IBD & Intestinal Disorders

Patients with inflammatory bowel disease (IBD) will soon have access to new biosimilars to infliximab, adalimumab, and other monoclonal antibodies, experts wrote in an American Gastroenterological Association clinical practice update.

“It is anticipated that biosimilars for IBD are here to stay,” wrote Laura E. Raffals, MD, of the Mayo Clinic in Rochester, Minn., and her associates in Clinical Gastroenterology and Hepatology. “Provided that the regulatory pathway remains rigorous and postmarketing surveillance is performed adequately, clinicians and patients can be reassured that these agents will provide the same well-described effectiveness for moderate to severe Crohn’s disease and ulcerative colitis, without new safety concerns.”

Evidence supports the use of biosimilars in IBD, but switching patients in stable remission on infliximab (Remicade) to a biosimilar, namely infliximab-dyyb (Inflectra), should remain a case-by-case choice, according to an AGA clinical practice update. Pending more safety data, the update’s authors recommended against nonmedical switches during pregnancy and urge special attention when considering whether to switch children.

Biologics have revolutionized IBD treatment, but at a steep price. As patents expire, companies have developed biosimilar agents that aim to conserve safety and efficacy at lower cost. Studies support this idea, although whether initiating or switching to biosimilars will save patients (versus hospitals or payers) money “remains to be seen,” the practice update states.

The FDA approval process for biosimilars is more rigorous than that for generics, but it skips the multiple phases of clinical trials required to approve reference biologics. Instead, the FDA requires robust evidence that the biosimilar has comparable structure, function, immunogenicity, animal toxicity, pharmacokinetics and pharmacodynamics, and clinical safety and efficacy in humans. Under U.S. law, a biosimilar cannot be FDA approved if its clinically active components differ from the reference product or it shows clinically meaningful differences in safety, potency, or purity.

So far, five biosimilars have been approved by the FDA for use in IBD, although not all are on the market yet: infliximab-dyyb (Inflectra), adalimumab-atta (Amjevita), infliximab-abda (Renflexis), adalimumab-adbm (Cyltezo), and infliximab-qbtx (Ixifi). Most postmarketing studies of their use involved patients on stable doses of Remicade who switched to biosimilar infliximab-dyyb (Inflectra).

The best known of these studies is the double-blind, randomized NOR-SWITCH trial, in which patients with Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, or chronic plaque psoriasis on Remicade either continued it or switched to biosimilar infliximab-dyyb (Inflectra). At week 52, both safety and the likelihood of worsening disease activity were similar regardless of treatment randomization. The study was not powered to assess subgroup outcomes in Crohn’s disease or ulcerative colitis, the practice update notes.

More recently, the results of the 16-week SECURE trial also indicated that switching to infliximab-dyyb (Inflectra) was safe and well tolerated by patients with remitted IBD. However, the FDA has not yet designated any biosimilar as “interchangeable” with an approved biologic confirmed safe in multiple switches, the practice update notes. As a result, state laws prohibit patients from being switched to a biosimilar without notification. Both the NOR-SWITCH and SECURE trials were done in Europe.

Clinicians also must understand that antidrug antibodies to originator and biosimilar infliximab cross-react with each other, the experts emphasized. Switching patients with antibodies to Remicade or a biosimilar to the other product therefore risks an immediate hypersensitivity reaction, including life-threatening anaphylaxis.

The authors disclosed no external funding sources. One author disclosed ties to AbbVie, Janssen, Pfizer, Merck, Samsung Bioepis, and Amgen. The rest reported having no conflicts of interest.

SOURCE: Raffals LA et al. Clin Gastroenterol Hepatol. 2018 Sep 6. doi: 10.1016/j.cgh.2018.08.064.

Patients with inflammatory bowel disease (IBD) will soon have access to new biosimilars to infliximab, adalimumab, and other monoclonal antibodies, experts wrote in an American Gastroenterological Association clinical practice update.

“It is anticipated that biosimilars for IBD are here to stay,” wrote Laura E. Raffals, MD, of the Mayo Clinic in Rochester, Minn., and her associates in Clinical Gastroenterology and Hepatology. “Provided that the regulatory pathway remains rigorous and postmarketing surveillance is performed adequately, clinicians and patients can be reassured that these agents will provide the same well-described effectiveness for moderate to severe Crohn’s disease and ulcerative colitis, without new safety concerns.”

Evidence supports the use of biosimilars in IBD, but switching patients in stable remission on infliximab (Remicade) to a biosimilar, namely infliximab-dyyb (Inflectra), should remain a case-by-case choice, according to an AGA clinical practice update. Pending more safety data, the update’s authors recommended against nonmedical switches during pregnancy and urge special attention when considering whether to switch children.

Biologics have revolutionized IBD treatment, but at a steep price. As patents expire, companies have developed biosimilar agents that aim to conserve safety and efficacy at lower cost. Studies support this idea, although whether initiating or switching to biosimilars will save patients (versus hospitals or payers) money “remains to be seen,” the practice update states.

The FDA approval process for biosimilars is more rigorous than that for generics, but it skips the multiple phases of clinical trials required to approve reference biologics. Instead, the FDA requires robust evidence that the biosimilar has comparable structure, function, immunogenicity, animal toxicity, pharmacokinetics and pharmacodynamics, and clinical safety and efficacy in humans. Under U.S. law, a biosimilar cannot be FDA approved if its clinically active components differ from the reference product or it shows clinically meaningful differences in safety, potency, or purity.

So far, five biosimilars have been approved by the FDA for use in IBD, although not all are on the market yet: infliximab-dyyb (Inflectra), adalimumab-atta (Amjevita), infliximab-abda (Renflexis), adalimumab-adbm (Cyltezo), and infliximab-qbtx (Ixifi). Most postmarketing studies of their use involved patients on stable doses of Remicade who switched to biosimilar infliximab-dyyb (Inflectra).

The best known of these studies is the double-blind, randomized NOR-SWITCH trial, in which patients with Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, or chronic plaque psoriasis on Remicade either continued it or switched to biosimilar infliximab-dyyb (Inflectra). At week 52, both safety and the likelihood of worsening disease activity were similar regardless of treatment randomization. The study was not powered to assess subgroup outcomes in Crohn’s disease or ulcerative colitis, the practice update notes.

More recently, the results of the 16-week SECURE trial also indicated that switching to infliximab-dyyb (Inflectra) was safe and well tolerated by patients with remitted IBD. However, the FDA has not yet designated any biosimilar as “interchangeable” with an approved biologic confirmed safe in multiple switches, the practice update notes. As a result, state laws prohibit patients from being switched to a biosimilar without notification. Both the NOR-SWITCH and SECURE trials were done in Europe.

Clinicians also must understand that antidrug antibodies to originator and biosimilar infliximab cross-react with each other, the experts emphasized. Switching patients with antibodies to Remicade or a biosimilar to the other product therefore risks an immediate hypersensitivity reaction, including life-threatening anaphylaxis.

The authors disclosed no external funding sources. One author disclosed ties to AbbVie, Janssen, Pfizer, Merck, Samsung Bioepis, and Amgen. The rest reported having no conflicts of interest.

SOURCE: Raffals LA et al. Clin Gastroenterol Hepatol. 2018 Sep 6. doi: 10.1016/j.cgh.2018.08.064.

Patients with inflammatory bowel disease (IBD) will soon have access to new biosimilars to infliximab, adalimumab, and other monoclonal antibodies, experts wrote in an American Gastroenterological Association clinical practice update.

“It is anticipated that biosimilars for IBD are here to stay,” wrote Laura E. Raffals, MD, of the Mayo Clinic in Rochester, Minn., and her associates in Clinical Gastroenterology and Hepatology. “Provided that the regulatory pathway remains rigorous and postmarketing surveillance is performed adequately, clinicians and patients can be reassured that these agents will provide the same well-described effectiveness for moderate to severe Crohn’s disease and ulcerative colitis, without new safety concerns.”

Evidence supports the use of biosimilars in IBD, but switching patients in stable remission on infliximab (Remicade) to a biosimilar, namely infliximab-dyyb (Inflectra), should remain a case-by-case choice, according to an AGA clinical practice update. Pending more safety data, the update’s authors recommended against nonmedical switches during pregnancy and urge special attention when considering whether to switch children.

Biologics have revolutionized IBD treatment, but at a steep price. As patents expire, companies have developed biosimilar agents that aim to conserve safety and efficacy at lower cost. Studies support this idea, although whether initiating or switching to biosimilars will save patients (versus hospitals or payers) money “remains to be seen,” the practice update states.

The FDA approval process for biosimilars is more rigorous than that for generics, but it skips the multiple phases of clinical trials required to approve reference biologics. Instead, the FDA requires robust evidence that the biosimilar has comparable structure, function, immunogenicity, animal toxicity, pharmacokinetics and pharmacodynamics, and clinical safety and efficacy in humans. Under U.S. law, a biosimilar cannot be FDA approved if its clinically active components differ from the reference product or it shows clinically meaningful differences in safety, potency, or purity.

So far, five biosimilars have been approved by the FDA for use in IBD, although not all are on the market yet: infliximab-dyyb (Inflectra), adalimumab-atta (Amjevita), infliximab-abda (Renflexis), adalimumab-adbm (Cyltezo), and infliximab-qbtx (Ixifi). Most postmarketing studies of their use involved patients on stable doses of Remicade who switched to biosimilar infliximab-dyyb (Inflectra).

The best known of these studies is the double-blind, randomized NOR-SWITCH trial, in which patients with Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, or chronic plaque psoriasis on Remicade either continued it or switched to biosimilar infliximab-dyyb (Inflectra). At week 52, both safety and the likelihood of worsening disease activity were similar regardless of treatment randomization. The study was not powered to assess subgroup outcomes in Crohn’s disease or ulcerative colitis, the practice update notes.

More recently, the results of the 16-week SECURE trial also indicated that switching to infliximab-dyyb (Inflectra) was safe and well tolerated by patients with remitted IBD. However, the FDA has not yet designated any biosimilar as “interchangeable” with an approved biologic confirmed safe in multiple switches, the practice update notes. As a result, state laws prohibit patients from being switched to a biosimilar without notification. Both the NOR-SWITCH and SECURE trials were done in Europe.

Clinicians also must understand that antidrug antibodies to originator and biosimilar infliximab cross-react with each other, the experts emphasized. Switching patients with antibodies to Remicade or a biosimilar to the other product therefore risks an immediate hypersensitivity reaction, including life-threatening anaphylaxis.

The authors disclosed no external funding sources. One author disclosed ties to AbbVie, Janssen, Pfizer, Merck, Samsung Bioepis, and Amgen. The rest reported having no conflicts of interest.

SOURCE: Raffals LA et al. Clin Gastroenterol Hepatol. 2018 Sep 6. doi: 10.1016/j.cgh.2018.08.064.

Ideally, pregnant women with inflammatory bowel disease (IBD) should receive coordinated care from gastroenterologists and maternal-fetal medicine specialists, plus additional input from nutritionists, lactation counselors, and colorectal surgeons as needed, states a new report from the American Gastroenterological Association.

But in reality, these women often receive scant and conflicting advice from health care providers, writes Uma Mahadevan, MD, of the University of California, San Francisco, with her associates in Gastroenterology.

An “explosion” of new treatments in the past 15 years has given hope to many women with IBD who wish to be healthy enough to conceive, the experts noted. But in a recent AGA survey, more than 40% of obstetrician/gynecologist (OB/GYN) providers felt that women with IBD received inadequate information about pregnancy, compared with patients with other immune-mediated diseases. Strikingly, 94% of surveyed clinicians said they had patients stop taking their IBD medications during pregnancy because they feared harm to the fetus. In doing so, these patients actually risked greater disease activity, perinatal flares, and adverse pregnancy outcomes.

Therefore, the AGA, in partnership with the Crohn’s & Colitis Foundation, the Society for Maternal-Fetal Medicine, and Girls With Guts, crafted a standardized, evidence-based care pathway for health care providers from diverse disciplines who treat women with IBD in all stages of family planning. Its authors recommended that a maternal-fetal medicine specialist oversee obstetric care whenever possible. A gastroenterologist should continue IBD care by seeing the patient once during the first or second trimester and thereafter depending on IBD severity. The patient should receive a “clear and easily understandable consensus plan” for managing complex care during and after pregnancy, according to the pathway.

Aminosalicylates, biologics, and immunomodulators can be continued during pregnancy and delivery. Biologics have not shown teratogenicity in large studies, but monotherapy is preferred to reduce infection risk in infants. Clinicians should calculate weight-based doses according to prepregnancy weight. Doses can be tweaked to achieve minimal trough levels near delivery.

During pregnancy, patients should stop antidiarrheal therapy with loperamide and diphenoxylate when possible. Proinflammatory mediators are known to damage hippocampal neurogenesis and neuronal cytoarchitecture during brain development, so patients should understand the need for good inflammatory control during pregnancy. However, biologic therapy is preferred, and patients should only use corticosteroids adjunctively if needed for flares.

The usual indications guide the choice between a vaginal or cesarean delivery, the pathway states. Vaginal delivery often is possible for patients without active perineal disease, while cesarean is recommended for women with prior perineal surgery or active perineal disease or rectovaginal fistulas. The perineal area can be examined for active disease during the routine visit for group B streptococcus screening culture at 35-37 weeks’ gestation. For women who have had ileal-pouch anal anastomosis surgery, mode of delivery does not seem to affect pouch function, but cesarean delivery is thought to prevent anal sphincter injury and the accompanying risk of incontinence.

For ostomy patients, stretching of the abdominal wall during pregnancy can lead to stomal problems, such as displacement, enlargement, retraction, stenosis, and prolapse. A nutritionist can help ostomy patients avoid excess weight gain, and a colorectal surgeon and ostomy/wound nurse can help coordinate postpartum care. If cesarean delivery is needed, simply covering the ostomy with gauze sufficiently protects the operative field.

Since IBD increases the risk of venous thromboembolism, clinicians should consider prophylactic anticoagulation after cesarean delivery and during a hospitalization for IBD flares, according to the care pathway. Breastfeeding women can receive unfractionated heparin, low-molecular-weight heparin, or warfarin up to 3-6 weeks post partum, but they should not receive oral direct thrombin or factor Xa inhibitors.

In addition, most IBD medications are either undetectable in breast milk or are secreted at such low concentrations that they pose no known risk to infants. Therefore, patients can continue IBD medications after delivery – except methotrexate, which has not been sufficiently studied to assess its safety. Breastfeeding women with IBD should avoid using fenugreek to increase milk production, since it can cause diarrhea and bleeding.

Finally, infants should not receive live vaccines during the first 6 months after birth if their mothers received biologics besides certolizumab during the third trimester, the pathway notes. In the United States, this applies only to the oral rotavirus vaccine.

For more information about the care pathway and resources for your patients, visit IBDParenthoodProject.org.

SOURCE: Mahadevan U et al. Gastroenterology. 2019 Jan 15. doi: 10.1053/j.gastro.2018.12.022.

Ideally, pregnant women with inflammatory bowel disease (IBD) should receive coordinated care from gastroenterologists and maternal-fetal medicine specialists, plus additional input from nutritionists, lactation counselors, and colorectal surgeons as needed, states a new report from the American Gastroenterological Association.

But in reality, these women often receive scant and conflicting advice from health care providers, writes Uma Mahadevan, MD, of the University of California, San Francisco, with her associates in Gastroenterology.

An “explosion” of new treatments in the past 15 years has given hope to many women with IBD who wish to be healthy enough to conceive, the experts noted. But in a recent AGA survey, more than 40% of obstetrician/gynecologist (OB/GYN) providers felt that women with IBD received inadequate information about pregnancy, compared with patients with other immune-mediated diseases. Strikingly, 94% of surveyed clinicians said they had patients stop taking their IBD medications during pregnancy because they feared harm to the fetus. In doing so, these patients actually risked greater disease activity, perinatal flares, and adverse pregnancy outcomes.

Therefore, the AGA, in partnership with the Crohn’s & Colitis Foundation, the Society for Maternal-Fetal Medicine, and Girls With Guts, crafted a standardized, evidence-based care pathway for health care providers from diverse disciplines who treat women with IBD in all stages of family planning. Its authors recommended that a maternal-fetal medicine specialist oversee obstetric care whenever possible. A gastroenterologist should continue IBD care by seeing the patient once during the first or second trimester and thereafter depending on IBD severity. The patient should receive a “clear and easily understandable consensus plan” for managing complex care during and after pregnancy, according to the pathway.

Aminosalicylates, biologics, and immunomodulators can be continued during pregnancy and delivery. Biologics have not shown teratogenicity in large studies, but monotherapy is preferred to reduce infection risk in infants. Clinicians should calculate weight-based doses according to prepregnancy weight. Doses can be tweaked to achieve minimal trough levels near delivery.

During pregnancy, patients should stop antidiarrheal therapy with loperamide and diphenoxylate when possible. Proinflammatory mediators are known to damage hippocampal neurogenesis and neuronal cytoarchitecture during brain development, so patients should understand the need for good inflammatory control during pregnancy. However, biologic therapy is preferred, and patients should only use corticosteroids adjunctively if needed for flares.

The usual indications guide the choice between a vaginal or cesarean delivery, the pathway states. Vaginal delivery often is possible for patients without active perineal disease, while cesarean is recommended for women with prior perineal surgery or active perineal disease or rectovaginal fistulas. The perineal area can be examined for active disease during the routine visit for group B streptococcus screening culture at 35-37 weeks’ gestation. For women who have had ileal-pouch anal anastomosis surgery, mode of delivery does not seem to affect pouch function, but cesarean delivery is thought to prevent anal sphincter injury and the accompanying risk of incontinence.

For ostomy patients, stretching of the abdominal wall during pregnancy can lead to stomal problems, such as displacement, enlargement, retraction, stenosis, and prolapse. A nutritionist can help ostomy patients avoid excess weight gain, and a colorectal surgeon and ostomy/wound nurse can help coordinate postpartum care. If cesarean delivery is needed, simply covering the ostomy with gauze sufficiently protects the operative field.

Since IBD increases the risk of venous thromboembolism, clinicians should consider prophylactic anticoagulation after cesarean delivery and during a hospitalization for IBD flares, according to the care pathway. Breastfeeding women can receive unfractionated heparin, low-molecular-weight heparin, or warfarin up to 3-6 weeks post partum, but they should not receive oral direct thrombin or factor Xa inhibitors.

In addition, most IBD medications are either undetectable in breast milk or are secreted at such low concentrations that they pose no known risk to infants. Therefore, patients can continue IBD medications after delivery – except methotrexate, which has not been sufficiently studied to assess its safety. Breastfeeding women with IBD should avoid using fenugreek to increase milk production, since it can cause diarrhea and bleeding.

Finally, infants should not receive live vaccines during the first 6 months after birth if their mothers received biologics besides certolizumab during the third trimester, the pathway notes. In the United States, this applies only to the oral rotavirus vaccine.

For more information about the care pathway and resources for your patients, visit IBDParenthoodProject.org.

SOURCE: Mahadevan U et al. Gastroenterology. 2019 Jan 15. doi: 10.1053/j.gastro.2018.12.022.

Ideally, pregnant women with inflammatory bowel disease (IBD) should receive coordinated care from gastroenterologists and maternal-fetal medicine specialists, plus additional input from nutritionists, lactation counselors, and colorectal surgeons as needed, states a new report from the American Gastroenterological Association.

But in reality, these women often receive scant and conflicting advice from health care providers, writes Uma Mahadevan, MD, of the University of California, San Francisco, with her associates in Gastroenterology.

An “explosion” of new treatments in the past 15 years has given hope to many women with IBD who wish to be healthy enough to conceive, the experts noted. But in a recent AGA survey, more than 40% of obstetrician/gynecologist (OB/GYN) providers felt that women with IBD received inadequate information about pregnancy, compared with patients with other immune-mediated diseases. Strikingly, 94% of surveyed clinicians said they had patients stop taking their IBD medications during pregnancy because they feared harm to the fetus. In doing so, these patients actually risked greater disease activity, perinatal flares, and adverse pregnancy outcomes.

Therefore, the AGA, in partnership with the Crohn’s & Colitis Foundation, the Society for Maternal-Fetal Medicine, and Girls With Guts, crafted a standardized, evidence-based care pathway for health care providers from diverse disciplines who treat women with IBD in all stages of family planning. Its authors recommended that a maternal-fetal medicine specialist oversee obstetric care whenever possible. A gastroenterologist should continue IBD care by seeing the patient once during the first or second trimester and thereafter depending on IBD severity. The patient should receive a “clear and easily understandable consensus plan” for managing complex care during and after pregnancy, according to the pathway.

Aminosalicylates, biologics, and immunomodulators can be continued during pregnancy and delivery. Biologics have not shown teratogenicity in large studies, but monotherapy is preferred to reduce infection risk in infants. Clinicians should calculate weight-based doses according to prepregnancy weight. Doses can be tweaked to achieve minimal trough levels near delivery.

During pregnancy, patients should stop antidiarrheal therapy with loperamide and diphenoxylate when possible. Proinflammatory mediators are known to damage hippocampal neurogenesis and neuronal cytoarchitecture during brain development, so patients should understand the need for good inflammatory control during pregnancy. However, biologic therapy is preferred, and patients should only use corticosteroids adjunctively if needed for flares.

The usual indications guide the choice between a vaginal or cesarean delivery, the pathway states. Vaginal delivery often is possible for patients without active perineal disease, while cesarean is recommended for women with prior perineal surgery or active perineal disease or rectovaginal fistulas. The perineal area can be examined for active disease during the routine visit for group B streptococcus screening culture at 35-37 weeks’ gestation. For women who have had ileal-pouch anal anastomosis surgery, mode of delivery does not seem to affect pouch function, but cesarean delivery is thought to prevent anal sphincter injury and the accompanying risk of incontinence.

For ostomy patients, stretching of the abdominal wall during pregnancy can lead to stomal problems, such as displacement, enlargement, retraction, stenosis, and prolapse. A nutritionist can help ostomy patients avoid excess weight gain, and a colorectal surgeon and ostomy/wound nurse can help coordinate postpartum care. If cesarean delivery is needed, simply covering the ostomy with gauze sufficiently protects the operative field.

Since IBD increases the risk of venous thromboembolism, clinicians should consider prophylactic anticoagulation after cesarean delivery and during a hospitalization for IBD flares, according to the care pathway. Breastfeeding women can receive unfractionated heparin, low-molecular-weight heparin, or warfarin up to 3-6 weeks post partum, but they should not receive oral direct thrombin or factor Xa inhibitors.

In addition, most IBD medications are either undetectable in breast milk or are secreted at such low concentrations that they pose no known risk to infants. Therefore, patients can continue IBD medications after delivery – except methotrexate, which has not been sufficiently studied to assess its safety. Breastfeeding women with IBD should avoid using fenugreek to increase milk production, since it can cause diarrhea and bleeding.

Finally, infants should not receive live vaccines during the first 6 months after birth if their mothers received biologics besides certolizumab during the third trimester, the pathway notes. In the United States, this applies only to the oral rotavirus vaccine.

For more information about the care pathway and resources for your patients, visit IBDParenthoodProject.org.

SOURCE: Mahadevan U et al. Gastroenterology. 2019 Jan 15. doi: 10.1053/j.gastro.2018.12.022.

MIAMI – Eating a Western diet correlated with significantly lower gut microbiome diversity in an observational study of 1,000 healthy men and women.

happy_lark/iStock/Getty Images

The chief culprits were fried foods, sodas, fatty sweets, processed meats, ready-cooked meals, and desserts, reported Valentin Partula, a PhD student at the Université Paris 13 Nord and his associates. The more often individuals reported consuming these, the fewer bacterial species were identified in their stool (P less than .05 for each association), the investigators wrote in a poster presented at the annual Gut Microbiota for Health World Summit.

Studies have linked decreased microbiota diversity with health conditions ranging from inflammatory bowel disease and colorectal cancer to diabetes mellitus. Obesity also is characterized by a less diverse microbiome and is linked to many of the same diseases, but the diversity (richness) of the gut microbiome appears to have more to do with diet than body mass index. However, interventional studies linking diet to microbiome shifts often have been small, narrow in scope, and short in duration, the researchers noted at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

To help fill these gaps, they administered a 19-item food-frequency questionnaire to 1,000 healthy men and women in France who were 20-69 years old. Each food question had six possible responses, ranging from “at least twice a day” to “never.” For 862 of these men and women, the researchers also analyzed stool samples using 16S rRNA sequencing – a standard test for microbiome diversity. These sequencing results were analyzed in terms of both alpha diversity (the number of species within a sample, and the relative abundance of each) and beta diversity (the degree of dissimilarity among different individuals).

The most significant correlate of low alpha diversity (that is, a less diverse gut microbiome) was frequent consumption of fried foods, followed by sodas or sugary drinks, fatty sweet products, processed meats, ready-cooked meals, and desserts (P less than .05 for each). Conversely, raw fruits and fish each correlated with having a richer microbiome (P less than .05). Consuming eggs and raw and cooked vegetables also correlated with greater diversity, but these associations did not reach statistical significance.

In terms of beta diversity (uniqueness of the microbiome signature), the strongest correlates were fresh fruit, fried products, ready-cooked meals, and cheese. The finding for fresh fruit might be an effect of weighting but needs further study, the researchers said. Taken together, however, the findings “extend and support mechanistic arguments linking Western diet to altered microbiota composition,” they said.

Next, they looked at how specific foods correlated with specific bacterial taxa. Consuming more dairy correlated with a greater abundance of Streptococcus salivarius, which disrupts S. pyogenes biofilms in the pharynx and thus might help prevent bacterial pharyngitis. Eating raw fruits was tied to increases in Eubacterium eligens, a nonpathogenic bacterium whose role in the gut remains unclear. Finally, frequent cheese consumption was linked to lower abundance of Akkermansia muciniphila, a bacterium that is thought to benefit metabolic pathways and immune signaling.

For the same 846 individuals, the researchers performed ¹hydrogen nuclear magnetic resonance metabolomic tests on plasma Carr-Purcell-Meiboom-Gill (CPMG)–pulse sequence and nuclear Overhauser enhancement spectroscopy (NOESY). Increased creatinine was associated with the highest number of bacterial taxa and might reflect effects on kidney function or trimethylamine N-oxide, they wrote. Greater microbiome diversity correlated with higher plasma levels of amino acids, proteins, creatinine, choline, glucose, and citrate. Lower diversity was tied to the presence of lipid-based metabolites, including ketones and esters.

The next step is to confirm the findings in a separate population and establish which of these associations are probably causal, the researchers wrote. “Mechanistic studies elucidating the metabolic capability of the organisms [also] are needed.”

No external funding sources or conflicts of interest were reported.

MIAMI – Eating a Western diet correlated with significantly lower gut microbiome diversity in an observational study of 1,000 healthy men and women.

happy_lark/iStock/Getty Images

The chief culprits were fried foods, sodas, fatty sweets, processed meats, ready-cooked meals, and desserts, reported Valentin Partula, a PhD student at the Université Paris 13 Nord and his associates. The more often individuals reported consuming these, the fewer bacterial species were identified in their stool (P less than .05 for each association), the investigators wrote in a poster presented at the annual Gut Microbiota for Health World Summit.

Studies have linked decreased microbiota diversity with health conditions ranging from inflammatory bowel disease and colorectal cancer to diabetes mellitus. Obesity also is characterized by a less diverse microbiome and is linked to many of the same diseases, but the diversity (richness) of the gut microbiome appears to have more to do with diet than body mass index. However, interventional studies linking diet to microbiome shifts often have been small, narrow in scope, and short in duration, the researchers noted at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

To help fill these gaps, they administered a 19-item food-frequency questionnaire to 1,000 healthy men and women in France who were 20-69 years old. Each food question had six possible responses, ranging from “at least twice a day” to “never.” For 862 of these men and women, the researchers also analyzed stool samples using 16S rRNA sequencing – a standard test for microbiome diversity. These sequencing results were analyzed in terms of both alpha diversity (the number of species within a sample, and the relative abundance of each) and beta diversity (the degree of dissimilarity among different individuals).

The most significant correlate of low alpha diversity (that is, a less diverse gut microbiome) was frequent consumption of fried foods, followed by sodas or sugary drinks, fatty sweet products, processed meats, ready-cooked meals, and desserts (P less than .05 for each). Conversely, raw fruits and fish each correlated with having a richer microbiome (P less than .05). Consuming eggs and raw and cooked vegetables also correlated with greater diversity, but these associations did not reach statistical significance.

In terms of beta diversity (uniqueness of the microbiome signature), the strongest correlates were fresh fruit, fried products, ready-cooked meals, and cheese. The finding for fresh fruit might be an effect of weighting but needs further study, the researchers said. Taken together, however, the findings “extend and support mechanistic arguments linking Western diet to altered microbiota composition,” they said.

Next, they looked at how specific foods correlated with specific bacterial taxa. Consuming more dairy correlated with a greater abundance of Streptococcus salivarius, which disrupts S. pyogenes biofilms in the pharynx and thus might help prevent bacterial pharyngitis. Eating raw fruits was tied to increases in Eubacterium eligens, a nonpathogenic bacterium whose role in the gut remains unclear. Finally, frequent cheese consumption was linked to lower abundance of Akkermansia muciniphila, a bacterium that is thought to benefit metabolic pathways and immune signaling.

For the same 846 individuals, the researchers performed ¹hydrogen nuclear magnetic resonance metabolomic tests on plasma Carr-Purcell-Meiboom-Gill (CPMG)–pulse sequence and nuclear Overhauser enhancement spectroscopy (NOESY). Increased creatinine was associated with the highest number of bacterial taxa and might reflect effects on kidney function or trimethylamine N-oxide, they wrote. Greater microbiome diversity correlated with higher plasma levels of amino acids, proteins, creatinine, choline, glucose, and citrate. Lower diversity was tied to the presence of lipid-based metabolites, including ketones and esters.

The next step is to confirm the findings in a separate population and establish which of these associations are probably causal, the researchers wrote. “Mechanistic studies elucidating the metabolic capability of the organisms [also] are needed.”

No external funding sources or conflicts of interest were reported.

MIAMI – Eating a Western diet correlated with significantly lower gut microbiome diversity in an observational study of 1,000 healthy men and women.

happy_lark/iStock/Getty Images

The chief culprits were fried foods, sodas, fatty sweets, processed meats, ready-cooked meals, and desserts, reported Valentin Partula, a PhD student at the Université Paris 13 Nord and his associates. The more often individuals reported consuming these, the fewer bacterial species were identified in their stool (P less than .05 for each association), the investigators wrote in a poster presented at the annual Gut Microbiota for Health World Summit.

Studies have linked decreased microbiota diversity with health conditions ranging from inflammatory bowel disease and colorectal cancer to diabetes mellitus. Obesity also is characterized by a less diverse microbiome and is linked to many of the same diseases, but the diversity (richness) of the gut microbiome appears to have more to do with diet than body mass index. However, interventional studies linking diet to microbiome shifts often have been small, narrow in scope, and short in duration, the researchers noted at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

To help fill these gaps, they administered a 19-item food-frequency questionnaire to 1,000 healthy men and women in France who were 20-69 years old. Each food question had six possible responses, ranging from “at least twice a day” to “never.” For 862 of these men and women, the researchers also analyzed stool samples using 16S rRNA sequencing – a standard test for microbiome diversity. These sequencing results were analyzed in terms of both alpha diversity (the number of species within a sample, and the relative abundance of each) and beta diversity (the degree of dissimilarity among different individuals).

The most significant correlate of low alpha diversity (that is, a less diverse gut microbiome) was frequent consumption of fried foods, followed by sodas or sugary drinks, fatty sweet products, processed meats, ready-cooked meals, and desserts (P less than .05 for each). Conversely, raw fruits and fish each correlated with having a richer microbiome (P less than .05). Consuming eggs and raw and cooked vegetables also correlated with greater diversity, but these associations did not reach statistical significance.

In terms of beta diversity (uniqueness of the microbiome signature), the strongest correlates were fresh fruit, fried products, ready-cooked meals, and cheese. The finding for fresh fruit might be an effect of weighting but needs further study, the researchers said. Taken together, however, the findings “extend and support mechanistic arguments linking Western diet to altered microbiota composition,” they said.

Next, they looked at how specific foods correlated with specific bacterial taxa. Consuming more dairy correlated with a greater abundance of Streptococcus salivarius, which disrupts S. pyogenes biofilms in the pharynx and thus might help prevent bacterial pharyngitis. Eating raw fruits was tied to increases in Eubacterium eligens, a nonpathogenic bacterium whose role in the gut remains unclear. Finally, frequent cheese consumption was linked to lower abundance of Akkermansia muciniphila, a bacterium that is thought to benefit metabolic pathways and immune signaling.

For the same 846 individuals, the researchers performed ¹hydrogen nuclear magnetic resonance metabolomic tests on plasma Carr-Purcell-Meiboom-Gill (CPMG)–pulse sequence and nuclear Overhauser enhancement spectroscopy (NOESY). Increased creatinine was associated with the highest number of bacterial taxa and might reflect effects on kidney function or trimethylamine N-oxide, they wrote. Greater microbiome diversity correlated with higher plasma levels of amino acids, proteins, creatinine, choline, glucose, and citrate. Lower diversity was tied to the presence of lipid-based metabolites, including ketones and esters.

The next step is to confirm the findings in a separate population and establish which of these associations are probably causal, the researchers wrote. “Mechanistic studies elucidating the metabolic capability of the organisms [also] are needed.”

No external funding sources or conflicts of interest were reported.

MIAMI – Hyperglycemia increases intestinal permeability, which facilitates enteric infections and systemic inflammation, reported Christoph Thaiss, PhD.

The findings upend the old idea that intestinal barrier dysfunction leads to diabetes, Dr. Thaiss said during a plenary session at the annual Gut Microbiota for Health World Summit. Multiple mouse models link hyperglycemia to intestinal barrier dysfunction, and hemoglobin A_1C (HbA_1c) levels in humans “highly correlate with the influx of microbial molecules into the intestinal epithelium.”

Researchers often struggle to decide if apparent causes are really confounders or even downstream results (reverse causation). In the metabolic syndrome, patients are known to have increased intestinal permeability – so-called leaky gut – and microbes crossing the gastrointestinal epithelium have been found to cause both gut mucosal infections and chronic systemic inflammation. But because these mechanisms were poorly understood, some experts posited that intestinal barrier dysfunction induced pancreatic beta cell inflammation, insulin resistance, and diabetes.

To take a deeper dive, Dr. Thaiss and his associates at the University of Pennsylvania, Philadelphia started with a mouse model of morbid obesity. The mice had multiple systemic sites with microbial pattern recognition ligands, signifying microbial influx from the gut. They also had genetic signatures indicating a marked disruption of junctions between epithelial cells, compared with healthy controls.

The obese mice also were much more susceptible to enteric infections with Citrobacter rodentium (a Salmonella analog), but obesity itself did not drive this risk, Dr. Thaiss explained. In fact, two different murine models of nonobese type 1 diabetes mellitus showed “leaky” intestinal epithelial adherence junctions, heightened susceptibility to C. rodentium infection, and showed systemic pathogen spread. Ribosomal DNA sequencing showed that these hyperglycemic (diabetic) mice had shifts in their gut microbiomes; however, translocating the altered microbiota to normal mice did not make them more susceptible to enteric infections or systemic inflammation.

Based on these findings, the researchers hypothesized that hyperglycemia itself drove susceptibility to enteric infections. They confirmed this by administering insulin to the mice with type 1 diabetes, which restored intestinal epithelial adherence junctions and stopped the systemic spread of pathogens. In vitro, exposing intestinal epithelial cells to glucose-induced barrier dysfunctions that increased over time and with higher glucose concentrations. RNA sequencing demonstrated that hyperglycemia markedly changed expression of genes that encode proteins that regulate intestinal barrier function. Moreover, hyperglycemic mice lacking the bidirectional glucose transporter GLUT2 showed no intestinal barrier dysfunction and were not susceptible to C. rodentium infection and systemic spread.

Finally, the investigators studied more than 30 clinical measures and microbial products in the systemic circulation of 27 healthy human volunteers. “Of all the variables we measured, HbA_1c showed the strongest correlation with the influx of microbial molecules,” said Dr. Thaiss. Serum HbA_1c correlated highly (P = .008) with levels of toll-like receptor 4, an indicator of systemic pathogens, but not with body mass index (P = .76).

The findings in humans confirm those in mice and indicate that hyperglycemia is a direct cause of intestinal barrier dysfunction and susceptibility to enteric infection, Dr. Thaiss said, adding that the systemic influx of microbial products might explain the wide range of otherwise unrelated inflammatory conditions seen in patients with metabolic syndrome. Future studies of therapies for enteric infection and systemic inflammation might focus on glucose as a modifier of intestinal barrier function.

These findings, reported at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, were also published in Science.

The work was supported by a Boehringer Ingelheim Funds PhD fellowship, the Leona M. and Harry B. Helmsley Charitable Trust, the Adelis Foundation, the Gurwin Family Fund for Scientific Research, the Crown Endowment Fund for Immunological Research, and others. Dr. Thaiss and his coinvestigators reported having no conflicts of interest.

SOURCE: Thaiss CA et al. Science. 2018;359(6382):1376-83.




 

MIAMI – Hyperglycemia increases intestinal permeability, which facilitates enteric infections and systemic inflammation, reported Christoph Thaiss, PhD.

The findings upend the old idea that intestinal barrier dysfunction leads to diabetes, Dr. Thaiss said during a plenary session at the annual Gut Microbiota for Health World Summit. Multiple mouse models link hyperglycemia to intestinal barrier dysfunction, and hemoglobin A_1C (HbA_1c) levels in humans “highly correlate with the influx of microbial molecules into the intestinal epithelium.”

Researchers often struggle to decide if apparent causes are really confounders or even downstream results (reverse causation). In the metabolic syndrome, patients are known to have increased intestinal permeability – so-called leaky gut – and microbes crossing the gastrointestinal epithelium have been found to cause both gut mucosal infections and chronic systemic inflammation. But because these mechanisms were poorly understood, some experts posited that intestinal barrier dysfunction induced pancreatic beta cell inflammation, insulin resistance, and diabetes.

To take a deeper dive, Dr. Thaiss and his associates at the University of Pennsylvania, Philadelphia started with a mouse model of morbid obesity. The mice had multiple systemic sites with microbial pattern recognition ligands, signifying microbial influx from the gut. They also had genetic signatures indicating a marked disruption of junctions between epithelial cells, compared with healthy controls.

The obese mice also were much more susceptible to enteric infections with Citrobacter rodentium (a Salmonella analog), but obesity itself did not drive this risk, Dr. Thaiss explained. In fact, two different murine models of nonobese type 1 diabetes mellitus showed “leaky” intestinal epithelial adherence junctions, heightened susceptibility to C. rodentium infection, and showed systemic pathogen spread. Ribosomal DNA sequencing showed that these hyperglycemic (diabetic) mice had shifts in their gut microbiomes; however, translocating the altered microbiota to normal mice did not make them more susceptible to enteric infections or systemic inflammation.

Based on these findings, the researchers hypothesized that hyperglycemia itself drove susceptibility to enteric infections. They confirmed this by administering insulin to the mice with type 1 diabetes, which restored intestinal epithelial adherence junctions and stopped the systemic spread of pathogens. In vitro, exposing intestinal epithelial cells to glucose-induced barrier dysfunctions that increased over time and with higher glucose concentrations. RNA sequencing demonstrated that hyperglycemia markedly changed expression of genes that encode proteins that regulate intestinal barrier function. Moreover, hyperglycemic mice lacking the bidirectional glucose transporter GLUT2 showed no intestinal barrier dysfunction and were not susceptible to C. rodentium infection and systemic spread.

Finally, the investigators studied more than 30 clinical measures and microbial products in the systemic circulation of 27 healthy human volunteers. “Of all the variables we measured, HbA_1c showed the strongest correlation with the influx of microbial molecules,” said Dr. Thaiss. Serum HbA_1c correlated highly (P = .008) with levels of toll-like receptor 4, an indicator of systemic pathogens, but not with body mass index (P = .76).

The findings in humans confirm those in mice and indicate that hyperglycemia is a direct cause of intestinal barrier dysfunction and susceptibility to enteric infection, Dr. Thaiss said, adding that the systemic influx of microbial products might explain the wide range of otherwise unrelated inflammatory conditions seen in patients with metabolic syndrome. Future studies of therapies for enteric infection and systemic inflammation might focus on glucose as a modifier of intestinal barrier function.

These findings, reported at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, were also published in Science.

The work was supported by a Boehringer Ingelheim Funds PhD fellowship, the Leona M. and Harry B. Helmsley Charitable Trust, the Adelis Foundation, the Gurwin Family Fund for Scientific Research, the Crown Endowment Fund for Immunological Research, and others. Dr. Thaiss and his coinvestigators reported having no conflicts of interest.

SOURCE: Thaiss CA et al. Science. 2018;359(6382):1376-83.




 

MIAMI – Hyperglycemia increases intestinal permeability, which facilitates enteric infections and systemic inflammation, reported Christoph Thaiss, PhD.

The findings upend the old idea that intestinal barrier dysfunction leads to diabetes, Dr. Thaiss said during a plenary session at the annual Gut Microbiota for Health World Summit. Multiple mouse models link hyperglycemia to intestinal barrier dysfunction, and hemoglobin A_1C (HbA_1c) levels in humans “highly correlate with the influx of microbial molecules into the intestinal epithelium.”

Researchers often struggle to decide if apparent causes are really confounders or even downstream results (reverse causation). In the metabolic syndrome, patients are known to have increased intestinal permeability – so-called leaky gut – and microbes crossing the gastrointestinal epithelium have been found to cause both gut mucosal infections and chronic systemic inflammation. But because these mechanisms were poorly understood, some experts posited that intestinal barrier dysfunction induced pancreatic beta cell inflammation, insulin resistance, and diabetes.

To take a deeper dive, Dr. Thaiss and his associates at the University of Pennsylvania, Philadelphia started with a mouse model of morbid obesity. The mice had multiple systemic sites with microbial pattern recognition ligands, signifying microbial influx from the gut. They also had genetic signatures indicating a marked disruption of junctions between epithelial cells, compared with healthy controls.

The obese mice also were much more susceptible to enteric infections with Citrobacter rodentium (a Salmonella analog), but obesity itself did not drive this risk, Dr. Thaiss explained. In fact, two different murine models of nonobese type 1 diabetes mellitus showed “leaky” intestinal epithelial adherence junctions, heightened susceptibility to C. rodentium infection, and showed systemic pathogen spread. Ribosomal DNA sequencing showed that these hyperglycemic (diabetic) mice had shifts in their gut microbiomes; however, translocating the altered microbiota to normal mice did not make them more susceptible to enteric infections or systemic inflammation.

Based on these findings, the researchers hypothesized that hyperglycemia itself drove susceptibility to enteric infections. They confirmed this by administering insulin to the mice with type 1 diabetes, which restored intestinal epithelial adherence junctions and stopped the systemic spread of pathogens. In vitro, exposing intestinal epithelial cells to glucose-induced barrier dysfunctions that increased over time and with higher glucose concentrations. RNA sequencing demonstrated that hyperglycemia markedly changed expression of genes that encode proteins that regulate intestinal barrier function. Moreover, hyperglycemic mice lacking the bidirectional glucose transporter GLUT2 showed no intestinal barrier dysfunction and were not susceptible to C. rodentium infection and systemic spread.

Finally, the investigators studied more than 30 clinical measures and microbial products in the systemic circulation of 27 healthy human volunteers. “Of all the variables we measured, HbA_1c showed the strongest correlation with the influx of microbial molecules,” said Dr. Thaiss. Serum HbA_1c correlated highly (P = .008) with levels of toll-like receptor 4, an indicator of systemic pathogens, but not with body mass index (P = .76).

The findings in humans confirm those in mice and indicate that hyperglycemia is a direct cause of intestinal barrier dysfunction and susceptibility to enteric infection, Dr. Thaiss said, adding that the systemic influx of microbial products might explain the wide range of otherwise unrelated inflammatory conditions seen in patients with metabolic syndrome. Future studies of therapies for enteric infection and systemic inflammation might focus on glucose as a modifier of intestinal barrier function.

These findings, reported at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, were also published in Science.

The work was supported by a Boehringer Ingelheim Funds PhD fellowship, the Leona M. and Harry B. Helmsley Charitable Trust, the Adelis Foundation, the Gurwin Family Fund for Scientific Research, the Crown Endowment Fund for Immunological Research, and others. Dr. Thaiss and his coinvestigators reported having no conflicts of interest.

SOURCE: Thaiss CA et al. Science. 2018;359(6382):1376-83.




 

MIAMI – High-fiber diets in the ICU were well tolerated and led to desirable shifts in the gut microbiome that correlated with decreased abdominal distension, according to the results of an observational cohort study.

“Higher fiber intake was associated with greater preservation of short-chain fatty acid–producing bacteria, even after we adjusted for antibiotics and acute severity of illness,” said Yichun Fu, a fourth-year medical student at Columbia University, New York, at the annual Gut Microbiota for Health World Summit.

She explained that, after 72 hours on the high-fiber diet, only 11% of patients had abdominal distension noted in their EMRs, compared with 36% of patients who received no dietary fiber (P less than .01). Fiber was not associated with bowel obstruction, high gastric residuals, enteric infections, edema, or diarrhea. She and her associates presented the findings in a poster at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

Dietary fiber is a prebiotic that increases the abundance of short-chain fatty acid (SCFA)–producing bacteria in the gut. Growing evidence links these bacteria and their metabolites – such as acetate, propionate, and butyrate – to immunomodulatory benefits and suggests that they help maintain gut barrier function, glucose homeostasis, adipose tissue lipolysis, and normal blood pressure. Thus, fiber for ICU patients might make sense, but relevant dietary guidelines rarely address the topic. In practice, fiber is often withheld in the ICU because of concerns that it might cause bloating or diarrhea, Ms. Fu said.

For the study, the researchers performed 16s ribosomal RNA sequencing on baseline and 72-hour rectal swabs collected from 129 consecutive adults newly admitted to the ICU. Patients were eligible for the study regardless of whether they received nothing by mouth, enteral feeding, or food by mouth. They were grouped in tertiles based on fiber intake over 72 hours, corrected by caloric intake. The resulting groups were dubbed “no fiber” (median and interquartile range, 0 grams), “low fiber” (median, 11.2 g; IQR, 3.8-18.2 g), and “high fiber” (median, 39.3 g; IQR, 4.7-50.2 g).

Patients in these three groups had a similar relative abundance of SCFA-producing bacteria at baseline. At 72 hours, the high-fiber group had a significantly greater relative abundance of SCFA producers than the no fiber group (P = .01). Compared with no fiber, high-fiber intake also correlated with significantly increased gut bacterial diversity (P = .04) and a lower relative abundance of Enterococcus bacteria (P less than .01). None of these measures differed significantly between the no-fiber and low-fiber groups.

The groups were demographically and clinically similar at baseline, except that the high-fiber group had lower Acute Physiology and Chronic Health Evaluation IV scores (P = .02) and was less likely to receive antibiotics, mechanical ventilation, hemodialysis, or vasopressors (P less than .01). After correcting for these differences, each 10-g increase in fiber intake over 72 hours correlated with a 0.3% median increase in the relative abundance of SCFA-producing bacteria (estimated IQR, 0.10%-0.46%; P less than .01).

“Fiber may be a simple candidate therapy for ICU patients,” the researchers concluded. The team is now designing a prospective, interventional study to further test whether fiber can modify the gut microbiome to benefit ICU patients, Ms. Fu explained.

Funders included the American Gastroenterological Association, the National Institutes of Health, and the Feldstein Medical Foundation. Ms. Fu reported no competing interests.

MIAMI – High-fiber diets in the ICU were well tolerated and led to desirable shifts in the gut microbiome that correlated with decreased abdominal distension, according to the results of an observational cohort study.

“Higher fiber intake was associated with greater preservation of short-chain fatty acid–producing bacteria, even after we adjusted for antibiotics and acute severity of illness,” said Yichun Fu, a fourth-year medical student at Columbia University, New York, at the annual Gut Microbiota for Health World Summit.

She explained that, after 72 hours on the high-fiber diet, only 11% of patients had abdominal distension noted in their EMRs, compared with 36% of patients who received no dietary fiber (P less than .01). Fiber was not associated with bowel obstruction, high gastric residuals, enteric infections, edema, or diarrhea. She and her associates presented the findings in a poster at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

Dietary fiber is a prebiotic that increases the abundance of short-chain fatty acid (SCFA)–producing bacteria in the gut. Growing evidence links these bacteria and their metabolites – such as acetate, propionate, and butyrate – to immunomodulatory benefits and suggests that they help maintain gut barrier function, glucose homeostasis, adipose tissue lipolysis, and normal blood pressure. Thus, fiber for ICU patients might make sense, but relevant dietary guidelines rarely address the topic. In practice, fiber is often withheld in the ICU because of concerns that it might cause bloating or diarrhea, Ms. Fu said.

For the study, the researchers performed 16s ribosomal RNA sequencing on baseline and 72-hour rectal swabs collected from 129 consecutive adults newly admitted to the ICU. Patients were eligible for the study regardless of whether they received nothing by mouth, enteral feeding, or food by mouth. They were grouped in tertiles based on fiber intake over 72 hours, corrected by caloric intake. The resulting groups were dubbed “no fiber” (median and interquartile range, 0 grams), “low fiber” (median, 11.2 g; IQR, 3.8-18.2 g), and “high fiber” (median, 39.3 g; IQR, 4.7-50.2 g).

Patients in these three groups had a similar relative abundance of SCFA-producing bacteria at baseline. At 72 hours, the high-fiber group had a significantly greater relative abundance of SCFA producers than the no fiber group (P = .01). Compared with no fiber, high-fiber intake also correlated with significantly increased gut bacterial diversity (P = .04) and a lower relative abundance of Enterococcus bacteria (P less than .01). None of these measures differed significantly between the no-fiber and low-fiber groups.

The groups were demographically and clinically similar at baseline, except that the high-fiber group had lower Acute Physiology and Chronic Health Evaluation IV scores (P = .02) and was less likely to receive antibiotics, mechanical ventilation, hemodialysis, or vasopressors (P less than .01). After correcting for these differences, each 10-g increase in fiber intake over 72 hours correlated with a 0.3% median increase in the relative abundance of SCFA-producing bacteria (estimated IQR, 0.10%-0.46%; P less than .01).

“Fiber may be a simple candidate therapy for ICU patients,” the researchers concluded. The team is now designing a prospective, interventional study to further test whether fiber can modify the gut microbiome to benefit ICU patients, Ms. Fu explained.

Funders included the American Gastroenterological Association, the National Institutes of Health, and the Feldstein Medical Foundation. Ms. Fu reported no competing interests.

MIAMI – High-fiber diets in the ICU were well tolerated and led to desirable shifts in the gut microbiome that correlated with decreased abdominal distension, according to the results of an observational cohort study.

“Higher fiber intake was associated with greater preservation of short-chain fatty acid–producing bacteria, even after we adjusted for antibiotics and acute severity of illness,” said Yichun Fu, a fourth-year medical student at Columbia University, New York, at the annual Gut Microbiota for Health World Summit.

She explained that, after 72 hours on the high-fiber diet, only 11% of patients had abdominal distension noted in their EMRs, compared with 36% of patients who received no dietary fiber (P less than .01). Fiber was not associated with bowel obstruction, high gastric residuals, enteric infections, edema, or diarrhea. She and her associates presented the findings in a poster at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.

Dietary fiber is a prebiotic that increases the abundance of short-chain fatty acid (SCFA)–producing bacteria in the gut. Growing evidence links these bacteria and their metabolites – such as acetate, propionate, and butyrate – to immunomodulatory benefits and suggests that they help maintain gut barrier function, glucose homeostasis, adipose tissue lipolysis, and normal blood pressure. Thus, fiber for ICU patients might make sense, but relevant dietary guidelines rarely address the topic. In practice, fiber is often withheld in the ICU because of concerns that it might cause bloating or diarrhea, Ms. Fu said.

For the study, the researchers performed 16s ribosomal RNA sequencing on baseline and 72-hour rectal swabs collected from 129 consecutive adults newly admitted to the ICU. Patients were eligible for the study regardless of whether they received nothing by mouth, enteral feeding, or food by mouth. They were grouped in tertiles based on fiber intake over 72 hours, corrected by caloric intake. The resulting groups were dubbed “no fiber” (median and interquartile range, 0 grams), “low fiber” (median, 11.2 g; IQR, 3.8-18.2 g), and “high fiber” (median, 39.3 g; IQR, 4.7-50.2 g).

Patients in these three groups had a similar relative abundance of SCFA-producing bacteria at baseline. At 72 hours, the high-fiber group had a significantly greater relative abundance of SCFA producers than the no fiber group (P = .01). Compared with no fiber, high-fiber intake also correlated with significantly increased gut bacterial diversity (P = .04) and a lower relative abundance of Enterococcus bacteria (P less than .01). None of these measures differed significantly between the no-fiber and low-fiber groups.

The groups were demographically and clinically similar at baseline, except that the high-fiber group had lower Acute Physiology and Chronic Health Evaluation IV scores (P = .02) and was less likely to receive antibiotics, mechanical ventilation, hemodialysis, or vasopressors (P less than .01). After correcting for these differences, each 10-g increase in fiber intake over 72 hours correlated with a 0.3% median increase in the relative abundance of SCFA-producing bacteria (estimated IQR, 0.10%-0.46%; P less than .01).

“Fiber may be a simple candidate therapy for ICU patients,” the researchers concluded. The team is now designing a prospective, interventional study to further test whether fiber can modify the gut microbiome to benefit ICU patients, Ms. Fu explained.

Funders included the American Gastroenterological Association, the National Institutes of Health, and the Feldstein Medical Foundation. Ms. Fu reported no competing interests.

A gene involved in coagulation may play a key role in inflammatory bowel disease (IBD) and offer a potential new treatment target, new research suggests.

Writing in Science Translational Medicine, researchers presented the findings of a transcriptome analysis of 1,800 intestinal biopsies from individuals with IBD across 14 different cohorts.

Their analysis revealed that the coagulation gene pathway is altered in a number of patients with active IBD and, in particular, among patients whose disease does not respond to anti–tumor necrosis factor (anti-TNF) therapy.

“Clinical studies have established that patients with IBD are at substantially increased risk for thrombotic events and those with active disease have abnormal blood coagulation parameters, but the function and mechanism remain unclear,” wrote Gerard E. Kaiko, PhD, from the University of Newcastle, Australia, in Callaghan and coauthors.

The analysis highlighted a particular component of the coagulation pathway – SERPINE1, which codes for the protein plasminogen activator inhibitor–1 (PAI-1) – whose expression was increased in colon biopsies taken from actively inflamed areas of disease, compared with biopsies of uninflamed areas, biopsies from patients in remission, or in biopsies from individuals without IBD.

The increased expression of SERPINE1/PAI-1 was mostly within epithelial cells, which the authors said supported the hypothesis that the gene is a key player in the inflammation/epithelium interface in the disease.

Researchers also found that SERPINE1 expression correlated with disease severity, and it was consistently higher in patients who had failed to respond to anti-TNF therapy. They suggested that SERPINE1/PAI-1 activity could potentially address an unmet clinical need for objective measures of disease activity and function as a way to predict response to biologic therapy.

“Although biologic therapies with anti-TNF are now a mainstay for IBD therapy, up to 40% of patients are nonresponsive, and patients lose responsiveness over time,” they wrote. “Furthermore, because more therapeutic options become available in IBD, a predictive biomarker is needed for personalized treatment.”

The authors further explored the role of SERPINE1/PAI-1 in an experimental mouse model of IBD. They found that colonic expression of the gene was around sixfold higher in mice with chemically induced colonic injury and inflammation, compared with untreated controls.

Researchers noted that PAI-1’s function is to bind and inhibit the activity of tissue plasminogen activator, which is a protein involved in the breakdown of blood clots and is coded by the gene PLAT.

They screened for which cytokine pathways might regulate PAI-1, PLAT, and tissue plasminogen activator, and they found that, while none increased SERPINE1 expression, interleukin-17A did appear to increase the expression of PLAT, which raises the possibility that IL-17A could counteract the effects of PAI-1.

The study also found that, in the colon biopsies from individuals with active disease, there was an imbalance in the ratio of PAI-1 to tissue plasminogen activator such that these biopsies showed lower levels of active tissue plasminogen activator.

“Therefore, the potentially protective mechanism of elevation of tPA [tissue plasminogen activator] does not occur properly in patients with IBD,” they wrote.

The next step was to see whether inhibiting the activity of SERPINE1 had any effect. In a mouse model of chemically induced colitis, the authors saw that treatment with a SERPINE1 inhibitor was associated with reduced weight change, mucosal damage, and reduced signs of inflammation, compared with untreated mice.

The study was supported by the Crohn’s & Colitis Foundation. Three authors were supported by grants from the National Health & Medical Research Council, one by the Cancer Institute NSW, one by an Alpha Omega Alpha – Carolyn L. Kuckein Student Research Fellowship, and two by the National Institutes of Health. Four authors have a patent pending related to PAI-1. Two authors declared advisory board positions with pharmaceutical companies, including the manufacturer of a product used in the study. Three authors are employees of Janssen R&D.

SOURCE: Kaiko GE et al. Sci. Transl. Med. 2019. doi: 10.1126/scitranslmed.aat0852.

A gene involved in coagulation may play a key role in inflammatory bowel disease (IBD) and offer a potential new treatment target, new research suggests.

Writing in Science Translational Medicine, researchers presented the findings of a transcriptome analysis of 1,800 intestinal biopsies from individuals with IBD across 14 different cohorts.

Their analysis revealed that the coagulation gene pathway is altered in a number of patients with active IBD and, in particular, among patients whose disease does not respond to anti–tumor necrosis factor (anti-TNF) therapy.

“Clinical studies have established that patients with IBD are at substantially increased risk for thrombotic events and those with active disease have abnormal blood coagulation parameters, but the function and mechanism remain unclear,” wrote Gerard E. Kaiko, PhD, from the University of Newcastle, Australia, in Callaghan and coauthors.

The analysis highlighted a particular component of the coagulation pathway – SERPINE1, which codes for the protein plasminogen activator inhibitor–1 (PAI-1) – whose expression was increased in colon biopsies taken from actively inflamed areas of disease, compared with biopsies of uninflamed areas, biopsies from patients in remission, or in biopsies from individuals without IBD.

The increased expression of SERPINE1/PAI-1 was mostly within epithelial cells, which the authors said supported the hypothesis that the gene is a key player in the inflammation/epithelium interface in the disease.

Researchers also found that SERPINE1 expression correlated with disease severity, and it was consistently higher in patients who had failed to respond to anti-TNF therapy. They suggested that SERPINE1/PAI-1 activity could potentially address an unmet clinical need for objective measures of disease activity and function as a way to predict response to biologic therapy.

“Although biologic therapies with anti-TNF are now a mainstay for IBD therapy, up to 40% of patients are nonresponsive, and patients lose responsiveness over time,” they wrote. “Furthermore, because more therapeutic options become available in IBD, a predictive biomarker is needed for personalized treatment.”

The authors further explored the role of SERPINE1/PAI-1 in an experimental mouse model of IBD. They found that colonic expression of the gene was around sixfold higher in mice with chemically induced colonic injury and inflammation, compared with untreated controls.

Researchers noted that PAI-1’s function is to bind and inhibit the activity of tissue plasminogen activator, which is a protein involved in the breakdown of blood clots and is coded by the gene PLAT.

They screened for which cytokine pathways might regulate PAI-1, PLAT, and tissue plasminogen activator, and they found that, while none increased SERPINE1 expression, interleukin-17A did appear to increase the expression of PLAT, which raises the possibility that IL-17A could counteract the effects of PAI-1.

The study also found that, in the colon biopsies from individuals with active disease, there was an imbalance in the ratio of PAI-1 to tissue plasminogen activator such that these biopsies showed lower levels of active tissue plasminogen activator.

“Therefore, the potentially protective mechanism of elevation of tPA [tissue plasminogen activator] does not occur properly in patients with IBD,” they wrote.

The next step was to see whether inhibiting the activity of SERPINE1 had any effect. In a mouse model of chemically induced colitis, the authors saw that treatment with a SERPINE1 inhibitor was associated with reduced weight change, mucosal damage, and reduced signs of inflammation, compared with untreated mice.

The study was supported by the Crohn’s & Colitis Foundation. Three authors were supported by grants from the National Health & Medical Research Council, one by the Cancer Institute NSW, one by an Alpha Omega Alpha – Carolyn L. Kuckein Student Research Fellowship, and two by the National Institutes of Health. Four authors have a patent pending related to PAI-1. Two authors declared advisory board positions with pharmaceutical companies, including the manufacturer of a product used in the study. Three authors are employees of Janssen R&D.

SOURCE: Kaiko GE et al. Sci. Transl. Med. 2019. doi: 10.1126/scitranslmed.aat0852.

A gene involved in coagulation may play a key role in inflammatory bowel disease (IBD) and offer a potential new treatment target, new research suggests.

Writing in Science Translational Medicine, researchers presented the findings of a transcriptome analysis of 1,800 intestinal biopsies from individuals with IBD across 14 different cohorts.

Their analysis revealed that the coagulation gene pathway is altered in a number of patients with active IBD and, in particular, among patients whose disease does not respond to anti–tumor necrosis factor (anti-TNF) therapy.

“Clinical studies have established that patients with IBD are at substantially increased risk for thrombotic events and those with active disease have abnormal blood coagulation parameters, but the function and mechanism remain unclear,” wrote Gerard E. Kaiko, PhD, from the University of Newcastle, Australia, in Callaghan and coauthors.

The analysis highlighted a particular component of the coagulation pathway – SERPINE1, which codes for the protein plasminogen activator inhibitor–1 (PAI-1) – whose expression was increased in colon biopsies taken from actively inflamed areas of disease, compared with biopsies of uninflamed areas, biopsies from patients in remission, or in biopsies from individuals without IBD.

The increased expression of SERPINE1/PAI-1 was mostly within epithelial cells, which the authors said supported the hypothesis that the gene is a key player in the inflammation/epithelium interface in the disease.

Researchers also found that SERPINE1 expression correlated with disease severity, and it was consistently higher in patients who had failed to respond to anti-TNF therapy. They suggested that SERPINE1/PAI-1 activity could potentially address an unmet clinical need for objective measures of disease activity and function as a way to predict response to biologic therapy.

“Although biologic therapies with anti-TNF are now a mainstay for IBD therapy, up to 40% of patients are nonresponsive, and patients lose responsiveness over time,” they wrote. “Furthermore, because more therapeutic options become available in IBD, a predictive biomarker is needed for personalized treatment.”

The authors further explored the role of SERPINE1/PAI-1 in an experimental mouse model of IBD. They found that colonic expression of the gene was around sixfold higher in mice with chemically induced colonic injury and inflammation, compared with untreated controls.

Researchers noted that PAI-1’s function is to bind and inhibit the activity of tissue plasminogen activator, which is a protein involved in the breakdown of blood clots and is coded by the gene PLAT.

They screened for which cytokine pathways might regulate PAI-1, PLAT, and tissue plasminogen activator, and they found that, while none increased SERPINE1 expression, interleukin-17A did appear to increase the expression of PLAT, which raises the possibility that IL-17A could counteract the effects of PAI-1.

The study also found that, in the colon biopsies from individuals with active disease, there was an imbalance in the ratio of PAI-1 to tissue plasminogen activator such that these biopsies showed lower levels of active tissue plasminogen activator.

“Therefore, the potentially protective mechanism of elevation of tPA [tissue plasminogen activator] does not occur properly in patients with IBD,” they wrote.

The next step was to see whether inhibiting the activity of SERPINE1 had any effect. In a mouse model of chemically induced colitis, the authors saw that treatment with a SERPINE1 inhibitor was associated with reduced weight change, mucosal damage, and reduced signs of inflammation, compared with untreated mice.

The study was supported by the Crohn’s & Colitis Foundation. Three authors were supported by grants from the National Health & Medical Research Council, one by the Cancer Institute NSW, one by an Alpha Omega Alpha – Carolyn L. Kuckein Student Research Fellowship, and two by the National Institutes of Health. Four authors have a patent pending related to PAI-1. Two authors declared advisory board positions with pharmaceutical companies, including the manufacturer of a product used in the study. Three authors are employees of Janssen R&D.

SOURCE: Kaiko GE et al. Sci. Transl. Med. 2019. doi: 10.1126/scitranslmed.aat0852.

For children and adolescents with strong clinical suspicion for celiac disease, repeated transglutaminase-2-IgA (TG2-IgA) levels that are more than 10 times higher than the upper limit of normal often suffices for diagnosis, according to an American Gastroenterological Association clinical practice update and expert review.

This approach precludes the need for esophagogastroduodenoscopy (EGD) in about 30%-50% of cases, wrote Steffen Husby, MD, PhD, of Odense University Hospital (Denmark), together with his associates in Gastroenterology. “When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for celiac disease is virtually 100%.” But for adults, they recommend confirmatory histologic analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry.

Transglutaminase-2 is the major autoantigen present in celiac disease and can now be assessed with accurate, convenient, high-throughput tests, such as enzyme-linked immunosorbent assays. To maximize test TG2-IgA accuracy, Dr. Husby and his associates recommend testing patients who have compatible signs and symptoms of celiac disease or are asymptomatic but have other risk factors, such as confirmed autoimmune diseases (type 1 diabetes, autoimmune thyroid or liver diseases), chromosome abnormalities (Down or Turner syndrome), or first-degree relatives with celiac disease.

Several other serologic tests are available but have a more limited role in diagnosing celiac disease, according to the practice update. Perhaps most useful is the endomysial antibody (EMA) test, which evaluates tissue-bound TG2-IgA. This test is highly specific but labor-intensive and user-sensitive and thus is best used to confirm a positive TG2-IgA result. Deamidated gliadin peptide antibody assays are less accurate than TG2-IgA, while HLA-DQ2/DQ8 testing is best reserved for cases where the diagnosis is complicated by a prior gluten-free diet or inconclusive antibody titers or histology.

SOURCE: Husby S et al. Gastroenterology. 2018 Dec 19. doi: 10.1053/j.gastro.2018.12.010.

For children and adolescents with strong clinical suspicion for celiac disease, repeated transglutaminase-2-IgA (TG2-IgA) levels that are more than 10 times higher than the upper limit of normal often suffices for diagnosis, according to an American Gastroenterological Association clinical practice update and expert review.

This approach precludes the need for esophagogastroduodenoscopy (EGD) in about 30%-50% of cases, wrote Steffen Husby, MD, PhD, of Odense University Hospital (Denmark), together with his associates in Gastroenterology. “When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for celiac disease is virtually 100%.” But for adults, they recommend confirmatory histologic analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry.

Transglutaminase-2 is the major autoantigen present in celiac disease and can now be assessed with accurate, convenient, high-throughput tests, such as enzyme-linked immunosorbent assays. To maximize test TG2-IgA accuracy, Dr. Husby and his associates recommend testing patients who have compatible signs and symptoms of celiac disease or are asymptomatic but have other risk factors, such as confirmed autoimmune diseases (type 1 diabetes, autoimmune thyroid or liver diseases), chromosome abnormalities (Down or Turner syndrome), or first-degree relatives with celiac disease.

Several other serologic tests are available but have a more limited role in diagnosing celiac disease, according to the practice update. Perhaps most useful is the endomysial antibody (EMA) test, which evaluates tissue-bound TG2-IgA. This test is highly specific but labor-intensive and user-sensitive and thus is best used to confirm a positive TG2-IgA result. Deamidated gliadin peptide antibody assays are less accurate than TG2-IgA, while HLA-DQ2/DQ8 testing is best reserved for cases where the diagnosis is complicated by a prior gluten-free diet or inconclusive antibody titers or histology.

SOURCE: Husby S et al. Gastroenterology. 2018 Dec 19. doi: 10.1053/j.gastro.2018.12.010.

For children and adolescents with strong clinical suspicion for celiac disease, repeated transglutaminase-2-IgA (TG2-IgA) levels that are more than 10 times higher than the upper limit of normal often suffices for diagnosis, according to an American Gastroenterological Association clinical practice update and expert review.

This approach precludes the need for esophagogastroduodenoscopy (EGD) in about 30%-50% of cases, wrote Steffen Husby, MD, PhD, of Odense University Hospital (Denmark), together with his associates in Gastroenterology. “When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for celiac disease is virtually 100%.” But for adults, they recommend confirmatory histologic analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry.

Transglutaminase-2 is the major autoantigen present in celiac disease and can now be assessed with accurate, convenient, high-throughput tests, such as enzyme-linked immunosorbent assays. To maximize test TG2-IgA accuracy, Dr. Husby and his associates recommend testing patients who have compatible signs and symptoms of celiac disease or are asymptomatic but have other risk factors, such as confirmed autoimmune diseases (type 1 diabetes, autoimmune thyroid or liver diseases), chromosome abnormalities (Down or Turner syndrome), or first-degree relatives with celiac disease.

Several other serologic tests are available but have a more limited role in diagnosing celiac disease, according to the practice update. Perhaps most useful is the endomysial antibody (EMA) test, which evaluates tissue-bound TG2-IgA. This test is highly specific but labor-intensive and user-sensitive and thus is best used to confirm a positive TG2-IgA result. Deamidated gliadin peptide antibody assays are less accurate than TG2-IgA, while HLA-DQ2/DQ8 testing is best reserved for cases where the diagnosis is complicated by a prior gluten-free diet or inconclusive antibody titers or histology.

SOURCE: Husby S et al. Gastroenterology. 2018 Dec 19. doi: 10.1053/j.gastro.2018.12.010.

A safety signal of pulmonary embolism and increased mortality has emerged in a postmarketing trial of tofacitinib (Xeljanz) in patients with rheumatoid arthritis, the Food and Drug Administration reported.

The trial’s Data Safety and Monitoring Board identified the signal in patients taking a 10-mg dose of tofacitinib twice daily, the FDA said in a safety announcement.

Pfizer, the trial’s sponsor, took “immediate action” to transition patients in the ongoing trial from the 10-mg, twice-daily dose to 5 mg twice daily, which is the approved dose for adult patients with moderate to severe rheumatoid arthritis, the agency said. The 10-mg, twice-daily dose is approved only in the dosing regimen for patients with ulcerative colitis. Xeljanz is also approved to treat psoriatic arthritis. The 11-mg, once-daily dose of Xeljanz XR that is approved to treat rheumatoid arthritis and psoriatic arthritis was not tested in the trial.

The ongoing study was designed to assess risks of cardiovascular events, cancer, and opportunistic infections with tofacitinib 10 mg twice daily or 5 mg twice daily versus the risks in a control group treated with a tumor necrosis factor (TNF) inhibitor, according to the statement.

Patients had to be 50 years of age or older and have at least one cardiovascular risk factor to be eligible for the study, which was required by the agency in 2012 when it approved tofacitinib, the statement says.

The FDA is reviewing trial data and working with Pfizer to better understand the safety signal, its effect on patients, and how tofacitinib should be used, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a news release. The trial will continue and is expected to be completed by the end of 2019.

“The agency will take appropriate action, as warranted, to ensure patients enrolled in this and other trials are protected and that health care professionals and clinical trial researchers understand the risks associated with this use,” she added.

Health care professionals should follow tofacitinib prescribing information, monitor patients for the signs and symptoms of pulmonary embolism, and advise patients to seek medical attention immediately if they experience those signs and symptoms, according to the statement.

“We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks,” Dr. Woodcock said in the release.

While not approved in rheumatoid arthritis, the 10-mg, twice-daily dose of tofacitinib is approved in the dosing regimen for patients with ulcerative colitis, the release says.

A safety signal of pulmonary embolism and increased mortality has emerged in a postmarketing trial of tofacitinib (Xeljanz) in patients with rheumatoid arthritis, the Food and Drug Administration reported.

The trial’s Data Safety and Monitoring Board identified the signal in patients taking a 10-mg dose of tofacitinib twice daily, the FDA said in a safety announcement.

Pfizer, the trial’s sponsor, took “immediate action” to transition patients in the ongoing trial from the 10-mg, twice-daily dose to 5 mg twice daily, which is the approved dose for adult patients with moderate to severe rheumatoid arthritis, the agency said. The 10-mg, twice-daily dose is approved only in the dosing regimen for patients with ulcerative colitis. Xeljanz is also approved to treat psoriatic arthritis. The 11-mg, once-daily dose of Xeljanz XR that is approved to treat rheumatoid arthritis and psoriatic arthritis was not tested in the trial.

The ongoing study was designed to assess risks of cardiovascular events, cancer, and opportunistic infections with tofacitinib 10 mg twice daily or 5 mg twice daily versus the risks in a control group treated with a tumor necrosis factor (TNF) inhibitor, according to the statement.

Patients had to be 50 years of age or older and have at least one cardiovascular risk factor to be eligible for the study, which was required by the agency in 2012 when it approved tofacitinib, the statement says.

The FDA is reviewing trial data and working with Pfizer to better understand the safety signal, its effect on patients, and how tofacitinib should be used, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a news release. The trial will continue and is expected to be completed by the end of 2019.

“The agency will take appropriate action, as warranted, to ensure patients enrolled in this and other trials are protected and that health care professionals and clinical trial researchers understand the risks associated with this use,” she added.

Health care professionals should follow tofacitinib prescribing information, monitor patients for the signs and symptoms of pulmonary embolism, and advise patients to seek medical attention immediately if they experience those signs and symptoms, according to the statement.

“We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks,” Dr. Woodcock said in the release.

While not approved in rheumatoid arthritis, the 10-mg, twice-daily dose of tofacitinib is approved in the dosing regimen for patients with ulcerative colitis, the release says.

A safety signal of pulmonary embolism and increased mortality has emerged in a postmarketing trial of tofacitinib (Xeljanz) in patients with rheumatoid arthritis, the Food and Drug Administration reported.

The trial’s Data Safety and Monitoring Board identified the signal in patients taking a 10-mg dose of tofacitinib twice daily, the FDA said in a safety announcement.

Pfizer, the trial’s sponsor, took “immediate action” to transition patients in the ongoing trial from the 10-mg, twice-daily dose to 5 mg twice daily, which is the approved dose for adult patients with moderate to severe rheumatoid arthritis, the agency said. The 10-mg, twice-daily dose is approved only in the dosing regimen for patients with ulcerative colitis. Xeljanz is also approved to treat psoriatic arthritis. The 11-mg, once-daily dose of Xeljanz XR that is approved to treat rheumatoid arthritis and psoriatic arthritis was not tested in the trial.

The ongoing study was designed to assess risks of cardiovascular events, cancer, and opportunistic infections with tofacitinib 10 mg twice daily or 5 mg twice daily versus the risks in a control group treated with a tumor necrosis factor (TNF) inhibitor, according to the statement.

Patients had to be 50 years of age or older and have at least one cardiovascular risk factor to be eligible for the study, which was required by the agency in 2012 when it approved tofacitinib, the statement says.

The FDA is reviewing trial data and working with Pfizer to better understand the safety signal, its effect on patients, and how tofacitinib should be used, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a news release. The trial will continue and is expected to be completed by the end of 2019.

“The agency will take appropriate action, as warranted, to ensure patients enrolled in this and other trials are protected and that health care professionals and clinical trial researchers understand the risks associated with this use,” she added.

Health care professionals should follow tofacitinib prescribing information, monitor patients for the signs and symptoms of pulmonary embolism, and advise patients to seek medical attention immediately if they experience those signs and symptoms, according to the statement.

“We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks,” Dr. Woodcock said in the release.

While not approved in rheumatoid arthritis, the 10-mg, twice-daily dose of tofacitinib is approved in the dosing regimen for patients with ulcerative colitis, the release says.

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. 

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.

Anatoliy Sizov/Getty Images

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.

Randy Dotinga/MDedge News

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.

Anatoliy Sizov/Getty Images

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.

Randy Dotinga/MDedge News

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.

Anatoliy Sizov/Getty Images

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.

Randy Dotinga/MDedge News

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.