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Experts: Consider enteral therapy in CD, with caveats
LAS VEGAS – Temporarily switching to an enteral diet – without solid food – has the potential to reverse Crohn’s disease (CD), especially in children, a panel of experts told gastroenterologists here.
They acknowledged the controversial treatment requires strict adherence and can be impossible for some patients to tolerate. But it can be successful too, said gastroenterologist Lindsey G. Albenberg, DO, of Children’s Hospital of Philadelphia, where enteral nutrition therapy (ENT) is commonly used in patients with CD.
“Parents are obviously thrilled that there’s no exposure to immunosuppressive medications,” she said in a discussion about ENT at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Typically, we provide 80%-90% of calorie needs through a polymeric formula by mouth. If we see clinical response at 4-6 weeks or even earlier, then we will pursue a course of about 8-12 weeks.”
Research into the best role for ENT therapy in CD is limited. A 2018 Cochrane Library review found there’s “very low quality evidence” suggesting that ENT is better than steroids to induce remission in children. It also found there’s “very low quality evidence” that steroids are better than ENT in adults with CD (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
According to clinician-scientist James D. Lewis, MD, MSCE, of the University of Pennsylvania, Philadelphia, ENT “has gotten a bad name in some ways because of a meta-analysis showing it was inferior to corticosteroids to induce remission.” In fact, he said, studies “didn’t look at mucosal healing and pooled together adults and children.”
In children, he said, the treatment seems to clearly be effective. The picture is less promising in adults. “Presumably that’s because those of you who are parents probably have more control over your young children than your own behavior,” he said, referring to management of food intake.
In adults, “there’s no reason to think it wouldn’t work,” he said. “But trying to convince adults to give up food is really challenging.”
Children who try ENT are often required to use a nasogastric feeding tube, an approach that adults tend to avoid. In kids, “it’s a question of knowing your patient,” said gastroenterologist David Suskind, MD, of Seattle Children’s Hospital. “If the patient says, ‘There’s no way you’ll put a nasal gastric tube in, and no way I will drink it [the ENT supplement],’ this may not be the best therapy. If they’re interested, we push forward. We get much better efficacy because the patients will do what we’re asking.”
Several panelists recommended that patients use polymeric formulations instead of elemental formulations because they’re more palatable. It can be a struggle, however, to stick with the treatment.
Kelly Issokson, MS, RD, CNSC, a dietitian with Cedars-Sinai Medical Center in Los Angeles, tried an ENT therapy for 30 days in order to understand what patients experience and said it was “very challenging.”
“When you sit down to a meal, you anticipate it, you start to salivate. With shakes, it was a lot more clinical,” she said. “The other thing I struggled with was texture and having it be so sweet. I’d freeze [the shakes] into ice cube trays and popsicles. That helped break the monotony. It changes the flavor and cuts the sweetness.”
Ms. Issokson urges her patients to stick with ENT for the entire period of therapy. “Studies show when patients introduce real foods the efficacy of inducing remission goes down. We recommend 100% calories and proteins coming from the formula,” she said. That means “no coffee, no broth, no tea, no nothing but the formula. Most of our patients are able to do that exclusively.”
Toward the end of therapy, around week 8 or 11, some patients tell her they crave food like soup. “I say OK, have a tiny bit,” she said, “but remember, this is only temporary. We’re almost at the end. Try to be 100% exclusive.”
Dr. Albenberg and Dr. Suskind report no disclosures. Ms. Issokson reports consulting fees (speaking and teaching) from AGA, Crohn’s & Colitis Foundation, Academy of Nutrition and Dietetics, and United Ostomy Association. Dr. Lewis reports many relationships – including consulting fees, ownership interest, and grant/research support – with Eli Lilly, Bristol‐Myers Squibb, Gilead, and others.
Correction, 2/22/19: An earlier version of this article misidentified the person in the first photo above.
LAS VEGAS – Temporarily switching to an enteral diet – without solid food – has the potential to reverse Crohn’s disease (CD), especially in children, a panel of experts told gastroenterologists here.
They acknowledged the controversial treatment requires strict adherence and can be impossible for some patients to tolerate. But it can be successful too, said gastroenterologist Lindsey G. Albenberg, DO, of Children’s Hospital of Philadelphia, where enteral nutrition therapy (ENT) is commonly used in patients with CD.
“Parents are obviously thrilled that there’s no exposure to immunosuppressive medications,” she said in a discussion about ENT at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Typically, we provide 80%-90% of calorie needs through a polymeric formula by mouth. If we see clinical response at 4-6 weeks or even earlier, then we will pursue a course of about 8-12 weeks.”
Research into the best role for ENT therapy in CD is limited. A 2018 Cochrane Library review found there’s “very low quality evidence” suggesting that ENT is better than steroids to induce remission in children. It also found there’s “very low quality evidence” that steroids are better than ENT in adults with CD (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
According to clinician-scientist James D. Lewis, MD, MSCE, of the University of Pennsylvania, Philadelphia, ENT “has gotten a bad name in some ways because of a meta-analysis showing it was inferior to corticosteroids to induce remission.” In fact, he said, studies “didn’t look at mucosal healing and pooled together adults and children.”
In children, he said, the treatment seems to clearly be effective. The picture is less promising in adults. “Presumably that’s because those of you who are parents probably have more control over your young children than your own behavior,” he said, referring to management of food intake.
In adults, “there’s no reason to think it wouldn’t work,” he said. “But trying to convince adults to give up food is really challenging.”
Children who try ENT are often required to use a nasogastric feeding tube, an approach that adults tend to avoid. In kids, “it’s a question of knowing your patient,” said gastroenterologist David Suskind, MD, of Seattle Children’s Hospital. “If the patient says, ‘There’s no way you’ll put a nasal gastric tube in, and no way I will drink it [the ENT supplement],’ this may not be the best therapy. If they’re interested, we push forward. We get much better efficacy because the patients will do what we’re asking.”
Several panelists recommended that patients use polymeric formulations instead of elemental formulations because they’re more palatable. It can be a struggle, however, to stick with the treatment.
Kelly Issokson, MS, RD, CNSC, a dietitian with Cedars-Sinai Medical Center in Los Angeles, tried an ENT therapy for 30 days in order to understand what patients experience and said it was “very challenging.”
“When you sit down to a meal, you anticipate it, you start to salivate. With shakes, it was a lot more clinical,” she said. “The other thing I struggled with was texture and having it be so sweet. I’d freeze [the shakes] into ice cube trays and popsicles. That helped break the monotony. It changes the flavor and cuts the sweetness.”
Ms. Issokson urges her patients to stick with ENT for the entire period of therapy. “Studies show when patients introduce real foods the efficacy of inducing remission goes down. We recommend 100% calories and proteins coming from the formula,” she said. That means “no coffee, no broth, no tea, no nothing but the formula. Most of our patients are able to do that exclusively.”
Toward the end of therapy, around week 8 or 11, some patients tell her they crave food like soup. “I say OK, have a tiny bit,” she said, “but remember, this is only temporary. We’re almost at the end. Try to be 100% exclusive.”
Dr. Albenberg and Dr. Suskind report no disclosures. Ms. Issokson reports consulting fees (speaking and teaching) from AGA, Crohn’s & Colitis Foundation, Academy of Nutrition and Dietetics, and United Ostomy Association. Dr. Lewis reports many relationships – including consulting fees, ownership interest, and grant/research support – with Eli Lilly, Bristol‐Myers Squibb, Gilead, and others.
Correction, 2/22/19: An earlier version of this article misidentified the person in the first photo above.
LAS VEGAS – Temporarily switching to an enteral diet – without solid food – has the potential to reverse Crohn’s disease (CD), especially in children, a panel of experts told gastroenterologists here.
They acknowledged the controversial treatment requires strict adherence and can be impossible for some patients to tolerate. But it can be successful too, said gastroenterologist Lindsey G. Albenberg, DO, of Children’s Hospital of Philadelphia, where enteral nutrition therapy (ENT) is commonly used in patients with CD.
“Parents are obviously thrilled that there’s no exposure to immunosuppressive medications,” she said in a discussion about ENT at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Typically, we provide 80%-90% of calorie needs through a polymeric formula by mouth. If we see clinical response at 4-6 weeks or even earlier, then we will pursue a course of about 8-12 weeks.”
Research into the best role for ENT therapy in CD is limited. A 2018 Cochrane Library review found there’s “very low quality evidence” suggesting that ENT is better than steroids to induce remission in children. It also found there’s “very low quality evidence” that steroids are better than ENT in adults with CD (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
According to clinician-scientist James D. Lewis, MD, MSCE, of the University of Pennsylvania, Philadelphia, ENT “has gotten a bad name in some ways because of a meta-analysis showing it was inferior to corticosteroids to induce remission.” In fact, he said, studies “didn’t look at mucosal healing and pooled together adults and children.”
In children, he said, the treatment seems to clearly be effective. The picture is less promising in adults. “Presumably that’s because those of you who are parents probably have more control over your young children than your own behavior,” he said, referring to management of food intake.
In adults, “there’s no reason to think it wouldn’t work,” he said. “But trying to convince adults to give up food is really challenging.”
Children who try ENT are often required to use a nasogastric feeding tube, an approach that adults tend to avoid. In kids, “it’s a question of knowing your patient,” said gastroenterologist David Suskind, MD, of Seattle Children’s Hospital. “If the patient says, ‘There’s no way you’ll put a nasal gastric tube in, and no way I will drink it [the ENT supplement],’ this may not be the best therapy. If they’re interested, we push forward. We get much better efficacy because the patients will do what we’re asking.”
Several panelists recommended that patients use polymeric formulations instead of elemental formulations because they’re more palatable. It can be a struggle, however, to stick with the treatment.
Kelly Issokson, MS, RD, CNSC, a dietitian with Cedars-Sinai Medical Center in Los Angeles, tried an ENT therapy for 30 days in order to understand what patients experience and said it was “very challenging.”
“When you sit down to a meal, you anticipate it, you start to salivate. With shakes, it was a lot more clinical,” she said. “The other thing I struggled with was texture and having it be so sweet. I’d freeze [the shakes] into ice cube trays and popsicles. That helped break the monotony. It changes the flavor and cuts the sweetness.”
Ms. Issokson urges her patients to stick with ENT for the entire period of therapy. “Studies show when patients introduce real foods the efficacy of inducing remission goes down. We recommend 100% calories and proteins coming from the formula,” she said. That means “no coffee, no broth, no tea, no nothing but the formula. Most of our patients are able to do that exclusively.”
Toward the end of therapy, around week 8 or 11, some patients tell her they crave food like soup. “I say OK, have a tiny bit,” she said, “but remember, this is only temporary. We’re almost at the end. Try to be 100% exclusive.”
Dr. Albenberg and Dr. Suskind report no disclosures. Ms. Issokson reports consulting fees (speaking and teaching) from AGA, Crohn’s & Colitis Foundation, Academy of Nutrition and Dietetics, and United Ostomy Association. Dr. Lewis reports many relationships – including consulting fees, ownership interest, and grant/research support – with Eli Lilly, Bristol‐Myers Squibb, Gilead, and others.
Correction, 2/22/19: An earlier version of this article misidentified the person in the first photo above.
EXPERT ANALYSIS FROM THE CROHN’S & COLITIS CONGRESS
Cochrane/IBD review roundup: Limited evidence keeps verdicts at bay
LAS VEGAS – Cochrane Library reviews of studies into inflammatory bowel disease (IBD) from 2018 revealed limited evidence – so far – to support enteral nutrition therapy (EN) and cannabis in Crohn’s disease (CD) and fecal transplantation in IBD.
But Morris Gordon, MBChB, MMed, PhD, a Cochrane Library researcher who provided a roundup for colleagues, said there’s tremendous opportunity to build upon existing research in these areas.
Dr. Gordon, a pediatrician with a special gastric interest at the University of Central Lancashire in Preston, England, spoke at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
In his presentation, Dr. Gordon discussed several Cochrane Library reviews published in 2018 in these topic areas:
Enteral therapy
EN was a hot topic at the Crohn’s & Colitics Congress, which devoted a large panel discussion to the benefits of its use in inducing remission in CD, especially in children.
However, an updated 2018 Cochrane Library systematic review found that “very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD” (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
The review recommended that “EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided.”
Another 2018 Cochrane Library Review concluded that “no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn” (Cochrane Database Syst Rev. 2018 Aug 11. doi: 10.1002/14651858.CD005984.pub3).
Dr. Gordon noted that IBD guidelines support EN to induce CD remission in children, and he called for “high quality research” to provide more evidence to support this recommendation.
Cannabis
In regard to cannabis, Dr. Gordon referred to a 2018 Cochrane review that examined three studies that investigated its use in CD and determined “the effects of cannabis and cannabis oil on Crohn’s disease are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012853.pub2).
He said future studies should focus on the effect of cannabis on quality of life and pain reduction. “That’s where the research needs to go,” he said.
Another 2018 Cochrane review examined two small studies exploring the use of cannabis in ulcerative colitis and reported similar findings, declaring that “the effects of cannabis and cannabidiol on UC are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012954.pub2).
Fecal transplantation
The Cochrane Library also examined research into fecal transplantation for IBD. A 2018 review reported that “fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time” (Cochrane Database Syst Rev. 2018 Nov 13. doi: 10.1002/14651858.CD012774.pub2).
Still, Dr. Gordon said, fecal transplantation is “really promising.”
Another 2018 Cochrane review of IBD research – this one focusing on natalizumab (Tysabri) as a tool for induction of remission of CD – was more conclusive. It examined five trials and found that “high quality data suggest that natalizumab is effective for induction of clinical remission and response in some patients with moderately to severely active CD”(Cochrane Database Syst Rev. 2018 Aug 1. doi: 10.1002/14651858.CD006097.pub3).
However, the review noted that none of the studies was high powered enough to detect rare serious adverse effects such as progressive multifocal leukoencephalopathy (PML). “Due to the association with PML, and the availability of alternative agents that are not associated with PML, natalizumab is not likely to be used in patients who fail currently available medical therapy,” the reviewers wrote. “Further studies of natalizumab are not likely to be done.”
Dr. Gordon reports unrestricted travel grants over the past 3 years from Ferring, Synergy, Tillotts, and BioGaia. He holds a National Institute for Health Research Cochrane IBD Program Grant.
LAS VEGAS – Cochrane Library reviews of studies into inflammatory bowel disease (IBD) from 2018 revealed limited evidence – so far – to support enteral nutrition therapy (EN) and cannabis in Crohn’s disease (CD) and fecal transplantation in IBD.
But Morris Gordon, MBChB, MMed, PhD, a Cochrane Library researcher who provided a roundup for colleagues, said there’s tremendous opportunity to build upon existing research in these areas.
Dr. Gordon, a pediatrician with a special gastric interest at the University of Central Lancashire in Preston, England, spoke at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
In his presentation, Dr. Gordon discussed several Cochrane Library reviews published in 2018 in these topic areas:
Enteral therapy
EN was a hot topic at the Crohn’s & Colitics Congress, which devoted a large panel discussion to the benefits of its use in inducing remission in CD, especially in children.
However, an updated 2018 Cochrane Library systematic review found that “very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD” (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
The review recommended that “EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided.”
Another 2018 Cochrane Library Review concluded that “no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn” (Cochrane Database Syst Rev. 2018 Aug 11. doi: 10.1002/14651858.CD005984.pub3).
Dr. Gordon noted that IBD guidelines support EN to induce CD remission in children, and he called for “high quality research” to provide more evidence to support this recommendation.
Cannabis
In regard to cannabis, Dr. Gordon referred to a 2018 Cochrane review that examined three studies that investigated its use in CD and determined “the effects of cannabis and cannabis oil on Crohn’s disease are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012853.pub2).
He said future studies should focus on the effect of cannabis on quality of life and pain reduction. “That’s where the research needs to go,” he said.
Another 2018 Cochrane review examined two small studies exploring the use of cannabis in ulcerative colitis and reported similar findings, declaring that “the effects of cannabis and cannabidiol on UC are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012954.pub2).
Fecal transplantation
The Cochrane Library also examined research into fecal transplantation for IBD. A 2018 review reported that “fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time” (Cochrane Database Syst Rev. 2018 Nov 13. doi: 10.1002/14651858.CD012774.pub2).
Still, Dr. Gordon said, fecal transplantation is “really promising.”
Another 2018 Cochrane review of IBD research – this one focusing on natalizumab (Tysabri) as a tool for induction of remission of CD – was more conclusive. It examined five trials and found that “high quality data suggest that natalizumab is effective for induction of clinical remission and response in some patients with moderately to severely active CD”(Cochrane Database Syst Rev. 2018 Aug 1. doi: 10.1002/14651858.CD006097.pub3).
However, the review noted that none of the studies was high powered enough to detect rare serious adverse effects such as progressive multifocal leukoencephalopathy (PML). “Due to the association with PML, and the availability of alternative agents that are not associated with PML, natalizumab is not likely to be used in patients who fail currently available medical therapy,” the reviewers wrote. “Further studies of natalizumab are not likely to be done.”
Dr. Gordon reports unrestricted travel grants over the past 3 years from Ferring, Synergy, Tillotts, and BioGaia. He holds a National Institute for Health Research Cochrane IBD Program Grant.
LAS VEGAS – Cochrane Library reviews of studies into inflammatory bowel disease (IBD) from 2018 revealed limited evidence – so far – to support enteral nutrition therapy (EN) and cannabis in Crohn’s disease (CD) and fecal transplantation in IBD.
But Morris Gordon, MBChB, MMed, PhD, a Cochrane Library researcher who provided a roundup for colleagues, said there’s tremendous opportunity to build upon existing research in these areas.
Dr. Gordon, a pediatrician with a special gastric interest at the University of Central Lancashire in Preston, England, spoke at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
In his presentation, Dr. Gordon discussed several Cochrane Library reviews published in 2018 in these topic areas:
Enteral therapy
EN was a hot topic at the Crohn’s & Colitics Congress, which devoted a large panel discussion to the benefits of its use in inducing remission in CD, especially in children.
However, an updated 2018 Cochrane Library systematic review found that “very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD” (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
The review recommended that “EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided.”
Another 2018 Cochrane Library Review concluded that “no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn” (Cochrane Database Syst Rev. 2018 Aug 11. doi: 10.1002/14651858.CD005984.pub3).
Dr. Gordon noted that IBD guidelines support EN to induce CD remission in children, and he called for “high quality research” to provide more evidence to support this recommendation.
Cannabis
In regard to cannabis, Dr. Gordon referred to a 2018 Cochrane review that examined three studies that investigated its use in CD and determined “the effects of cannabis and cannabis oil on Crohn’s disease are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012853.pub2).
He said future studies should focus on the effect of cannabis on quality of life and pain reduction. “That’s where the research needs to go,” he said.
Another 2018 Cochrane review examined two small studies exploring the use of cannabis in ulcerative colitis and reported similar findings, declaring that “the effects of cannabis and cannabidiol on UC are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012954.pub2).
Fecal transplantation
The Cochrane Library also examined research into fecal transplantation for IBD. A 2018 review reported that “fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time” (Cochrane Database Syst Rev. 2018 Nov 13. doi: 10.1002/14651858.CD012774.pub2).
Still, Dr. Gordon said, fecal transplantation is “really promising.”
Another 2018 Cochrane review of IBD research – this one focusing on natalizumab (Tysabri) as a tool for induction of remission of CD – was more conclusive. It examined five trials and found that “high quality data suggest that natalizumab is effective for induction of clinical remission and response in some patients with moderately to severely active CD”(Cochrane Database Syst Rev. 2018 Aug 1. doi: 10.1002/14651858.CD006097.pub3).
However, the review noted that none of the studies was high powered enough to detect rare serious adverse effects such as progressive multifocal leukoencephalopathy (PML). “Due to the association with PML, and the availability of alternative agents that are not associated with PML, natalizumab is not likely to be used in patients who fail currently available medical therapy,” the reviewers wrote. “Further studies of natalizumab are not likely to be done.”
Dr. Gordon reports unrestricted travel grants over the past 3 years from Ferring, Synergy, Tillotts, and BioGaia. He holds a National Institute for Health Research Cochrane IBD Program Grant.
EXPERT ANALYSIS FROM THE CROHN’S & COLITIS CONGRESS
TNF inhibitor prices rose despite increased drug class competition
according to a new analysis of Medicare claims data and wholesale acquisition costs published online in JAMA Internal Medicine.
A research team led by Alvaro San-Juan-Rodriguez, PharmD, of the University of Pittsburgh said their analysis illustrates “a market failure contributing to the rising costs of prescription drugs.”
Before 2009, etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira) were the only tumor necrosis factor (TNF) inhibitors approved by the Food and Drug Administration for treating rheumatoid arthritis; infliximab and adalimumab are also approved to treat inflammatory bowel disease. In 2009, subcutaneous golimumab (Simponi) and certolizumab pegol (Cimzia) entered the market, followed by intravenous golimumab (Simponi ARIA) in 2013.
The researchers used an interrupted time series analysis with a linear model that “regressed the annual cost of existing TNF inhibitors against a continuous variable for month, two indicator variables for each period after market entry of new drugs, and the interactions between them.”
Using estimates from this model, the researchers calculated the trends in costs that would have been expected if new anti-TNFs had not entered the market. They examined costs for TNF inhibitors typically reimbursed under Medicare Part D (Enbrel, Humira, Simponi, and Cimzia) and adjusted the data for increases in manufacturer rebates, but “owing to lack of data,” they could not “assess how purchasing prices for drugs typically reimbursed under Medicare Part B [Remicade and Simponi ARIA] changed over time.” All estimates for annual costs of treatment were based on dosing recommendations for a standard 80-kg patient with rheumatoid arthritis.
The annual treatment costs with existing TNF inhibitors increased after the three new agents entered the market. For example, when wholesale acquisition cost data was applied, annual treatment costs with existing TNF inhibitors increased by 144% from April 2009 to December 2016 after new drug entry (from $15.809 to $38,574). However, in the absence of new drugs’ entry, the researchers estimated that annual treatment costs would have increased by 34% (from $15,809 to $21,184).
Medicare annual treatment costs increased by 139% (from $14,901 to $35,613), compared with a 43% increase expected in the absence of new drugs’ entry (from $14,901 to $21,308). Medicare spending increased in parallel with increases in annual treatment costs, but out-of-pocket costs and manufacturer coverage gap discounts remained relatively constant over time.
The research team noted that if cost trends had not changed after the entry of new products, the costs of Enbrel, Remicade, and Humira in December 2016 would have been 40%-45% lower.
“These increases were born solely by Medicare, while patient out-of-pocket spending remained flat. In addition, these increases were not offset by manufacturer discounts in the Medicare Part D coverage gap. The rising costs of existing products may reflect manufacturers’ opportunism in response to payers’ increased willingness to pay for TNF inhibitors after market entry of new, more expensive agents,” the research team noted.
The study was funded in part by the Myers Family Foundation and one author reported funding from the National Heart, Lung, and Blood Institute.
SOURCE: San-Juan-Rodriguez A et al. JAMA Intern Med. 2019 Feb 18. doi: 10.1001/jamainternmed.2018.7656
according to a new analysis of Medicare claims data and wholesale acquisition costs published online in JAMA Internal Medicine.
A research team led by Alvaro San-Juan-Rodriguez, PharmD, of the University of Pittsburgh said their analysis illustrates “a market failure contributing to the rising costs of prescription drugs.”
Before 2009, etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira) were the only tumor necrosis factor (TNF) inhibitors approved by the Food and Drug Administration for treating rheumatoid arthritis; infliximab and adalimumab are also approved to treat inflammatory bowel disease. In 2009, subcutaneous golimumab (Simponi) and certolizumab pegol (Cimzia) entered the market, followed by intravenous golimumab (Simponi ARIA) in 2013.
The researchers used an interrupted time series analysis with a linear model that “regressed the annual cost of existing TNF inhibitors against a continuous variable for month, two indicator variables for each period after market entry of new drugs, and the interactions between them.”
Using estimates from this model, the researchers calculated the trends in costs that would have been expected if new anti-TNFs had not entered the market. They examined costs for TNF inhibitors typically reimbursed under Medicare Part D (Enbrel, Humira, Simponi, and Cimzia) and adjusted the data for increases in manufacturer rebates, but “owing to lack of data,” they could not “assess how purchasing prices for drugs typically reimbursed under Medicare Part B [Remicade and Simponi ARIA] changed over time.” All estimates for annual costs of treatment were based on dosing recommendations for a standard 80-kg patient with rheumatoid arthritis.
The annual treatment costs with existing TNF inhibitors increased after the three new agents entered the market. For example, when wholesale acquisition cost data was applied, annual treatment costs with existing TNF inhibitors increased by 144% from April 2009 to December 2016 after new drug entry (from $15.809 to $38,574). However, in the absence of new drugs’ entry, the researchers estimated that annual treatment costs would have increased by 34% (from $15,809 to $21,184).
Medicare annual treatment costs increased by 139% (from $14,901 to $35,613), compared with a 43% increase expected in the absence of new drugs’ entry (from $14,901 to $21,308). Medicare spending increased in parallel with increases in annual treatment costs, but out-of-pocket costs and manufacturer coverage gap discounts remained relatively constant over time.
The research team noted that if cost trends had not changed after the entry of new products, the costs of Enbrel, Remicade, and Humira in December 2016 would have been 40%-45% lower.
“These increases were born solely by Medicare, while patient out-of-pocket spending remained flat. In addition, these increases were not offset by manufacturer discounts in the Medicare Part D coverage gap. The rising costs of existing products may reflect manufacturers’ opportunism in response to payers’ increased willingness to pay for TNF inhibitors after market entry of new, more expensive agents,” the research team noted.
The study was funded in part by the Myers Family Foundation and one author reported funding from the National Heart, Lung, and Blood Institute.
SOURCE: San-Juan-Rodriguez A et al. JAMA Intern Med. 2019 Feb 18. doi: 10.1001/jamainternmed.2018.7656
according to a new analysis of Medicare claims data and wholesale acquisition costs published online in JAMA Internal Medicine.
A research team led by Alvaro San-Juan-Rodriguez, PharmD, of the University of Pittsburgh said their analysis illustrates “a market failure contributing to the rising costs of prescription drugs.”
Before 2009, etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira) were the only tumor necrosis factor (TNF) inhibitors approved by the Food and Drug Administration for treating rheumatoid arthritis; infliximab and adalimumab are also approved to treat inflammatory bowel disease. In 2009, subcutaneous golimumab (Simponi) and certolizumab pegol (Cimzia) entered the market, followed by intravenous golimumab (Simponi ARIA) in 2013.
The researchers used an interrupted time series analysis with a linear model that “regressed the annual cost of existing TNF inhibitors against a continuous variable for month, two indicator variables for each period after market entry of new drugs, and the interactions between them.”
Using estimates from this model, the researchers calculated the trends in costs that would have been expected if new anti-TNFs had not entered the market. They examined costs for TNF inhibitors typically reimbursed under Medicare Part D (Enbrel, Humira, Simponi, and Cimzia) and adjusted the data for increases in manufacturer rebates, but “owing to lack of data,” they could not “assess how purchasing prices for drugs typically reimbursed under Medicare Part B [Remicade and Simponi ARIA] changed over time.” All estimates for annual costs of treatment were based on dosing recommendations for a standard 80-kg patient with rheumatoid arthritis.
The annual treatment costs with existing TNF inhibitors increased after the three new agents entered the market. For example, when wholesale acquisition cost data was applied, annual treatment costs with existing TNF inhibitors increased by 144% from April 2009 to December 2016 after new drug entry (from $15.809 to $38,574). However, in the absence of new drugs’ entry, the researchers estimated that annual treatment costs would have increased by 34% (from $15,809 to $21,184).
Medicare annual treatment costs increased by 139% (from $14,901 to $35,613), compared with a 43% increase expected in the absence of new drugs’ entry (from $14,901 to $21,308). Medicare spending increased in parallel with increases in annual treatment costs, but out-of-pocket costs and manufacturer coverage gap discounts remained relatively constant over time.
The research team noted that if cost trends had not changed after the entry of new products, the costs of Enbrel, Remicade, and Humira in December 2016 would have been 40%-45% lower.
“These increases were born solely by Medicare, while patient out-of-pocket spending remained flat. In addition, these increases were not offset by manufacturer discounts in the Medicare Part D coverage gap. The rising costs of existing products may reflect manufacturers’ opportunism in response to payers’ increased willingness to pay for TNF inhibitors after market entry of new, more expensive agents,” the research team noted.
The study was funded in part by the Myers Family Foundation and one author reported funding from the National Heart, Lung, and Blood Institute.
SOURCE: San-Juan-Rodriguez A et al. JAMA Intern Med. 2019 Feb 18. doi: 10.1001/jamainternmed.2018.7656
FROM JAMA INTERNAL MEDICINE
Enterovirus in at-risk children associated with later celiac disease
“We found a significant association between exposure to enterovirus and subsequent risk of celiac disease,” wrote lead author Christian R. Kahrs of the University of Oslo and his coauthors, adding that “adenovirus was not associated with celiac disease.” The study was published in the BMJ.
From 2001 to 2007, 46,939 newborns in Norway were screened for the HLA-DQ2/DQ8 genotype, which is associated with an increased risk of celiac disease. The genotype was identified in 912 children, and blood and stool sample collection began at 3 months. Children who were still contributing blood samples by 2014-2016 were invited to be screened for celiac disease.
Of the 220 children screened, 25 were diagnosed with celiac disease. Enterovirus was detected in 370 (17%) of the 2,135 stool samples and was more frequent in children who developed celiac disease antibodies than in matched controls (adjusted odds ratio, 1.49; 95% confidence interval, 1.07-2.06; P = .02). There was a significant association between later development of celiac disease and the commonly identified enterovirus A (aOR, 1.62; 95% CI, 1.04-2.53; P = .03) and enterovirus B (aOR, 2.27; 95% CI, 1.33-3.88; P = .003). No adenovirus types were associated with development of celiac disease.
The authors acknowledged their study’s limitations, including the possibility that children might be diagnosed with celiac disease later than the study’s roughly 10-year follow-up and the limited number of children with the disease despite a large number of analyzed samples. They noted that, “given the limited number of cases, we call for corroboration in similar studies and preferably interventional studies to reach conclusions about causality.”
The study was funded by the Research Council of Norway, the Project for the Conceptual Development of Research Organization, and the Norwegian Coeliac Society. Two authors reported grant support from trusts and foundations in Norway and Switzerland; no conflicts of interest were reported.
SOURCE: Kahrs CR et al. BMJ. 2019 Feb 13. doi: 10.1136/bmj.l231.
“We found a significant association between exposure to enterovirus and subsequent risk of celiac disease,” wrote lead author Christian R. Kahrs of the University of Oslo and his coauthors, adding that “adenovirus was not associated with celiac disease.” The study was published in the BMJ.
From 2001 to 2007, 46,939 newborns in Norway were screened for the HLA-DQ2/DQ8 genotype, which is associated with an increased risk of celiac disease. The genotype was identified in 912 children, and blood and stool sample collection began at 3 months. Children who were still contributing blood samples by 2014-2016 were invited to be screened for celiac disease.
Of the 220 children screened, 25 were diagnosed with celiac disease. Enterovirus was detected in 370 (17%) of the 2,135 stool samples and was more frequent in children who developed celiac disease antibodies than in matched controls (adjusted odds ratio, 1.49; 95% confidence interval, 1.07-2.06; P = .02). There was a significant association between later development of celiac disease and the commonly identified enterovirus A (aOR, 1.62; 95% CI, 1.04-2.53; P = .03) and enterovirus B (aOR, 2.27; 95% CI, 1.33-3.88; P = .003). No adenovirus types were associated with development of celiac disease.
The authors acknowledged their study’s limitations, including the possibility that children might be diagnosed with celiac disease later than the study’s roughly 10-year follow-up and the limited number of children with the disease despite a large number of analyzed samples. They noted that, “given the limited number of cases, we call for corroboration in similar studies and preferably interventional studies to reach conclusions about causality.”
The study was funded by the Research Council of Norway, the Project for the Conceptual Development of Research Organization, and the Norwegian Coeliac Society. Two authors reported grant support from trusts and foundations in Norway and Switzerland; no conflicts of interest were reported.
SOURCE: Kahrs CR et al. BMJ. 2019 Feb 13. doi: 10.1136/bmj.l231.
“We found a significant association between exposure to enterovirus and subsequent risk of celiac disease,” wrote lead author Christian R. Kahrs of the University of Oslo and his coauthors, adding that “adenovirus was not associated with celiac disease.” The study was published in the BMJ.
From 2001 to 2007, 46,939 newborns in Norway were screened for the HLA-DQ2/DQ8 genotype, which is associated with an increased risk of celiac disease. The genotype was identified in 912 children, and blood and stool sample collection began at 3 months. Children who were still contributing blood samples by 2014-2016 were invited to be screened for celiac disease.
Of the 220 children screened, 25 were diagnosed with celiac disease. Enterovirus was detected in 370 (17%) of the 2,135 stool samples and was more frequent in children who developed celiac disease antibodies than in matched controls (adjusted odds ratio, 1.49; 95% confidence interval, 1.07-2.06; P = .02). There was a significant association between later development of celiac disease and the commonly identified enterovirus A (aOR, 1.62; 95% CI, 1.04-2.53; P = .03) and enterovirus B (aOR, 2.27; 95% CI, 1.33-3.88; P = .003). No adenovirus types were associated with development of celiac disease.
The authors acknowledged their study’s limitations, including the possibility that children might be diagnosed with celiac disease later than the study’s roughly 10-year follow-up and the limited number of children with the disease despite a large number of analyzed samples. They noted that, “given the limited number of cases, we call for corroboration in similar studies and preferably interventional studies to reach conclusions about causality.”
The study was funded by the Research Council of Norway, the Project for the Conceptual Development of Research Organization, and the Norwegian Coeliac Society. Two authors reported grant support from trusts and foundations in Norway and Switzerland; no conflicts of interest were reported.
SOURCE: Kahrs CR et al. BMJ. 2019 Feb 13. doi: 10.1136/bmj.l231.
FROM THE BMJ
Delays of 1-2+ years in IBD diagnosis are common, patients say
LAS VEGAS – Delays in diagnosis of inflammatory bowel disease (IBD) appear to be very common and often extensive, a new survey of U.S. patients suggests. Nearly two-thirds said their diagnosis was delayed past symptom onset for more than a year, and almost half reported a delay of more than 2 years.
On average, patients who experienced diagnosis delays said they’d seen an average of 3.5 physicians. “Most patients reported that they received an uncertain or wrong diagnosis by their primary care physician or gastroenterologist,” said study coauthor Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, in an interview prior to the presentation of the study findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
“Working at a tertiary care IBD center, we noticed that many patients tell us it took them a long time to get diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC],” said Dr. Ungaro. “There are some studies on delay in diagnosis in Europe but none in the U.S. We hypothesized that diagnostic delay is a major issue for IBD patients in the U.S.”
The study authors offered a survey to 2,341 patients with IBD; 1,121 responded to the questions. Of those, 68% reported their diagnosis was delayed, with 64% reporting a delay of over 1 year and 48% reporting a delay over 2 years.
Compared with those with UC, patients with CD were more likely to report more than 1-year delays (70% vs. 48%; P less than .0001) and more than 2-year delays (52% vs. 37%; P = .0008).
Patients who reported delays said they saw an average of 3.5 physicians before getting an IBD diagnosis. The patients most commonly blamed their incorrect diagnosis on primary care providers (58%) and gastroenterologists (28%).
“Most likely, CD may be misdiagnosed because the common presenting symptoms – abdominal pain, diarrhea – are also seen in other common gastrointestinal conditions such as irritable bowel syndrome,” Dr. Ungaro said. “In contrast, most patients with UC present with rectal bleeding which is a ‘red flag’ symptom that is more likely to get worked up.”
In some cases, patients blamed themselves, reporting “that they personally did not feel their symptoms warranted work-up or were too embarrassed by their symptoms to tell anyone,” Dr. Ungaro said. “The other theme that was noted was access – delay or difficulty seeing a gastroenterologist.”
Going forward, “diagnostic delay may be improved through patient education regarding awareness of alarm symptoms for IBD,” said gastroenterologist and study lead author Zane Gallinger, MD, FRCPC, of the University of Toronto at Mount Sinai Hospital, in an interview. According to him, these symptoms include diarrhea, abdominal pain, weight loss, family history of CD, perianal abscess, and fistula and fever.
At the primary care level, Dr. Gallinger said that noninvasive tests such as fecal calprotectin can help identify patients with inflammatory conditions and that “more rapid access to gastroenterologists for earlier diagnosis of IBD can improve patient outcomes.”
The Crohn’s and Colitis Foundation funded the study. Dr. Gallinger reported relationships with Takeda and AbbVie.
SOURCE: Gallinger Z et al. Crohn’s & Colitis Congress, Abstract P030.
LAS VEGAS – Delays in diagnosis of inflammatory bowel disease (IBD) appear to be very common and often extensive, a new survey of U.S. patients suggests. Nearly two-thirds said their diagnosis was delayed past symptom onset for more than a year, and almost half reported a delay of more than 2 years.
On average, patients who experienced diagnosis delays said they’d seen an average of 3.5 physicians. “Most patients reported that they received an uncertain or wrong diagnosis by their primary care physician or gastroenterologist,” said study coauthor Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, in an interview prior to the presentation of the study findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
“Working at a tertiary care IBD center, we noticed that many patients tell us it took them a long time to get diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC],” said Dr. Ungaro. “There are some studies on delay in diagnosis in Europe but none in the U.S. We hypothesized that diagnostic delay is a major issue for IBD patients in the U.S.”
The study authors offered a survey to 2,341 patients with IBD; 1,121 responded to the questions. Of those, 68% reported their diagnosis was delayed, with 64% reporting a delay of over 1 year and 48% reporting a delay over 2 years.
Compared with those with UC, patients with CD were more likely to report more than 1-year delays (70% vs. 48%; P less than .0001) and more than 2-year delays (52% vs. 37%; P = .0008).
Patients who reported delays said they saw an average of 3.5 physicians before getting an IBD diagnosis. The patients most commonly blamed their incorrect diagnosis on primary care providers (58%) and gastroenterologists (28%).
“Most likely, CD may be misdiagnosed because the common presenting symptoms – abdominal pain, diarrhea – are also seen in other common gastrointestinal conditions such as irritable bowel syndrome,” Dr. Ungaro said. “In contrast, most patients with UC present with rectal bleeding which is a ‘red flag’ symptom that is more likely to get worked up.”
In some cases, patients blamed themselves, reporting “that they personally did not feel their symptoms warranted work-up or were too embarrassed by their symptoms to tell anyone,” Dr. Ungaro said. “The other theme that was noted was access – delay or difficulty seeing a gastroenterologist.”
Going forward, “diagnostic delay may be improved through patient education regarding awareness of alarm symptoms for IBD,” said gastroenterologist and study lead author Zane Gallinger, MD, FRCPC, of the University of Toronto at Mount Sinai Hospital, in an interview. According to him, these symptoms include diarrhea, abdominal pain, weight loss, family history of CD, perianal abscess, and fistula and fever.
At the primary care level, Dr. Gallinger said that noninvasive tests such as fecal calprotectin can help identify patients with inflammatory conditions and that “more rapid access to gastroenterologists for earlier diagnosis of IBD can improve patient outcomes.”
The Crohn’s and Colitis Foundation funded the study. Dr. Gallinger reported relationships with Takeda and AbbVie.
SOURCE: Gallinger Z et al. Crohn’s & Colitis Congress, Abstract P030.
LAS VEGAS – Delays in diagnosis of inflammatory bowel disease (IBD) appear to be very common and often extensive, a new survey of U.S. patients suggests. Nearly two-thirds said their diagnosis was delayed past symptom onset for more than a year, and almost half reported a delay of more than 2 years.
On average, patients who experienced diagnosis delays said they’d seen an average of 3.5 physicians. “Most patients reported that they received an uncertain or wrong diagnosis by their primary care physician or gastroenterologist,” said study coauthor Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, in an interview prior to the presentation of the study findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
“Working at a tertiary care IBD center, we noticed that many patients tell us it took them a long time to get diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC],” said Dr. Ungaro. “There are some studies on delay in diagnosis in Europe but none in the U.S. We hypothesized that diagnostic delay is a major issue for IBD patients in the U.S.”
The study authors offered a survey to 2,341 patients with IBD; 1,121 responded to the questions. Of those, 68% reported their diagnosis was delayed, with 64% reporting a delay of over 1 year and 48% reporting a delay over 2 years.
Compared with those with UC, patients with CD were more likely to report more than 1-year delays (70% vs. 48%; P less than .0001) and more than 2-year delays (52% vs. 37%; P = .0008).
Patients who reported delays said they saw an average of 3.5 physicians before getting an IBD diagnosis. The patients most commonly blamed their incorrect diagnosis on primary care providers (58%) and gastroenterologists (28%).
“Most likely, CD may be misdiagnosed because the common presenting symptoms – abdominal pain, diarrhea – are also seen in other common gastrointestinal conditions such as irritable bowel syndrome,” Dr. Ungaro said. “In contrast, most patients with UC present with rectal bleeding which is a ‘red flag’ symptom that is more likely to get worked up.”
In some cases, patients blamed themselves, reporting “that they personally did not feel their symptoms warranted work-up or were too embarrassed by their symptoms to tell anyone,” Dr. Ungaro said. “The other theme that was noted was access – delay or difficulty seeing a gastroenterologist.”
Going forward, “diagnostic delay may be improved through patient education regarding awareness of alarm symptoms for IBD,” said gastroenterologist and study lead author Zane Gallinger, MD, FRCPC, of the University of Toronto at Mount Sinai Hospital, in an interview. According to him, these symptoms include diarrhea, abdominal pain, weight loss, family history of CD, perianal abscess, and fistula and fever.
At the primary care level, Dr. Gallinger said that noninvasive tests such as fecal calprotectin can help identify patients with inflammatory conditions and that “more rapid access to gastroenterologists for earlier diagnosis of IBD can improve patient outcomes.”
The Crohn’s and Colitis Foundation funded the study. Dr. Gallinger reported relationships with Takeda and AbbVie.
SOURCE: Gallinger Z et al. Crohn’s & Colitis Congress, Abstract P030.
REPORTING FROM THE CROHN’S & COLITIS CONGRESS
Racial disparities uncovered in IBD-related myelosuppressive hospitalizations
LAS VEGAS – Immunosuppressant thiopurine drugs are a common and often successful treatment for patients with inflammatory bowel disease (IBD), but they can cause serious side effects via myelosuppression. Now, a new study suggests that a racial gap may prevent minority patients from being promptly diagnosed with myelosuppressive side effects.
“We found that minority IBD patients – black, Hispanic, Asian/Pacific Islander – had significantly higher hospitalization rates that were due to myelosuppressive events compared to white IBD patients,” lead author Ryan Suk, MS, said in an interview. “Among those IBD patients who were hospitalized due to myelosuppression, black and Hispanic IBD patients had a significantly higher chance of getting admitted as urgent compared to white IBD patients.”
Ms. Suk, a health economics graduate student at the University of Texas, Houston, spoke in an interview prior to the presentation of her study’s findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
According to Ms. Suk, multiple studies have previously revealed racial and ethnic disparities in health care access and use by minority patients with IBD.
She pointed to a 2010 study that found black patients with IBD were much less likely than whites were to see a gastroenterologist or IBD specialist at least once a year. She also cited a 2009 study that found black patients with IBD were significantly less adherent than were white patients; researchers linked older age and higher trust in physicians to higher levels of adherence (Am J Gastroenterol. 2010 Oct;105[10]:2202-8; Inflamm Bowel Dis. 2009 Aug;15[8]:1233-9).
In light of these findings, she said, “we questioned what the possible results of thiopurine use could be in minority patients without proper and consistent routine IBD care.”
While thiopurine is considered a standard form of care for IBD patients, Ms. Suk said an estimated one-third of patients must stop the treatment because of side effects such as anemia, leukopenia/neutropenia, and thrombocytopenia.
For the new study, Ms. Suk and her colleagues tracked patients who were hospitalized with a primary diagnosis of IBD or IBD-related complications from 2003-2014 via the Nationwide Inpatient Sample. There were 249,253 white patients, 192,864 black patients, 28,956 Hispanic patients, 17,073 Asian/Pacific Islander patients, and 2,849 patients in the “other” category.
The researchers found higher odds of hospitalization for myelosuppression in minorities compared with non-Hispanic whites: Non-Hispanic blacks (adjusted odds ratio = 1.3; 95% confidence interval [1.2-1.4], vs. whites), Hispanics (aOR = 1.6; 95% CI [1.4-1.7], vs. whites), and Asian/Pacific Islanders (aOR = 2.3; 95% CI [1.9-2.8], vs. whites).
The researchers found that among patients diagnosed with myelosuppression, two groups – non-Hispanic blacks and Hispanics – had higher odds of being admitted urgently, compared with non-Hispanic whites (aOR = 1.7; 95% CI [1.2-2.3] and aOR = 1.6; 95% CI [1.1-2.2] vs. whites, respectively).
“Unlike Asian/Pacific Islander patients, black and Hispanic patients had a higher likelihood of getting hospitalized from myelosuppression and also higher likelihood to get admitted urgently compared to the white cohort,” Ms. Suk said. “It is possible that they have less access to thiopurine management and monitoring, leading to developing more severe adverse events and therefore having urgent myelosuppressive hospitalizations.”
As for Asian/Pacific Islander patients, she noted that they had the highest likelihood of myelosuppression hospitalization but did not have the highest chance of getting admitted as urgent. “We think that Asians have a higher risk of myelosuppression due to genetic factors, not from less access to care, and thus they had more elective hospitalizations,” she said.
The researchers also linked Medicaid, self-pay, and no-charge patients to higher levels of myelosuppression hospitalizations. “This shows that patients who have less access to care [need more] urgent admission from myelosuppressive events,” Ms. Suk said.
No funding was reported, and the study authors had no relevant disclosures.
SOURCE: Suk R et al. Crohn’s & Colitis Congress, Abstract P059.
LAS VEGAS – Immunosuppressant thiopurine drugs are a common and often successful treatment for patients with inflammatory bowel disease (IBD), but they can cause serious side effects via myelosuppression. Now, a new study suggests that a racial gap may prevent minority patients from being promptly diagnosed with myelosuppressive side effects.
“We found that minority IBD patients – black, Hispanic, Asian/Pacific Islander – had significantly higher hospitalization rates that were due to myelosuppressive events compared to white IBD patients,” lead author Ryan Suk, MS, said in an interview. “Among those IBD patients who were hospitalized due to myelosuppression, black and Hispanic IBD patients had a significantly higher chance of getting admitted as urgent compared to white IBD patients.”
Ms. Suk, a health economics graduate student at the University of Texas, Houston, spoke in an interview prior to the presentation of her study’s findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
According to Ms. Suk, multiple studies have previously revealed racial and ethnic disparities in health care access and use by minority patients with IBD.
She pointed to a 2010 study that found black patients with IBD were much less likely than whites were to see a gastroenterologist or IBD specialist at least once a year. She also cited a 2009 study that found black patients with IBD were significantly less adherent than were white patients; researchers linked older age and higher trust in physicians to higher levels of adherence (Am J Gastroenterol. 2010 Oct;105[10]:2202-8; Inflamm Bowel Dis. 2009 Aug;15[8]:1233-9).
In light of these findings, she said, “we questioned what the possible results of thiopurine use could be in minority patients without proper and consistent routine IBD care.”
While thiopurine is considered a standard form of care for IBD patients, Ms. Suk said an estimated one-third of patients must stop the treatment because of side effects such as anemia, leukopenia/neutropenia, and thrombocytopenia.
For the new study, Ms. Suk and her colleagues tracked patients who were hospitalized with a primary diagnosis of IBD or IBD-related complications from 2003-2014 via the Nationwide Inpatient Sample. There were 249,253 white patients, 192,864 black patients, 28,956 Hispanic patients, 17,073 Asian/Pacific Islander patients, and 2,849 patients in the “other” category.
The researchers found higher odds of hospitalization for myelosuppression in minorities compared with non-Hispanic whites: Non-Hispanic blacks (adjusted odds ratio = 1.3; 95% confidence interval [1.2-1.4], vs. whites), Hispanics (aOR = 1.6; 95% CI [1.4-1.7], vs. whites), and Asian/Pacific Islanders (aOR = 2.3; 95% CI [1.9-2.8], vs. whites).
The researchers found that among patients diagnosed with myelosuppression, two groups – non-Hispanic blacks and Hispanics – had higher odds of being admitted urgently, compared with non-Hispanic whites (aOR = 1.7; 95% CI [1.2-2.3] and aOR = 1.6; 95% CI [1.1-2.2] vs. whites, respectively).
“Unlike Asian/Pacific Islander patients, black and Hispanic patients had a higher likelihood of getting hospitalized from myelosuppression and also higher likelihood to get admitted urgently compared to the white cohort,” Ms. Suk said. “It is possible that they have less access to thiopurine management and monitoring, leading to developing more severe adverse events and therefore having urgent myelosuppressive hospitalizations.”
As for Asian/Pacific Islander patients, she noted that they had the highest likelihood of myelosuppression hospitalization but did not have the highest chance of getting admitted as urgent. “We think that Asians have a higher risk of myelosuppression due to genetic factors, not from less access to care, and thus they had more elective hospitalizations,” she said.
The researchers also linked Medicaid, self-pay, and no-charge patients to higher levels of myelosuppression hospitalizations. “This shows that patients who have less access to care [need more] urgent admission from myelosuppressive events,” Ms. Suk said.
No funding was reported, and the study authors had no relevant disclosures.
SOURCE: Suk R et al. Crohn’s & Colitis Congress, Abstract P059.
LAS VEGAS – Immunosuppressant thiopurine drugs are a common and often successful treatment for patients with inflammatory bowel disease (IBD), but they can cause serious side effects via myelosuppression. Now, a new study suggests that a racial gap may prevent minority patients from being promptly diagnosed with myelosuppressive side effects.
“We found that minority IBD patients – black, Hispanic, Asian/Pacific Islander – had significantly higher hospitalization rates that were due to myelosuppressive events compared to white IBD patients,” lead author Ryan Suk, MS, said in an interview. “Among those IBD patients who were hospitalized due to myelosuppression, black and Hispanic IBD patients had a significantly higher chance of getting admitted as urgent compared to white IBD patients.”
Ms. Suk, a health economics graduate student at the University of Texas, Houston, spoke in an interview prior to the presentation of her study’s findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
According to Ms. Suk, multiple studies have previously revealed racial and ethnic disparities in health care access and use by minority patients with IBD.
She pointed to a 2010 study that found black patients with IBD were much less likely than whites were to see a gastroenterologist or IBD specialist at least once a year. She also cited a 2009 study that found black patients with IBD were significantly less adherent than were white patients; researchers linked older age and higher trust in physicians to higher levels of adherence (Am J Gastroenterol. 2010 Oct;105[10]:2202-8; Inflamm Bowel Dis. 2009 Aug;15[8]:1233-9).
In light of these findings, she said, “we questioned what the possible results of thiopurine use could be in minority patients without proper and consistent routine IBD care.”
While thiopurine is considered a standard form of care for IBD patients, Ms. Suk said an estimated one-third of patients must stop the treatment because of side effects such as anemia, leukopenia/neutropenia, and thrombocytopenia.
For the new study, Ms. Suk and her colleagues tracked patients who were hospitalized with a primary diagnosis of IBD or IBD-related complications from 2003-2014 via the Nationwide Inpatient Sample. There were 249,253 white patients, 192,864 black patients, 28,956 Hispanic patients, 17,073 Asian/Pacific Islander patients, and 2,849 patients in the “other” category.
The researchers found higher odds of hospitalization for myelosuppression in minorities compared with non-Hispanic whites: Non-Hispanic blacks (adjusted odds ratio = 1.3; 95% confidence interval [1.2-1.4], vs. whites), Hispanics (aOR = 1.6; 95% CI [1.4-1.7], vs. whites), and Asian/Pacific Islanders (aOR = 2.3; 95% CI [1.9-2.8], vs. whites).
The researchers found that among patients diagnosed with myelosuppression, two groups – non-Hispanic blacks and Hispanics – had higher odds of being admitted urgently, compared with non-Hispanic whites (aOR = 1.7; 95% CI [1.2-2.3] and aOR = 1.6; 95% CI [1.1-2.2] vs. whites, respectively).
“Unlike Asian/Pacific Islander patients, black and Hispanic patients had a higher likelihood of getting hospitalized from myelosuppression and also higher likelihood to get admitted urgently compared to the white cohort,” Ms. Suk said. “It is possible that they have less access to thiopurine management and monitoring, leading to developing more severe adverse events and therefore having urgent myelosuppressive hospitalizations.”
As for Asian/Pacific Islander patients, she noted that they had the highest likelihood of myelosuppression hospitalization but did not have the highest chance of getting admitted as urgent. “We think that Asians have a higher risk of myelosuppression due to genetic factors, not from less access to care, and thus they had more elective hospitalizations,” she said.
The researchers also linked Medicaid, self-pay, and no-charge patients to higher levels of myelosuppression hospitalizations. “This shows that patients who have less access to care [need more] urgent admission from myelosuppressive events,” Ms. Suk said.
No funding was reported, and the study authors had no relevant disclosures.
SOURCE: Suk R et al. Crohn’s & Colitis Congress, Abstract P059.
REPORTING FROM THE CROHN’S & COLITIS CONGRESS
Survey: Reproductive counseling is often MIA in IBD
LAS VEGAS – Inflammatory bowel disease (IBD) can disrupt both fertility and pregnancy, especially if it’s not fully controlled, and there’s a risk that the condition can be passed onto an unborn child. Still a new study suggests many patients with IBD don’t receive appropriate reproductive counseling.
Nearly two-thirds of 100 patients surveyed at a single center reported that no physician had talked to them about reproductive topics, and some said they’d considered not having children because of the condition. “Really fundamental subjects have not made their way into the interactions between patients and their care teams,” coauthor and gastroenterologist Sarah Streett, MD, AGAF, of Stanford (Calif.) University, said in an interview before the study was presented at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
IBD can lower fertility in both sexes and boost complications in pregnancy. “The good news is that almost all the medications used for IBD appear safe,” Dr. Streett said. “In fact, the safety risks for the baby and the pregnancy revolve around not having IBD under good control.”
Unfortunately, she said, misinformation is common. “Patients who become pregnant or are trying to become pregnant, and are worried about potential harm to the baby, will stop the medications due to incorrect information. Or they’ll be told by their health care team to stop their medications.”
Dr. Streett and study lead author Aarti Rao, MD, a gastroenterology fellow at Stanford, launched their study of IBD clinic patients to gain more understanding about patient knowledge. “We know from research already published that those with IBD have a lot of concerns about starting families and don’t have a lot of information to base their decision making on,” Dr. Streett said. “We wanted to evaluate that in our population and see how much people knew and what the need was.”
In 2018 and 2019, Dr. Streett and Dr. Rao gave an anonymous, validated 17-question survey to patients aged 18-45 with IBD. One hundred patients responded (median age = 30, 54% female, 59% white, 66% with incomes over $100,000, 52% with ulcerative colitis, 21% with prior IBD surgery, 71% with prior IBD hospitalization).
Just over a third – 35% – of the patients said they’d been counseled about reproductive health by a physician. This finding reflects findings in previous research, said Dr. Rao, who spoke in an interview.
Just 15% of those who’d undergone IBD surgery reported getting guidance about the effects of surgery on fertility.
More than a third (35%) of women and 15% of men said they’d considered not having children because of their IBD. In fact, “most potential dads and moms have the chance to do very well,” Dr. Streett said.
Without reproductive counseling, she added, parents won’t know about the risks of passing on IBD. According to Dr. Rao, there’s an estimated less than 5% chance that IBD will be passed on to children if one parent has the condition; the risk is much higher if both parents have it.
Going forward, “there’s a really urgent need for proactive counseling on the part of gastroenterologists and health care teams to give people of childbearing age the right information so they can be informed to make the best decisions,” Dr. Streett said.
The study was funded by a philanthropic grant. The study authors report no relevant disclosures.
With proper planning, care and coordination among treating health care providers via a multidisciplinary approach, women with IBD can have healthy pregnancies and healthy babies. Learn more at www.IBDParenthoodProject.org.
SOURCE: Rao A et al. Crohn’s & Colitis Congress, Abstract P009.
LAS VEGAS – Inflammatory bowel disease (IBD) can disrupt both fertility and pregnancy, especially if it’s not fully controlled, and there’s a risk that the condition can be passed onto an unborn child. Still a new study suggests many patients with IBD don’t receive appropriate reproductive counseling.
Nearly two-thirds of 100 patients surveyed at a single center reported that no physician had talked to them about reproductive topics, and some said they’d considered not having children because of the condition. “Really fundamental subjects have not made their way into the interactions between patients and their care teams,” coauthor and gastroenterologist Sarah Streett, MD, AGAF, of Stanford (Calif.) University, said in an interview before the study was presented at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
IBD can lower fertility in both sexes and boost complications in pregnancy. “The good news is that almost all the medications used for IBD appear safe,” Dr. Streett said. “In fact, the safety risks for the baby and the pregnancy revolve around not having IBD under good control.”
Unfortunately, she said, misinformation is common. “Patients who become pregnant or are trying to become pregnant, and are worried about potential harm to the baby, will stop the medications due to incorrect information. Or they’ll be told by their health care team to stop their medications.”
Dr. Streett and study lead author Aarti Rao, MD, a gastroenterology fellow at Stanford, launched their study of IBD clinic patients to gain more understanding about patient knowledge. “We know from research already published that those with IBD have a lot of concerns about starting families and don’t have a lot of information to base their decision making on,” Dr. Streett said. “We wanted to evaluate that in our population and see how much people knew and what the need was.”
In 2018 and 2019, Dr. Streett and Dr. Rao gave an anonymous, validated 17-question survey to patients aged 18-45 with IBD. One hundred patients responded (median age = 30, 54% female, 59% white, 66% with incomes over $100,000, 52% with ulcerative colitis, 21% with prior IBD surgery, 71% with prior IBD hospitalization).
Just over a third – 35% – of the patients said they’d been counseled about reproductive health by a physician. This finding reflects findings in previous research, said Dr. Rao, who spoke in an interview.
Just 15% of those who’d undergone IBD surgery reported getting guidance about the effects of surgery on fertility.
More than a third (35%) of women and 15% of men said they’d considered not having children because of their IBD. In fact, “most potential dads and moms have the chance to do very well,” Dr. Streett said.
Without reproductive counseling, she added, parents won’t know about the risks of passing on IBD. According to Dr. Rao, there’s an estimated less than 5% chance that IBD will be passed on to children if one parent has the condition; the risk is much higher if both parents have it.
Going forward, “there’s a really urgent need for proactive counseling on the part of gastroenterologists and health care teams to give people of childbearing age the right information so they can be informed to make the best decisions,” Dr. Streett said.
The study was funded by a philanthropic grant. The study authors report no relevant disclosures.
With proper planning, care and coordination among treating health care providers via a multidisciplinary approach, women with IBD can have healthy pregnancies and healthy babies. Learn more at www.IBDParenthoodProject.org.
SOURCE: Rao A et al. Crohn’s & Colitis Congress, Abstract P009.
LAS VEGAS – Inflammatory bowel disease (IBD) can disrupt both fertility and pregnancy, especially if it’s not fully controlled, and there’s a risk that the condition can be passed onto an unborn child. Still a new study suggests many patients with IBD don’t receive appropriate reproductive counseling.
Nearly two-thirds of 100 patients surveyed at a single center reported that no physician had talked to them about reproductive topics, and some said they’d considered not having children because of the condition. “Really fundamental subjects have not made their way into the interactions between patients and their care teams,” coauthor and gastroenterologist Sarah Streett, MD, AGAF, of Stanford (Calif.) University, said in an interview before the study was presented at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
IBD can lower fertility in both sexes and boost complications in pregnancy. “The good news is that almost all the medications used for IBD appear safe,” Dr. Streett said. “In fact, the safety risks for the baby and the pregnancy revolve around not having IBD under good control.”
Unfortunately, she said, misinformation is common. “Patients who become pregnant or are trying to become pregnant, and are worried about potential harm to the baby, will stop the medications due to incorrect information. Or they’ll be told by their health care team to stop their medications.”
Dr. Streett and study lead author Aarti Rao, MD, a gastroenterology fellow at Stanford, launched their study of IBD clinic patients to gain more understanding about patient knowledge. “We know from research already published that those with IBD have a lot of concerns about starting families and don’t have a lot of information to base their decision making on,” Dr. Streett said. “We wanted to evaluate that in our population and see how much people knew and what the need was.”
In 2018 and 2019, Dr. Streett and Dr. Rao gave an anonymous, validated 17-question survey to patients aged 18-45 with IBD. One hundred patients responded (median age = 30, 54% female, 59% white, 66% with incomes over $100,000, 52% with ulcerative colitis, 21% with prior IBD surgery, 71% with prior IBD hospitalization).
Just over a third – 35% – of the patients said they’d been counseled about reproductive health by a physician. This finding reflects findings in previous research, said Dr. Rao, who spoke in an interview.
Just 15% of those who’d undergone IBD surgery reported getting guidance about the effects of surgery on fertility.
More than a third (35%) of women and 15% of men said they’d considered not having children because of their IBD. In fact, “most potential dads and moms have the chance to do very well,” Dr. Streett said.
Without reproductive counseling, she added, parents won’t know about the risks of passing on IBD. According to Dr. Rao, there’s an estimated less than 5% chance that IBD will be passed on to children if one parent has the condition; the risk is much higher if both parents have it.
Going forward, “there’s a really urgent need for proactive counseling on the part of gastroenterologists and health care teams to give people of childbearing age the right information so they can be informed to make the best decisions,” Dr. Streett said.
The study was funded by a philanthropic grant. The study authors report no relevant disclosures.
With proper planning, care and coordination among treating health care providers via a multidisciplinary approach, women with IBD can have healthy pregnancies and healthy babies. Learn more at www.IBDParenthoodProject.org.
SOURCE: Rao A et al. Crohn’s & Colitis Congress, Abstract P009.
REPORTING FROM THE CROHN’S & COLITIS CONGRESS
Key clinical point: Patients with inflammatory bowel disease aren’t getting proper guidance regarding fertility, pregnancy, and genetic risks.
Major finding: Among surveyed patients, 65% said they’d never received reproductive counseling from a physician.
Study details: Single-center survey of 100 patients (median age = 30, 54% female).
Disclosures: The study was funded by a philanthropic grant. The study authors report no relevant disclosures.
Source: Rao A et al. Crohn’s & Colitis Congress 2019, Abstract P009.
Acceptance and commitment therapy reduced IBD stress, depression
Eight weeks of a mindfulness intervention known as acceptance and commitment therapy (ACT) significantly improved stress and depression among patients with inflammatory bowel disease, and these improvements persisted for at least 12 weeks after therapy ended, according to the results of a randomized, controlled trial.
Source: The American Gastroenterological Association
In the intention-to-treat analysis, stress symptoms, as measured by the Depression Anxiety and Stress Scales (DASS-21), improved by 39% at week 8 and by 45% at week 20, reported Brona Wynne, PhD, of University College Dublin together with her associates. These improvements were highly significant compared with baseline and treatment as usual (P = .001 for both comparisons). “Post hoc analyses indicated that baseline stress levels were similar in control and treatment groups,” the researchers wrote in Gastroenterology. “The results of the per protocol analysis were comparable, with a 43% and 49% reduction in stress in the treatment group from baseline to 8 and 20 weeks.”
Multiple studies have documented high levels of stress and psychological dysfunction among patients with Crohn’s disease and ulcerative colitis. Studies of various mindfulness therapy, relaxation, stress management, cognitive-behavioral therapy, and hypnotherapy interventions often failed to collect key clinical data or were underpowered, uncontrolled, and unrandomized. Acceptance and commitment therapy uses mindfulness to identify adverse thoughts and experiences, accept these as part of life, and recommit to “move towards values that have been identified and adopted by the individual,” the investigators wrote. “This can be defined as the ability to contact the present moment more fully as a conscious human being and to change, or persist in, behavior when doing so serves valued ends.”
Their single-center study, which they said was the first to evaluate ACT in IBD patients, included 79 individuals with stable or mildly active Crohn’s disease (38 patients) or ulcerative colitis (41 patients) who were randomly assigned to ACT (37 patients) or control treatment as usual (42 patients). The two comparison groups were demographically and clinically similar. The ACT program involved eight 90-minute, weekly sessions of groups of 14-16 individuals, led by a single psychologist who tailored the course material toward IBD with a focus on lowering stress. An independent psychologist observed each session to assess adherence to protocol.
Not only did ACT meet the primary study endpoint, it also produced a 25% decrease in perceived stress (on a 1-10 scale) by week 8 and a 27% decrease in perceived stress by week 20 (P less than .001 versus treatment as usual). Depression scores in the ACT group also fell by 47% by week 8 and by 45% at week 20 (P = .01 versus treatment as usual). Anxiety levels decreased by 29% at week 8 and by 31% at week 20, but these improvements did not significantly differ from those in the control group (P = .39).
Interestingly, ACT did not significantly improve symptom burden, activities of daily living, disease-related worry, general well-being, C-reactive protein (CRP) levels, fecal calprotectin levels, or scores on the version used of the Clinical Assessment of Depression (CAD) or the short Mayo assessment. Hair cortisol levels showed an association with baseline stress and anxiety, but not with treatment response.
Care programs for IBD increasingly emphasize mental health services despite a lack of robust trials to support these interventions, the investigators noted. Thus, their findings highlight “the need for researchers and clinicians to further develop and optimize the content and delivery of psychological programs for IBD patients.”
Tillotts Pharma and Boston Scientific provided partial funding, but had no other role in the study. The researchers reported having no relevant conflicts of interest.
SOURCE: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.
Factors that affect stress level and mood symptoms are vast when it comes to living with inflammatory bowel disease (IBD). Comorbid mood symptoms are common in patients with IBD, and psychological interventions are increasingly recommended as part of holistic, multidisciplinary treatment planning. Additionally, patients are open to GI-focused psychology treatments given the recognition that the complexities of living with IBD strongly influence emotional factors.
What must be acknowledged is the importance of long-term adherence to skills learned during the 8 weeks of ACT. Stress and mood symptoms tend to be more prevalent during times of flare. Given the relapsing and remitting nature of IBD, it must be conveyed that patients will need to continue the practice of this mindfulness-based intervention in the long term. Future studies are encouraged to look at longitudinal data assessing the manner in which these patients used their skill set during periods of flare or disease-related stress.
Factors that affect stress level and mood symptoms are vast when it comes to living with inflammatory bowel disease (IBD). Comorbid mood symptoms are common in patients with IBD, and psychological interventions are increasingly recommended as part of holistic, multidisciplinary treatment planning. Additionally, patients are open to GI-focused psychology treatments given the recognition that the complexities of living with IBD strongly influence emotional factors.
What must be acknowledged is the importance of long-term adherence to skills learned during the 8 weeks of ACT. Stress and mood symptoms tend to be more prevalent during times of flare. Given the relapsing and remitting nature of IBD, it must be conveyed that patients will need to continue the practice of this mindfulness-based intervention in the long term. Future studies are encouraged to look at longitudinal data assessing the manner in which these patients used their skill set during periods of flare or disease-related stress.
Factors that affect stress level and mood symptoms are vast when it comes to living with inflammatory bowel disease (IBD). Comorbid mood symptoms are common in patients with IBD, and psychological interventions are increasingly recommended as part of holistic, multidisciplinary treatment planning. Additionally, patients are open to GI-focused psychology treatments given the recognition that the complexities of living with IBD strongly influence emotional factors.
What must be acknowledged is the importance of long-term adherence to skills learned during the 8 weeks of ACT. Stress and mood symptoms tend to be more prevalent during times of flare. Given the relapsing and remitting nature of IBD, it must be conveyed that patients will need to continue the practice of this mindfulness-based intervention in the long term. Future studies are encouraged to look at longitudinal data assessing the manner in which these patients used their skill set during periods of flare or disease-related stress.
Eight weeks of a mindfulness intervention known as acceptance and commitment therapy (ACT) significantly improved stress and depression among patients with inflammatory bowel disease, and these improvements persisted for at least 12 weeks after therapy ended, according to the results of a randomized, controlled trial.
Source: The American Gastroenterological Association
In the intention-to-treat analysis, stress symptoms, as measured by the Depression Anxiety and Stress Scales (DASS-21), improved by 39% at week 8 and by 45% at week 20, reported Brona Wynne, PhD, of University College Dublin together with her associates. These improvements were highly significant compared with baseline and treatment as usual (P = .001 for both comparisons). “Post hoc analyses indicated that baseline stress levels were similar in control and treatment groups,” the researchers wrote in Gastroenterology. “The results of the per protocol analysis were comparable, with a 43% and 49% reduction in stress in the treatment group from baseline to 8 and 20 weeks.”
Multiple studies have documented high levels of stress and psychological dysfunction among patients with Crohn’s disease and ulcerative colitis. Studies of various mindfulness therapy, relaxation, stress management, cognitive-behavioral therapy, and hypnotherapy interventions often failed to collect key clinical data or were underpowered, uncontrolled, and unrandomized. Acceptance and commitment therapy uses mindfulness to identify adverse thoughts and experiences, accept these as part of life, and recommit to “move towards values that have been identified and adopted by the individual,” the investigators wrote. “This can be defined as the ability to contact the present moment more fully as a conscious human being and to change, or persist in, behavior when doing so serves valued ends.”
Their single-center study, which they said was the first to evaluate ACT in IBD patients, included 79 individuals with stable or mildly active Crohn’s disease (38 patients) or ulcerative colitis (41 patients) who were randomly assigned to ACT (37 patients) or control treatment as usual (42 patients). The two comparison groups were demographically and clinically similar. The ACT program involved eight 90-minute, weekly sessions of groups of 14-16 individuals, led by a single psychologist who tailored the course material toward IBD with a focus on lowering stress. An independent psychologist observed each session to assess adherence to protocol.
Not only did ACT meet the primary study endpoint, it also produced a 25% decrease in perceived stress (on a 1-10 scale) by week 8 and a 27% decrease in perceived stress by week 20 (P less than .001 versus treatment as usual). Depression scores in the ACT group also fell by 47% by week 8 and by 45% at week 20 (P = .01 versus treatment as usual). Anxiety levels decreased by 29% at week 8 and by 31% at week 20, but these improvements did not significantly differ from those in the control group (P = .39).
Interestingly, ACT did not significantly improve symptom burden, activities of daily living, disease-related worry, general well-being, C-reactive protein (CRP) levels, fecal calprotectin levels, or scores on the version used of the Clinical Assessment of Depression (CAD) or the short Mayo assessment. Hair cortisol levels showed an association with baseline stress and anxiety, but not with treatment response.
Care programs for IBD increasingly emphasize mental health services despite a lack of robust trials to support these interventions, the investigators noted. Thus, their findings highlight “the need for researchers and clinicians to further develop and optimize the content and delivery of psychological programs for IBD patients.”
Tillotts Pharma and Boston Scientific provided partial funding, but had no other role in the study. The researchers reported having no relevant conflicts of interest.
SOURCE: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.
Eight weeks of a mindfulness intervention known as acceptance and commitment therapy (ACT) significantly improved stress and depression among patients with inflammatory bowel disease, and these improvements persisted for at least 12 weeks after therapy ended, according to the results of a randomized, controlled trial.
Source: The American Gastroenterological Association
In the intention-to-treat analysis, stress symptoms, as measured by the Depression Anxiety and Stress Scales (DASS-21), improved by 39% at week 8 and by 45% at week 20, reported Brona Wynne, PhD, of University College Dublin together with her associates. These improvements were highly significant compared with baseline and treatment as usual (P = .001 for both comparisons). “Post hoc analyses indicated that baseline stress levels were similar in control and treatment groups,” the researchers wrote in Gastroenterology. “The results of the per protocol analysis were comparable, with a 43% and 49% reduction in stress in the treatment group from baseline to 8 and 20 weeks.”
Multiple studies have documented high levels of stress and psychological dysfunction among patients with Crohn’s disease and ulcerative colitis. Studies of various mindfulness therapy, relaxation, stress management, cognitive-behavioral therapy, and hypnotherapy interventions often failed to collect key clinical data or were underpowered, uncontrolled, and unrandomized. Acceptance and commitment therapy uses mindfulness to identify adverse thoughts and experiences, accept these as part of life, and recommit to “move towards values that have been identified and adopted by the individual,” the investigators wrote. “This can be defined as the ability to contact the present moment more fully as a conscious human being and to change, or persist in, behavior when doing so serves valued ends.”
Their single-center study, which they said was the first to evaluate ACT in IBD patients, included 79 individuals with stable or mildly active Crohn’s disease (38 patients) or ulcerative colitis (41 patients) who were randomly assigned to ACT (37 patients) or control treatment as usual (42 patients). The two comparison groups were demographically and clinically similar. The ACT program involved eight 90-minute, weekly sessions of groups of 14-16 individuals, led by a single psychologist who tailored the course material toward IBD with a focus on lowering stress. An independent psychologist observed each session to assess adherence to protocol.
Not only did ACT meet the primary study endpoint, it also produced a 25% decrease in perceived stress (on a 1-10 scale) by week 8 and a 27% decrease in perceived stress by week 20 (P less than .001 versus treatment as usual). Depression scores in the ACT group also fell by 47% by week 8 and by 45% at week 20 (P = .01 versus treatment as usual). Anxiety levels decreased by 29% at week 8 and by 31% at week 20, but these improvements did not significantly differ from those in the control group (P = .39).
Interestingly, ACT did not significantly improve symptom burden, activities of daily living, disease-related worry, general well-being, C-reactive protein (CRP) levels, fecal calprotectin levels, or scores on the version used of the Clinical Assessment of Depression (CAD) or the short Mayo assessment. Hair cortisol levels showed an association with baseline stress and anxiety, but not with treatment response.
Care programs for IBD increasingly emphasize mental health services despite a lack of robust trials to support these interventions, the investigators noted. Thus, their findings highlight “the need for researchers and clinicians to further develop and optimize the content and delivery of psychological programs for IBD patients.”
Tillotts Pharma and Boston Scientific provided partial funding, but had no other role in the study. The researchers reported having no relevant conflicts of interest.
SOURCE: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.
FROM GASTROENTEROLOGY
Key clinical point: An 8-week course of acceptance and commitment therapy improved stress and depression in patients with inflammatory bowel disease.
Major finding: Compared with controls, the intervention group experienced significant improvements in stress (P = .001) and depression (P = .01), but not anxiety.
Study details: Randomized controlled trial of 79 patients.
Disclosures: Tillotts Pharma and Boston Scientific provided partial funding but had no other role in the study. The researchers reported having no relevant conflicts of interest.
Source: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.
Herpes zoster could pose special threat to younger IBD patients
LAS VEGAS – Herpes zoster infection could pose a special risk for younger patients with inflammatory bowel disease who are on immunosuppressant or biologic therapies, a new study suggests.
About 3% of inflammatory bowel disease (IBD) patients developed herpes zoster (HZ) over a 5-year period at a single center, researchers found, and their average age was 37 years. The mean national age of HZ diagnosis is 59 years, and the latest guidelines from the Centers for Disease Control and Prevention do not recommend that people get vaccinated against HZ, or shingles, until age 50.
“Increased efforts should be made to administer herpes zoster vaccine in all eligible IBD patients, and said gastroenterologist and study coauthor Marie L. Borum, MD, MPH, of George Washington University, Washington. She spoke in an interview before presenting the study findings at the the Crohn’s & Colitis Congress – a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Borum and her associates launched the study, published in Inflammatory Bowel Diseases, after noticing an increase in HZ cases among patients with IBD. The authors retrospectively analyzed the medical charts of all patients with IBD who were treated at a single center from 2012 to 2017 (n = 393; 55% female; average age, 44 years). Nearly all had ulcerative colitis (71%) or Crohn’s disease (24%).
Over the 5-year period, 11 patients – 5 with ulcerative colitis, 5 with Crohn’s disease, and 1 patient with unspecified colitis – were diagnosed with HZ. All were taking immunosuppressant or biologic medications, and none had been vaccinated against HZ.
The difference in the average age of diagnosis of the infected patients versus the national mean age (37 years vs. 59 years) was statistically significant (P less than .0001).
The IBD patients with HZ often had postherpetic neuralgia, Dr. Borum said.
Previous studies also have linked IBD to higher rates of HZ. A 2018 retrospective study of veterans found that “the incidence rates of herpes zoster in all age groups and all IBD medication subgroups were substantially higher than that in the oldest group of patients without IBD [older than 60 years]” (Clin Gastroenterol Hepatol. 2018 Dec;16[12]:1919-27).
In 2017, researchers at the University of Wisconsin–Madison received a grant to study immunity to the varicella zoster virus in patients with IBD. A university press release said the results “could support recommendations for universal herpes zoster immunization for all IBD patients above the age of 40.”
Why might IBD boost the risk of HZ? “Individuals with IBD may have an increased risk of developing more episodes of herpes zoster due to immune dysregulation,” Dr. Borum said. “Those on immunosuppressants or biologic therapies have greater risk of more frequent and severe complications. It has been speculated that Janus kinase inhibitors may be associated with an increased risk for developing HZ.”
Dr. Borum noted that the study is limited by its size and single-center design. “However, it supports the recommendations that additional research is needed to fully understand the potential impact of HZ on IBD patients.”
The study authors reported no relevant disclosures.
SOURCE: Borum ML et al. Inflamm Bowel Dis. 2019 Feb 7. doi: 10.1093/ibd/izy393.073.
LAS VEGAS – Herpes zoster infection could pose a special risk for younger patients with inflammatory bowel disease who are on immunosuppressant or biologic therapies, a new study suggests.
About 3% of inflammatory bowel disease (IBD) patients developed herpes zoster (HZ) over a 5-year period at a single center, researchers found, and their average age was 37 years. The mean national age of HZ diagnosis is 59 years, and the latest guidelines from the Centers for Disease Control and Prevention do not recommend that people get vaccinated against HZ, or shingles, until age 50.
“Increased efforts should be made to administer herpes zoster vaccine in all eligible IBD patients, and said gastroenterologist and study coauthor Marie L. Borum, MD, MPH, of George Washington University, Washington. She spoke in an interview before presenting the study findings at the the Crohn’s & Colitis Congress – a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Borum and her associates launched the study, published in Inflammatory Bowel Diseases, after noticing an increase in HZ cases among patients with IBD. The authors retrospectively analyzed the medical charts of all patients with IBD who were treated at a single center from 2012 to 2017 (n = 393; 55% female; average age, 44 years). Nearly all had ulcerative colitis (71%) or Crohn’s disease (24%).
Over the 5-year period, 11 patients – 5 with ulcerative colitis, 5 with Crohn’s disease, and 1 patient with unspecified colitis – were diagnosed with HZ. All were taking immunosuppressant or biologic medications, and none had been vaccinated against HZ.
The difference in the average age of diagnosis of the infected patients versus the national mean age (37 years vs. 59 years) was statistically significant (P less than .0001).
The IBD patients with HZ often had postherpetic neuralgia, Dr. Borum said.
Previous studies also have linked IBD to higher rates of HZ. A 2018 retrospective study of veterans found that “the incidence rates of herpes zoster in all age groups and all IBD medication subgroups were substantially higher than that in the oldest group of patients without IBD [older than 60 years]” (Clin Gastroenterol Hepatol. 2018 Dec;16[12]:1919-27).
In 2017, researchers at the University of Wisconsin–Madison received a grant to study immunity to the varicella zoster virus in patients with IBD. A university press release said the results “could support recommendations for universal herpes zoster immunization for all IBD patients above the age of 40.”
Why might IBD boost the risk of HZ? “Individuals with IBD may have an increased risk of developing more episodes of herpes zoster due to immune dysregulation,” Dr. Borum said. “Those on immunosuppressants or biologic therapies have greater risk of more frequent and severe complications. It has been speculated that Janus kinase inhibitors may be associated with an increased risk for developing HZ.”
Dr. Borum noted that the study is limited by its size and single-center design. “However, it supports the recommendations that additional research is needed to fully understand the potential impact of HZ on IBD patients.”
The study authors reported no relevant disclosures.
SOURCE: Borum ML et al. Inflamm Bowel Dis. 2019 Feb 7. doi: 10.1093/ibd/izy393.073.
LAS VEGAS – Herpes zoster infection could pose a special risk for younger patients with inflammatory bowel disease who are on immunosuppressant or biologic therapies, a new study suggests.
About 3% of inflammatory bowel disease (IBD) patients developed herpes zoster (HZ) over a 5-year period at a single center, researchers found, and their average age was 37 years. The mean national age of HZ diagnosis is 59 years, and the latest guidelines from the Centers for Disease Control and Prevention do not recommend that people get vaccinated against HZ, or shingles, until age 50.
“Increased efforts should be made to administer herpes zoster vaccine in all eligible IBD patients, and said gastroenterologist and study coauthor Marie L. Borum, MD, MPH, of George Washington University, Washington. She spoke in an interview before presenting the study findings at the the Crohn’s & Colitis Congress – a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Borum and her associates launched the study, published in Inflammatory Bowel Diseases, after noticing an increase in HZ cases among patients with IBD. The authors retrospectively analyzed the medical charts of all patients with IBD who were treated at a single center from 2012 to 2017 (n = 393; 55% female; average age, 44 years). Nearly all had ulcerative colitis (71%) or Crohn’s disease (24%).
Over the 5-year period, 11 patients – 5 with ulcerative colitis, 5 with Crohn’s disease, and 1 patient with unspecified colitis – were diagnosed with HZ. All were taking immunosuppressant or biologic medications, and none had been vaccinated against HZ.
The difference in the average age of diagnosis of the infected patients versus the national mean age (37 years vs. 59 years) was statistically significant (P less than .0001).
The IBD patients with HZ often had postherpetic neuralgia, Dr. Borum said.
Previous studies also have linked IBD to higher rates of HZ. A 2018 retrospective study of veterans found that “the incidence rates of herpes zoster in all age groups and all IBD medication subgroups were substantially higher than that in the oldest group of patients without IBD [older than 60 years]” (Clin Gastroenterol Hepatol. 2018 Dec;16[12]:1919-27).
In 2017, researchers at the University of Wisconsin–Madison received a grant to study immunity to the varicella zoster virus in patients with IBD. A university press release said the results “could support recommendations for universal herpes zoster immunization for all IBD patients above the age of 40.”
Why might IBD boost the risk of HZ? “Individuals with IBD may have an increased risk of developing more episodes of herpes zoster due to immune dysregulation,” Dr. Borum said. “Those on immunosuppressants or biologic therapies have greater risk of more frequent and severe complications. It has been speculated that Janus kinase inhibitors may be associated with an increased risk for developing HZ.”
Dr. Borum noted that the study is limited by its size and single-center design. “However, it supports the recommendations that additional research is needed to fully understand the potential impact of HZ on IBD patients.”
The study authors reported no relevant disclosures.
SOURCE: Borum ML et al. Inflamm Bowel Dis. 2019 Feb 7. doi: 10.1093/ibd/izy393.073.
REPORTING FROM THE CROHN’S & COLITIS CONGRESS
Key clinical point: Younger patients with inflammatory bowel disease may face a higher risk of infection with herpes zoster.
Major finding: About 3% of patients with inflammatory bowel disease were diagnosed with herpes zoster infection, and their average age was 37 years.
Study details: A retrospective 5-year chart review of 393 patients with inflammatory bowel disease.
Disclosures: The authors reported no relevant disclosures.
Source: Borum ML et al. Inflamm Bowel Dis. 2019 Feb 7. doi: 10.1093/ibd/izy393.073.
Maltodextrin may increase colitis risk
The food additive maltodextrin may increase risk of inflammatory bowel disease, according to a recent study.
Compared with control subjects, mice given drinking water that contained 5% maltodextrin were significantly more likely to develop colitis and lose weight when challenged with dextran sodium sulfate (DSS), reported lead author Federica Laudisi, PhD, of the department of systems medicine at the University of Rome Tor Vergata in Rome, and her colleagues.
Further experiments with murine intestinal crypts and a human cell line echoed these results and offered mechanistic insight. Treatment with maltodextrin stressed the endoplasmic reticulum of goblet cells, predisposing the intestinal epithelium to mucus depletion and inflammation. With these results, maltodextrin joins polysorbate 80 and carboxymethylcellulose on a growing list of food additives in the Western diet with proinflammatory potential.
“Although the U.S. Food and Drug Administration recognizes these dietary elements as safe,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, “their use has been linked to the development of intestinal pathologies in both animals and human beings.
“It also has been shown that the polysaccharide maltodextrin, which is commonly used as a filler and thickener during food processing, can alter microbial phenotype and host antibacterial defenses. Maltodextrin expands the Escherichia coli population in the ileum and induces necrotizing enterocolitis in preterm piglets (Am J Physiol Gastrointest Liver Physiol. 2009 Dec;297:G1115-25).”
The present study began by administering three compounds dissolved in drinking water to wild-type Balb/c mice for 45 days: 5% maltodextrin, 0.5% propylene glycol, or 5 g/L animal gelatin. Control mice drank plain water. None of the treatments triggered clinical or histologic signs of colitis, and stool levels of lipocalin-2 (Lcn-2), a biomarker of intestinal inflammation, remained comparable with that of control mice. However, outcomes changed when mice were challenged with DSS (1.75% in drinking water) on days 35-45 or injected subcutaneously with indomethacin (5 mg/kg) on day 35 and sacrificed 24 hours later. When challenged with DSS, mice in the maltodextrin group developed severe colitis and lost 10%-15% of body weight, compared with minimal colitis and negligible weight loss in the other groups. In addition, compared with other mice, maltodextrin-fed mice had increased colon tissue expression of Lcn-2 and inflammatory cytokine interleukin (IL)-1beta. These initial findings suggested that dietary maltodextrin could increase susceptibility to clinical colitis.
To determine the pathophysiology of this phenomenon, the investigators performed microarray analysis of colonic samples. Multiple genes associated with carbohydrate and lipid metabolism were upregulated in maltodextrin-fed mice, including genes that controlled the unfolded protein response (UPR), a process in which unfolded proteins accumulate in the endoplasmic reticulum (ER) during ER stress. The most prominently expressed among the UPR-related genes was Ern-2, which regulates inositol-requiring enzyme 1beta, found exclusively in the ER of goblet cells in the small intestine and colon. When maltodextrin causes ER stress in goblet cells, it leads to misfolding of mucin glycoprotein Mucin-2 (Muc-2), a major component of gut mucus, causing gut mucus levels to drop. A diminished mucus barrier exposes the intestine to infection and damage, as demonstrated by higher rates of pathogenic bacteria in Muc-2–deficient mice than in control mice, and more severe intestinal damage than in controls when Muc-2 mice are deliberately infected with pathogens.
The investigators found that humans likely have similar responses to dietary maltodextrin. Treating the mucus-secreting HT29-methotrexate treated (HT29-MTX) cell line with 5% maltodextrin resulted in upregulation of Ern-2, which is the same mechanism observed in mice. Additional testing showed that this process was mediated by p38 mitogen-activated protein kinase, and pharmacologic inhibition or knockdown of p38 suppressed RNA expression of Ern-2. The investigators found that p38 was similarly involved in maltodextrin-fed mice.
To show that maltodextrin enhances susceptibility to inflammation via ER stress, the investigators used tauroursodeoxycholic acid (TUDCA) to inhibit ER stress. Indeed, inhibition led to reduced Ern-2 expression in HT29-MTX cells and in mice treated with maltodextrin. Giving TUDCA to maltodextrin-fed mice resulted in less weight loss, improved histology, and lower expression of Lcn-2 and IL-1beta.
The study concluded with three final experiments: The first showed that maltodextrin did not alter mucosa-associated microbiota; the second showed that mice fed 5% maltodextrin long term (for 10 weeks) had low-grade intestinal inflammation on histology, albeit without clinical colitis or weight loss; and the third showed that mice consuming maltodextrin long term had higher 15-hour fasting blood glycemic levels than control mice, supporting recent research suggesting that food additives can disrupt metabolism in a nonsusceptible host.
“In conclusion,” the investigators wrote, “this study shows that a maltodextrin-enriched diet reduces the intestinal content of Muc-2, thus making the host more sensitive to colitogenic stimuli. These data, together with the demonstration that maltodextrin can promote epithelial intestinal adhesion of pathogenic bacteria, supports the hypothesis that Western diets rich in maltodextrin can contribute to gut disease susceptibility.”
The study was funded by the Italian Ministry of Education, Universities, and Research. The authors reported no conflicts of interest.
SOURCE: Laudisi F et al. CMGH. 2019 Jan 18. doi: 10.1016/j.jcmgh.2018.09.002.
Maltodextrin is a polysaccharide derived from starch hydrolysis and broadly used as a thickener and filler in processed food. While it is regarded as inert and considered “generally regarded as safe” by the U.S. Food and Drug Administration, multiple recent studies have demonstrated detrimental roles played by maltodextrin in the intestinal environment, suggesting that this broadly used food additive may play a role in chronic inflammatory diseases.
Importantly, in addition to the use of a murine model of colitis, Laudisi and colleagues also investigated the impact that maltodextrin may have on a “normal” host, i.e. without genetic susceptibility nor induced colitis. While maltodextrin did not induce visible levels of intestinal inflammation, it led to the development of low-grade intestinal inflammation, characterized by subtle but nonetheless consistent elevation in intestinal inflammatory markers, ultimately leading to metabolic abnormalities.
Altogether, these recent results, together with previous reports, suggest that consumption of the food additive maltodextrin may be a risk factor for the IBD-prone population, as well as a factor promoting chronic low-grade intestinal inflammation leading to metabolic abnormalities in the general population. These findings further support the concept that FDA testing of food additives should be performed in disease-prone and resistant host models, designed to detect chronic and low-grade inflammation, as well as consider impacts on the gut microbiota.
Benoit Chassaing, PhD, is an assistant professor in the Neuroscience Institute and Institute for Biomedical Sciences, Georgia State University, Atlanta. He has no conflicts. These remarks are excerpted from an editorial accompanying Dr. Laudisi’s article (CMGH. 2019 Jan 18. doi.org/10.1016/j.jcmgh.2018.09.002).
Maltodextrin is a polysaccharide derived from starch hydrolysis and broadly used as a thickener and filler in processed food. While it is regarded as inert and considered “generally regarded as safe” by the U.S. Food and Drug Administration, multiple recent studies have demonstrated detrimental roles played by maltodextrin in the intestinal environment, suggesting that this broadly used food additive may play a role in chronic inflammatory diseases.
Importantly, in addition to the use of a murine model of colitis, Laudisi and colleagues also investigated the impact that maltodextrin may have on a “normal” host, i.e. without genetic susceptibility nor induced colitis. While maltodextrin did not induce visible levels of intestinal inflammation, it led to the development of low-grade intestinal inflammation, characterized by subtle but nonetheless consistent elevation in intestinal inflammatory markers, ultimately leading to metabolic abnormalities.
Altogether, these recent results, together with previous reports, suggest that consumption of the food additive maltodextrin may be a risk factor for the IBD-prone population, as well as a factor promoting chronic low-grade intestinal inflammation leading to metabolic abnormalities in the general population. These findings further support the concept that FDA testing of food additives should be performed in disease-prone and resistant host models, designed to detect chronic and low-grade inflammation, as well as consider impacts on the gut microbiota.
Benoit Chassaing, PhD, is an assistant professor in the Neuroscience Institute and Institute for Biomedical Sciences, Georgia State University, Atlanta. He has no conflicts. These remarks are excerpted from an editorial accompanying Dr. Laudisi’s article (CMGH. 2019 Jan 18. doi.org/10.1016/j.jcmgh.2018.09.002).
Maltodextrin is a polysaccharide derived from starch hydrolysis and broadly used as a thickener and filler in processed food. While it is regarded as inert and considered “generally regarded as safe” by the U.S. Food and Drug Administration, multiple recent studies have demonstrated detrimental roles played by maltodextrin in the intestinal environment, suggesting that this broadly used food additive may play a role in chronic inflammatory diseases.
Importantly, in addition to the use of a murine model of colitis, Laudisi and colleagues also investigated the impact that maltodextrin may have on a “normal” host, i.e. without genetic susceptibility nor induced colitis. While maltodextrin did not induce visible levels of intestinal inflammation, it led to the development of low-grade intestinal inflammation, characterized by subtle but nonetheless consistent elevation in intestinal inflammatory markers, ultimately leading to metabolic abnormalities.
Altogether, these recent results, together with previous reports, suggest that consumption of the food additive maltodextrin may be a risk factor for the IBD-prone population, as well as a factor promoting chronic low-grade intestinal inflammation leading to metabolic abnormalities in the general population. These findings further support the concept that FDA testing of food additives should be performed in disease-prone and resistant host models, designed to detect chronic and low-grade inflammation, as well as consider impacts on the gut microbiota.
Benoit Chassaing, PhD, is an assistant professor in the Neuroscience Institute and Institute for Biomedical Sciences, Georgia State University, Atlanta. He has no conflicts. These remarks are excerpted from an editorial accompanying Dr. Laudisi’s article (CMGH. 2019 Jan 18. doi.org/10.1016/j.jcmgh.2018.09.002).
The food additive maltodextrin may increase risk of inflammatory bowel disease, according to a recent study.
Compared with control subjects, mice given drinking water that contained 5% maltodextrin were significantly more likely to develop colitis and lose weight when challenged with dextran sodium sulfate (DSS), reported lead author Federica Laudisi, PhD, of the department of systems medicine at the University of Rome Tor Vergata in Rome, and her colleagues.
Further experiments with murine intestinal crypts and a human cell line echoed these results and offered mechanistic insight. Treatment with maltodextrin stressed the endoplasmic reticulum of goblet cells, predisposing the intestinal epithelium to mucus depletion and inflammation. With these results, maltodextrin joins polysorbate 80 and carboxymethylcellulose on a growing list of food additives in the Western diet with proinflammatory potential.
“Although the U.S. Food and Drug Administration recognizes these dietary elements as safe,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, “their use has been linked to the development of intestinal pathologies in both animals and human beings.
“It also has been shown that the polysaccharide maltodextrin, which is commonly used as a filler and thickener during food processing, can alter microbial phenotype and host antibacterial defenses. Maltodextrin expands the Escherichia coli population in the ileum and induces necrotizing enterocolitis in preterm piglets (Am J Physiol Gastrointest Liver Physiol. 2009 Dec;297:G1115-25).”
The present study began by administering three compounds dissolved in drinking water to wild-type Balb/c mice for 45 days: 5% maltodextrin, 0.5% propylene glycol, or 5 g/L animal gelatin. Control mice drank plain water. None of the treatments triggered clinical or histologic signs of colitis, and stool levels of lipocalin-2 (Lcn-2), a biomarker of intestinal inflammation, remained comparable with that of control mice. However, outcomes changed when mice were challenged with DSS (1.75% in drinking water) on days 35-45 or injected subcutaneously with indomethacin (5 mg/kg) on day 35 and sacrificed 24 hours later. When challenged with DSS, mice in the maltodextrin group developed severe colitis and lost 10%-15% of body weight, compared with minimal colitis and negligible weight loss in the other groups. In addition, compared with other mice, maltodextrin-fed mice had increased colon tissue expression of Lcn-2 and inflammatory cytokine interleukin (IL)-1beta. These initial findings suggested that dietary maltodextrin could increase susceptibility to clinical colitis.
To determine the pathophysiology of this phenomenon, the investigators performed microarray analysis of colonic samples. Multiple genes associated with carbohydrate and lipid metabolism were upregulated in maltodextrin-fed mice, including genes that controlled the unfolded protein response (UPR), a process in which unfolded proteins accumulate in the endoplasmic reticulum (ER) during ER stress. The most prominently expressed among the UPR-related genes was Ern-2, which regulates inositol-requiring enzyme 1beta, found exclusively in the ER of goblet cells in the small intestine and colon. When maltodextrin causes ER stress in goblet cells, it leads to misfolding of mucin glycoprotein Mucin-2 (Muc-2), a major component of gut mucus, causing gut mucus levels to drop. A diminished mucus barrier exposes the intestine to infection and damage, as demonstrated by higher rates of pathogenic bacteria in Muc-2–deficient mice than in control mice, and more severe intestinal damage than in controls when Muc-2 mice are deliberately infected with pathogens.
The investigators found that humans likely have similar responses to dietary maltodextrin. Treating the mucus-secreting HT29-methotrexate treated (HT29-MTX) cell line with 5% maltodextrin resulted in upregulation of Ern-2, which is the same mechanism observed in mice. Additional testing showed that this process was mediated by p38 mitogen-activated protein kinase, and pharmacologic inhibition or knockdown of p38 suppressed RNA expression of Ern-2. The investigators found that p38 was similarly involved in maltodextrin-fed mice.
To show that maltodextrin enhances susceptibility to inflammation via ER stress, the investigators used tauroursodeoxycholic acid (TUDCA) to inhibit ER stress. Indeed, inhibition led to reduced Ern-2 expression in HT29-MTX cells and in mice treated with maltodextrin. Giving TUDCA to maltodextrin-fed mice resulted in less weight loss, improved histology, and lower expression of Lcn-2 and IL-1beta.
The study concluded with three final experiments: The first showed that maltodextrin did not alter mucosa-associated microbiota; the second showed that mice fed 5% maltodextrin long term (for 10 weeks) had low-grade intestinal inflammation on histology, albeit without clinical colitis or weight loss; and the third showed that mice consuming maltodextrin long term had higher 15-hour fasting blood glycemic levels than control mice, supporting recent research suggesting that food additives can disrupt metabolism in a nonsusceptible host.
“In conclusion,” the investigators wrote, “this study shows that a maltodextrin-enriched diet reduces the intestinal content of Muc-2, thus making the host more sensitive to colitogenic stimuli. These data, together with the demonstration that maltodextrin can promote epithelial intestinal adhesion of pathogenic bacteria, supports the hypothesis that Western diets rich in maltodextrin can contribute to gut disease susceptibility.”
The study was funded by the Italian Ministry of Education, Universities, and Research. The authors reported no conflicts of interest.
SOURCE: Laudisi F et al. CMGH. 2019 Jan 18. doi: 10.1016/j.jcmgh.2018.09.002.
The food additive maltodextrin may increase risk of inflammatory bowel disease, according to a recent study.
Compared with control subjects, mice given drinking water that contained 5% maltodextrin were significantly more likely to develop colitis and lose weight when challenged with dextran sodium sulfate (DSS), reported lead author Federica Laudisi, PhD, of the department of systems medicine at the University of Rome Tor Vergata in Rome, and her colleagues.
Further experiments with murine intestinal crypts and a human cell line echoed these results and offered mechanistic insight. Treatment with maltodextrin stressed the endoplasmic reticulum of goblet cells, predisposing the intestinal epithelium to mucus depletion and inflammation. With these results, maltodextrin joins polysorbate 80 and carboxymethylcellulose on a growing list of food additives in the Western diet with proinflammatory potential.
“Although the U.S. Food and Drug Administration recognizes these dietary elements as safe,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, “their use has been linked to the development of intestinal pathologies in both animals and human beings.
“It also has been shown that the polysaccharide maltodextrin, which is commonly used as a filler and thickener during food processing, can alter microbial phenotype and host antibacterial defenses. Maltodextrin expands the Escherichia coli population in the ileum and induces necrotizing enterocolitis in preterm piglets (Am J Physiol Gastrointest Liver Physiol. 2009 Dec;297:G1115-25).”
The present study began by administering three compounds dissolved in drinking water to wild-type Balb/c mice for 45 days: 5% maltodextrin, 0.5% propylene glycol, or 5 g/L animal gelatin. Control mice drank plain water. None of the treatments triggered clinical or histologic signs of colitis, and stool levels of lipocalin-2 (Lcn-2), a biomarker of intestinal inflammation, remained comparable with that of control mice. However, outcomes changed when mice were challenged with DSS (1.75% in drinking water) on days 35-45 or injected subcutaneously with indomethacin (5 mg/kg) on day 35 and sacrificed 24 hours later. When challenged with DSS, mice in the maltodextrin group developed severe colitis and lost 10%-15% of body weight, compared with minimal colitis and negligible weight loss in the other groups. In addition, compared with other mice, maltodextrin-fed mice had increased colon tissue expression of Lcn-2 and inflammatory cytokine interleukin (IL)-1beta. These initial findings suggested that dietary maltodextrin could increase susceptibility to clinical colitis.
To determine the pathophysiology of this phenomenon, the investigators performed microarray analysis of colonic samples. Multiple genes associated with carbohydrate and lipid metabolism were upregulated in maltodextrin-fed mice, including genes that controlled the unfolded protein response (UPR), a process in which unfolded proteins accumulate in the endoplasmic reticulum (ER) during ER stress. The most prominently expressed among the UPR-related genes was Ern-2, which regulates inositol-requiring enzyme 1beta, found exclusively in the ER of goblet cells in the small intestine and colon. When maltodextrin causes ER stress in goblet cells, it leads to misfolding of mucin glycoprotein Mucin-2 (Muc-2), a major component of gut mucus, causing gut mucus levels to drop. A diminished mucus barrier exposes the intestine to infection and damage, as demonstrated by higher rates of pathogenic bacteria in Muc-2–deficient mice than in control mice, and more severe intestinal damage than in controls when Muc-2 mice are deliberately infected with pathogens.
The investigators found that humans likely have similar responses to dietary maltodextrin. Treating the mucus-secreting HT29-methotrexate treated (HT29-MTX) cell line with 5% maltodextrin resulted in upregulation of Ern-2, which is the same mechanism observed in mice. Additional testing showed that this process was mediated by p38 mitogen-activated protein kinase, and pharmacologic inhibition or knockdown of p38 suppressed RNA expression of Ern-2. The investigators found that p38 was similarly involved in maltodextrin-fed mice.
To show that maltodextrin enhances susceptibility to inflammation via ER stress, the investigators used tauroursodeoxycholic acid (TUDCA) to inhibit ER stress. Indeed, inhibition led to reduced Ern-2 expression in HT29-MTX cells and in mice treated with maltodextrin. Giving TUDCA to maltodextrin-fed mice resulted in less weight loss, improved histology, and lower expression of Lcn-2 and IL-1beta.
The study concluded with three final experiments: The first showed that maltodextrin did not alter mucosa-associated microbiota; the second showed that mice fed 5% maltodextrin long term (for 10 weeks) had low-grade intestinal inflammation on histology, albeit without clinical colitis or weight loss; and the third showed that mice consuming maltodextrin long term had higher 15-hour fasting blood glycemic levels than control mice, supporting recent research suggesting that food additives can disrupt metabolism in a nonsusceptible host.
“In conclusion,” the investigators wrote, “this study shows that a maltodextrin-enriched diet reduces the intestinal content of Muc-2, thus making the host more sensitive to colitogenic stimuli. These data, together with the demonstration that maltodextrin can promote epithelial intestinal adhesion of pathogenic bacteria, supports the hypothesis that Western diets rich in maltodextrin can contribute to gut disease susceptibility.”
The study was funded by the Italian Ministry of Education, Universities, and Research. The authors reported no conflicts of interest.
SOURCE: Laudisi F et al. CMGH. 2019 Jan 18. doi: 10.1016/j.jcmgh.2018.09.002.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The food additive maltodextrin may increase risk of inflammatory bowel disease.
Major finding: When challenged with dextran sulfate sodium, mice consuming maltodextrin developed colitis and lost about 10%-15% of original body weight, compared with negligible inflammation and weight loss in mice not receiving maltodextrin.
Study details: A prospective study involving in vivo experiments with wild-type Balb/c mice and in vitro experiments with murine intestinal crypts and a human intestinal cell line.
Disclosures: The study was funded by the Italian Ministry of Education, Universities, and Research. The investigators reported no conflicts of interest.
Source: Laudisi F et al. CMGH. 2019 Jan 18. doi: 10.1016/j.jcmgh.2018.09.002.