Pediatricians and public health researchers know they have to be on the lookout for lead exposure from paint chips and contaminated drinking water. A new report suggests food – particularly baby food – could be a problem, too.

The Environmental Defense Fund, in an analysis of 11 years of federal data, found detectable levels of lead in 20% of 2,164 baby food samples. The toxic metal was most commonly found in fruit juices such as grape and apple, root vegetables such as sweet potatoes and carrots, and cookies such as teething biscuits.

The organization’s primary focus was on the baby foods because lead can be so detrimental to child development.

“Lead can have a number of effects on children, and it’s especially harmful during critical windows of development,” said Aparna Bole, MD, pediatrician at University Hospitals Rainbow Babies and Children’s Hospital in Cleveland, who was not involved with the report. “The largest burden that we often think about is neurocognitive that can occur even at low levels of lead exposure.”

Lead can cause problems with attention and behavior, cognitive development, the cardiovascular system, and immune system, Dr. Bole said.

The samples studied were not identified by brand, and the levels of lead are thought to be relatively low. Still, according to the Centers for Disease Control and Prevention, no safe blood lead level in children has been identified.

In a draft report released earlier this year, the Environmental Protection Agency estimated that over 5% of children consume more than 6 micrograms per day of lead – the maximum daily intake level set by the Food and Drug Administration in 1993 – in their diet.

This surprised Tom Neltner, JD, Environmental Defense Fund’s chemicals policy director, who has spent 20 years researching and working to reduce lead exposures. His further analysis of the EPA report was that food is the major source of lead exposure in two-thirds of toddlers.

This spurred the organization to examine data from the FDA’s Total Diet Study for specific sources of exposure for kids.

In the resulting report, releasedThursday, Mr. Neltner found that the baby food versions of apple juice, grape juice, and carrots had detectable lead more often than the regular versions. Researchers could determine how frequently contamination occurred, but not at what levels.

According to the FDA, lead makes its way into food through contaminated soil, but Mr. Neltner suspects that processing may also play a role.

“I can’t explain it other than I assume baby food is processed more,” Mr. Neltner said.

The Environmental Defense Fund report notes that more research on the sources of contamination is needed.

FDA has set guidance levels of 100 parts per billion (ppb) for candy and dried fruit and 50 ppb for fruit juices. The allowable level for lead in bottled water is 5 ppb.

Concern over fruit juices flared up in 2012 when Consumer Reports found that one in four samples of apple and grape juices had lead levels higher than the FDA’s bottled-water limit of 5 ppb.

“The FDA is continuing to work with industry to further limit the amount of lead in foods to the greatest extent feasible, especially in foods frequently consumed by children,” read an agency statement in response to the report. “The agency is in the process of reevaluating the analytical methods it uses for determining when it should take action with respect to measured levels of lead in particular foods, including those consumed by infants and toddlers.”

Mr. Neltner said he’s glad the FDA is working on the issue but wants them to “get it done. Move quicker.”

The Environmental Defense Fund isn’t recommending that parents avoid certain foods or brands for their children but does advise that they consult their pediatricians about all means of lead exposure.

“In many American communities, the most significant route of lead exposure is from paint and soil,” Dr. Bole said. “Avoiding all sources of exposure of lead poisoning is incredibly important … but the last thing I would want is for a parent to restrict their child’s diet or limit their intake of healthy food groups.”

She added that pediatricians recommend limiting or eliminating fruit juices from children’s diets, anyway, for nutritional reasons. “There are good reasons to limit juice other than this particular report,” Dr. Bole said.

But she said she wouldn’t want parents to avoid root vegetables altogether. “The benefits of those nutritious foods far outweigh any risk,” she said, especially in the context of where kids are most exposed to lead.

In response to a request for comment, Gerber said that samples of its baby foods and juices “consistently fall well within the available guidance levels and meet our own strict standards.” And samples of Gerber juices were all below the EPA standard for drinking water.

“We know parents may be concerned about a recent report on lead in foods and want to reassure them that Gerber foods and juices are safe,” the statement read.

The Environmental Defense Fund report was ultimately directed at the food industry and FDA in the hopes of getting limits and standards updated.

But lead in paint and drinking water shouldn’t fall by the wayside, Mr. Neltner said. “You’ve got to deal with this issue on multiple fronts.”
 

This story was produced by Kaiser Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Pediatricians and public health researchers know they have to be on the lookout for lead exposure from paint chips and contaminated drinking water. A new report suggests food – particularly baby food – could be a problem, too.

The Environmental Defense Fund, in an analysis of 11 years of federal data, found detectable levels of lead in 20% of 2,164 baby food samples. The toxic metal was most commonly found in fruit juices such as grape and apple, root vegetables such as sweet potatoes and carrots, and cookies such as teething biscuits.

The organization’s primary focus was on the baby foods because lead can be so detrimental to child development.

“Lead can have a number of effects on children, and it’s especially harmful during critical windows of development,” said Aparna Bole, MD, pediatrician at University Hospitals Rainbow Babies and Children’s Hospital in Cleveland, who was not involved with the report. “The largest burden that we often think about is neurocognitive that can occur even at low levels of lead exposure.”

Lead can cause problems with attention and behavior, cognitive development, the cardiovascular system, and immune system, Dr. Bole said.

The samples studied were not identified by brand, and the levels of lead are thought to be relatively low. Still, according to the Centers for Disease Control and Prevention, no safe blood lead level in children has been identified.

In a draft report released earlier this year, the Environmental Protection Agency estimated that over 5% of children consume more than 6 micrograms per day of lead – the maximum daily intake level set by the Food and Drug Administration in 1993 – in their diet.

This surprised Tom Neltner, JD, Environmental Defense Fund’s chemicals policy director, who has spent 20 years researching and working to reduce lead exposures. His further analysis of the EPA report was that food is the major source of lead exposure in two-thirds of toddlers.

This spurred the organization to examine data from the FDA’s Total Diet Study for specific sources of exposure for kids.

In the resulting report, releasedThursday, Mr. Neltner found that the baby food versions of apple juice, grape juice, and carrots had detectable lead more often than the regular versions. Researchers could determine how frequently contamination occurred, but not at what levels.

According to the FDA, lead makes its way into food through contaminated soil, but Mr. Neltner suspects that processing may also play a role.

“I can’t explain it other than I assume baby food is processed more,” Mr. Neltner said.

The Environmental Defense Fund report notes that more research on the sources of contamination is needed.

FDA has set guidance levels of 100 parts per billion (ppb) for candy and dried fruit and 50 ppb for fruit juices. The allowable level for lead in bottled water is 5 ppb.

Concern over fruit juices flared up in 2012 when Consumer Reports found that one in four samples of apple and grape juices had lead levels higher than the FDA’s bottled-water limit of 5 ppb.

“The FDA is continuing to work with industry to further limit the amount of lead in foods to the greatest extent feasible, especially in foods frequently consumed by children,” read an agency statement in response to the report. “The agency is in the process of reevaluating the analytical methods it uses for determining when it should take action with respect to measured levels of lead in particular foods, including those consumed by infants and toddlers.”

Mr. Neltner said he’s glad the FDA is working on the issue but wants them to “get it done. Move quicker.”

The Environmental Defense Fund isn’t recommending that parents avoid certain foods or brands for their children but does advise that they consult their pediatricians about all means of lead exposure.

“In many American communities, the most significant route of lead exposure is from paint and soil,” Dr. Bole said. “Avoiding all sources of exposure of lead poisoning is incredibly important … but the last thing I would want is for a parent to restrict their child’s diet or limit their intake of healthy food groups.”

She added that pediatricians recommend limiting or eliminating fruit juices from children’s diets, anyway, for nutritional reasons. “There are good reasons to limit juice other than this particular report,” Dr. Bole said.

But she said she wouldn’t want parents to avoid root vegetables altogether. “The benefits of those nutritious foods far outweigh any risk,” she said, especially in the context of where kids are most exposed to lead.

In response to a request for comment, Gerber said that samples of its baby foods and juices “consistently fall well within the available guidance levels and meet our own strict standards.” And samples of Gerber juices were all below the EPA standard for drinking water.

“We know parents may be concerned about a recent report on lead in foods and want to reassure them that Gerber foods and juices are safe,” the statement read.

The Environmental Defense Fund report was ultimately directed at the food industry and FDA in the hopes of getting limits and standards updated.

But lead in paint and drinking water shouldn’t fall by the wayside, Mr. Neltner said. “You’ve got to deal with this issue on multiple fronts.”
 

This story was produced by Kaiser Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Pediatricians and public health researchers know they have to be on the lookout for lead exposure from paint chips and contaminated drinking water. A new report suggests food – particularly baby food – could be a problem, too.

The Environmental Defense Fund, in an analysis of 11 years of federal data, found detectable levels of lead in 20% of 2,164 baby food samples. The toxic metal was most commonly found in fruit juices such as grape and apple, root vegetables such as sweet potatoes and carrots, and cookies such as teething biscuits.

The organization’s primary focus was on the baby foods because lead can be so detrimental to child development.

“Lead can have a number of effects on children, and it’s especially harmful during critical windows of development,” said Aparna Bole, MD, pediatrician at University Hospitals Rainbow Babies and Children’s Hospital in Cleveland, who was not involved with the report. “The largest burden that we often think about is neurocognitive that can occur even at low levels of lead exposure.”

Lead can cause problems with attention and behavior, cognitive development, the cardiovascular system, and immune system, Dr. Bole said.

The samples studied were not identified by brand, and the levels of lead are thought to be relatively low. Still, according to the Centers for Disease Control and Prevention, no safe blood lead level in children has been identified.

In a draft report released earlier this year, the Environmental Protection Agency estimated that over 5% of children consume more than 6 micrograms per day of lead – the maximum daily intake level set by the Food and Drug Administration in 1993 – in their diet.

This surprised Tom Neltner, JD, Environmental Defense Fund’s chemicals policy director, who has spent 20 years researching and working to reduce lead exposures. His further analysis of the EPA report was that food is the major source of lead exposure in two-thirds of toddlers.

This spurred the organization to examine data from the FDA’s Total Diet Study for specific sources of exposure for kids.

In the resulting report, releasedThursday, Mr. Neltner found that the baby food versions of apple juice, grape juice, and carrots had detectable lead more often than the regular versions. Researchers could determine how frequently contamination occurred, but not at what levels.

According to the FDA, lead makes its way into food through contaminated soil, but Mr. Neltner suspects that processing may also play a role.

“I can’t explain it other than I assume baby food is processed more,” Mr. Neltner said.

The Environmental Defense Fund report notes that more research on the sources of contamination is needed.

FDA has set guidance levels of 100 parts per billion (ppb) for candy and dried fruit and 50 ppb for fruit juices. The allowable level for lead in bottled water is 5 ppb.

Concern over fruit juices flared up in 2012 when Consumer Reports found that one in four samples of apple and grape juices had lead levels higher than the FDA’s bottled-water limit of 5 ppb.

“The FDA is continuing to work with industry to further limit the amount of lead in foods to the greatest extent feasible, especially in foods frequently consumed by children,” read an agency statement in response to the report. “The agency is in the process of reevaluating the analytical methods it uses for determining when it should take action with respect to measured levels of lead in particular foods, including those consumed by infants and toddlers.”

Mr. Neltner said he’s glad the FDA is working on the issue but wants them to “get it done. Move quicker.”

The Environmental Defense Fund isn’t recommending that parents avoid certain foods or brands for their children but does advise that they consult their pediatricians about all means of lead exposure.

“In many American communities, the most significant route of lead exposure is from paint and soil,” Dr. Bole said. “Avoiding all sources of exposure of lead poisoning is incredibly important … but the last thing I would want is for a parent to restrict their child’s diet or limit their intake of healthy food groups.”

She added that pediatricians recommend limiting or eliminating fruit juices from children’s diets, anyway, for nutritional reasons. “There are good reasons to limit juice other than this particular report,” Dr. Bole said.

But she said she wouldn’t want parents to avoid root vegetables altogether. “The benefits of those nutritious foods far outweigh any risk,” she said, especially in the context of where kids are most exposed to lead.

In response to a request for comment, Gerber said that samples of its baby foods and juices “consistently fall well within the available guidance levels and meet our own strict standards.” And samples of Gerber juices were all below the EPA standard for drinking water.

“We know parents may be concerned about a recent report on lead in foods and want to reassure them that Gerber foods and juices are safe,” the statement read.

The Environmental Defense Fund report was ultimately directed at the food industry and FDA in the hopes of getting limits and standards updated.

But lead in paint and drinking water shouldn’t fall by the wayside, Mr. Neltner said. “You’ve got to deal with this issue on multiple fronts.”
 

This story was produced by Kaiser Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

MADRID – With biosimilar infliximab on the U.S. market since November 2016 and producing an immediate, albeit modest, price drop for this tumor necrosis factor inhibitor (TNFi) and a second biosimilar infliximab now approved by the Food and Drug Administration and awaiting market entry, biosimilars are in a new phase of integration into U.S. practice.

“Physicians are willing to prescribe Inflectra,” the first biosimilar infliximab and the first TNFi to be sold in the United States last November, Jonathan Kay, MD, said in a video interview during the European Congress of Rheumatology. “Rheumatologists who were initially skeptical are now on the bandwagon and willing to prescribe biosimilars,” said Dr. Kay, a rheumatologist who has often consulted on biosimilar issues and has recently spoken to rheumatologists at various state society meetings to explain the U.S. biosimilar regulatory concepts and spread the message of the societal value of these agents.

“This is not a quick and casual drug evaluation” that produces “knockoff drugs,” but a “careful and extensive” FDA review that results in drugs that are equivalent in efficacy, safety, and immunogenicity to the reference drug and only compete on price, he explained.

When Pfizer began marketing Inflectra last Fall, it set the drug’s list price 15% lower than the list price at the time for Remicade, the reference-product infliximab. However, complex pricing and rebate strategies actually led to Remicade selling for a lower price than Inflectra, at least for some U.S. hospitals, including the University of Massachusetts in Worcester, where Dr. Kay is a professor of medicine.

“The effect of biosimilars is to reduce the cost to patients of an effective treatment. Whether that cost is for the reference drug or for the biosimilar drug doesn’t matter [from society’s perspective] as long as patients are able to receive an effective therapy at a [more] affordable cost, making the effective therapy available to more patients,” he said.

While Inflectra’s price impact my have been modest so far, the biosimilar effect on infliximab’s cost may soon intensify now that a second biosimilar of this TNFi, Renflexis – made by Samsung Bioepis and with U.S. marketing by Merck, received FDA approval on April 21, 2017. Until recently, U.S. pharmaceutical regulations had been understood to require a 180-day hiatus between FDA marketing approval for a biosimilar and the start of U.S. sales. But, on June 12, 2017, the U.S. Supreme Court, in a 9-0 decision, ruled that this 180-day wait was not required, making it possible for U.S. marketing of Renflexis to begin soon. (In mid-June, a statement on the Merck U.S. website for Renflexis says that the product is not currently available.)

Availability of a second biosimilar infliximab “is likely to drive the price down rapidly,” predicted Dr. Kay, citing what happened when multiple biosimilars for a reference drug came onto the European market.

Two other biosimilar TNFi have also received FDA marketing approvals but remain on hold as patent issues and litigation barriers play out. Erelzi – biosimilar etanercept – received FDA approval in August 2016, and Amjevita, biosimilar adalimumab, received FDA approval last September.

The efficacy and safety of Inflectra specifically, and by extension all biosimilars, received a recent boost with publication of findings from a randomized study with 482 patients that provided a real-world test of the core principle of biosimilar equivalence. After Inflectra came onto the Norwegian market, during July 2014 to August 2015, Norwegian researchers ran the NOR-SWTICH trial, which randomized patients who were on stable treatment with Remicade for a variety of indications (including 41% with a rheumatologic disease) to either stay on Remicade or to abruptly switch to treatment with Inflectra. During 1-year follow-up, the incidence of adverse effects and of episodes of disease worsening were virtually identical in the two treatment arms (Lancet. 2017 June 10;389[10086]:2304-16).

Dr. Kay has been a consultant to several companies that develop or market biosimilars, including Samsung Bioepis, Amgen, Pfizer, and Sandoz (Novartis), and to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Janssen, Roche, and UCB.

[email protected]

On Twitter @mitchelzoler

MADRID – With biosimilar infliximab on the U.S. market since November 2016 and producing an immediate, albeit modest, price drop for this tumor necrosis factor inhibitor (TNFi) and a second biosimilar infliximab now approved by the Food and Drug Administration and awaiting market entry, biosimilars are in a new phase of integration into U.S. practice.

“Physicians are willing to prescribe Inflectra,” the first biosimilar infliximab and the first TNFi to be sold in the United States last November, Jonathan Kay, MD, said in a video interview during the European Congress of Rheumatology. “Rheumatologists who were initially skeptical are now on the bandwagon and willing to prescribe biosimilars,” said Dr. Kay, a rheumatologist who has often consulted on biosimilar issues and has recently spoken to rheumatologists at various state society meetings to explain the U.S. biosimilar regulatory concepts and spread the message of the societal value of these agents.

“This is not a quick and casual drug evaluation” that produces “knockoff drugs,” but a “careful and extensive” FDA review that results in drugs that are equivalent in efficacy, safety, and immunogenicity to the reference drug and only compete on price, he explained.

When Pfizer began marketing Inflectra last Fall, it set the drug’s list price 15% lower than the list price at the time for Remicade, the reference-product infliximab. However, complex pricing and rebate strategies actually led to Remicade selling for a lower price than Inflectra, at least for some U.S. hospitals, including the University of Massachusetts in Worcester, where Dr. Kay is a professor of medicine.

“The effect of biosimilars is to reduce the cost to patients of an effective treatment. Whether that cost is for the reference drug or for the biosimilar drug doesn’t matter [from society’s perspective] as long as patients are able to receive an effective therapy at a [more] affordable cost, making the effective therapy available to more patients,” he said.

While Inflectra’s price impact my have been modest so far, the biosimilar effect on infliximab’s cost may soon intensify now that a second biosimilar of this TNFi, Renflexis – made by Samsung Bioepis and with U.S. marketing by Merck, received FDA approval on April 21, 2017. Until recently, U.S. pharmaceutical regulations had been understood to require a 180-day hiatus between FDA marketing approval for a biosimilar and the start of U.S. sales. But, on June 12, 2017, the U.S. Supreme Court, in a 9-0 decision, ruled that this 180-day wait was not required, making it possible for U.S. marketing of Renflexis to begin soon. (In mid-June, a statement on the Merck U.S. website for Renflexis says that the product is not currently available.)

Availability of a second biosimilar infliximab “is likely to drive the price down rapidly,” predicted Dr. Kay, citing what happened when multiple biosimilars for a reference drug came onto the European market.

Two other biosimilar TNFi have also received FDA marketing approvals but remain on hold as patent issues and litigation barriers play out. Erelzi – biosimilar etanercept – received FDA approval in August 2016, and Amjevita, biosimilar adalimumab, received FDA approval last September.

The efficacy and safety of Inflectra specifically, and by extension all biosimilars, received a recent boost with publication of findings from a randomized study with 482 patients that provided a real-world test of the core principle of biosimilar equivalence. After Inflectra came onto the Norwegian market, during July 2014 to August 2015, Norwegian researchers ran the NOR-SWTICH trial, which randomized patients who were on stable treatment with Remicade for a variety of indications (including 41% with a rheumatologic disease) to either stay on Remicade or to abruptly switch to treatment with Inflectra. During 1-year follow-up, the incidence of adverse effects and of episodes of disease worsening were virtually identical in the two treatment arms (Lancet. 2017 June 10;389[10086]:2304-16).

Dr. Kay has been a consultant to several companies that develop or market biosimilars, including Samsung Bioepis, Amgen, Pfizer, and Sandoz (Novartis), and to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Janssen, Roche, and UCB.

[email protected]

On Twitter @mitchelzoler

MADRID – With biosimilar infliximab on the U.S. market since November 2016 and producing an immediate, albeit modest, price drop for this tumor necrosis factor inhibitor (TNFi) and a second biosimilar infliximab now approved by the Food and Drug Administration and awaiting market entry, biosimilars are in a new phase of integration into U.S. practice.

“Physicians are willing to prescribe Inflectra,” the first biosimilar infliximab and the first TNFi to be sold in the United States last November, Jonathan Kay, MD, said in a video interview during the European Congress of Rheumatology. “Rheumatologists who were initially skeptical are now on the bandwagon and willing to prescribe biosimilars,” said Dr. Kay, a rheumatologist who has often consulted on biosimilar issues and has recently spoken to rheumatologists at various state society meetings to explain the U.S. biosimilar regulatory concepts and spread the message of the societal value of these agents.

“This is not a quick and casual drug evaluation” that produces “knockoff drugs,” but a “careful and extensive” FDA review that results in drugs that are equivalent in efficacy, safety, and immunogenicity to the reference drug and only compete on price, he explained.

When Pfizer began marketing Inflectra last Fall, it set the drug’s list price 15% lower than the list price at the time for Remicade, the reference-product infliximab. However, complex pricing and rebate strategies actually led to Remicade selling for a lower price than Inflectra, at least for some U.S. hospitals, including the University of Massachusetts in Worcester, where Dr. Kay is a professor of medicine.

“The effect of biosimilars is to reduce the cost to patients of an effective treatment. Whether that cost is for the reference drug or for the biosimilar drug doesn’t matter [from society’s perspective] as long as patients are able to receive an effective therapy at a [more] affordable cost, making the effective therapy available to more patients,” he said.

While Inflectra’s price impact my have been modest so far, the biosimilar effect on infliximab’s cost may soon intensify now that a second biosimilar of this TNFi, Renflexis – made by Samsung Bioepis and with U.S. marketing by Merck, received FDA approval on April 21, 2017. Until recently, U.S. pharmaceutical regulations had been understood to require a 180-day hiatus between FDA marketing approval for a biosimilar and the start of U.S. sales. But, on June 12, 2017, the U.S. Supreme Court, in a 9-0 decision, ruled that this 180-day wait was not required, making it possible for U.S. marketing of Renflexis to begin soon. (In mid-June, a statement on the Merck U.S. website for Renflexis says that the product is not currently available.)

Availability of a second biosimilar infliximab “is likely to drive the price down rapidly,” predicted Dr. Kay, citing what happened when multiple biosimilars for a reference drug came onto the European market.

Two other biosimilar TNFi have also received FDA marketing approvals but remain on hold as patent issues and litigation barriers play out. Erelzi – biosimilar etanercept – received FDA approval in August 2016, and Amjevita, biosimilar adalimumab, received FDA approval last September.

The efficacy and safety of Inflectra specifically, and by extension all biosimilars, received a recent boost with publication of findings from a randomized study with 482 patients that provided a real-world test of the core principle of biosimilar equivalence. After Inflectra came onto the Norwegian market, during July 2014 to August 2015, Norwegian researchers ran the NOR-SWTICH trial, which randomized patients who were on stable treatment with Remicade for a variety of indications (including 41% with a rheumatologic disease) to either stay on Remicade or to abruptly switch to treatment with Inflectra. During 1-year follow-up, the incidence of adverse effects and of episodes of disease worsening were virtually identical in the two treatment arms (Lancet. 2017 June 10;389[10086]:2304-16).

Dr. Kay has been a consultant to several companies that develop or market biosimilars, including Samsung Bioepis, Amgen, Pfizer, and Sandoz (Novartis), and to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Janssen, Roche, and UCB.

[email protected]

On Twitter @mitchelzoler

MADRID – Adding ultrasound exams to a treat to target (T2T) protocol did not improve remission outcomes in patients with rheumatoid arthritis.

In fact, seven-joint ultrasound actually reduced the chance that patients would achieve clinical remission in several remission assessment tools, Alexandre Sepriano, MD, said at the European Congress of Rheumatology.

“We saw no advantage in using ultrasound of seven joints in addition to clinical examination, compared to clinical examination alone,” said Dr. Sepriano of Leiden (the Netherlands) University Medical Center. “We can speculate on the reasons why, but, in truth, this is the same message we have now seen in two other studies.”

Subclinical, ultrasound-detected synovitis has been shown to be predictive of disease flare in people with rheumatoid arthritis (RA), suggesting that ultrasound may have a role in defining treatment strategies, but recent trials integrating musculoskeletal ultrasound assessments into a T2T protocol have not shown better outcomes than when standard clinical definitions of remission are used.

Dr. Sepriano presented findings from BIODAM, a 2-year observational cohort of RA patients across 10 countries who are managed under a T2T protocol.

Several studies, including BIODAM, have helped to establish T2T – which intensifies treatment if patients are not in remission and eases treatment intensity when patients are in remission – as an optimal management strategy in RA. Dr. Sepriano and his colleagues set out to learn whether using ultrasound data in T2T would result in better outcomes, by creating a combined new strategy using both ultrasound and clinical measures, than does use of the established T2T strategy that uses only clinical data.

To do this, they looked at a subgroup of 130 patients from six countries who were treated at the BIODAM centers that had expertise in ultrasound. Patients’ clinical and ultrasound data were collected every 3 months through 2 years (for 1,037 visits in total) and were managed by rheumatologists under established T2T protocols. These patients were a mean of 55 years old, with a mean disease duration of 6 years.

As in the broader BIODAM study, the researchers used multiple clinical definitions of remission, including 28-joint and 44-joint Disease Activity Scores and the European League against Rheumatism/American College of Rheumatology–Boolean criteria. For the ultrasound measure, they used the previously validated US-7, which looks at seven joints for signs of synovitis.

In general, the proportion of patients in clinical remission rose over the study period, no matter what assessment tool was used. However, Dr. Sepriano and his colleagues found that the combined clinical and ultrasound benchmark for T2T decreased the likelihood of DAS-44 clinical remission after 3 months by 41% when compared with the conventional strategy. The story was similar for other assessments: The reduction was 49% on the DAS-28, 55% on Boolean remission, and 66% on Simple Disease Activity Index remission.

The reasons for this finding are difficult to discern, Dr. Sepriano said, and are complicated by the fact that this study was not a randomized, controlled trial but a longitudinal cohort in real-world practice settings.

Given the many variables involved, Dr. Sepriano said, “it may be not entirely linear to have an explanation as to why, when we used ultrasound, we actually got worse results.”

But, he noted, results from two randomized trials in more restricted populations of RA patients have also shown no benefit from adding ultrasound.

“What the data are telling us is that the clinician should be encouraged to use clinical data in his or her decisions – so we stress the importance of following a T2T strategy according to clinical data,” Dr. Sepriano said. “Adding ultrasound may not be an advantage in this scenario.”

Additional studies may end up changing this outlook on ultrasound, but, for now, the evidence does not exist, he said in a video interview.

Dr. Sepriano and his associates had no conflicts of interest to declare.

MADRID – Adding ultrasound exams to a treat to target (T2T) protocol did not improve remission outcomes in patients with rheumatoid arthritis.

In fact, seven-joint ultrasound actually reduced the chance that patients would achieve clinical remission in several remission assessment tools, Alexandre Sepriano, MD, said at the European Congress of Rheumatology.

“We saw no advantage in using ultrasound of seven joints in addition to clinical examination, compared to clinical examination alone,” said Dr. Sepriano of Leiden (the Netherlands) University Medical Center. “We can speculate on the reasons why, but, in truth, this is the same message we have now seen in two other studies.”

Subclinical, ultrasound-detected synovitis has been shown to be predictive of disease flare in people with rheumatoid arthritis (RA), suggesting that ultrasound may have a role in defining treatment strategies, but recent trials integrating musculoskeletal ultrasound assessments into a T2T protocol have not shown better outcomes than when standard clinical definitions of remission are used.

Dr. Sepriano presented findings from BIODAM, a 2-year observational cohort of RA patients across 10 countries who are managed under a T2T protocol.

Several studies, including BIODAM, have helped to establish T2T – which intensifies treatment if patients are not in remission and eases treatment intensity when patients are in remission – as an optimal management strategy in RA. Dr. Sepriano and his colleagues set out to learn whether using ultrasound data in T2T would result in better outcomes, by creating a combined new strategy using both ultrasound and clinical measures, than does use of the established T2T strategy that uses only clinical data.

To do this, they looked at a subgroup of 130 patients from six countries who were treated at the BIODAM centers that had expertise in ultrasound. Patients’ clinical and ultrasound data were collected every 3 months through 2 years (for 1,037 visits in total) and were managed by rheumatologists under established T2T protocols. These patients were a mean of 55 years old, with a mean disease duration of 6 years.

As in the broader BIODAM study, the researchers used multiple clinical definitions of remission, including 28-joint and 44-joint Disease Activity Scores and the European League against Rheumatism/American College of Rheumatology–Boolean criteria. For the ultrasound measure, they used the previously validated US-7, which looks at seven joints for signs of synovitis.

In general, the proportion of patients in clinical remission rose over the study period, no matter what assessment tool was used. However, Dr. Sepriano and his colleagues found that the combined clinical and ultrasound benchmark for T2T decreased the likelihood of DAS-44 clinical remission after 3 months by 41% when compared with the conventional strategy. The story was similar for other assessments: The reduction was 49% on the DAS-28, 55% on Boolean remission, and 66% on Simple Disease Activity Index remission.

The reasons for this finding are difficult to discern, Dr. Sepriano said, and are complicated by the fact that this study was not a randomized, controlled trial but a longitudinal cohort in real-world practice settings.

Given the many variables involved, Dr. Sepriano said, “it may be not entirely linear to have an explanation as to why, when we used ultrasound, we actually got worse results.”

But, he noted, results from two randomized trials in more restricted populations of RA patients have also shown no benefit from adding ultrasound.

“What the data are telling us is that the clinician should be encouraged to use clinical data in his or her decisions – so we stress the importance of following a T2T strategy according to clinical data,” Dr. Sepriano said. “Adding ultrasound may not be an advantage in this scenario.”

Additional studies may end up changing this outlook on ultrasound, but, for now, the evidence does not exist, he said in a video interview.

Dr. Sepriano and his associates had no conflicts of interest to declare.

MADRID – Adding ultrasound exams to a treat to target (T2T) protocol did not improve remission outcomes in patients with rheumatoid arthritis.

In fact, seven-joint ultrasound actually reduced the chance that patients would achieve clinical remission in several remission assessment tools, Alexandre Sepriano, MD, said at the European Congress of Rheumatology.

“We saw no advantage in using ultrasound of seven joints in addition to clinical examination, compared to clinical examination alone,” said Dr. Sepriano of Leiden (the Netherlands) University Medical Center. “We can speculate on the reasons why, but, in truth, this is the same message we have now seen in two other studies.”

Subclinical, ultrasound-detected synovitis has been shown to be predictive of disease flare in people with rheumatoid arthritis (RA), suggesting that ultrasound may have a role in defining treatment strategies, but recent trials integrating musculoskeletal ultrasound assessments into a T2T protocol have not shown better outcomes than when standard clinical definitions of remission are used.

Dr. Sepriano presented findings from BIODAM, a 2-year observational cohort of RA patients across 10 countries who are managed under a T2T protocol.

Several studies, including BIODAM, have helped to establish T2T – which intensifies treatment if patients are not in remission and eases treatment intensity when patients are in remission – as an optimal management strategy in RA. Dr. Sepriano and his colleagues set out to learn whether using ultrasound data in T2T would result in better outcomes, by creating a combined new strategy using both ultrasound and clinical measures, than does use of the established T2T strategy that uses only clinical data.

To do this, they looked at a subgroup of 130 patients from six countries who were treated at the BIODAM centers that had expertise in ultrasound. Patients’ clinical and ultrasound data were collected every 3 months through 2 years (for 1,037 visits in total) and were managed by rheumatologists under established T2T protocols. These patients were a mean of 55 years old, with a mean disease duration of 6 years.

As in the broader BIODAM study, the researchers used multiple clinical definitions of remission, including 28-joint and 44-joint Disease Activity Scores and the European League against Rheumatism/American College of Rheumatology–Boolean criteria. For the ultrasound measure, they used the previously validated US-7, which looks at seven joints for signs of synovitis.

In general, the proportion of patients in clinical remission rose over the study period, no matter what assessment tool was used. However, Dr. Sepriano and his colleagues found that the combined clinical and ultrasound benchmark for T2T decreased the likelihood of DAS-44 clinical remission after 3 months by 41% when compared with the conventional strategy. The story was similar for other assessments: The reduction was 49% on the DAS-28, 55% on Boolean remission, and 66% on Simple Disease Activity Index remission.

The reasons for this finding are difficult to discern, Dr. Sepriano said, and are complicated by the fact that this study was not a randomized, controlled trial but a longitudinal cohort in real-world practice settings.

Given the many variables involved, Dr. Sepriano said, “it may be not entirely linear to have an explanation as to why, when we used ultrasound, we actually got worse results.”

But, he noted, results from two randomized trials in more restricted populations of RA patients have also shown no benefit from adding ultrasound.

“What the data are telling us is that the clinician should be encouraged to use clinical data in his or her decisions – so we stress the importance of following a T2T strategy according to clinical data,” Dr. Sepriano said. “Adding ultrasound may not be an advantage in this scenario.”

Additional studies may end up changing this outlook on ultrasound, but, for now, the evidence does not exist, he said in a video interview.

Dr. Sepriano and his associates had no conflicts of interest to declare.

MADRID – Pain is common in patients with psoriatic arthritis (PsA) and can be disruptive to their lives and jobs, even among those whose inflammatory symptoms have been treated with biologic drugs for 3 months or longer, according to findings from a multinational survey.

At the European Congress of Rheumatology, Dr. Philip G. Conaghan of the University of Leeds (England) presented findings from the survey of 782 consecutive PsA patients from 13 countries in Europe, the Middle East, Asia, and the Americas, as well as Australia. All patients included in the analysis were on biologic agents – mainly tumor necrosis factor inhibitors – for at least 90 days.

EULAR2017 - Streaming.hr

MADRID – Pain is common in patients with psoriatic arthritis (PsA) and can be disruptive to their lives and jobs, even among those whose inflammatory symptoms have been treated with biologic drugs for 3 months or longer, according to findings from a multinational survey.

At the European Congress of Rheumatology, Dr. Philip G. Conaghan of the University of Leeds (England) presented findings from the survey of 782 consecutive PsA patients from 13 countries in Europe, the Middle East, Asia, and the Americas, as well as Australia. All patients included in the analysis were on biologic agents – mainly tumor necrosis factor inhibitors – for at least 90 days.

EULAR2017 - Streaming.hr

MADRID – Pain is common in patients with psoriatic arthritis (PsA) and can be disruptive to their lives and jobs, even among those whose inflammatory symptoms have been treated with biologic drugs for 3 months or longer, according to findings from a multinational survey.

At the European Congress of Rheumatology, Dr. Philip G. Conaghan of the University of Leeds (England) presented findings from the survey of 782 consecutive PsA patients from 13 countries in Europe, the Middle East, Asia, and the Americas, as well as Australia. All patients included in the analysis were on biologic agents – mainly tumor necrosis factor inhibitors – for at least 90 days.

EULAR2017 - Streaming.hr

Presenter

Neal Birnbaum, MD

Session Summary

Dr. Birnbaum began with the differential diagnosis of acute monoarthritis, which is one of the more common reasons for inpatient rheumatology consultation and includes crystalline (e.g., gout), septic, autoimmune (psoriasis), traumatic, and hemorrhagic.

The synovial fluid will give an idea as to whether one is more likely than the other, he said. Normal synovial fluid is transparent, clear, has a low cell count, and is very viscous in nature. Noninflammatory etiologies (osteoarthritis) will have some cells but will largely be similar to normal synovial fluid. Inflammatory causes will have higher cell counts (2-10K WBC) but will have much lower viscosity. Septic joints will look pustular with very high cell counts (sometimes too high to be recorded) and will be positive on fluid culture (unless the patient has already received antimicrobial therapy). Hemorrhagic fluid will look like blood, and the history will give clues as to whether that is the case (recent trauma, history of hemophilia).

Key takeaways for HM

• Know the differential diagnosis of acute monoarticular arthritis and how the synovial fluid will vary depending on the diagnosis.
• Gout can manifest in other joints besides the first toe. One can use allopurinol even in the acute setting. The goal is to attain a uric acid level of less than 6.0.
• Pseudogout should be considered in patients older than 70 years with acute arthritis. There is no allopurinol equivalent for chronic management.
• Positive ANAs are common, but they do not make the diagnosis of SLE (although a negative ANA generally does rule out SLE).
• SLE is a clinical diagnosis that requires multiple symptoms and findings to make the diagnosis. Please refer to the ACR classification criteria.
• Think of vasculitis in terms of small versus large vessel disease and think of the differential diagnosis as to the etiology (realizing that 33%-50% will end up being idiopathic).
• Chikungunya is mosquito-borne and associated with severe joint pains, headaches, and fevers but can also have joint swelling. While often acute, the symptoms can last for up to a year. Treatment is symptomatic management.
• Think of IgG4-related disease in patients with pancreatitis without the usual causes (alcohol, gallstones). Diagnosis is based on pathology and IgG4 levels. Treatment is with steroids and/or rituximab.

Dr. Kim is a hospitalist who works at Emory University Hospital in Atlanta and is an editorial board member of The Hospitalist.

Presenter

Neal Birnbaum, MD

Session Summary

Dr. Birnbaum began with the differential diagnosis of acute monoarthritis, which is one of the more common reasons for inpatient rheumatology consultation and includes crystalline (e.g., gout), septic, autoimmune (psoriasis), traumatic, and hemorrhagic.

The synovial fluid will give an idea as to whether one is more likely than the other, he said. Normal synovial fluid is transparent, clear, has a low cell count, and is very viscous in nature. Noninflammatory etiologies (osteoarthritis) will have some cells but will largely be similar to normal synovial fluid. Inflammatory causes will have higher cell counts (2-10K WBC) but will have much lower viscosity. Septic joints will look pustular with very high cell counts (sometimes too high to be recorded) and will be positive on fluid culture (unless the patient has already received antimicrobial therapy). Hemorrhagic fluid will look like blood, and the history will give clues as to whether that is the case (recent trauma, history of hemophilia).

Key takeaways for HM

• Know the differential diagnosis of acute monoarticular arthritis and how the synovial fluid will vary depending on the diagnosis.
• Gout can manifest in other joints besides the first toe. One can use allopurinol even in the acute setting. The goal is to attain a uric acid level of less than 6.0.
• Pseudogout should be considered in patients older than 70 years with acute arthritis. There is no allopurinol equivalent for chronic management.
• Positive ANAs are common, but they do not make the diagnosis of SLE (although a negative ANA generally does rule out SLE).
• SLE is a clinical diagnosis that requires multiple symptoms and findings to make the diagnosis. Please refer to the ACR classification criteria.
• Think of vasculitis in terms of small versus large vessel disease and think of the differential diagnosis as to the etiology (realizing that 33%-50% will end up being idiopathic).
• Chikungunya is mosquito-borne and associated with severe joint pains, headaches, and fevers but can also have joint swelling. While often acute, the symptoms can last for up to a year. Treatment is symptomatic management.
• Think of IgG4-related disease in patients with pancreatitis without the usual causes (alcohol, gallstones). Diagnosis is based on pathology and IgG4 levels. Treatment is with steroids and/or rituximab.

Dr. Kim is a hospitalist who works at Emory University Hospital in Atlanta and is an editorial board member of The Hospitalist.

Presenter

Neal Birnbaum, MD

Session Summary

Dr. Birnbaum began with the differential diagnosis of acute monoarthritis, which is one of the more common reasons for inpatient rheumatology consultation and includes crystalline (e.g., gout), septic, autoimmune (psoriasis), traumatic, and hemorrhagic.

The synovial fluid will give an idea as to whether one is more likely than the other, he said. Normal synovial fluid is transparent, clear, has a low cell count, and is very viscous in nature. Noninflammatory etiologies (osteoarthritis) will have some cells but will largely be similar to normal synovial fluid. Inflammatory causes will have higher cell counts (2-10K WBC) but will have much lower viscosity. Septic joints will look pustular with very high cell counts (sometimes too high to be recorded) and will be positive on fluid culture (unless the patient has already received antimicrobial therapy). Hemorrhagic fluid will look like blood, and the history will give clues as to whether that is the case (recent trauma, history of hemophilia).

Key takeaways for HM

• Know the differential diagnosis of acute monoarticular arthritis and how the synovial fluid will vary depending on the diagnosis.
• Gout can manifest in other joints besides the first toe. One can use allopurinol even in the acute setting. The goal is to attain a uric acid level of less than 6.0.
• Pseudogout should be considered in patients older than 70 years with acute arthritis. There is no allopurinol equivalent for chronic management.
• Positive ANAs are common, but they do not make the diagnosis of SLE (although a negative ANA generally does rule out SLE).
• SLE is a clinical diagnosis that requires multiple symptoms and findings to make the diagnosis. Please refer to the ACR classification criteria.
• Think of vasculitis in terms of small versus large vessel disease and think of the differential diagnosis as to the etiology (realizing that 33%-50% will end up being idiopathic).
• Chikungunya is mosquito-borne and associated with severe joint pains, headaches, and fevers but can also have joint swelling. While often acute, the symptoms can last for up to a year. Treatment is symptomatic management.
• Think of IgG4-related disease in patients with pancreatitis without the usual causes (alcohol, gallstones). Diagnosis is based on pathology and IgG4 levels. Treatment is with steroids and/or rituximab.

Dr. Kim is a hospitalist who works at Emory University Hospital in Atlanta and is an editorial board member of The Hospitalist.

CHICAGO – After Shirley A. Mertz, JD, was diagnosed with metastatic breast cancer, she was surprised to learn the government wasn’t counting people like her in data gathered on the disease. Only a minority of women with the disease – those diagnosed de novo – are included in Surveillance, Epidemiology and End Results (SEER) data, she said in a video interview at the annual meeting of the American Society of Clinical Oncology.

A recently published report by a National Cancer Institute mathematician and her associates estimates that about 155,000 women are living with metastatic breast cancer and that three-quarters of those women were initially diagnosed with lower-stage disease that progressed to stage IV. Ms. Mertz, president of the Metastatic Breast Cancer Network, says the estimate is a good start, but it’s important to go further and include those diagnosed with a metastatic recurrence in SEER data to get an accurate view.

“If we are not counted, then it appears we don’t matter, and how can we know if we are doing better if we don’t know how many of us are out there,” she said.

[email protected]

On Twitter @NikolaidesLaura

CHICAGO – After Shirley A. Mertz, JD, was diagnosed with metastatic breast cancer, she was surprised to learn the government wasn’t counting people like her in data gathered on the disease. Only a minority of women with the disease – those diagnosed de novo – are included in Surveillance, Epidemiology and End Results (SEER) data, she said in a video interview at the annual meeting of the American Society of Clinical Oncology.

A recently published report by a National Cancer Institute mathematician and her associates estimates that about 155,000 women are living with metastatic breast cancer and that three-quarters of those women were initially diagnosed with lower-stage disease that progressed to stage IV. Ms. Mertz, president of the Metastatic Breast Cancer Network, says the estimate is a good start, but it’s important to go further and include those diagnosed with a metastatic recurrence in SEER data to get an accurate view.

“If we are not counted, then it appears we don’t matter, and how can we know if we are doing better if we don’t know how many of us are out there,” she said.

[email protected]

On Twitter @NikolaidesLaura

CHICAGO – After Shirley A. Mertz, JD, was diagnosed with metastatic breast cancer, she was surprised to learn the government wasn’t counting people like her in data gathered on the disease. Only a minority of women with the disease – those diagnosed de novo – are included in Surveillance, Epidemiology and End Results (SEER) data, she said in a video interview at the annual meeting of the American Society of Clinical Oncology.

A recently published report by a National Cancer Institute mathematician and her associates estimates that about 155,000 women are living with metastatic breast cancer and that three-quarters of those women were initially diagnosed with lower-stage disease that progressed to stage IV. Ms. Mertz, president of the Metastatic Breast Cancer Network, says the estimate is a good start, but it’s important to go further and include those diagnosed with a metastatic recurrence in SEER data to get an accurate view.

“If we are not counted, then it appears we don’t matter, and how can we know if we are doing better if we don’t know how many of us are out there,” she said.

[email protected]

On Twitter @NikolaidesLaura

SAN DIEGO – A new study reports that about half of assessed U.S. veterans with schizophrenia or bipolar I disorder have tried to kill themselves. Nearly 70% of those with schizophrenia had documented suicidal behavior or ideation, as did more than 82% of those with bipolar I disorder.

“The VA struggles to predict suicidal ideation and behavior,” said study lead author Philip D. Harvey, PhD, of the Carter VA Medical Center in Miami, in an interview. “These data suggest that having one of these diagnoses is a major risk factor. Regular assessment makes considerable sense.”

Dr. Harvey released the study findings in a poster at the annual meeting of the American Psychiatric Association.

For the study, Dr. Harvey and his colleagues examined findings from a VA research project into the genetics behind functional disability in schizophrenia and bipolar illness.

“We know that suicide risk is higher in veterans than in the general population. We also know that the current focus is on returning veterans who were deployed in combat operations,” said Dr. Harvey, who also is affiliated with the University of Miami. “We wanted to evaluate the risk for suicidal ideation and behavior in the segment of the veteran population who have recently or ever been exposed to military trauma.”

The project assessed VA patients with schizophrenia (N = 3,941) or bipolar I disorder (N = 5,414) through in-person evaluations regarding issues like cognitive and functional status, and history of posttraumatic stress disorder. All of the subjects were outpatients at 26 VA medical centers.

Combined, the mean age of the study participants was 53.6 years, plus or minus 11 years, and 86.2% were male. Whites made up 57.4% of the sample, followed by blacks (37.0%) and other (5.6%). A total of 27% had no comorbid psychiatric conditions.

The study authors found documented suicidal ideation or suicidal behavior in 69.9% of veterans with schizophrenia and 82.3% of those with bipolar disorder; the percentages who reported making actual suicide attempts was 46.1% schizophrenia and 54.5% bipolar disorder.

The risk of suicidal ideation was lower in schizophrenia vs. bipolar disorder (odds ratio, 0.82; 95% confidence interval, 0.71-0.95), as was suicidal behavior (OR, 0.81; 95% CI, 0.71-0.93).

Dr. Harvey said this is not surprising. “The combination of a history of euphoric mood and significant depression [characteristic of bipolar disorder] is very challenging.”

Other factors lowered risk: College education vs. high school or less (OR, 0.82; 95% CI, 0.67-1.00 for ideation; OR, 0.70; 95% CI, 0.58-0.84 for behavior). In addition, lower risk was found among black vs. white patients (OR, 0.72; 95% CI, 0.63-0.84 for ideation; OR, 0.82; 95% CI, 0.72-0.93, for behavior).

These factors boosted risk: multiple psychiatric comorbidities vs. none (OR, 2.61; 95% CI, 2.22-3.07 for ideation; OR, 3.82; 95% CI, 3.30-4.41, for behavior), and those with a history of being ever vs. never married (OR, 1.18; 95% CI, 1.02-1.37 for ideation; OR, 1.36; 95% CI, 1.19-1.55, for behavior). Most of those who had been married later were divorced.

“These findings underscore the need for continuous monitoring for suicidality in veteran populations, regardless of age or psychiatric diagnosis, and especially with multiple psychiatric comorbidities,” the authors wrote.

The study was funded by the Department of Veterans Affairs Cooperative Study Program. Dr. Harvey reported no relevant disclosures.
 

SAN DIEGO – A new study reports that about half of assessed U.S. veterans with schizophrenia or bipolar I disorder have tried to kill themselves. Nearly 70% of those with schizophrenia had documented suicidal behavior or ideation, as did more than 82% of those with bipolar I disorder.

“The VA struggles to predict suicidal ideation and behavior,” said study lead author Philip D. Harvey, PhD, of the Carter VA Medical Center in Miami, in an interview. “These data suggest that having one of these diagnoses is a major risk factor. Regular assessment makes considerable sense.”

Dr. Harvey released the study findings in a poster at the annual meeting of the American Psychiatric Association.

For the study, Dr. Harvey and his colleagues examined findings from a VA research project into the genetics behind functional disability in schizophrenia and bipolar illness.

“We know that suicide risk is higher in veterans than in the general population. We also know that the current focus is on returning veterans who were deployed in combat operations,” said Dr. Harvey, who also is affiliated with the University of Miami. “We wanted to evaluate the risk for suicidal ideation and behavior in the segment of the veteran population who have recently or ever been exposed to military trauma.”

The project assessed VA patients with schizophrenia (N = 3,941) or bipolar I disorder (N = 5,414) through in-person evaluations regarding issues like cognitive and functional status, and history of posttraumatic stress disorder. All of the subjects were outpatients at 26 VA medical centers.

Combined, the mean age of the study participants was 53.6 years, plus or minus 11 years, and 86.2% were male. Whites made up 57.4% of the sample, followed by blacks (37.0%) and other (5.6%). A total of 27% had no comorbid psychiatric conditions.

The study authors found documented suicidal ideation or suicidal behavior in 69.9% of veterans with schizophrenia and 82.3% of those with bipolar disorder; the percentages who reported making actual suicide attempts was 46.1% schizophrenia and 54.5% bipolar disorder.

The risk of suicidal ideation was lower in schizophrenia vs. bipolar disorder (odds ratio, 0.82; 95% confidence interval, 0.71-0.95), as was suicidal behavior (OR, 0.81; 95% CI, 0.71-0.93).

Dr. Harvey said this is not surprising. “The combination of a history of euphoric mood and significant depression [characteristic of bipolar disorder] is very challenging.”

Other factors lowered risk: College education vs. high school or less (OR, 0.82; 95% CI, 0.67-1.00 for ideation; OR, 0.70; 95% CI, 0.58-0.84 for behavior). In addition, lower risk was found among black vs. white patients (OR, 0.72; 95% CI, 0.63-0.84 for ideation; OR, 0.82; 95% CI, 0.72-0.93, for behavior).

These factors boosted risk: multiple psychiatric comorbidities vs. none (OR, 2.61; 95% CI, 2.22-3.07 for ideation; OR, 3.82; 95% CI, 3.30-4.41, for behavior), and those with a history of being ever vs. never married (OR, 1.18; 95% CI, 1.02-1.37 for ideation; OR, 1.36; 95% CI, 1.19-1.55, for behavior). Most of those who had been married later were divorced.

“These findings underscore the need for continuous monitoring for suicidality in veteran populations, regardless of age or psychiatric diagnosis, and especially with multiple psychiatric comorbidities,” the authors wrote.

The study was funded by the Department of Veterans Affairs Cooperative Study Program. Dr. Harvey reported no relevant disclosures.
 

SAN DIEGO – A new study reports that about half of assessed U.S. veterans with schizophrenia or bipolar I disorder have tried to kill themselves. Nearly 70% of those with schizophrenia had documented suicidal behavior or ideation, as did more than 82% of those with bipolar I disorder.

“The VA struggles to predict suicidal ideation and behavior,” said study lead author Philip D. Harvey, PhD, of the Carter VA Medical Center in Miami, in an interview. “These data suggest that having one of these diagnoses is a major risk factor. Regular assessment makes considerable sense.”

Dr. Harvey released the study findings in a poster at the annual meeting of the American Psychiatric Association.

For the study, Dr. Harvey and his colleagues examined findings from a VA research project into the genetics behind functional disability in schizophrenia and bipolar illness.

“We know that suicide risk is higher in veterans than in the general population. We also know that the current focus is on returning veterans who were deployed in combat operations,” said Dr. Harvey, who also is affiliated with the University of Miami. “We wanted to evaluate the risk for suicidal ideation and behavior in the segment of the veteran population who have recently or ever been exposed to military trauma.”

The project assessed VA patients with schizophrenia (N = 3,941) or bipolar I disorder (N = 5,414) through in-person evaluations regarding issues like cognitive and functional status, and history of posttraumatic stress disorder. All of the subjects were outpatients at 26 VA medical centers.

Combined, the mean age of the study participants was 53.6 years, plus or minus 11 years, and 86.2% were male. Whites made up 57.4% of the sample, followed by blacks (37.0%) and other (5.6%). A total of 27% had no comorbid psychiatric conditions.

The study authors found documented suicidal ideation or suicidal behavior in 69.9% of veterans with schizophrenia and 82.3% of those with bipolar disorder; the percentages who reported making actual suicide attempts was 46.1% schizophrenia and 54.5% bipolar disorder.

The risk of suicidal ideation was lower in schizophrenia vs. bipolar disorder (odds ratio, 0.82; 95% confidence interval, 0.71-0.95), as was suicidal behavior (OR, 0.81; 95% CI, 0.71-0.93).

Dr. Harvey said this is not surprising. “The combination of a history of euphoric mood and significant depression [characteristic of bipolar disorder] is very challenging.”

Other factors lowered risk: College education vs. high school or less (OR, 0.82; 95% CI, 0.67-1.00 for ideation; OR, 0.70; 95% CI, 0.58-0.84 for behavior). In addition, lower risk was found among black vs. white patients (OR, 0.72; 95% CI, 0.63-0.84 for ideation; OR, 0.82; 95% CI, 0.72-0.93, for behavior).

These factors boosted risk: multiple psychiatric comorbidities vs. none (OR, 2.61; 95% CI, 2.22-3.07 for ideation; OR, 3.82; 95% CI, 3.30-4.41, for behavior), and those with a history of being ever vs. never married (OR, 1.18; 95% CI, 1.02-1.37 for ideation; OR, 1.36; 95% CI, 1.19-1.55, for behavior). Most of those who had been married later were divorced.

“These findings underscore the need for continuous monitoring for suicidality in veteran populations, regardless of age or psychiatric diagnosis, and especially with multiple psychiatric comorbidities,” the authors wrote.

The study was funded by the Department of Veterans Affairs Cooperative Study Program. Dr. Harvey reported no relevant disclosures.
 

Photo © ASCO/Danny Morton 2017

CHICAGO—The experimental mutant IDH2 (mIDH2) inhibitor enasidenib has produced “admirable” overall survival in patients with mIDH2 relapsed or refractory acute myeloid leukemia (AML), according to Eytan M. Stein, MD, an investigator on the phase 1 dose escalation and expansion study.

Patients who achieved a complete remission (CR) had a median overall survival (OS) of 19.7 months and non-CR responders, 13.8 months.

“I really want to make the point,” Dr Stein said, “this is a group of patients that are highly refractory, either refractory to induction chemotherapy, refractory to standard of care approaches for patients who are unable to get induction chemotherapy, so refractory to hypomethylating agents or low-dose cytarabine.”

Mutations in IDH2 occur in approximately 12% of AML patients.

Dr Stein explained that the mutant protein converts alpha ketoglutarate to beta hydroxyglutarate (2-HG). And increased levels of intracellular 2-HG lead to methylation changes in the cell that cause a block in myeloid differentiation.

Enasidenib, also known as AG-221, is a selective, oral, potent inhibitor of the mIDH2 enzyyme.

Dr Stein, of Memorial Sloan Kettering Cancer Center in New York, New York, presented the results during the ASCO 2017 Annual Meeting (abstract 7004).

The clinical and translational papers were published simultaneously in Blood.

Study design

The phase 1/2 study had a large dose-escalation component, with 113 patients enrolled. Patients had to have an advanced hematologic malignancy with an IDH2 mutation.

Patients received cumulative daily doses of 50 mg – 650 mg of enasidenib in continuous 28-day cycles.

Four expansion arms were added, with 126 patients.

Two expansion arms were in relapsed/refractory AML patients: one in patients 60 years or older or any age if they had relapsed after bone marrow transplant (BMT), and the other in patients younger than 60 excluding those relapsed after BMT.

The other 2 expansion arms were in untreated AML patients and in patients with any hematologic malignancy ineligible for the other arms.

Dr Stein presented results for the relapsed/refractory AML patients in the dose escalation and expansion phases of the study.

The key endpoints were safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicities; response rates as assessed by the local investigator according to IWG criteria; and assessment of clinical activity.

Dr Stein noted the phase 2 study is now completely accrued (n=91) and the recommended enasidenib dose is 100 mg/day in relapsed/refractory AML.

The MTD was not reached at doses up to 650 mg/day.

Baseline characteristics

Median age of all 239 phase 1 patients was 70 years (range, 19-100), 57% were male, and almost all patients had intermediate- or poor-risk disease.

The investigators were also interested in the co-occurring mutations in patients on screening and whether there were differences between patients with mIDH2 at R172 and R140.

Seventy-five percent of the patients (n=179) had R140 and 24% had R172 (n=57).

There was a statistically significant difference in the number of co-occurring mutations in the R140 and R172 patients, with the R140 patients having a higher co-mutation burden compared with the R172 patients, (P=0.020).

The most frequent mutations co-occurring in R140 patients were SRSF2, followed by, in descending order of frequency, DNMT3A, RUNX1, ASXL1, and 24 others.

SFSR2 does not occur in R172 patients. DNMT3A was the most frequently co-occurring mutation in R172, followed by ASXL1, BCOR, NRAS, RUNX1, KMT2A, KRAS, and STAG2.

Safety

The most common treatment-emergent adverse events (TEAE) that occurred in 20% or more of all patients of any grade included nausea (46%), hyperbilirubinemia (45%), diarrhea and fatigue (40% each), decreased appetite (38%), vomiting (32%), dyspnea (31%), cough (29%), pyrexia and febrile neutropenia (28% each), thrombocytopenia, anemia, constipation, hypokalemia, and peripheral edema (27% each), pneumonia (21%), and hyperuricemia (20%).

The only 2 grade 3/4 TEAEs that rose above the level of 5% were hyperbilirubinemia (12%) and thrombocytopenia (6%).

“The hyperbilirubinemia, as I’ve mentioned in a number of meetings before this,” Dr Stein clarified, “is one that occurs because the enzyme is an off-target effect of inhibiting the UGT1A1 enzyme, which conjugates bilirubin.”

“So a patient who goes on this study who has a defect in bilirubin conjugation because they have Gilbert’s disease, they will have a higher level of bilirubin compared to a patient who doesn’t have Gilbert’s disease. This does not appear to have any clinical sequelae. You’ll also notice AST, ALT, alkaline phosphatase or any liver failure is not on this [TEAE] list.”

Response

The overall response rate for the patients who received enasidenib 100 mg/day was 38.5% (42/109) and for all doses 40.3% (71/176).

The true CR rate was 20.2% (100 mg/day) and 19.3% for all doses.

An additional 20% achieved a CR with incomplete hematologic recovery, CR with incomplete platelet recovery, partial response (PR), and morphologic leukemia-free state  with either 100 mg enasidenib daily or all doses.

“Time to first response is not immediate,” Dr Stein pointed out. “It takes a median of 1.9 months to get there, and the time to complete remission takes even longer, a median of 3.7 months in the 100-mg experience, 3.8 months in all doses, to get to that best response.”

“I think the clinical importance of this is,” he added, “for a patient that one might have who is on this drug, it is important to keep them on the drug for a prolonged period of time so that they have the opportunity to have that response.”

Hematologic parameters also improved gradually.

Increases in platelet count, absolute neutrophil count, and hemoglobin level did not rise exponentially upon administration of study drug, but rather they slowly rose, “again getting to this point, that the drug takes time to work,” Dr Stein emphasized.

Patients in CR had very high transfusion independence rates, “which is what I would expect,” Dr Stein said. “If you are in complete remission, you should be transfusion independent.”

“What’s a little bit more interesting, though,” Dr Stein added, “is those patients who are non-CR responders. [I]n those patients who have responded but have less than a complete remission, 50% of them are independent of red cell transfusions and 50% of them are independent of platelet transfusions.”

Survival

The CR data and transfusion independence data translated into a median OS in these relapsed and refractory AML patients of 9.3 months.

And about 10% - 15% of the patients had prolonged survival up to 2 years and longer on the single agent.

Analysis of OS by best response revealed that for patients with a CR, “they really have an admirable overall survival of 19.7 months, almost 20 months,” Dr Stein said.

Patients who had a non-CR response had a median OS of 13.8 months, and non-responders had a median OS of 7.0 months.

And there was a qualitative improvement in response over time: the number of patients with CRs and PRs increased, while the number with stable disease decreased.

“Again, I think getting at the point it takes time for these responses to occur,” Dr Stein iterated.

Over the course of therapy, some responders had a differentiation of myeloblasts, so that by cycle 3, the marrow looked largely normal.

The investigators did not observe any morphological evidence of cytotoxicity or cellular aplasia.

But they did observe myeloid differentiation using FISH.

Trisomy 8 that was evident at the time of screening in responders’ myeloblasts, persisted in the promyelocytes and mature granulocyte population, and was no longer evident in the lymphoid compartment.

Baseline 2-HG levels and mIDH2 variant allele frequency were similar for responding and non-responding patients.

The investigators believe that differentiation of myeloblsts, not cytotoxicity, may drive the clinical efficacy of enasidenib.

A phase 3 trial of enasidenib monotherapy versus conventional care regimens is underway in older patients with late-stage AML, and phase 1/2 studies of enasidenib combinations are ongoing in newly diagnosed AML patients.

Enasidenib, which also has efficacy in myelodysplastic syndromes, has been granted priority review for relapsed/refractory AML by the US Food and Drug Administration. 

Photo © ASCO/Danny Morton 2017

CHICAGO—The experimental mutant IDH2 (mIDH2) inhibitor enasidenib has produced “admirable” overall survival in patients with mIDH2 relapsed or refractory acute myeloid leukemia (AML), according to Eytan M. Stein, MD, an investigator on the phase 1 dose escalation and expansion study.

Patients who achieved a complete remission (CR) had a median overall survival (OS) of 19.7 months and non-CR responders, 13.8 months.

“I really want to make the point,” Dr Stein said, “this is a group of patients that are highly refractory, either refractory to induction chemotherapy, refractory to standard of care approaches for patients who are unable to get induction chemotherapy, so refractory to hypomethylating agents or low-dose cytarabine.”

Mutations in IDH2 occur in approximately 12% of AML patients.

Dr Stein explained that the mutant protein converts alpha ketoglutarate to beta hydroxyglutarate (2-HG). And increased levels of intracellular 2-HG lead to methylation changes in the cell that cause a block in myeloid differentiation.

Enasidenib, also known as AG-221, is a selective, oral, potent inhibitor of the mIDH2 enzyyme.

Dr Stein, of Memorial Sloan Kettering Cancer Center in New York, New York, presented the results during the ASCO 2017 Annual Meeting (abstract 7004).

The clinical and translational papers were published simultaneously in Blood.

Study design

The phase 1/2 study had a large dose-escalation component, with 113 patients enrolled. Patients had to have an advanced hematologic malignancy with an IDH2 mutation.

Patients received cumulative daily doses of 50 mg – 650 mg of enasidenib in continuous 28-day cycles.

Four expansion arms were added, with 126 patients.

Two expansion arms were in relapsed/refractory AML patients: one in patients 60 years or older or any age if they had relapsed after bone marrow transplant (BMT), and the other in patients younger than 60 excluding those relapsed after BMT.

The other 2 expansion arms were in untreated AML patients and in patients with any hematologic malignancy ineligible for the other arms.

Dr Stein presented results for the relapsed/refractory AML patients in the dose escalation and expansion phases of the study.

The key endpoints were safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicities; response rates as assessed by the local investigator according to IWG criteria; and assessment of clinical activity.

Dr Stein noted the phase 2 study is now completely accrued (n=91) and the recommended enasidenib dose is 100 mg/day in relapsed/refractory AML.

The MTD was not reached at doses up to 650 mg/day.

Baseline characteristics

Median age of all 239 phase 1 patients was 70 years (range, 19-100), 57% were male, and almost all patients had intermediate- or poor-risk disease.

The investigators were also interested in the co-occurring mutations in patients on screening and whether there were differences between patients with mIDH2 at R172 and R140.

Seventy-five percent of the patients (n=179) had R140 and 24% had R172 (n=57).

There was a statistically significant difference in the number of co-occurring mutations in the R140 and R172 patients, with the R140 patients having a higher co-mutation burden compared with the R172 patients, (P=0.020).

The most frequent mutations co-occurring in R140 patients were SRSF2, followed by, in descending order of frequency, DNMT3A, RUNX1, ASXL1, and 24 others.

SFSR2 does not occur in R172 patients. DNMT3A was the most frequently co-occurring mutation in R172, followed by ASXL1, BCOR, NRAS, RUNX1, KMT2A, KRAS, and STAG2.

Safety

The most common treatment-emergent adverse events (TEAE) that occurred in 20% or more of all patients of any grade included nausea (46%), hyperbilirubinemia (45%), diarrhea and fatigue (40% each), decreased appetite (38%), vomiting (32%), dyspnea (31%), cough (29%), pyrexia and febrile neutropenia (28% each), thrombocytopenia, anemia, constipation, hypokalemia, and peripheral edema (27% each), pneumonia (21%), and hyperuricemia (20%).

The only 2 grade 3/4 TEAEs that rose above the level of 5% were hyperbilirubinemia (12%) and thrombocytopenia (6%).

“The hyperbilirubinemia, as I’ve mentioned in a number of meetings before this,” Dr Stein clarified, “is one that occurs because the enzyme is an off-target effect of inhibiting the UGT1A1 enzyme, which conjugates bilirubin.”

“So a patient who goes on this study who has a defect in bilirubin conjugation because they have Gilbert’s disease, they will have a higher level of bilirubin compared to a patient who doesn’t have Gilbert’s disease. This does not appear to have any clinical sequelae. You’ll also notice AST, ALT, alkaline phosphatase or any liver failure is not on this [TEAE] list.”

Response

The overall response rate for the patients who received enasidenib 100 mg/day was 38.5% (42/109) and for all doses 40.3% (71/176).

The true CR rate was 20.2% (100 mg/day) and 19.3% for all doses.

An additional 20% achieved a CR with incomplete hematologic recovery, CR with incomplete platelet recovery, partial response (PR), and morphologic leukemia-free state  with either 100 mg enasidenib daily or all doses.

“Time to first response is not immediate,” Dr Stein pointed out. “It takes a median of 1.9 months to get there, and the time to complete remission takes even longer, a median of 3.7 months in the 100-mg experience, 3.8 months in all doses, to get to that best response.”

“I think the clinical importance of this is,” he added, “for a patient that one might have who is on this drug, it is important to keep them on the drug for a prolonged period of time so that they have the opportunity to have that response.”

Hematologic parameters also improved gradually.

Increases in platelet count, absolute neutrophil count, and hemoglobin level did not rise exponentially upon administration of study drug, but rather they slowly rose, “again getting to this point, that the drug takes time to work,” Dr Stein emphasized.

Patients in CR had very high transfusion independence rates, “which is what I would expect,” Dr Stein said. “If you are in complete remission, you should be transfusion independent.”

“What’s a little bit more interesting, though,” Dr Stein added, “is those patients who are non-CR responders. [I]n those patients who have responded but have less than a complete remission, 50% of them are independent of red cell transfusions and 50% of them are independent of platelet transfusions.”

Survival

The CR data and transfusion independence data translated into a median OS in these relapsed and refractory AML patients of 9.3 months.

And about 10% - 15% of the patients had prolonged survival up to 2 years and longer on the single agent.

Analysis of OS by best response revealed that for patients with a CR, “they really have an admirable overall survival of 19.7 months, almost 20 months,” Dr Stein said.

Patients who had a non-CR response had a median OS of 13.8 months, and non-responders had a median OS of 7.0 months.

And there was a qualitative improvement in response over time: the number of patients with CRs and PRs increased, while the number with stable disease decreased.

“Again, I think getting at the point it takes time for these responses to occur,” Dr Stein iterated.

Over the course of therapy, some responders had a differentiation of myeloblasts, so that by cycle 3, the marrow looked largely normal.

The investigators did not observe any morphological evidence of cytotoxicity or cellular aplasia.

But they did observe myeloid differentiation using FISH.

Trisomy 8 that was evident at the time of screening in responders’ myeloblasts, persisted in the promyelocytes and mature granulocyte population, and was no longer evident in the lymphoid compartment.

Baseline 2-HG levels and mIDH2 variant allele frequency were similar for responding and non-responding patients.

The investigators believe that differentiation of myeloblsts, not cytotoxicity, may drive the clinical efficacy of enasidenib.

A phase 3 trial of enasidenib monotherapy versus conventional care regimens is underway in older patients with late-stage AML, and phase 1/2 studies of enasidenib combinations are ongoing in newly diagnosed AML patients.

Enasidenib, which also has efficacy in myelodysplastic syndromes, has been granted priority review for relapsed/refractory AML by the US Food and Drug Administration. 

Photo © ASCO/Danny Morton 2017

CHICAGO—The experimental mutant IDH2 (mIDH2) inhibitor enasidenib has produced “admirable” overall survival in patients with mIDH2 relapsed or refractory acute myeloid leukemia (AML), according to Eytan M. Stein, MD, an investigator on the phase 1 dose escalation and expansion study.

Patients who achieved a complete remission (CR) had a median overall survival (OS) of 19.7 months and non-CR responders, 13.8 months.

“I really want to make the point,” Dr Stein said, “this is a group of patients that are highly refractory, either refractory to induction chemotherapy, refractory to standard of care approaches for patients who are unable to get induction chemotherapy, so refractory to hypomethylating agents or low-dose cytarabine.”

Mutations in IDH2 occur in approximately 12% of AML patients.

Dr Stein explained that the mutant protein converts alpha ketoglutarate to beta hydroxyglutarate (2-HG). And increased levels of intracellular 2-HG lead to methylation changes in the cell that cause a block in myeloid differentiation.

Enasidenib, also known as AG-221, is a selective, oral, potent inhibitor of the mIDH2 enzyyme.

Dr Stein, of Memorial Sloan Kettering Cancer Center in New York, New York, presented the results during the ASCO 2017 Annual Meeting (abstract 7004).

The clinical and translational papers were published simultaneously in Blood.

Study design

The phase 1/2 study had a large dose-escalation component, with 113 patients enrolled. Patients had to have an advanced hematologic malignancy with an IDH2 mutation.

Patients received cumulative daily doses of 50 mg – 650 mg of enasidenib in continuous 28-day cycles.

Four expansion arms were added, with 126 patients.

Two expansion arms were in relapsed/refractory AML patients: one in patients 60 years or older or any age if they had relapsed after bone marrow transplant (BMT), and the other in patients younger than 60 excluding those relapsed after BMT.

The other 2 expansion arms were in untreated AML patients and in patients with any hematologic malignancy ineligible for the other arms.

Dr Stein presented results for the relapsed/refractory AML patients in the dose escalation and expansion phases of the study.

The key endpoints were safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicities; response rates as assessed by the local investigator according to IWG criteria; and assessment of clinical activity.

Dr Stein noted the phase 2 study is now completely accrued (n=91) and the recommended enasidenib dose is 100 mg/day in relapsed/refractory AML.

The MTD was not reached at doses up to 650 mg/day.

Baseline characteristics

Median age of all 239 phase 1 patients was 70 years (range, 19-100), 57% were male, and almost all patients had intermediate- or poor-risk disease.

The investigators were also interested in the co-occurring mutations in patients on screening and whether there were differences between patients with mIDH2 at R172 and R140.

Seventy-five percent of the patients (n=179) had R140 and 24% had R172 (n=57).

There was a statistically significant difference in the number of co-occurring mutations in the R140 and R172 patients, with the R140 patients having a higher co-mutation burden compared with the R172 patients, (P=0.020).

The most frequent mutations co-occurring in R140 patients were SRSF2, followed by, in descending order of frequency, DNMT3A, RUNX1, ASXL1, and 24 others.

SFSR2 does not occur in R172 patients. DNMT3A was the most frequently co-occurring mutation in R172, followed by ASXL1, BCOR, NRAS, RUNX1, KMT2A, KRAS, and STAG2.

Safety

The most common treatment-emergent adverse events (TEAE) that occurred in 20% or more of all patients of any grade included nausea (46%), hyperbilirubinemia (45%), diarrhea and fatigue (40% each), decreased appetite (38%), vomiting (32%), dyspnea (31%), cough (29%), pyrexia and febrile neutropenia (28% each), thrombocytopenia, anemia, constipation, hypokalemia, and peripheral edema (27% each), pneumonia (21%), and hyperuricemia (20%).

The only 2 grade 3/4 TEAEs that rose above the level of 5% were hyperbilirubinemia (12%) and thrombocytopenia (6%).

“The hyperbilirubinemia, as I’ve mentioned in a number of meetings before this,” Dr Stein clarified, “is one that occurs because the enzyme is an off-target effect of inhibiting the UGT1A1 enzyme, which conjugates bilirubin.”

“So a patient who goes on this study who has a defect in bilirubin conjugation because they have Gilbert’s disease, they will have a higher level of bilirubin compared to a patient who doesn’t have Gilbert’s disease. This does not appear to have any clinical sequelae. You’ll also notice AST, ALT, alkaline phosphatase or any liver failure is not on this [TEAE] list.”

Response

The overall response rate for the patients who received enasidenib 100 mg/day was 38.5% (42/109) and for all doses 40.3% (71/176).

The true CR rate was 20.2% (100 mg/day) and 19.3% for all doses.

An additional 20% achieved a CR with incomplete hematologic recovery, CR with incomplete platelet recovery, partial response (PR), and morphologic leukemia-free state  with either 100 mg enasidenib daily or all doses.

“Time to first response is not immediate,” Dr Stein pointed out. “It takes a median of 1.9 months to get there, and the time to complete remission takes even longer, a median of 3.7 months in the 100-mg experience, 3.8 months in all doses, to get to that best response.”

“I think the clinical importance of this is,” he added, “for a patient that one might have who is on this drug, it is important to keep them on the drug for a prolonged period of time so that they have the opportunity to have that response.”

Hematologic parameters also improved gradually.

Increases in platelet count, absolute neutrophil count, and hemoglobin level did not rise exponentially upon administration of study drug, but rather they slowly rose, “again getting to this point, that the drug takes time to work,” Dr Stein emphasized.

Patients in CR had very high transfusion independence rates, “which is what I would expect,” Dr Stein said. “If you are in complete remission, you should be transfusion independent.”

“What’s a little bit more interesting, though,” Dr Stein added, “is those patients who are non-CR responders. [I]n those patients who have responded but have less than a complete remission, 50% of them are independent of red cell transfusions and 50% of them are independent of platelet transfusions.”

Survival

The CR data and transfusion independence data translated into a median OS in these relapsed and refractory AML patients of 9.3 months.

And about 10% - 15% of the patients had prolonged survival up to 2 years and longer on the single agent.

Analysis of OS by best response revealed that for patients with a CR, “they really have an admirable overall survival of 19.7 months, almost 20 months,” Dr Stein said.

Patients who had a non-CR response had a median OS of 13.8 months, and non-responders had a median OS of 7.0 months.

And there was a qualitative improvement in response over time: the number of patients with CRs and PRs increased, while the number with stable disease decreased.

“Again, I think getting at the point it takes time for these responses to occur,” Dr Stein iterated.

Over the course of therapy, some responders had a differentiation of myeloblasts, so that by cycle 3, the marrow looked largely normal.

The investigators did not observe any morphological evidence of cytotoxicity or cellular aplasia.

But they did observe myeloid differentiation using FISH.

Trisomy 8 that was evident at the time of screening in responders’ myeloblasts, persisted in the promyelocytes and mature granulocyte population, and was no longer evident in the lymphoid compartment.

Baseline 2-HG levels and mIDH2 variant allele frequency were similar for responding and non-responding patients.

The investigators believe that differentiation of myeloblsts, not cytotoxicity, may drive the clinical efficacy of enasidenib.

A phase 3 trial of enasidenib monotherapy versus conventional care regimens is underway in older patients with late-stage AML, and phase 1/2 studies of enasidenib combinations are ongoing in newly diagnosed AML patients.

Enasidenib, which also has efficacy in myelodysplastic syndromes, has been granted priority review for relapsed/refractory AML by the US Food and Drug Administration. 

Adolescents with major depressive disorder (MDD) were more likely to lose weight, but treatment with some SSRIs was associated with weight gain, based on data from a longitudinal study of 264 participants published online June 16 in Pediatrics.

MDD was associated with decrease in body mass index (BMI), fat mass index (FMI), and lean BMI (LBMI) z scores after controlling for factors including age, sex, physical activity, dietary intake, and length of study participation. However, dosage and duration of treatment with SSRIs were associated with increases in BMI, FMI, and LBMI z scores (Pediatrics. 2017. doi: 10.1542/peds.2016-3943).

Maya23K/Thinkstock

[email protected]

Adolescents with major depressive disorder (MDD) were more likely to lose weight, but treatment with some SSRIs was associated with weight gain, based on data from a longitudinal study of 264 participants published online June 16 in Pediatrics.

MDD was associated with decrease in body mass index (BMI), fat mass index (FMI), and lean BMI (LBMI) z scores after controlling for factors including age, sex, physical activity, dietary intake, and length of study participation. However, dosage and duration of treatment with SSRIs were associated with increases in BMI, FMI, and LBMI z scores (Pediatrics. 2017. doi: 10.1542/peds.2016-3943).

Maya23K/Thinkstock

[email protected]

Adolescents with major depressive disorder (MDD) were more likely to lose weight, but treatment with some SSRIs was associated with weight gain, based on data from a longitudinal study of 264 participants published online June 16 in Pediatrics.

MDD was associated with decrease in body mass index (BMI), fat mass index (FMI), and lean BMI (LBMI) z scores after controlling for factors including age, sex, physical activity, dietary intake, and length of study participation. However, dosage and duration of treatment with SSRIs were associated with increases in BMI, FMI, and LBMI z scores (Pediatrics. 2017. doi: 10.1542/peds.2016-3943).

Maya23K/Thinkstock

[email protected]

When the first issue of Pediatric News was published 50 years ago, I was starting the second half of my first year in medical school. Over the ensuing 50 years, I have lived through and witnessed some dramatic changes in pediatrics. Here are just a few of the transitions that I’ve observed and Pediatric News has covered:

The birth of interventional neonatology

When I was an intern at Duke University Medical Center in Durham, N.C., a paper appeared in the New England Journal of Medicine describing the use of a simple continuous positive pressure apparatus for the treatment of respiratory distress syndrome entitled, “Treatment of idiopathic respiratory-distress syndrome with continuous positive airway pressure,” (1971 Jun 17;284[24]:1333-40). After seeing the paper, George Brumley, MD, the head of nursery, immediately had the hospital engineers build us our own setup, and we became part of what could arguably be called the revolution that turned neonatology into an interventional specialty.

Courtesy Dr. William G. Wilkoff

From meningitis to mental health

Although it came gradually, one of the most significant changes over the last 50 years has been the shift in the mix of pathology presenting to the general pediatrician. In the 1970s and 1980s, the threat of invasive bacterial disease, usually from Haemophilus influenzae, was always hanging over us. It was not unusual for a single community pediatrician to see four or five cases of meningitis in a year. The introduction of effective vaccines and more potent antibiotics lessened the threat of serious bacterial infection, and in its place came a flood of mental health complaints, including anxiety (25% prevalence among 13- to 18-year-olds, depression (13% prevalence among 12- to 17-year-olds) and attention-deficit/hyperactivity disorder (ADHD) (9% prevalence among 13- to 18-year-olds). The result is the impression that, at times, being a general pediatrician today feels like being a more than part-time psychiatrist/psychologist.

Mental retardation and autism

In the 1970s and 1980s, the diagnosis of autism was usually reserved for children with serious communication difficulties. Many physicians and the lay public expected that a child who was diagnosed with autism would have no speech at all. The prevalence of the condition in the last quarter of the century was felt to be about 1 in 2,000.

The more common diagnosis during that period was mental retardation. However, as the result of insensitive stereotyping, “mental retardation” has become an offensive term and has vanished from the pediatric lexicon.

Autism, however, has flourished, and a recent estimate cited by the CDC pegs its prevalence at 1 in 68. Based on my observations, I expect that much, if not most, of this increase is the result of expanded diagnostic criteria and relabeling.

Chicken scratches to mouse clicks

In keeping with a long tradition in medicine, my office notes when I began in practice were unreadable by anyone except a very few my long-term coworkers. My scribbles were brief and often included sketches of wounds and body parts. Their primary purpose was to remind me what had transpired at that office visit and to record the biometrics. Unfortunately, as the cloud of malpractice crept over the landscape, with it came the nonsensical mantra, “if it wasn’t documented, it didn’t happen.”

With the introduction of computers, medical records became inflated and often inaccurate, documents to be used primarily for data collection and risk management. The physician now is tasked with being the data entry clerk who must keep her eyes on the computer screen at the expense of a meaningful interaction with the patient. Sadly, the physician-unfriendliness of electronic medical records has driven many older and experienced pediatricians into premature retirement, robbing general pediatrics of their accumulated wisdom.

A part-time job

In 1975, there were 22,730 practicing pediatricians, of whom 23% were women. In 2011, there were 80,992 pediatricians, of whom 56.6% were women. The percentage of women practicing pediatrics continues to climb, with the most recent figure being 58%. From the patient perspective, this shift in gender dominance has been well received.

At the same time, there has been a trend toward more pediatricians of both genders pursuing part-time employment. The model of the physician being the owner/operator of a medical practice that was flourishing when I began in practice has been replaced by one in which the physician is an employee of a much larger entity, which is pressured from all sides to cut costs. To make matters worse, the Medical Home model that currently is in vogue is proving to be a more expensive vehicle for delivering health care. The patient now is asked to view his physician as the director of a team and may see him or her only infrequently, at the expense of the therapeutic benefits of familiarity.

When I was in medical school, the tuition was around $2,500/year, and I graduated with a debt of about $3,000 – with an interest rate so low that I was in no rush to pay it off. Now a student entering medical school can expect to pay around $60,000/year – an amount that has far outstripped inflation.

These realities combine to create a potentially unsustainable economic climate for pediatricians. I have had a wonderful 50 years being a pediatrician. But I can’t promise the same level of enjoyment to the next generation of pediatricians, unless someone can figure how to cut the expense of medical school and/or make part-time employment fit into a health care delivery system that must contain costs to survive.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].

When the first issue of Pediatric News was published 50 years ago, I was starting the second half of my first year in medical school. Over the ensuing 50 years, I have lived through and witnessed some dramatic changes in pediatrics. Here are just a few of the transitions that I’ve observed and Pediatric News has covered:

The birth of interventional neonatology

When I was an intern at Duke University Medical Center in Durham, N.C., a paper appeared in the New England Journal of Medicine describing the use of a simple continuous positive pressure apparatus for the treatment of respiratory distress syndrome entitled, “Treatment of idiopathic respiratory-distress syndrome with continuous positive airway pressure,” (1971 Jun 17;284[24]:1333-40). After seeing the paper, George Brumley, MD, the head of nursery, immediately had the hospital engineers build us our own setup, and we became part of what could arguably be called the revolution that turned neonatology into an interventional specialty.

Courtesy Dr. William G. Wilkoff

From meningitis to mental health

Although it came gradually, one of the most significant changes over the last 50 years has been the shift in the mix of pathology presenting to the general pediatrician. In the 1970s and 1980s, the threat of invasive bacterial disease, usually from Haemophilus influenzae, was always hanging over us. It was not unusual for a single community pediatrician to see four or five cases of meningitis in a year. The introduction of effective vaccines and more potent antibiotics lessened the threat of serious bacterial infection, and in its place came a flood of mental health complaints, including anxiety (25% prevalence among 13- to 18-year-olds, depression (13% prevalence among 12- to 17-year-olds) and attention-deficit/hyperactivity disorder (ADHD) (9% prevalence among 13- to 18-year-olds). The result is the impression that, at times, being a general pediatrician today feels like being a more than part-time psychiatrist/psychologist.

Mental retardation and autism

In the 1970s and 1980s, the diagnosis of autism was usually reserved for children with serious communication difficulties. Many physicians and the lay public expected that a child who was diagnosed with autism would have no speech at all. The prevalence of the condition in the last quarter of the century was felt to be about 1 in 2,000.

The more common diagnosis during that period was mental retardation. However, as the result of insensitive stereotyping, “mental retardation” has become an offensive term and has vanished from the pediatric lexicon.

Autism, however, has flourished, and a recent estimate cited by the CDC pegs its prevalence at 1 in 68. Based on my observations, I expect that much, if not most, of this increase is the result of expanded diagnostic criteria and relabeling.

Chicken scratches to mouse clicks

In keeping with a long tradition in medicine, my office notes when I began in practice were unreadable by anyone except a very few my long-term coworkers. My scribbles were brief and often included sketches of wounds and body parts. Their primary purpose was to remind me what had transpired at that office visit and to record the biometrics. Unfortunately, as the cloud of malpractice crept over the landscape, with it came the nonsensical mantra, “if it wasn’t documented, it didn’t happen.”

With the introduction of computers, medical records became inflated and often inaccurate, documents to be used primarily for data collection and risk management. The physician now is tasked with being the data entry clerk who must keep her eyes on the computer screen at the expense of a meaningful interaction with the patient. Sadly, the physician-unfriendliness of electronic medical records has driven many older and experienced pediatricians into premature retirement, robbing general pediatrics of their accumulated wisdom.

A part-time job

In 1975, there were 22,730 practicing pediatricians, of whom 23% were women. In 2011, there were 80,992 pediatricians, of whom 56.6% were women. The percentage of women practicing pediatrics continues to climb, with the most recent figure being 58%. From the patient perspective, this shift in gender dominance has been well received.

At the same time, there has been a trend toward more pediatricians of both genders pursuing part-time employment. The model of the physician being the owner/operator of a medical practice that was flourishing when I began in practice has been replaced by one in which the physician is an employee of a much larger entity, which is pressured from all sides to cut costs. To make matters worse, the Medical Home model that currently is in vogue is proving to be a more expensive vehicle for delivering health care. The patient now is asked to view his physician as the director of a team and may see him or her only infrequently, at the expense of the therapeutic benefits of familiarity.

When I was in medical school, the tuition was around $2,500/year, and I graduated with a debt of about $3,000 – with an interest rate so low that I was in no rush to pay it off. Now a student entering medical school can expect to pay around $60,000/year – an amount that has far outstripped inflation.

These realities combine to create a potentially unsustainable economic climate for pediatricians. I have had a wonderful 50 years being a pediatrician. But I can’t promise the same level of enjoyment to the next generation of pediatricians, unless someone can figure how to cut the expense of medical school and/or make part-time employment fit into a health care delivery system that must contain costs to survive.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].

When the first issue of Pediatric News was published 50 years ago, I was starting the second half of my first year in medical school. Over the ensuing 50 years, I have lived through and witnessed some dramatic changes in pediatrics. Here are just a few of the transitions that I’ve observed and Pediatric News has covered:

The birth of interventional neonatology

When I was an intern at Duke University Medical Center in Durham, N.C., a paper appeared in the New England Journal of Medicine describing the use of a simple continuous positive pressure apparatus for the treatment of respiratory distress syndrome entitled, “Treatment of idiopathic respiratory-distress syndrome with continuous positive airway pressure,” (1971 Jun 17;284[24]:1333-40). After seeing the paper, George Brumley, MD, the head of nursery, immediately had the hospital engineers build us our own setup, and we became part of what could arguably be called the revolution that turned neonatology into an interventional specialty.

Courtesy Dr. William G. Wilkoff

From meningitis to mental health

Although it came gradually, one of the most significant changes over the last 50 years has been the shift in the mix of pathology presenting to the general pediatrician. In the 1970s and 1980s, the threat of invasive bacterial disease, usually from Haemophilus influenzae, was always hanging over us. It was not unusual for a single community pediatrician to see four or five cases of meningitis in a year. The introduction of effective vaccines and more potent antibiotics lessened the threat of serious bacterial infection, and in its place came a flood of mental health complaints, including anxiety (25% prevalence among 13- to 18-year-olds, depression (13% prevalence among 12- to 17-year-olds) and attention-deficit/hyperactivity disorder (ADHD) (9% prevalence among 13- to 18-year-olds). The result is the impression that, at times, being a general pediatrician today feels like being a more than part-time psychiatrist/psychologist.

Mental retardation and autism

In the 1970s and 1980s, the diagnosis of autism was usually reserved for children with serious communication difficulties. Many physicians and the lay public expected that a child who was diagnosed with autism would have no speech at all. The prevalence of the condition in the last quarter of the century was felt to be about 1 in 2,000.

The more common diagnosis during that period was mental retardation. However, as the result of insensitive stereotyping, “mental retardation” has become an offensive term and has vanished from the pediatric lexicon.

Autism, however, has flourished, and a recent estimate cited by the CDC pegs its prevalence at 1 in 68. Based on my observations, I expect that much, if not most, of this increase is the result of expanded diagnostic criteria and relabeling.

Chicken scratches to mouse clicks

In keeping with a long tradition in medicine, my office notes when I began in practice were unreadable by anyone except a very few my long-term coworkers. My scribbles were brief and often included sketches of wounds and body parts. Their primary purpose was to remind me what had transpired at that office visit and to record the biometrics. Unfortunately, as the cloud of malpractice crept over the landscape, with it came the nonsensical mantra, “if it wasn’t documented, it didn’t happen.”

With the introduction of computers, medical records became inflated and often inaccurate, documents to be used primarily for data collection and risk management. The physician now is tasked with being the data entry clerk who must keep her eyes on the computer screen at the expense of a meaningful interaction with the patient. Sadly, the physician-unfriendliness of electronic medical records has driven many older and experienced pediatricians into premature retirement, robbing general pediatrics of their accumulated wisdom.

A part-time job

In 1975, there were 22,730 practicing pediatricians, of whom 23% were women. In 2011, there were 80,992 pediatricians, of whom 56.6% were women. The percentage of women practicing pediatrics continues to climb, with the most recent figure being 58%. From the patient perspective, this shift in gender dominance has been well received.

At the same time, there has been a trend toward more pediatricians of both genders pursuing part-time employment. The model of the physician being the owner/operator of a medical practice that was flourishing when I began in practice has been replaced by one in which the physician is an employee of a much larger entity, which is pressured from all sides to cut costs. To make matters worse, the Medical Home model that currently is in vogue is proving to be a more expensive vehicle for delivering health care. The patient now is asked to view his physician as the director of a team and may see him or her only infrequently, at the expense of the therapeutic benefits of familiarity.

When I was in medical school, the tuition was around $2,500/year, and I graduated with a debt of about $3,000 – with an interest rate so low that I was in no rush to pay it off. Now a student entering medical school can expect to pay around $60,000/year – an amount that has far outstripped inflation.

These realities combine to create a potentially unsustainable economic climate for pediatricians. I have had a wonderful 50 years being a pediatrician. But I can’t promise the same level of enjoyment to the next generation of pediatricians, unless someone can figure how to cut the expense of medical school and/or make part-time employment fit into a health care delivery system that must contain costs to survive.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].