, said Dr. Hales, a medical epidemiologist at the Centers for Disease Control and Prevention in Hyattsville, Md.

According to practice guidelines published by the Endocrine Society, all drugs in the classes of glucocorticoids, beta-blockers, and antihistamines are obesogenic, as well as selected agents in the classes of antidepressant drugs, antipsychotics, antidepressants, antidiabetics, and contraceptives that are progestin only, said Dr. Hales (J Clin Endocrinol Metab. 2015 Feb;100[2]:342-62).

The data he reported came from the National Health and Nutrition Examination Survey (NHANES) run by the CDC during 2013-2016 that included 11,055 adults who were at least 20 years old. The findings showed that 23% of those adults had taken at least one drug that was considered obesogenic during the 30 days preceding the survey date. By comparison, 35% of the same adults had taken any type of prescription drug during the previous 30 days. That meant that overall, 40% of surveyed adults who had recently used any prescription medication had taken an obesogenic drug.

The 23% prevalence of recent obesogenic drug use was fairly stable at that level during several preceding NHANES surveys going back to 2001, suggesting that the increasing use of obesogenic drugs during the period since 2001 was not a factor in the recent increased prevalence of obesity among U.S. residents, added Dr. Hales.

The 2013-2016 analysis also showed a strong link between obesogenic drug use and increasing obesity severity. Among survey participants with a body mass index (BMI) in the normal range (18.5-24 kg/m²), 16% had recent use of an obesogenic drug. This prevalence increased to 22% among those who were overweight (BMI, 25-29 kg/m²), 29% among those with class 1 or 2 obesity (BMI, 30-39 kg/m²), and 33% among those with class 3 obesity (BMI, 40 kg/m² or greater).

In contrast, recent use of prescription medications that do not contribute to obesity showed no significant relationship with BMI, with rates that ranged from 34% among those with a normal BMI, to 37% among those with class 3 obesity.

As an example of this relationship for a specific obesogenic drug class, the prevalence of beta-blocker use was about 7% among people with a normal BMI, about 10% among those who were overweight, about 14% among people with class 1 or 2 obesity, and about 17% among people with class 3 obesity, a statistically significant link suggesting that the relationship between use of obesogenic drugs and obesity is “bidirectional,” Dr. Hales said, in that increasing obesogenic drug use likely contributes to obesity, while simultaneously, the more obese people become, the more likely they are to take additional prescription drugs, particularly those that are obesogenic.

NHANES is run by the CDC and receives no commercial funding. The authors reported no conflicts of interest.

[email protected]

SOURCE: Hales CM et al. Obesity Week 2019, Abstract T-OR-2037.

LAS VEGAS – Nearly a quarter of American adults are on a prescription drug that often produces obesity as a side effect, and use of such obesogenic drugs was significantly higher among patients who already are obese, based on national U.S. data collected during 2013-2016.

Mitchel L. Zoler/MDedge News

The Endocrine Society, the STOP Obesity Alliance, and other medical societies have recommended that clinicians try to minimize use of obesogenic drugs and focus on prescribing agents that are weight neutral or that trigger weight loss when those options are available and appropriate, and the new findings add further evidence that clinicians need to be more mindful of this issue, Craig M. Hales, MD, said at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Among the American adults interviewed for the survey, 40% of those on at least one prescription medication were on at least one drug that is considered obesogenic, said Dr. Hales, a medical epidemiologist at the Centers for Disease Control and Prevention in Hyattsville, Md.

According to practice guidelines published by the Endocrine Society, all drugs in the classes of glucocorticoids, beta-blockers, and antihistamines are obesogenic, as well as selected agents in the classes of antidepressant drugs, antipsychotics, antidepressants, antidiabetics, and contraceptives that are progestin only, said Dr. Hales (J Clin Endocrinol Metab. 2015 Feb;100[2]:342-62).

The data he reported came from the National Health and Nutrition Examination Survey (NHANES) run by the CDC during 2013-2016 that included 11,055 adults who were at least 20 years old. The findings showed that 23% of those adults had taken at least one drug that was considered obesogenic during the 30 days preceding the survey date. By comparison, 35% of the same adults had taken any type of prescription drug during the previous 30 days. That meant that overall, 40% of surveyed adults who had recently used any prescription medication had taken an obesogenic drug.

The 23% prevalence of recent obesogenic drug use was fairly stable at that level during several preceding NHANES surveys going back to 2001, suggesting that the increasing use of obesogenic drugs during the period since 2001 was not a factor in the recent increased prevalence of obesity among U.S. residents, added Dr. Hales.

The 2013-2016 analysis also showed a strong link between obesogenic drug use and increasing obesity severity. Among survey participants with a body mass index (BMI) in the normal range (18.5-24 kg/m²), 16% had recent use of an obesogenic drug. This prevalence increased to 22% among those who were overweight (BMI, 25-29 kg/m²), 29% among those with class 1 or 2 obesity (BMI, 30-39 kg/m²), and 33% among those with class 3 obesity (BMI, 40 kg/m² or greater).

In contrast, recent use of prescription medications that do not contribute to obesity showed no significant relationship with BMI, with rates that ranged from 34% among those with a normal BMI, to 37% among those with class 3 obesity.

As an example of this relationship for a specific obesogenic drug class, the prevalence of beta-blocker use was about 7% among people with a normal BMI, about 10% among those who were overweight, about 14% among people with class 1 or 2 obesity, and about 17% among people with class 3 obesity, a statistically significant link suggesting that the relationship between use of obesogenic drugs and obesity is “bidirectional,” Dr. Hales said, in that increasing obesogenic drug use likely contributes to obesity, while simultaneously, the more obese people become, the more likely they are to take additional prescription drugs, particularly those that are obesogenic.

NHANES is run by the CDC and receives no commercial funding. The authors reported no conflicts of interest.

[email protected]

SOURCE: Hales CM et al. Obesity Week 2019, Abstract T-OR-2037.

LAS VEGAS – Nearly a quarter of American adults are on a prescription drug that often produces obesity as a side effect, and use of such obesogenic drugs was significantly higher among patients who already are obese, based on national U.S. data collected during 2013-2016.

Mitchel L. Zoler/MDedge News

The Endocrine Society, the STOP Obesity Alliance, and other medical societies have recommended that clinicians try to minimize use of obesogenic drugs and focus on prescribing agents that are weight neutral or that trigger weight loss when those options are available and appropriate, and the new findings add further evidence that clinicians need to be more mindful of this issue, Craig M. Hales, MD, said at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Among the American adults interviewed for the survey, 40% of those on at least one prescription medication were on at least one drug that is considered obesogenic, said Dr. Hales, a medical epidemiologist at the Centers for Disease Control and Prevention in Hyattsville, Md.

According to practice guidelines published by the Endocrine Society, all drugs in the classes of glucocorticoids, beta-blockers, and antihistamines are obesogenic, as well as selected agents in the classes of antidepressant drugs, antipsychotics, antidepressants, antidiabetics, and contraceptives that are progestin only, said Dr. Hales (J Clin Endocrinol Metab. 2015 Feb;100[2]:342-62).

The data he reported came from the National Health and Nutrition Examination Survey (NHANES) run by the CDC during 2013-2016 that included 11,055 adults who were at least 20 years old. The findings showed that 23% of those adults had taken at least one drug that was considered obesogenic during the 30 days preceding the survey date. By comparison, 35% of the same adults had taken any type of prescription drug during the previous 30 days. That meant that overall, 40% of surveyed adults who had recently used any prescription medication had taken an obesogenic drug.

The 23% prevalence of recent obesogenic drug use was fairly stable at that level during several preceding NHANES surveys going back to 2001, suggesting that the increasing use of obesogenic drugs during the period since 2001 was not a factor in the recent increased prevalence of obesity among U.S. residents, added Dr. Hales.

The 2013-2016 analysis also showed a strong link between obesogenic drug use and increasing obesity severity. Among survey participants with a body mass index (BMI) in the normal range (18.5-24 kg/m²), 16% had recent use of an obesogenic drug. This prevalence increased to 22% among those who were overweight (BMI, 25-29 kg/m²), 29% among those with class 1 or 2 obesity (BMI, 30-39 kg/m²), and 33% among those with class 3 obesity (BMI, 40 kg/m² or greater).

In contrast, recent use of prescription medications that do not contribute to obesity showed no significant relationship with BMI, with rates that ranged from 34% among those with a normal BMI, to 37% among those with class 3 obesity.

As an example of this relationship for a specific obesogenic drug class, the prevalence of beta-blocker use was about 7% among people with a normal BMI, about 10% among those who were overweight, about 14% among people with class 1 or 2 obesity, and about 17% among people with class 3 obesity, a statistically significant link suggesting that the relationship between use of obesogenic drugs and obesity is “bidirectional,” Dr. Hales said, in that increasing obesogenic drug use likely contributes to obesity, while simultaneously, the more obese people become, the more likely they are to take additional prescription drugs, particularly those that are obesogenic.

NHANES is run by the CDC and receives no commercial funding. The authors reported no conflicts of interest.

[email protected]

SOURCE: Hales CM et al. Obesity Week 2019, Abstract T-OR-2037.